Science.gov

Sample records for solid lipid nanoparticles

  1. Solid lipid nanoparticles for parenteral drug delivery.

    PubMed

    Wissing, S A; Kayser, O; Müller, R H

    2004-05-01

    This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC) nanoparticles are introduced and structural differences are pointed out. Different production methods including the suitability for large scale production are described. Stability issues and drug incorporation mechanisms into the particles are discussed. In the second part, the biological activity of parenterally applied SLN and biopharmaceutical aspects such as pharmacokinetic profiles as well as toxicity aspects are reviewed. PMID:15109768

  2. Sustained release Curcumin loaded Solid Lipid Nanoparticles

    PubMed Central

    Jourghanian, Parisa; Ghaffari, Solmaz; Ardjmand, Mehdi; Haghighat, Setareh; Mohammadnejad, Mahdieh

    2016-01-01

    Purpose: curcumin is poorly water soluble drug with low bioavailability. Use of lipid systems in lipophilic substances increases solubility and bioavailability of poorly soluble drugs. The aim of this study was to prepare curcumin loaded Solid Lipid Nanoparticles (SLNs) with high loading efficiency, small particle size and prolonged release profile with enhanced antibacterial efficacy. Methods: to synthesize stable SLNs, freeze- Drying was done using mannitol as cryoprotectant. Cholesterol was used as carrier because of good tolerability and biocompatibility. SLNs were prepared using high pressure homogenization method. Results: optimized SLNs had 112 and 163 nm particle size before and after freeze drying, respectively. The prepared SLNs had 71% loading efficiency. 90% of loaded curcumin was released after 48 hours. Morphologic study for formulation was done by taking SEM pictures of curcumin SLNs. Results show the spherical shape of curcumin SLNs. DSC studies were performed to determine prolonged release mechanism. Antimicrobial studies were done to compare the antimicrobial efficacy of curcumin SLNs with free curcumin. DSC studies showed probability of formation of hydrogen bonds between cholesterol and curcumin which resulted in prolonged release of curcumin. Lipid structure of cholesterol could cause enhanced permeability in studied bacteria to increase antibacterial characteristics of curcumin. Conclusion: the designed curcumin SLNs could be candidate for formulation of different dosage forms or cosmeceutical products. PMID:27123413

  3. Solid Lipid Nanoparticles of a Water Soluble Drug, Ciprofloxacin Hydrochloride

    PubMed Central

    Shah, M.; Agrawal, Y. K.; Garala, K.; Ramkishan, A.

    2012-01-01

    The aim of this study was to understand and investigate the relationship between experimental factors and their responses in the preparation of ciprofloxacin hydrochloride based solid lipid nanoparticles. A quadratic relationship was studied by developing central composite rotatable design. Amount of lipid and drug, stirring speed and stirring time were selected as experimental factors while particle size, zeta potential and drug entrapment were used as responses. Prior to the experimental design, a qualitative prescreening study was performed to check the effect of various solid lipids and their combinations. Results showed that changing the amount of lipid, stirring speed and stirring time had a noticeable influence on the entrapment efficiencies and particle size of the prepared solid lipid nanoparticles. The particle size of a solid lipid nanoparticle was in the range of 159-246 nm and drug encapsulation efficiencies were marginally improved by choosing a binary mixture of physically incompatible solid lipids. Release of ciprofloxacin hydrochloride from solid lipid nanoparticle was considerably slow, and it shows Higuchi matrix model as the best fitted model. Study of solid lipid nanoparticle suggested that the lipid based carrier system could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release for water soluble actives. PMID:23716872

  4. Recent advances and patents on solid lipid nanoparticles.

    PubMed

    Sawant, Krutika K; Dodiya, Shamsunder S

    2008-01-01

    Solid Lipid Nanoparticles (SLNs) have attracted increasing scientific and commercial attention as colloidal drug carriers during the last decade. They have emerged as a potential alternative compared to other colloidal systems like polymeric nanoparticles, liposomes and fat emulsions, as they have been claimed to combine their advantages but successfully overcome their drawbacks. SLN formulations are extensively developed and characterized for their in vitro and in vivo applications by various routes like parenteral, oral, pulmonary, ocular, and dermal. SLNs are being widely investigated as carriers for delivery of macromolecules like proteins, oligonucleotides and DNA. SLNs have already been taken up for medium and large scale production using two of its reported production methods. In fact, the first SLN based product has recently been introduced in the Poland market as a topically applied moisturizer. Newer methods for production of SLNs and their applications are being reported and patented. Nanostructured lipid carriers (NLC) are mixture of solid lipid and liquid lipid while Lipid Drug Conjugates (LDC) are water insoluble lipid carrier for loading of poorly lipid soluble drugs. These new generation of lipid nanoparticles have been claimed to overcome the shortcomings of SLNs. This article reviews the formulation, characterization, applications, and patents on the advances and research on SLNs, NLC and LDC. PMID:19075903

  5. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations.

    PubMed

    Müller, R H; Radtke, M; Wissing, S A

    2002-11-01

    Solid lipid nanoparticles (SLN) were developed at the beginning of the 1990 s as an alternative carrier system to emulsions, liposomes and polymeric nanoparticles. The paper reviews advantages-also potential limitations-of SLN for the use in topical cosmetic and pharmaceutical formulations. Features discussed include stabilisation of incorporated compounds, controlled release, occlusivity, film formation on skin including in vivo effects on the skin. As a novel type of lipid nanoparticles with solid matrix, the nanostructured lipid carriers (NLC) are presented, the structural specialties described and improvements discussed, for example, increase in loading capacity, physical and chemical long-term stability, triggered release and potentially supersaturated topical formulations. For both SLN and NLC, the technologies to produce the final topical formulation are described, especially the production of highly concentrated lipid nanoparticle dispersions >30-80% lipid content. Production issues also include clinical batch production, large scale production and regulatory aspects (e. g. status of excipients or proof of physical stability). PMID:12460720

  6. Anionic solid lipid nanoparticles supported on protamine/DNA complexes

    NASA Astrophysics Data System (ADS)

    Ye, Jiesheng; Wang, Aihua; Liu, Chunxi; Chen, Zhijin; Zhang, Na

    2008-07-01

    The objective of this study was to design novel anionic ternary nanoparticles for gene delivery. These ternary nanoparticles were equipped with protamine/DNA binary complexes (150-200 nm) as the support, and the anionic formation was achieved by absorption of anionic solid lipid nanoparticles (<=20 nm) onto the surface of the binary complexes. The small solid lipid nanoparticles (SLNs) were prepared by a modified film dispersion-ultrasonication method, and adsorption of the anionic SLNs onto the binary complexes was typically carried out in water via electrostatic interaction. The formulated ternary nanoparticles were found to be relatively uniform in size (257.7 ± 10.6 nm) with a 'bumpy' surface, and the surface charge inversion from 19.28 ± 1.14 mV to -17.16 ± 1.92 mV could be considered as evidence of the formation of the ternary nanoparticles. The fluorescence intensity measurements from three batches of the ternary nanoparticles gave a mean adsorption efficiency of 96.75 ± 1.13%. Circular dichroism spectra analysis showed that the protamine/DNA complexes had been coated by small SLNs, and that the anionic ternary nanoparticles formed did not disturb the construction of the binary complexes. SYBR Green I analysis suggested that the ternary nanoparticles could protect the DNA from nuclease degradation, and cell viability assay results showed that they exhibit lower cytotoxicity to A549 cells compared with the binary complexes and lipofectamine. The transfection efficiency of the ternary nanoparticles was better than that of naked DNA and the binary complexes, and almost equal to that of lipofectamine/DNA complexes, as revealed by inversion fluorescence microscope observation. These results indicated that the anionic ternary nanoparticles could facilitate gene transfer in cultured cells, and might alleviate the drawbacks of the conventional cationic vector/DNA complexes for gene delivery in vivo.

  7. Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Structure, Preparation and Application

    PubMed Central

    Naseri, Neda; Valizadeh, Hadi; Zakeri-Milani, Parvin

    2015-01-01

    Lipid nanoparticles (LNPs) have attracted special interest during last few decades. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are two major types of Lipid-based nanoparticles. SLNs were developed to overcome the limitations of other colloidal carriers, such as emulsions, liposomes and polymeric nanoparticles because they have advantages like good release profile and targeted drug delivery with excellent physical stability. In the next generation of the lipid nanoparticle, NLCs are modified SLNs which improve the stability and capacity loading. Three structural models of NLCs have been proposed. These LNPs have potential applications in drug delivery field, research, cosmetics, clinical medicine, etc. This article focuses on features, structure and innovation of LNPs and presents a wide discussion about preparation methods, advantages, disadvantages and applications of LNPs by focusing on SLNs and NLCs. PMID:26504751

  8. Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Structure, Preparation and Application.

    PubMed

    Naseri, Neda; Valizadeh, Hadi; Zakeri-Milani, Parvin

    2015-09-01

    Lipid nanoparticles (LNPs) have attracted special interest during last few decades. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are two major types of Lipid-based nanoparticles. SLNs were developed to overcome the limitations of other colloidal carriers, such as emulsions, liposomes and polymeric nanoparticles because they have advantages like good release profile and targeted drug delivery with excellent physical stability. In the next generation of the lipid nanoparticle, NLCs are modified SLNs which improve the stability and capacity loading. Three structural models of NLCs have been proposed. These LNPs have potential applications in drug delivery field, research, cosmetics, clinical medicine, etc. This article focuses on features, structure and innovation of LNPs and presents a wide discussion about preparation methods, advantages, disadvantages and applications of LNPs by focusing on SLNs and NLCs. PMID:26504751

  9. Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles.

    PubMed

    Wong, Ho Lun; Bendayan, Reina; Rauth, Andrew M; Li, Yongqiang; Wu, Xiao Yu

    2007-07-10

    The prospect of improved cancer chemotherapy using solid lipid nanoparticles (SLN) as a drug delivery system is promising. Several obstacles frequently encountered with anticancer compounds, such as normal tissue toxicity, poor specificity and stability and a high incidence of drug-resistant tumor cells, are at least partially overcome by delivering them using SLN. The emergence of the newer forms of SLN such as polymer-lipid hybrid nanoparticles, nanostructured lipid carriers and long-circulating SLN may further expand the role of this versatile drug carrier in cancer treatment. This review focuses on the current use of SLN for the encapsulation and delivery of cytotoxic anticancer compounds. It also discusses more recent trends in the use of SLN as vehicles for delivery of chemosensitizers and cytotoxic therapeutic molecules. It is anticipated that, in the near future, SLN will be further improved to deliver anticancer compounds in a more efficient, specific and safer manner. PMID:17532091

  10. Solid lipid nanoparticles for antifungal drugs delivery for topical applications.

    PubMed

    Trombino, Sonia; Mellace, Silvia; Cassano, Roberta

    2016-09-01

    Systemic and local infections caused by fungi, in particular those concerning the skin and nails, are increasing. Various drugs are used for mycoses treatment such as amphotericin B, nystatin and ketoconazole, fluconazole, itraconazole and fluconazole, among others. Unfortunately, many of these antifungal agents can cause side effects such as allergic and severe skin reaction. With the aim to reduce these side effects and maximize the antifungal drug activity, various drug-delivery systems have been formulated and been investigated in the last few years. In this context, solid lipid nanoparticles are attracting great attention. The aim of this review is to highlight the role of solid lipid nanoparticles as carriers of antifungal drugs for topical applications. PMID:27582235

  11. Solid lipid nanoparticles: a modern formulation approach in drug delivery system.

    PubMed

    Mukherjee, S; Ray, S; Thakur, R S

    2009-07-01

    Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, clinical medicine and research, as well as in other varied sciences. Due to their unique size-dependent properties, lipid nanoparticles offer the possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could be used for secondary and tertiary levels of drug targeting. Hence, solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence have attracted wide attention of researchers. This review presents a broad treatment of solid lipid nanoparticles discussing their advantages, limitations and their possible remedies. The different types of nanocarriers which were based on solid lipid like solid lipid nanoparticles, nanostructured lipid carriers, lipid drug conjugates are discussed with their structural differences. Different production methods which are suitable for large scale production and applications of solid lipid nanoparticles are described. Appropriate analytical techniques for characterization of solid lipid nanoparticles like photon correlation spectroscopy, scanning electron microscopy, differential scanning calorimetry are highlighted. Aspects of solid lipid nanoparticles route of administration and their biodistribution are also incorporated. If appropriately investigated, solid lipid nanoparticles may open new vistas in therapy of complex diseases. PMID:20502539

  12. Effect of different lipids and surfactants on formulation of solid lipid nanoparticles incorporating tamoxifen citrate.

    PubMed

    Upadhyay, S U; Patel, J K; Patel, V A; Saluja, A K

    2012-03-01

    Tamoxifen Citrate (TC) is an estrogen receptor antagonist and drug of choice for hormone sensitive breast cancer. Solid Lipid Nanoparticles loaded with TC were prepared by High Shear Homogenization followed by Ultrasonication. The aim of the present work is to study the effect of four different Solid Lipids and three Surfactants on Formulation and Stability of SLN. They were characterized for Particle size, Polydispersity Index and Zeta Potential by Zetasizer Nano. SLN prepared by Solid Lipid Compritol 888 (Glyceryldibehenate) and Tween 80 (1%) showed desired Particle Size of 206.9 nm, PDI of 0.046 and Zeta Potential of 9.32 mV. PMID:23066183

  13. Chemiluminescent solid lipid nanoparticles (SLN) and interations with intact skin

    NASA Astrophysics Data System (ADS)

    Breidenich, Jennifer; Patrone, Julia; Kelly, Lisa; Benkoski, Jason; Le, Huong; Sample, Jennifer

    2009-08-01

    We report the synthesis and characterization of a novel nanoparticle formulation designed for skin penetration for the purpose of skin imaging. Solid lipid nanoparticles (SLNs), a drug delivery vehicle, were used as the matrix for targeted delivery of peroxide-sensitive chemiluminescent compounds to the epidermis. Luminol and oxalate were chosen as the chemiluminescent test systems, and a formulation was determined based upon non-toxic components, lotion-like properties, and longevity/visibility of a chemiluminescent signal. The luminescence lifetime was extended in the lipid formulation in comparison to the chemiluminescent system in solution. When applied to porcine skin, our formulation remained detectable relative to negative and positive controls. Initial MTT toxicity testing using HepG2 cells have indicated that this formulation is relatively non-toxic. This formulation could be used to image native peroxides present in tissue that may be indicative of skin disease.

  14. Solid lipid nanoparticles: promising therapeutic nanocarriers for drug delivery.

    PubMed

    Thukral, Dipti Kakkar; Dumoga, Shweta; Mishra, Anil K

    2014-01-01

    Development of colloidal delivery systems has opened new avenues/frontiers for improving drug delivery. Solid lipid nanoparticles have come up as the latest development in the arena of lipid based colloidal delivery systems after nanoemulsion and liposomes ever since their introduction in the early 1990s. In this review, the authors have made efforts to bring forth the essential and practically relevant aspects of SLNs. This review gives an overview of the preparation methods of solid lipid nanoparticles while mainly focussing on their biological applications including their projected applications in drug delivery. This review critically examines the influential factors governing the formation of SLNs and then discussing in detail the several techniques being utilized for their characterization. This review discusses the drug loading and drug release aspects of SLNs as these are useful biocompatible carriers of lipophilic and to a certain extent hydrophilic drugs. An updated list of drugs encapsulated into various lipids to prepare SLN formulations has been provided. Other relevant aspects pertaining to the clinical use of SLN formulations like their sterilization and storage stability have also been explained. A unique facet of this review is the discussion on the challenging issues of in vivo applications and recent progresses in overcoming these challenges which follows in the end. PMID:25469779

  15. Continuous manufacturing of solid lipid nanoparticles by hot melt extrusion.

    PubMed

    Patil, Hemlata; Kulkarni, Vijay; Majumdar, Soumyajit; Repka, Michael A

    2014-08-25

    Solid lipid nanoparticles (SLN) can either be produced by hot homogenization of melted lipids at higher temperatures or by a cold homogenization process. This paper proposes and demonstrates the formulation of SLN for pharmaceutical applications by combining two processes: hot melt extrusion (HME) technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. This work aimed at developing continuous and scalable processes for SLN by mixing a lipid and aqueous phase containing an emulsifier in the extruder barrel at temperatures above the melting point of the lipid and further reducing the particle size of emulsion by HPH linked to HME in a sequence. The developed novel platform demonstrated better process control and size reduction compared to the conventional process of hot homogenization (batch process). Varying the process parameters enabled the production of SLN below 200 nm (for 60 mg/ml lipid solution at a flow rate of 100ml/min). Among the several process parameters investigated, the lipid concentration, residence time and screw design played major roles in influencing the size of the SLN. This new process demonstrates the potential use of hot melt extrusion technology for continuous and large-scale production of SLN.

  16. Improved antimycobacterial activity of rifampin using solid lipid nanoparticles

    NASA Astrophysics Data System (ADS)

    Aboutaleb, Ehsan; Noori, Massoumeh; Gandomi, Narges; Atyabi, Fatemeh; Fazeli, Mohammad Reza; Jamalifar, Hossein; Dinarvand, Rassoul

    2012-10-01

    Rifampin (RIF) is one of the front-line drugs in therapy of tuberculosis (TB). The emergence of multidrug-resistant strains of mycobacteria has greatly contributed to the increased incidence of TB. Nano-based formulation of several antimicrobials has been shown to improve either antibacterial efficacy or pharmacokinetic behavior. In this study, RIF-loaded solid lipid nanoparticles (SLNs) were prepared by a modified microemulsion-based method and their particle size, zeta potential, encapsulation efficiency, morphology, and antibacterial activity against Mycobacterium fortuitum were evaluated. The resulting SLNs were spherical with diameter of about 100 nm, with low negative zeta potential, and an encapsulation efficiency of 82%. The formulation also sustained the drug release for 72 h. The antimycobacterial efficacy was greatly improved against M. fortuitum, and the minimum inhibitory concentration of drug-loaded SLNs was eight times less than free RIF. Drug-free SLNs and the ingredients showed no antibacterial effect. It can be concluded that as expected, solid lipid nanoparticles are promising vehicles for enhanced antimycobacterial effect of rifampin.

  17. Solid lipid nanoparticles of guggul lipid as drug carrier for transdermal drug delivery.

    PubMed

    Gaur, Praveen Kumar; Mishra, Shikha; Purohit, Suresh

    2013-01-01

    Diclofenac sodium loaded solid lipid nanoparticles (SLNs) were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG) and plain carbopol gel containing drug (CG) for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1) and stearic acid nanoparticle 1 (SAN-1) gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3) showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher C(max) than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile.

  18. Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

    PubMed Central

    Gaur, Praveen Kumar; Mishra, Shikha; Purohit, Suresh

    2013-01-01

    Diclofenac sodium loaded solid lipid nanoparticles (SLNs) were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG) and plain carbopol gel containing drug (CG) for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1) and stearic acid nanoparticle 1 (SAN-1) gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3) showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher Cmax than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile. PMID:24058913

  19. The production and characteristics of solid lipid nanoparticles (SLNs).

    PubMed

    Hou, DongZhi; Xie, ChangSheng; Huang, KaiJin; Zhu, ChangHong

    2003-05-01

    Modified high shear homogenization and ultrasound techniques were employed to produce solid lipid nanoparticles (SLNs). Model drug mifepristone had been incorporated in SLNs. The mean particle size measured by laser diffractometry (LD) was found to be 106 nm with a narrow particle distribution of polydispersity index, 0.278. Differential scanning calorimetry and X-ray diffraction measurements suggested that the majority of the SLNs were less ordered arrangement of crystals, and this was favorable for increasing the drug loading capacity. The drug entrapment efficiency (EE%) of SLNs was more than 87 percent and showed relatively long-term physical stability as the leakage was very small after being stored for one month. Therefore, seemed this modified method could prepare high quality SLNs loading lipophilic drugs. It is a simple, available and effective method to produce SLNs.

  20. Controlling solid lipid nanoparticle adhesion by polyelectrolyte multilayer surface modifications.

    PubMed

    Finke, Jan Henrik; Schmolke, Hannah; Klages, C-P; Müller-Goymann, Christel C

    2013-06-01

    This study addresses the tunability of polyelectrolyte multilayers (PEM) toward adsorption of solid lipid nanoparticles (SLN). In SLN production for pharmaceutical applications, repellence from production equipment is desired while targeted adsorption is necessary for the functionalization of surfaces. SLN containing triglyceride/phospholipid or wax matrices were exposed to different PEM (consisting of poly(allylamine hydrochloride) (PAH), poly(diallyldimethylammonium chloride), and poly(acrylic acid)). PEM varied regarding layer architecture and surface properties by means of deposition pH, top layer variation, PEGylation with poly(acrylic acid)-graft-poly(ethylene glycol) copolymer, and thermal crosslinking. FTIR-ATR and SEM revealed SLN adhesion depending on PEM composition. Particle adsorption was tunable toward attraction as well as repellence: PEGylated PEM displayed lowest adsorption while PEM capped with PAH provided the strongest attraction of particles. Examinations at elevated temperatures resembled production conditions of SLN where these are processed as emulsions. Crystalline triglyceride SLN displayed high anisometry and, consequently, a large specific surface area. These platelets were more adherend than spherical droplets from the same formulation as an emulsion. Wax-based nanoparticles showed spherical shape, both in crystalline and molten state. However, adsorption was fostered as the fluidity of the disperse phase increased upon melting. Additionally, coalescence of adsorbed droplets took place, further increasing adsorption. PMID:23591009

  1. Controlling solid lipid nanoparticle adhesion by polyelectrolyte multilayer surface modifications.

    PubMed

    Finke, Jan Henrik; Schmolke, Hannah; Klages, C-P; Müller-Goymann, Christel C

    2013-06-01

    This study addresses the tunability of polyelectrolyte multilayers (PEM) toward adsorption of solid lipid nanoparticles (SLN). In SLN production for pharmaceutical applications, repellence from production equipment is desired while targeted adsorption is necessary for the functionalization of surfaces. SLN containing triglyceride/phospholipid or wax matrices were exposed to different PEM (consisting of poly(allylamine hydrochloride) (PAH), poly(diallyldimethylammonium chloride), and poly(acrylic acid)). PEM varied regarding layer architecture and surface properties by means of deposition pH, top layer variation, PEGylation with poly(acrylic acid)-graft-poly(ethylene glycol) copolymer, and thermal crosslinking. FTIR-ATR and SEM revealed SLN adhesion depending on PEM composition. Particle adsorption was tunable toward attraction as well as repellence: PEGylated PEM displayed lowest adsorption while PEM capped with PAH provided the strongest attraction of particles. Examinations at elevated temperatures resembled production conditions of SLN where these are processed as emulsions. Crystalline triglyceride SLN displayed high anisometry and, consequently, a large specific surface area. These platelets were more adherend than spherical droplets from the same formulation as an emulsion. Wax-based nanoparticles showed spherical shape, both in crystalline and molten state. However, adsorption was fostered as the fluidity of the disperse phase increased upon melting. Additionally, coalescence of adsorbed droplets took place, further increasing adsorption.

  2. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery.

    PubMed

    Das, Surajit; Chaudhury, Anumita

    2011-03-01

    Lipid nanoparticles based on solid matrix have emerged as potential drug carriers to improve gastrointestinal (GI) absorption and oral bioavailability of several drugs, especially lipophilic compounds. These formulations may also be used for sustained drug release. Solid lipid nanoparticle (SLN) and the newer generation lipid nanoparticle, nanostructured lipid carrier (NLC), have been studied for their capability as oral drug carriers. Biodegradable, biocompatible, and physiological lipids are generally used to prepare these nanoparticles. Hence, toxicity problems related with the polymeric nanoparticles can be minimized. Furthermore, stability of the formulations might increase than other liquid nano-carriers due to the solid matrix of these lipid nanoparticles. These nanoparticles can be produced by different formulation techniques. Scaling up of the production process from lab scale to industrial scale can be easily achieved. Reasonably high drug encapsulation efficiency of the nanoparticles was documented. Oral absorption and bioavailability of several drugs were improved after oral administration of the drug-loaded SLNs or NLCs. In this review, pros and cons, different formulation and characterization techniques, drug incorporation models, GI absorption and oral bioavailability enhancement mechanisms, stability and storage condition of the formulations, and recent advances in oral delivery of the lipid nanoparticles based on solid matrix will be discussed. PMID:21174180

  3. Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles

    PubMed Central

    Cai, Shuang; Zhang, Qiuhong; Bagby, Taryn; Forrest, M. Laird

    2011-01-01

    The lymphatic system plays a crucial role in the immune system’s recognition and response to disease, and most solid cancers initially spread from the primary site via the tumor’s surrounding lymphatics before hematological dissemination. Hence, the lymphatic system is an important target for developing new vaccines, cancer treatments, and diagnostic agents. Targeting the lymphatic system by subcutaneous, intestinal, and pulmonary routes has been evaluated and subsequently utilized to improve lymphatic penetration and retention of drug molecules, reduce drug-related systemic toxicities, and enhance bioavailability of poorly soluble and unstable drugs. Lymphatic imaging is an essential tool for the detection and staging of cancer. New nano-based technologies offer improved detection and characterization of the nodal diseases, while new delivery devices can better target and confine treatments to tumors within the nodal space while sparing healthy tissues. This manuscript reviews recent advances in the field of lymphatic drug delivery and imaging and focuses specifically on the development ofliposomes and solid lipid nanoparticles for lymphatic introduction via the subcutaneous, intestinal, and pulmonary routes. PMID:21712055

  4. Enhanced dermal delivery of acyclovir using solid lipid nanoparticles.

    PubMed

    Jain, Sanyog; Mistry, Meghal A; Swarnakar, Nitin K

    2011-10-01

    The present investigation was enthused by the possibility to develop solid lipid nanoparticles (SLNs) of hydrophilic drug acyclovir (ACV) and evaluate their potential as the carrier for dermal delivery. ACV-loaded SLNs (ACV-SLNs) were prepared by the optimized double emulsion process using Compritol 888 ATO as solid lipid. The prepared SLNs were smooth and spherical in shape with average diameter, polydispersity index, and entrapment efficiency of 262 ± 13 nm, 0.280 ± 0.01, and 40.08 ± 4.39% at 10% (w/w) theoretical drug loading with respect to Compritol 888 ATO content. Differential scanning calorimetry and powder X-ray diffraction pattern revealed that ACV was present in the amorphous state inside the SLNs. In vitro skin permeation studies on human cadaver and Sprague-Dawley rat skin revealed 17.65 and 15.17 times higher accumulation of ACV-SLNs in the dermal tissues in comparison to commercially available ACV cream after 24 h. Mechanism of topical permeation and dermal distribution was studied qualitatively using confocal laser scanning microscopy. While free dye (calcein) failed to penetrate skin barrier, the same encapsulated in SLNs penetrated deeply into the dermal tissue suggesting that pilosebaceous route was followed by SLNs for skin penetration. Histological examination and transdermal epidermal water loss measurement suggested that no major morphological changes occurred on rat skin surface due to the application of SLNs. Overall, it was concluded that ACV-loaded SLNs might be beneficial in improving dermal delivery of antiviral agent(s) for the treatment of topical herpes simplex infection.

  5. Solid lipid nanoparticles for delivery of Calendula officinalis extract.

    PubMed

    Arana, Lide; Salado, Clarisa; Vega, Sandra; Aizpurua-Olaizola, Oier; de la Arada, Igor; Suarez, Tatiana; Usobiaga, Aresatz; Arrondo, José Luis R; Alonso, Alicia; Goñi, Félix M; Alkorta, Itziar

    2015-11-01

    Solid lipid nanoparticles (SLN) composed of long-chain fatty acids (palmitic acid, stearic acid or arachidic acid), Epikuron 200 (purified phosphatidylcholine), and bile salts (cholate, taurocholate or taurodeoxycholate) have been prepared by dilution of a microemulsion. A total of five different systems were prepared, and characterized by photon correlation spectroscopy, transmission electron microscopy, differential scanning calorimetry, and infrared spectroscopy. The SLN formulation showing optimal properties (lowest size and polydispersity index and highest zeta potential) was obtained with stearic acid and taurodeoxycholate as cosurfactant. This formulation was loaded with Calendula officinalis extract, a natural compound used on ophthalmic formulations given its anti-inflammatory, emollient, and wound repairing activity. Calendula-loaded SLN preparations were characterized in order to determine loading capacity and entrapment efficiency. In vitro cytotoxicity and wound healing efficacy of Calendula-loaded SLN compared to that of a free plant extract were evaluated on a conjunctival epithelium cell line WKD. Our results suggest that this SLN formulation is a safe and solvent-free Calendula extract delivery system which could provide a controlled therapeutic alternative for reducing disease-related symptoms and improving epithelium repair in ocular surface. PMID:26231862

  6. Low Density Lipid Nanoparticles for Solid Tumor Targeting

    PubMed Central

    Shrivastava, Mayank; Jain, Aviral; Gulbake, Arvind; Hurkat, Pooja; Jain, Neeti; Vijayraghwan, R.; Jain, Sanjay K.

    2014-01-01

    Abstract One of the most significant characteristics of cancer cells is their rapid dividing ability and overexpression of LDL receptors, which offers an opportunity for the selective targeting of these cells. 5-Fluorouracil (5-FU)-encapsulated low density lipid nanoparticles (LDLN) were prepared by the emulsion congealing method which mimics the plasma-derived LDL by acquiring the apolipoprotein B-100 from the blood. The average particle size, transmission electron microscope (TEM), and drug content of the prepared LDLN dispersion were found to be 161±3.5 nm, with spherical shape, and 0.370±0.05 mg/mL, respectively. In vitro release studies revealed a sustained profile which decreased with a lapse of time. In vivo studies of 5-FU serum concentration and biodistribution revealed a 5-FU serum concentration of 8.5% in tumor cells and about 2.1% in the liver at the end of 24 hr from LDLN. Tumor growth suppression studies showed 185.42% average tumor growth and 89.76% tumor height as compared to the control exhibiting tumor growth at 1166.47% and tumor height at 176.07%. On the basis of these collective data, it is suggested that a higher accumulation of LDLN, when given as an IV, in solid tumors is attributed to the active uptake of LDLN via LDL receptors via apolipoprotein B-100. PMID:26279976

  7. Preparation and pharmacokinetic evaluation of Tashinone IIA solid lipid nanoparticles.

    PubMed

    Liu, Jianping; Zhu, Jiabi; Du, Zhiyong; Qin, Bin

    2005-07-01

    Tashinone IIA loaded solid lipid nanoparticles (TA-SLN) coated with poloxamer 188 was prepared by emulsification/evaporation. The TA-SLN was characterized by transmission electron microscope and dynamic light scattering (DLS). The results showed that the TA-SLN had an average diameter of 98.7 nm with a zeta potential of - 31.6 mv and the drug loading of 4.6% and entrapment efficiency of 87.7%. In vitro release experiment showed that the release of Tashinone IIA from TA-SLN was in accordance with the Weibull equation. The best model fitting experimental data was a two-compartment open model with first-order. The area under curve of plasma concentration-time (AUC) and mean residence time (MRT) of TA-SLN were much higher than those of Tashinone IIA control solution (TA-SOL). The results of pharmacokinetic studies in rabbits indicated that the formulation of TA-SLN was successful in providing a delivery of slow release of Tashinone IIA. PMID:16109628

  8. Galactose engineered solid lipid nanoparticles for targeted delivery of doxorubicin.

    PubMed

    Jain, Ashay; Kesharwani, Prashant; Garg, Neeraj K; Jain, Atul; Jain, Som Akshay; Jain, Amit Kumar; Nirbhavane, Pradip; Ghanghoria, Raksha; Tyagi, Rajeev Kumar; Katare, Om Prakash

    2015-10-01

    The present investigation reports the preparation, optimization, and characterization of surface engineered solid lipid nanoparticles (SLNs) encapsulated with doxorubicin (DOX). Salient features such as biocompatibility, controlled release, target competency, potential of penetration, improved physical stability, low cost and ease of scaling-up make SLNs viable alternative to liposomes for effective drug delivery. Galactosylation of SLNs instructs some gratifying characteristic, which leads to the evolution of promising delivery vehicles. The impendence of lectin receptors on different cell surfaces makes the galactosylated carriers admirable for targeted delivery of drugs to ameliorate their therapeutic index. Active participation of some lectin receptors in immune responses to antigen overlaid the application of galactosylated carriers in delivery of antigen and immunotherapy for treatment of maladies like cancer. These advantages revealed the promising potential of galactosylated carriers in each perspective of drug delivery. The developed DOX loaded galactosylated SLNs formulation was found to have particle size 239 ± 2.40 nm, PDI 0.307 ± 0.004, entrapment efficiency 72.3 ± 0.9%. Higher cellular uptake, cytotoxicity, and nuclear localization of galactosylated SLNs against A549 cells revealed higher efficiency of the formulation. In a nutshell, the galactosylation strategy with SLNs could be a promising approach in improving the delivery of DOX for cancer therapy. PMID:26142628

  9. Solid lipid nanoparticles for delivery of Calendula officinalis extract.

    PubMed

    Arana, Lide; Salado, Clarisa; Vega, Sandra; Aizpurua-Olaizola, Oier; de la Arada, Igor; Suarez, Tatiana; Usobiaga, Aresatz; Arrondo, José Luis R; Alonso, Alicia; Goñi, Félix M; Alkorta, Itziar

    2015-11-01

    Solid lipid nanoparticles (SLN) composed of long-chain fatty acids (palmitic acid, stearic acid or arachidic acid), Epikuron 200 (purified phosphatidylcholine), and bile salts (cholate, taurocholate or taurodeoxycholate) have been prepared by dilution of a microemulsion. A total of five different systems were prepared, and characterized by photon correlation spectroscopy, transmission electron microscopy, differential scanning calorimetry, and infrared spectroscopy. The SLN formulation showing optimal properties (lowest size and polydispersity index and highest zeta potential) was obtained with stearic acid and taurodeoxycholate as cosurfactant. This formulation was loaded with Calendula officinalis extract, a natural compound used on ophthalmic formulations given its anti-inflammatory, emollient, and wound repairing activity. Calendula-loaded SLN preparations were characterized in order to determine loading capacity and entrapment efficiency. In vitro cytotoxicity and wound healing efficacy of Calendula-loaded SLN compared to that of a free plant extract were evaluated on a conjunctival epithelium cell line WKD. Our results suggest that this SLN formulation is a safe and solvent-free Calendula extract delivery system which could provide a controlled therapeutic alternative for reducing disease-related symptoms and improving epithelium repair in ocular surface.

  10. Influence of Surfactant and Lipid Type on the Physicochemical Properties and Biocompatibility of Solid Lipid Nanoparticles

    PubMed Central

    Pizzol, Carine Dal; Filippin-Monteiro, Fabíola Branco; Restrepo, Jelver Alexander Sierra; Pittella, Frederico; Silva, Adny Henrique; de Souza, Paula Alves; de Campos, Angela Machado; Creczynski-Pasa, Tânia Beatriz

    2014-01-01

    Nine types of solid lipid nanoparticle (SLN) formulations were produced using tripalmitin (TPM), glyceryl monostearate (GM) or stearic acid (SA), stabilized with lecithin S75 and polysorbate 80. Formulations were prepared presenting PI values within 0.25 to 0.30, and the physicochemical properties, stability upon storage and biocompatibility were evaluated. The average particle size ranged from 116 to 306 nm, with a negative surface charge around −11 mV. SLN presented good stability up to 60 days. The SLN manufactured using SA could not be measured by DLS due to the reflective feature of this formulation. However, TEM images revealed that SA nanoparticles presented square/rod shapes with an approximate size of 100 nm. Regarding biocompatibility aspects, SA nanoparticles showed toxicity in fibroblasts, causing cell death, and produced high hemolytic rates, indicating toxicity to red blood cells. This finding might be related to lipid type, as well as, the shape of the nanoparticles. No morphological alterations and hemolytic effects were observed in cells incubated with SLN containing TPM and GM. The SLN containing TPM and GM showed long-term stability, suggesting good shelf-life. The results indicate high toxicity of SLN prepared with SA, and strongly suggest that the components of the formulation should be analyzed in combination rather than separately to avoid misinterpretation of the results. PMID:25141003

  11. Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis

    PubMed Central

    Soni, Maheshkumar P.; Shelkar, Nilakash; Gaikwad, Rajiv V.; Vanage, Geeta R.; Samad, Abdul; Devarajan, Padma V.

    2014-01-01

    Background: Buparvaquone (BPQ), a hydroxynaphthoquinone derivative, has been investigated for the treatment of many infections and is recommended as the gold standard for the treatment of theileriosis. Theileriosis, an intramacrophage infection is localized mainly in reticuloendotheileial system (RES) organs. The present study investigates development of solid lipid nanoparticles (SLN) of BPQ for targeted delivery to the RES. Materials and Methods: BPQ SLN was prepared using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80°C). Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN of designed size were obtained using ultraturrax and high pressure homogenizer. A freeze and thaw study was used to optimize type and concentration of cryoprotectant with Sf: Mean particle size, Si: Initial particle size <1.3. Differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and scanning electron microscope (SEM) study was performed on optimized formulation. Formulation was investigated for in vitro serum stability, hemolysis and cell uptake study. Pharmacokinetic and biodistribution study was performed in Holtzman rat. Results: Based on solubility in lipid; glyceryl monostearate (GMS) was selected for preparation of BPQ SLN. Batches of BPQ SLN were optimized for average particle size and entrapment efficiency at <100 mg solid content. A combination of Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning electron microscope revealed spherical morphology. BPQ SLN revealed good stability at 4°C and 25°C. Low hemolytic potential (<8%) and in vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937 cell was low. The macrophage cell line revealed high (52%) uptake of BPQ SLN in 1 h suggesting the potential to RES uptake. SLN revealed longer

  12. Recent Techniques and Patents on Solid Lipid Nanoparticles as Novel Carrier for Drug Delivery.

    PubMed

    Khatak, Sunil; Dureja, Harish

    2015-01-01

    The various approaches have been utilized in the treatment of a variety of diseases by applying drug delivery system such as polymeric nanoparticles, self-emulsifying delivery systems, liposomes, microemulsions and micellar solutions. Recently, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and lipid-drug conjugates (LDCs) have been exploited as a carrier of lipophilic and hydrophilic/amphiphilic substances for invasive and non-invasive routes of delivery. SLNs are colloidal drug carrier system and are like nanoemulsion, however, the lipid content in SLNs is solid in nature. These novel type of lipid nanoparticles with solid matrix offers to develop new prototype therapeutics in drug delivery, which could be used for controlled release, drug targeting, gene therapy, physical and chemical stability and site-specific drug delivery and thereby attracted the research groups worldwide. This manuscript overviews the recent patents, advantages, formulation techniques, stability aspects and applications of SLNs. PMID:27009132

  13. Formulation and Evaluation of Morin-Loaded Solid Lipid Nanoparticles.

    PubMed

    Ikeuchi-Takahashi, Yuri; Ishihara, Chizuko; Onishi, Hiraku

    2016-09-01

    In this study, solid lipid nanoparticle (SLN) suspensions were prepared using a base of hard fat with or without ethylcellulose (EC) and polyvinyl alcohols (PVA) and polysorbate (Tween) 60 surfactants. Commercially available PVAs vary in their degree of saponification and polymerization, and the appropriate PVAs to form SLNs from hard fat with or without EC were investigated. A relatively low-saponification-degree PVA was required to reproducibly form SLN suspensions without EC and relatively high-saponification-degree PVAs were suitable for SLNs with EC. The release of morin from SLNs with EC was more sustained than that from SLNs without EC. The maximum plasma concentration (Cmax) of SLNs with and without EC were almost the same, and both were higher than that of a morin suspension. The area under the curve for 0 to 360 min (AUC0-360) of SLNs with EC was increased compared with those of a morin suspension and SLNs without EC. The median diameter of SLNs with EC and a very low-saponification-degree PVA was decreased compared to other formulation, and morin release was more sustained for this formulation. SLNs with EC and a very low-saponification-degree PVA showed higher Cmax and AUC0-360 than SLNs with EC lacking a very low-saponification-degree PVA. The optimized SLNs with EC and a very low-saponification-degree PVA improved bioavailability via increased accessibility to the enterocyte surface by decreased particle size and increased permeation of SLN encapsulated morin through the intestinal membrane by sustained release properties.

  14. Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) for pulmonary application: a review of the state of the art.

    PubMed

    Weber, S; Zimmer, A; Pardeike, J

    2014-01-01

    Drug delivery by inhalation is a noninvasive means of administration that has following advantages for local treatment for airway diseases: reaching the epithelium directly, circumventing first pass metabolism and avoiding systemic toxicity. Moreover, from the physiological point of view, the lung provides advantages for systemic delivery of drugs including its large surface area, a thin alveolar epithelium and extensive vasculature which allow rapid and effective drug absorption. Therefore, pulmonary application is considered frequently for both, the local and the systemic delivery of drugs. Lipid nanoparticles - Solid Lipid Nanoparticles and Nanostructured Lipid Carriers - are nanosized carrier systems in which solid particles consisting of a lipid matrix are stabilized by surfactants in an aqueous phase. Advantages of lipid nanoparticles for the pulmonary application are the possibility of a deep lung deposition as they can be incorporated into respirables carriers due to their small size, prolonged release and low toxicity. This paper will give an overview of the existing literature about lipid nanoparticles for pulmonary application. Moreover, it will provide the reader with some background information for pulmonary drug delivery, i.e., anatomy and physiology of the respiratory system, formulation requirements, application forms, clearance from the lung, pharmacological benefits and nanotoxicity. PMID:24007657

  15. Preparation of solid lipid nanoparticles by a solvent emulsification-diffusion technique.

    PubMed

    Trotta, Michele; Debernardi, Francesca; Caputo, Otto

    2003-05-12

    A preparation method for nanoparticles based on the emulsification of a butyl lactate or benzyl alcohol solution of a solid lipid in an aqueous solution of different emulsifiers, followed by dilution of the emulsion with water, was used to prepare glyceryl monostearate nanodispersions with narrow size distribution. To increase the lipid load the process was conducted at 47+/-2 degrees C and in order to reach submicron size a high-shear homogenizer was used. Particle size of the solid lipid nanoparticles (SLN) was affected by using different emulsifiers and different lipid loads. By using lecithin and taurodeoxycholic acid sodium salt, on increasing the GMS percentage from 2.5 to 10% an increase of the mean diameter from 205 to 695 nm and from 320 to 368nm was observed for the SLN prepared using benzyl alcohol and butyl lactate, respectively. Transmission electron micrographs of SLN reveal nanospheres with a smooth surface.

  16. Effect of surfactant on temperature stability of solid lipid nanoparticles studied by dynamic light scattering

    NASA Astrophysics Data System (ADS)

    Kumar, Sacheen; Kaur, Jaspreet

    2013-06-01

    Solid lipid nanoparticles are new paradigm of drug delivery system of water insoluble active pharmaceutical ingredient. Paliperidone, an antipsychotic used in treatment of schizophrenia is a water insoluble molecule with low bioavailability was studied. Macrogol glyceride surfactant, bile salt based surfactant and sodium dodecyl sulphate were used to stabilize the solid lipid as dispersed nanoparticles form by adsorbing on the surface of the nanoparticles. Anionic surfactants bile salt and sodium dodecyl sulphate were found to stabilize forming a monomolecular layer of surfactants on the surface of nanoparticles; whereas macrogol glyceride based surfactant have intrusion in the matrix of lipid nanoparticles. So intrusion of macrogol glyceride in matrix was observed by studying the change in size of nanoparticles with respect to temperature with the help of dynamic light scattering. In case of macrogol glyceride size decrease start form 50°C, for bile salt and sodium dodecyl sulphate size deacrease start at 60°C. So that structural disturbance of nanoparticles by the macrogol glyceride on the surface was found maximum as compared to anionic surfactant.

  17. The Impact of Variables on Particle Size of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers; A Comparative Literature Review.

    PubMed

    Azhar Shekoufeh Bahari, Leila; Hamishehkar, Hamed

    2016-06-01

    During the past decade, pharmaceutical science has seen rapid growth in interest for nanoscale materials. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are popular research topics recently introduced as nano-scale drug carriers; they have shown numerous merits in drug delivery. Size is the most important index in a nanocarrier affecting its drug delivery efficiency. The influence of preparation conditions and type of lipidic components on the size of SLN and NLC in comparable states seems to be interesting for researchers who investigate these types of carriers. This review highlights the results of SLN and NLC particle size and size distribution comparisons. PMID:27478775

  18. The Impact of Variables on Particle Size of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers; A Comparative Literature Review

    PubMed Central

    Azhar Shekoufeh Bahari, Leila; Hamishehkar, Hamed

    2016-01-01

    During the past decade, pharmaceutical science has seen rapid growth in interest for nanoscale materials. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are popular research topics recently introduced as nano-scale drug carriers; they have shown numerous merits in drug delivery. Size is the most important index in a nanocarrier affecting its drug delivery efficiency. The influence of preparation conditions and type of lipidic components on the size of SLN and NLC in comparable states seems to be interesting for researchers who investigate these types of carriers. This review highlights the results of SLN and NLC particle size and size distribution comparisons. PMID:27478775

  19. Quillaja saponin: A prospective emulsifier for the preparation of solid lipid nanoparticles.

    PubMed

    Karthik, Siram; Raghavan, Chellan Vijaya; Marslin, Gregory; Rahman, Habibur; Selvaraj, Divakar; Balakumar, Krishnamoorthy; Franklin, Gregory

    2016-11-01

    Quillaja saponin (QS) is a non-ionic amphiphilic surfactant of natural origin. In the present study, we evaluated its potential to form solid lipid nanoparticles (SLNs) in the presence of stearic acid (SA) as a lipid carrier and imatinib mesylate (IM) as a model drug. IM loaded solid lipid nanoparticles (IMSLNs) were prepared using the hot homogenisation method. Characterisation of IMSLNs revealed that they were quasi-spherical in shape, neutrally charged and 143.5-641.9nm in size. Haemolysis, a toxicity issue of QS was not observed in SLNs. Comparative in vitro cytotoxicity analyses performed in human breast cancer cell line MCF7 revealed that IMSLNs were more toxic than IM. On the other hand, in vitro viability studies in the RAW264.7 cell line did not show any sign of toxicity by IMSLNs. Our results indicate that QS hold great potential in nano drug delivery as an emulsifier. PMID:27521748

  20. Quillaja saponin: A prospective emulsifier for the preparation of solid lipid nanoparticles.

    PubMed

    Karthik, Siram; Raghavan, Chellan Vijaya; Marslin, Gregory; Rahman, Habibur; Selvaraj, Divakar; Balakumar, Krishnamoorthy; Franklin, Gregory

    2016-11-01

    Quillaja saponin (QS) is a non-ionic amphiphilic surfactant of natural origin. In the present study, we evaluated its potential to form solid lipid nanoparticles (SLNs) in the presence of stearic acid (SA) as a lipid carrier and imatinib mesylate (IM) as a model drug. IM loaded solid lipid nanoparticles (IMSLNs) were prepared using the hot homogenisation method. Characterisation of IMSLNs revealed that they were quasi-spherical in shape, neutrally charged and 143.5-641.9nm in size. Haemolysis, a toxicity issue of QS was not observed in SLNs. Comparative in vitro cytotoxicity analyses performed in human breast cancer cell line MCF7 revealed that IMSLNs were more toxic than IM. On the other hand, in vitro viability studies in the RAW264.7 cell line did not show any sign of toxicity by IMSLNs. Our results indicate that QS hold great potential in nano drug delivery as an emulsifier.

  1. Solid Lipid Nanoparticles Loaded with Retinoic Acid and Lauric Acid as an Alternative for Topical Treatment of Acne Vulgaris.

    PubMed

    Silva, Elton Luiz; Carneiro, Guilherme; De Araújo, Lidiane Advíncula; Trindade, Mariana de Jesus Vaz; Yoshida, Maria Irene; Oréfice, Rodrigo Lambert; Farias, Luis de Macêdo; De Carvalho, Maria Auxiliadora Roque; Dos Santos, Simone Gonçalves; Goulart, Gisele Assis Castro; Alves, Ricardo José; Ferreira, Lucas Antônio Miranda

    2015-01-01

    Topical therapy is the first choice for the treatment of mild to moderate acne and all-trans retinoic acid is one of the most used drugs. The combination of retinoids and antimicrobials is an innovative approach for acne therapy. Recently, lauric acid, a saturated fatty acid, has shown strong antimicrobial activity against Propionibacterium acnes. However, topical application of retinoic acid is followed by high incidence of side-effects, including erythema and irritation. Solid lipid nanoparticles represent an alternative to overcome these side-effects. This work aims to develop solid lipid nanoparticles loaded with retinoic acid and lauric acid and evaluate their antibacterial activity. The influence of lipophilic stearylamine on the characteristics of solid lipid nanoparticles was investigated. Solid lipid nanoparticles were characterized for size, zeta potential, encapsulation efficiency, differential scanning calorimetry and X-ray diffraction. The in vitro inhibitory activity of retinoic acid-lauric acid-loaded solid lipid nanoparticles was evaluated against Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis. High encapsulation efficiency was obtained at initial time (94 ± 7% and 100 ± 4% for retinoic acid and lauric acid, respectively) and it was demonstrated that lauric acid-loaded-solid lipid nanoparticles provided the incorporation of retinoic acid. However, the presence of stearylamine is necessary to ensure stability of encapsulation. Moreover, retinoic acid-lauric acid-loaded solid lipid nanoparticles showed growth inhibitory activity against Staphylococcus epidermidis, Propionibacterium acnes and Staphylococcus aureus, representing an interesting alternative for the topical therapy of acne vulgaris. PMID:26328443

  2. Lipid nanoparticles with a solid matrix (SLN, NLC, LDC) for oral drug delivery.

    PubMed

    Muchow, Marc; Maincent, Philippe; Muller, Rainer H

    2008-12-01

    Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and lipid-drug conjugates (LDC), commonly produced by high-pressure homogenization, are interesting vectors for oral delivery of lipophilic and, to a certain extent, hydrophilic substances. Their production can be done without the use of organic solvents. Techniques to make them a physically stable delivery system have been developed. Scaling up of the production process from lab-size to large-scale dimensions using high-pressure homogenization can be easily achieved by using a different type of homogenizer. The machines used for large-scale production often yield an even better product quality than the lab-scale types. This review article covers the methods of production, characterization, mechanisms of oral bioavailability enhancement, scale-up, final oral dosage forms, and regulatory aspects of lipid nanoparticles for oral drug delivery. It focuses mainly on high-pressure homogenization production methods. PMID:18665980

  3. Nanotoxicology applied to solid lipid nanoparticles and nanostructured lipid carriers - a systematic review of in vitro data.

    PubMed

    Doktorovova, Slavomira; Souto, Eliana B; Silva, Amélia M

    2014-05-01

    Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were developed as alternative to other colloidal carriers. They were designed to overcome lipid nanoemulsions and liposomes in stability and ability to control the release of an encapsulated substance, and at the same time to be better tolerated than polymeric nanoparticles. Since the patenting of SLN discovery, large amount of data became available on the behaviour of these systems in vitro. SLN/NLC have many prerequisites to be a well tolerated carrier - the currently available data seem to confirm it, but there are also some contradictory results. In this review, we collected the available data from cytotoxicity, oxidative stress and hemocompatibility studies in vitro and analysed their outcomes. We also provide a summary of the available data in a form of reference table. PMID:24530885

  4. Effect of sterilization on the physical stability of brimonidine-loaded solid lipid nanoparticles and nanostructured lipid carriers.

    PubMed

    El-Salamouni, Noha S; Farid, Ragwa M; El-Kamel, Amal H; El-Gamal, Safaa S

    2015-12-30

    Nanoparticulate delivery systems have recently been under consideration for topical ophthalmic drug delivery. Brimonidine base-loaded solid lipid nanoparticles and nanostructured lipid carrier formulations were prepared using glyceryl monostearate as solid lipid and were evaluated for their physical stability following sterilization by autoclaving at 121°C for 15min. The objective of this work was to evaluate the effect of autoclaving on the physical appearance, particle size, polydispersity index, zeta potential, entrapment efficiency and particle morphology of the prepared formulations, compared to non-autoclaved ones. Results showed that, autoclaving at 121°C for 15min allowed the production of physically stable formulations in nanometric range, below 500nm suitable for ophthalmic application. Moreover, the autoclaved samples appeared to be superior to non-autoclaved ones, due to their increased zeta potential values, indicating a better physical stability. As well as, increased amount of brimonidine base entrapped in the tested formulations.

  5. Solid and liquid lipid-based binary solid lipid nanoparticles of diacerein: in vitro evaluation of sustained release, simultaneous loading of gold nanoparticles, and potential thermoresponsive behavior

    PubMed Central

    Rehman, Mubashar; Madni, Asadullah; Ihsan, Ayesha; Khan, Waheed Samraiz; Khan, Muhammad Imran; Mahmood, Muhammad Ahmad; Ashfaq, Muhammad; Bajwa, Sadia Zafar; Shakir, Imran

    2015-01-01

    Binary fatty acid mixture-based solid lipid nanoparticles (SLNs) were prepared for delivery of diacerein, a novel disease-modifying osteoarthritis drug, with and without simultaneously loaded gold nanoparticles (GNPs). In order to optimize SLNs for temperature-responsive release, lipid mixtures were prepared using different ratios of solid (stearic acid or lauric acid) and liquid (oleic acid) fatty acids. SLNs were prepared by microemulsification (53 nm), hot melt encapsulation (10.4 nm), and a solvent emulsification-evaporation technique (7.8 nm). The physicochemical characteristics of SLNs were studied by Zetasizer, Fourier transform infrared, and X-ray diffraction analysis. High encapsulation of diacerein was achieved with diacerein-loaded and simultaneously GNP-diacerein-loaded SLNs. In vitro dissolution studies revealed a sustained release pattern for diacerein over 72 hours for diacerein-loaded SLNs and 12 hours for GNP-diacerein-loaded SLNs. An increase in diacerein payload increased the release time of diacerein while GNPs decreased it. In addition, rapid release of diacerein over 4 hours was observed at 40°C (melting point of optimized fatty acid mixture), demonstrating that these binary SLNs could be used for thermoresponsive drug delivery. Kinetic modeling indicated that drug release followed zero order and Higuchi diffusion models (R10>0.9), while the Korsmeyer-Peppas model predicted a diffusion release mechanism (n<0.5). PMID:25897224

  6. Solid and liquid lipid-based binary solid lipid nanoparticles of diacerein: in vitro evaluation of sustained release, simultaneous loading of gold nanoparticles, and potential thermoresponsive behavior.

    PubMed

    Rehman, Mubashar; Madni, Asadullah; Ihsan, Ayesha; Khan, Waheed Samraiz; Khan, Muhammad Imran; Mahmood, Muhammad Ahmad; Ashfaq, Muhammad; Bajwa, Sadia Zafar; Shakir, Imran

    2015-01-01

    Binary fatty acid mixture-based solid lipid nanoparticles (SLNs) were prepared for delivery of diacerein, a novel disease-modifying osteoarthritis drug, with and without simultaneously loaded gold nanoparticles (GNPs). In order to optimize SLNs for temperature-responsive release, lipid mixtures were prepared using different ratios of solid (stearic acid or lauric acid) and liquid (oleic acid) fatty acids. SLNs were prepared by microemulsification (53 nm), hot melt encapsulation (10.4 nm), and a solvent emulsification-evaporation technique (7.8 nm). The physicochemical characteristics of SLNs were studied by Zetasizer, Fourier transform infrared, and X-ray diffraction analysis. High encapsulation of diacerein was achieved with diacerein-loaded and simultaneously GNP-diacerein-loaded SLNs. In vitro dissolution studies revealed a sustained release pattern for diacerein over 72 hours for diacerein-loaded SLNs and 12 hours for GNP-diacerein-loaded SLNs. An increase in diacerein payload increased the release time of diacerein while GNPs decreased it. In addition, rapid release of diacerein over 4 hours was observed at 40°C (melting point of optimized fatty acid mixture), demonstrating that these binary SLNs could be used for thermoresponsive drug delivery. Kinetic modeling indicated that drug release followed zero order and Higuchi diffusion models (R(2)>0.9), while the Korsmeyer-Peppas model predicted a diffusion release mechanism (n<0.5).

  7. Solid lipid nanoparticles regulate functional assortment of mouse mesenchymal stem cells.

    PubMed

    Chabra, S; Ranjan, M; Bhandari, R; Kaur, T; Aggrawal, M; Puri, V; Mahajan, N; Kaur, I P; Puri, S; Sobti, R C

    2011-01-01

    A rapid decline in self-renewability, viability and function, of isolated stem cells are major hurdles in developing cell based therapies. There has been an increasing interest towards identifying a support material for maintaining stem cell features of the isolated cells. Pioneering observations of the present paper, demonstrate functionally diverse potential of Solid Lipid Nanoparticles (SLNs) in deciding the fate & behavior of mouse mesenchymal stem cell. The evidences are provided to show the dual nature of the SLNs for being a scaffold for the stem cell attachment, to retain stemness, and as reagent for inducing stem cell differentiation. Scanning electron microscopic examinations together with expression analysis were used to conform to such observations. Results of the study thus suggest that Solid lipid nanoparticles can be used as a good support material when functionalized to achieve adhesive properties and as a molecular paradigm for studying the adipocytic differentiation. We envisage a new role of SLNs towards regulating stem cell character by orchestrating the structural alignment during preparation of Solid lipid nanoparticles.

  8. Physical-Chemical Characterization and Formulation Considerations for Solid Lipid Nanoparticles.

    PubMed

    Chauhan, Harsh; Mohapatra, Sarat; Munt, Daniel J; Chandratre, Shantanu; Dash, Alekha

    2016-06-01

    Pure glyceryl mono-oleate (GMO) (lipid) and different batches of GMO commonly used for the preparation of GMO-chitosan nanoparticles were characterized by modulated differential scanning calorimetry (MDSC), cryo-microscopy, and cryo-X-ray powder diffraction techniques. GMO-chitosan nanoparticles containing poloxamer 407 as a stabilizer in the absence and presence of polymers as crystallization inhibitors were prepared by ultrasonication. The effect of polymers (polyvinyl pyrrolidone (PVP), Eudragits, hydroxyl propyl methyl cellulose (HPMC), polyethylene glycol (PEG)), surfactants (poloxamer), and oils (mineral oil and olive oil) on the crystallization of GMO was investigated. GMO showed an exothermic peak at around -10°C while cooling and another exothermic peak at around -12°C while heating. It was followed by two endothermic peaks between 15 and 30 C, indicative of GMO melting. The results are corroborated by cryo-microscopy and cryo-X-ray. Significant differences in exothermic and endothermic transition were observed between different grades of GMO and pure GMO. GMO-chitosan nanoparticles resulted in a significant increase in particle size after lyophilization. MDSC confirmed that nanoparticles showed similar exothermic crystallization behavior of lipid GMO. MDSC experiments showed that PVP inhibits GMO crystallization and addition of PVP showed no significant increase in particle size of solid lipid nanoparticle (SLN) during lyophilization. The research highlights the importance of extensive physical-chemical characterization for successful formulation of SLN.

  9. Development and evaluation of solid lipid nanoparticles of raloxifene hydrochloride for enhanced bioavailability.

    PubMed

    Kushwaha, Anand Kumar; Vuddanda, Parameswara Rao; Karunanidhi, Priyanka; Singh, Sanjay Kumar; Singh, Sanjay

    2013-01-01

    Raloxifene hydrochloride (RL-HCL) is an orally selective estrogen receptor modulator (SERM) with poor bioavailability of nearly 2% due to its poor aqueous solubility and extensive first pass metabolism. In order to improve the oral bioavailability of raloxifene, raloxifene loaded solid lipid nanoparticles (SLN) have been developed using Compritol 888 ATO as lipid carrier and Pluronic F68 as surfactant. Raloxifene loaded SLN were prepared by solvent emulsification/evaporation method, and different concentrations of surfactant, and homogenization speed were taken as process variables for optimization. SLN were characterized for particle size, zeta potential, entrapment efficiency, surface morphology, and crystallinity of lipid and drug. In vitro drug release studies were performed in phosphate buffer of pH 6.8 using dialysis bag diffusion technique. Particle sizes of all the formulations were in the range of 250 to 1406 nm, and the entrapment efficiency ranges from 55 to 66%. FTIR and DSC studies indicated no interaction between drug and lipid, and the XRD spectrum showed that RL-HCL is in amorphous form in the formulation. In vitro release profiles were biphasic in nature and followed Higuchi model of release kinetics. Pharmacokinetics of raloxifene loaded solid lipid nanoparticles after oral administration to Wistar rats was studied. Bioavailability of RL-HCL loaded SLN was nearly five times than that of pure RL-HCL. PMID:24228255

  10. Development and Evaluation of Solid Lipid Nanoparticles of Raloxifene Hydrochloride for Enhanced Bioavailability

    PubMed Central

    Kushwaha, Anand Kumar; Vuddanda, Parameswara Rao; Karunanidhi, Priyanka; Singh, Sanjay Kumar; Singh, Sanjay

    2013-01-01

    Raloxifene hydrochloride (RL-HCL) is an orally selective estrogen receptor modulator (SERM) with poor bioavailability of nearly 2% due to its poor aqueous solubility and extensive first pass metabolism. In order to improve the oral bioavailability of raloxifene, raloxifene loaded solid lipid nanoparticles (SLN) have been developed using Compritol 888 ATO as lipid carrier and Pluronic F68 as surfactant. Raloxifene loaded SLN were prepared by solvent emulsification/evaporation method, and different concentrations of surfactant, and homogenization speed were taken as process variables for optimization. SLN were characterized for particle size, zeta potential, entrapment efficiency, surface morphology, and crystallinity of lipid and drug. In vitro drug release studies were performed in phosphate buffer of pH 6.8 using dialysis bag diffusion technique. Particle sizes of all the formulations were in the range of 250 to 1406 nm, and the entrapment efficiency ranges from 55 to 66%. FTIR and DSC studies indicated no interaction between drug and lipid, and the XRD spectrum showed that RL-HCL is in amorphous form in the formulation. In vitro release profiles were biphasic in nature and followed Higuchi model of release kinetics. Pharmacokinetics of raloxifene loaded solid lipid nanoparticles after oral administration to Wistar rats was studied. Bioavailability of RL-HCL loaded SLN was nearly five times than that of pure RL-HCL. PMID:24228255

  11. Solid lipid nanoparticles with and without hydroxypropyl-β-cyclodextrin: a comparative study of nanoparticles designed for colonic drug delivery

    NASA Astrophysics Data System (ADS)

    Spada, Gianpiera; Gavini, Elisabetta; Cossu, Massimo; Rassu, Giovanna; Giunchedi, Paolo

    2012-03-01

    New solid lipid nanoparticles (SLN), composed of Compritol ATO888 (C) and hydroxypropyl-β-cyclodextrin (HP), were developed in order to study a new colon-specific formulation for diclofenac sodium (D) delivery. The prepared batches differ from each other by the molecular ratio between HP and D and by the composition of the matrix. Nanoparticles composed of an exclusively lipid matrix and nanoparticles with an oligomeric and lipid matrix were compared in order to establish the effect of both components on the drug delivery tests performed. The SLN preparation method was based on the oil/water hot homogenization process. Emulsions produced were cooled at room temperature and lyophilized in order to obtain dried nanoparticles; possible damage to nanoparticle shape and size was avoided by the addition of cryoprotectants to the aqueous dispersion of nanoparticles before exsiccation. An in vitro toxicity study was performed using CaCo2 cells to establish the safety of the prepared SLN. Data obtained showed that production method studied guarantees emulsions composed of nanosized drops which can be dried by lyophilization into SLN with a size range of 300-600 nm. In vitro and ex vivo tests demonstrated that dried SLN can be considered as colon delivery systems; however, the matrix composition as well as the presence of cryoprotectant on their surface influences the release and permeation rate of D. The in vitro toxicity studies indicated that the SLN are well tolerated.

  12. Influence of encapsulated functional lipids on crystal structure and chemical stability in solid lipid nanoparticles: Towards bioactive-based design of delivery systems.

    PubMed

    Salminen, Hanna; Gömmel, Christina; Leuenberger, Bruno H; Weiss, Jochen

    2016-01-01

    We investigated the influence of physicochemical properties of encapsulated functional lipids--vitamin A, β-carotene and ω-3 fish oil--on the structural arrangement of solid lipid nanoparticles (SLN). The relationship between the crystal structure and chemical stability of the incorporated bioactive lipids was evaluated with different emulsifier compositions of a saponin-rich, food-grade Quillaja extract alone or combined with high-melting or low-melting lecithins. The major factors influencing the structural arrangement and chemical stability of functional lipids in solid lipid dispersions were their solubility in the aqueous phase and their crystallization temperature in relation to that of the carrier lipid. The results showed that the stabilization of the α-subcell crystals in the lattice of the carrier lipid is a key parameter for forming stable solid lipid dispersions. This study contributes to a better understanding of SLN as a function of the bioactive lipid.

  13. Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia

    PubMed Central

    Hosny, Khaled Mohamed; Banjar, Zainy Mohammed; Hariri, Amani H; Hassan, Ali Habiballah

    2015-01-01

    According to the World Health Organization, 46% of the world’s children suffer from anemia, which is usually treated with iron supplements such as ferrous sulfate. The aim of this study was to prepare iron as solid lipid nanoparticles, in order to find an innovative way for alleviating the disadvantages associated with commercially available tablets. These limitations include adverse effects on the digestive system resulting in constipation and blood in the stool. The second drawback is the high variability in the absorption of iron and thus in its bioavailability. Iron solid lipid nanoparticles (Fe-SLNs) were prepared by hot homogenization/ultrasonication. Solubility of ferrous sulfate in different solid lipids was measured, and effects of process variables such as the surfactant type and concentration, homogenization and ultrasonication times, and charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release and in vivo pharmacokinetics were studied in rabbits. Results indicated that Fe-SLNs consisted of 3% Compritol 888 ATO, 1% Lecithin, 3% Poloxamer 188, and 0.2% dicetylphosphate, with an average particle size of 25 nm with 92.3% entrapment efficiency. In vivo pharmacokinetic study revealed more than fourfold enhanced bioavailability. In conclusion, Fe-SLNs could be a promising carrier for iron with enhanced oral bioavailability. PMID:25609917

  14. Preparation and characterization of solid lipid nanoparticles containing cyclosporine by the emulsification-diffusion method.

    PubMed

    Urbán-Morlán, Zaida; Ganem-Rondero, Adriana; Melgoza-Contreras, Luz María; Escobar-Chávez, José Juan; Nava-Arzaluz, María Guadalupe; Quintanar-Guerrero, David

    2010-09-07

    Solid lipid nanoparticles (SLNs) have been used for carrying different therapeutic agents because they improve absorption and bioavailability. The aim of the study was to prepare lipidic nanoparticles containing cyclosporine (CyA) by the emulsification-diffusion method and to study their physicochemical stability. Glyceryl behenate (Compritol(®) ATO 888) and lauroyl macrogolglycerides (Gelucire(®) 44/14) were used as carrier materials. Nanoparticles with good stability were obtained with Gelucire(®), while it was difficult to obtain stable systems with Compritol(®). Systems with Gelucire(®) were characterized by particle size, Z-potential, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), entrapment efficiency and in vitro release. Particle size and Z-potential were evaluated for at least three months. With a high CyA content (≥60 mg) in Gelucire(®) SLNs, variations in size were greater and particle size also increased over time in all batches; this effect may have been caused by a probable expulsion of the drug due to the lipid's partial rearrangement. While the Z-potential decreased 10 mV after three months, this effect may be explained by the superficial properties of the drug that make the molecules to be preferably oriented at the solid-liquid interface, causing a change in the net charge of the particle. SEM confirmed size and shape of the nanoparticles. DSC studies evidenced that CyA affects the lipid structure by a mechanism still unknown. The entrapment efficiency was higher than 92%, and CyA release from SLNs was relatively fast (99.60% in 45 min).

  15. Preparation and characterization of solid lipid nanoparticles loaded with total flavones of Hippophae rhamnoides (TFH).

    PubMed

    Wang, Dongkai; Zhao, Peng; Cuia, Fude; Li, Xiang

    2007-01-01

    Solid lipid nanoparticles (SLNs) containing total flavones of Hippophae rhamnoides (TFH) were prepared by high-pressure homogenization (HPH), by both hot HPH and cold HPH. The influence of process parameters (lipid matrix, lipid concentration, carbohydrate type and its concentration) on the SLN size distribution, zeta potential, entrapment efficiency, crystal form, and in vitro release profile was investigated. The highest entrapment efficiency for TFH, at around 93%, was found for SLNs composed of TFH/Compritol 888 ATO in a 1:30 molar ratio and made by cold HPH. The advantages of TFH SLNs are the improved oral bioavailability of TFH and the prolonged mean retention time and drug release time. PMID:17479719

  16. Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization.

    PubMed

    Hazzah, Heba A; Farid, Ragwa M; Nasra, Maha M A; El-Massik, Magda A; Abdallah, Ossama Y

    2015-08-15

    This study aimed to prepare and evaluate mucoadhesive sponges as dosage forms for delivering solid lipid nanoparticles. For this purpose curcumin (Cur) was formulated as solid nanoparticles (SLN) using Gelucire 50/13, and polaxomer 407. The prepared CurSLN dispersion was thickened with different mucoadhesive polymers. Different concentrations of glycerol, and mannitol of range (0.25-20%), and (0-1%), respectively were also examined. The formed gel was poured into oblong molds and freeze dried to form mucoadhesive sponge to be applied to the buccal mucosa. The prepared sponges were evaluated for their, in-vivo residence time, in-vitro and in-vivo drug release, and hydration capacity. Surface morphology for the different sponges were examined using SEM. TEM was also carried out for sponge fragments previously dispersed into water. Infrared spectroscopy was conducted to investigate interaction between used ingredients. The results showed that the CurSLN loaded HPMC, and Polycarbophil sponges showed 4, and 15 h in-vivo residence time, respectively, providing a considerable amount of curcumin into saliva. The incorporation of glycerol and mannitol at concentration of 1% provided elegant and flexible sponges. The SEM showed that the deposition of CurSLN differed according to the type of polymer used. TEM confirmed the integrity of liberated CurSLN from sponges. IR spectra showed an interaction between HPMC and poloxamer 407, which affected its behavior as a gelling agent. The obtained results provide an efficient approach for delivering solid lipid nanoparticles in a solid dosage form keeping the nanoparticle characters and integrity.

  17. Preparation, characterization and physico-chemical properties of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): their benefits as colloidal drug carrier systems.

    PubMed

    Uner, M

    2006-05-01

    Solid lipid nanoparticles (SLN) have attracted increasing attention by various research groups and companies since the early 1990s. Their advantages over existing traditional carriers have been clearly documented. In addition, modified SLN have been described which are nanostructured lipid carriers (NLC) composed of liquid lipid blended with a solid lipid to form a nanostructured solid particle matrix. NLC combine controlled release characteristics with some advantages over SLN. This paper reviews the production techniques, characterization and physical stability of these systems including destabilizing factors and principles of drug loading, then considers aspects and benefits of SLN and NLC as colloidal drug carriers. PMID:16724531

  18. Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells

    PubMed Central

    Varshosaz, Jaleh; Sadeghi Aliabadi, Hojatollah

    2014-01-01

    The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs) of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (P < 0.05). After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma. PMID:24868467

  19. Preparation, in vitro release, and pharmacokinetics in rabbits of lyophilized injection of sorafenib solid lipid nanoparticles

    PubMed Central

    Zhang, Hong; Zhang, Fu-Ming; Yan, Shi-Jun

    2012-01-01

    Sorafenib solid lipid nanoparticles (S-SLN) were prepared by emulsion evaporation–solidification at low temperature. Morphology was examined by transmission electron microscope. Particle size and zeta potential were determined by laser granularity equipment. Encapsulation efficiency (EE) was detected by Sephadex gel chromatography and high-performance liquid chromatography (HPLC). The in vitro release profile of S-SLN was studied with dialysis technology. The lyophilized injection of S-SLN was prepared by freeze drying and analyzed by differential scanning calorimetry. The plasma concentration of sorafenib in blood was determined by HPLC. The solid lipid nanoparticles assumed a spherical shape with an even distribution of diameter and particle size 108.23 ± 7.01 nm (n = 3). The polydispersity index, zeta potential, and EE were determined to be 0.25 ± 0.02, −16.37 ± 0.65 mV, and 93.49% ± 1.87%, respectively (n = 3). The in vitro release accorded with the Weibull distribution model. An equal volume of 15% (w/v) mannitol performed better as the protective agent for a lyophilized injection of S-SLN with a new material phase formation. The pharmacokinetic processes of sorafenib solution and lyophilized injection of S-SLN in vivo were in accordance with the two-compartment and one-compartment models, respectively. S-SLN nanoparticles are thus considered a promising drug-delivery system. PMID:22787390

  20. Preparation and characterization of solid lipid nanoparticles containing cyclosporine by the emulsification-diffusion method

    PubMed Central

    Urbán-Morlán, Zaida; Ganem-Rondero, Adriana; Melgoza-Contreras, Luz María; Escobar-Chávez, José Juan; Nava-Arzaluz, María Guadalupe; Quintanar-Guerrero, David

    2010-01-01

    Solid lipid nanoparticles (SLNs) have been used for carrying different therapeutic agents because they improve absorption and bioavailability. The aim of the study was to prepare lipidic nanoparticles containing cyclosporine (CyA) by the emulsification-diffusion method and to study their physicochemical stability. Glyceryl behenate (Compritol® ATO 888) and lauroyl macrogolglycerides (Gelucire® 44/14) were used as carrier materials. Nanoparticles with good stability were obtained with Gelucire®, while it was difficult to obtain stable systems with Compritol®. Systems with Gelucire® were characterized by particle size, Z-potential, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), entrapment efficiency and in vitro release. Particle size and Z-potential were evaluated for at least three months. With a high CyA content (≥60 mg) in Gelucire® SLNs, variations in size were greater and particle size also increased over time in all batches; this effect may have been caused by a probable expulsion of the drug due to the lipid’s partial rearrangement. While the Z-potential decreased 10 mV after three months, this effect may be explained by the superficial properties of the drug that make the molecules to be preferably oriented at the solid-liquid interface, causing a change in the net charge of the particle. SEM confirmed size and shape of the nanoparticles. DSC studies evidenced that CyA affects the lipid structure by a mechanism still unknown. The entrapment efficiency was higher than 92%, and CyA release from SLNs was relatively fast (99.60% in 45 min). PMID:20856836

  1. Solid Matrix Based Lipidic Nanoparticles in Oral Cancer Chemotherapy: Applications and Pharmacokinetics.

    PubMed

    Ahmad, Javed; Amin, Saima; Rahman, Mahfoozur; Rub, Rehan Abdur; Singhal, Madhur; Ahmad, Mohammad Zaki; Rahman, Ziyaur; Addo, Richard T; Ahmad, Farhan Jalees; Mushtaq, Gohar; Kamal, Mohammad Amjad; Akhter, Sohail

    2015-01-01

    Chemotherapeutic delivery by oral route in cancer patients has the potential to create "hospitalization free chemotherapy" which is a vision of oncologists, formulation scientists and patients. Such a therapeutic approach will improve patients' compliance, ease the burden of the patients' caregivers and significantly reduce the cost of treatment. In current clinical practice, chemotherapy carried out by intravenous injection or infusion leads to undesired side-effects such as plasma concentrations crossing the maximum safe concentration, rapid body clearance and lower bioavailability. Despite the presence of challenges such as poor aqueous solubility and stability of drugs and the presence of biological barriers like multidrug efflux transporter in the GI tract, oral cancer chemotherapy has the potential to surmount those obstacles. Lipid nanoparticles (LNPs) such as solid lipid nanoparticle, nanostructured lipid carriers, nano lipid-drug conjugates, mixed micelles, liposomes and nanoemulsions have shown some promising results for use in oral anticancer drug delivery through nanotechnological approach. LNPs demonstrate enhanced oral bioavailability owing to their ability to inhibit first pass metabolism via lymphatic absorption by chylomicron-linked and/or M-cell uptake. LNPs reduce the inter- and intrasubject pharmacokinetics variability of administrated drugs. Moreover, certain classes of phospholipids and surfactants used in the formulations of LNPs can suppress the P-glycoprotein efflux system. Here, we shall be discussing the biopharmaceutical challenges in oral cancer chemotherapy and how the LNPs may provide solutions to such challenges. The effect of GI tract environment on LNPs and pharmacokinetics shall also be discussed. PMID:26264206

  2. Effect of liquid-to-solid lipid ratio on characterizations of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for transdermal administration.

    PubMed

    Song, Aihua; Zhang, Xiaoshu; Li, Yanting; Mao, Xinjuan; Han, Fei

    2016-08-01

    The aim of this study is to evaluate the effect of liquid-to-solid lipid ratio on properties of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and to clarify the superiority of NLCs over SLNs for transdermal administration. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, differential scanning calorimetry, X-ray diffractometry, in vitro percutaneous permeation profile, and stability of SLNs and NLCs were compared. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, and in vitro percutaneous permeation amount of the developed NLCs were all <200 nm, < -20 mV, >78%, >35, and >240 μg/cm(2), respectively, however, for SLNs were 280 nm, -29.11 mV, 63.2%, 32.54, and 225.9 μg/cm(2), respectively. After 3 months storage at 4 °C and 25 °C, almost no significant differences between the evaluated parameters of NLCs were observed. However, for SLNs, particle size was increased to higher than 300 nm (4 °C and 25 °C), drug encapsulation efficiency was decreased to 51.2 (25 °C), in vitro occlusion factor was also decreased to lower than 25 (4 °C and 25 °C), and the cumulative amount was decreased to 148.9 μg/cm(2) (25 °C) and 184.4 μg/cm(2) (4 °C), respectively. And DSC and XRD studies indicated that not only the crystalline peaks of the encapsulated flurbiprofen disappeared but also obvious difference between samples and bulk Compritol® ATO 888 was seen. It could be concluded that liquid-to-solid lipid ratio has significant impact on the properties of SLNs and NLCs, and NLCs showed better stability than SLNs. Therefore, NLCs might be a better option than SLNs for transdermal administration.

  3. Cytotoxicity of solid lipid nanoparticles and nanostructured lipid carriers containing the local anesthetic dibucaine designed for topical application

    NASA Astrophysics Data System (ADS)

    Barbosa, R. M.; da Silva, C. M. G.; Bella, T. S.; de Araújo, D. R.; Marcato, P. D.; Durán, N.; de Paula, E.

    2013-04-01

    Dibucaine (DBC) is powerful long-lasting local anesthetic, but it is also considered fairly toxic to the CNS. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have attracted attention as carriers for drug delivery. The aim of this study was to develop and to evaluate the cytotoxic activity of DBC-loaded SLN and NLC against 3T3 fibroblast and HaCat keratinocyte cells. The SLN and NLC had myristyl myristate and Liponate®GC as their lipid matrices, respectively, plus a surfactant. SLN and NLC were characterized in terms in their diameter, size distribution, surface charge and DBC encapsulation efficiency. The particle size of SLN and NLC were around 234.33 and 166.62 nm, respectively. The polydispersity index was kept below 0.2 for both nanomaterials. Negative surface charges were observed for both nanoparticles, which decreased in the presence of the anesthetic. Encapsulation efficiency reached 76% and 90%, respectively, in SLN and NLC. DBC alone was found to be toxic to 3T3 and HaCat cells in culture. However, NLC and SLN loaded DBC decreased its intrinsic cytotoxic effect against 3T3 and HaCat cells. In conclusion, encapsulation of DBC in SLN and NLC decreased the in vitro toxicity of the local anesthetic, indicating the potential of these nanocarriers for clinical applications.

  4. Solid Lipid Nanoparticles as Efficient Drug and Gene Delivery Systems: Recent Breakthroughs

    PubMed Central

    Ezzati Nazhad Dolatabadi, Jafar; Valizadeh, Hadi; Hamishehkar, Hamed

    2015-01-01

    In recent years, nanomaterials have been widely applied as advanced drug and gene delivery nanosystems. Among them, solid lipid nanoparticles (SLNs) have attracted great attention as colloidal drug delivery systems for incorporating hydrophilic or lipophilic drugs and various macromolecules as well as proteins and nucleic acids. Therefore, SLNs offer great promise for controlled and site specific drug and gene delivery. This article includes general information about SLN structures and properties, production procedures, characterization. In addition, recent progress on development of drug and gene delivery systems using SLNs was reviewed. PMID:26236652

  5. Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications

    PubMed Central

    Campos, Estefânia Vangelie Ramos; Oliveira, Jhones Luiz de; da Silva, Camila Morais Gonçalves; Pascoli, Mônica; Pasquoto, Tatiane; Lima, Renata; Abhilash, P. C.; Fernandes Fraceto, Leonardo

    2015-01-01

    Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants. PMID:26346969

  6. Preparation, characterisation and antibacterial activity of a florfenicol-loaded solid lipid nanoparticle suspension.

    PubMed

    Wang, Ting; Chen, Xiaojin; Lu, Mengmeng; Li, Xihe; Zhou, WenZhong

    2015-12-01

    A florfenicol-loaded solid lipid nanoparticle (FFC-SLN) suspension was prepared by hot homogenisation and ultrasonic technique. The suspension was characterised for its release profile, stability, toxicity, and the physicochemical properties of the nanoparticles. Antibacterial activity of the suspension was evaluated in vitro and in vivo. The results showed that the mean diameter, polydispersity index and zeta potential of the nanoparticles were 253 ± 3 nm, 0.409 ± 0.022 and 47.5 ± 0.21 mV, respectively. In vitro release profile showed the FFC-SLN suspension had sustained release effect. The minimum inhibition concentration values of the FFC-SLN suspension were 6 and 3 µg/mL against Staphylococcus aureus and Escherichia coli respectively, compared with 3.5 and 2 µg/mL of native florfenicol. The suspension was relatively stable at 4°C and less stable at room temperature during 9 months storage. Although the nanoparticle carriers exhibited cytotoxicity in cell cultures, the LD50 of the lyophilised dry power of the suspension was higher than 5 g/kg body weight. Mortality protection against E. coli lethal infection in mice showed that the nanoparticle suspension had much better efficacy (6/10) than native drug (1/10). These results indicate that FFC-SLN suspension could be a promising formulation in veterinary medicine. PMID:26647811

  7. Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications

    NASA Astrophysics Data System (ADS)

    Campos, Estefânia Vangelie Ramos; Oliveira, Jhones Luiz De; da Silva, Camila Morais Gonçalves; Pascoli, Mônica; Pasquoto, Tatiane; Lima, Renata; Abhilash, P. C.; Fernandes Fraceto, Leonardo

    2015-09-01

    Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants.

  8. Preparation, characterisation and antibacterial activity of a florfenicol-loaded solid lipid nanoparticle suspension.

    PubMed

    Wang, Ting; Chen, Xiaojin; Lu, Mengmeng; Li, Xihe; Zhou, WenZhong

    2015-12-01

    A florfenicol-loaded solid lipid nanoparticle (FFC-SLN) suspension was prepared by hot homogenisation and ultrasonic technique. The suspension was characterised for its release profile, stability, toxicity, and the physicochemical properties of the nanoparticles. Antibacterial activity of the suspension was evaluated in vitro and in vivo. The results showed that the mean diameter, polydispersity index and zeta potential of the nanoparticles were 253 ± 3 nm, 0.409 ± 0.022 and 47.5 ± 0.21 mV, respectively. In vitro release profile showed the FFC-SLN suspension had sustained release effect. The minimum inhibition concentration values of the FFC-SLN suspension were 6 and 3 µg/mL against Staphylococcus aureus and Escherichia coli respectively, compared with 3.5 and 2 µg/mL of native florfenicol. The suspension was relatively stable at 4°C and less stable at room temperature during 9 months storage. Although the nanoparticle carriers exhibited cytotoxicity in cell cultures, the LD50 of the lyophilised dry power of the suspension was higher than 5 g/kg body weight. Mortality protection against E. coli lethal infection in mice showed that the nanoparticle suspension had much better efficacy (6/10) than native drug (1/10). These results indicate that FFC-SLN suspension could be a promising formulation in veterinary medicine.

  9. Cefuroxime axetil loaded solid lipid nanoparticles for enhanced activity against S. aureus biofilm.

    PubMed

    Singh, Bhupender; Vuddanda, Parameswara Rao; M R, Vijayakumar; Kumar, Vinod; Saxena, Preeti S; Singh, Sanjay

    2014-09-01

    The present research work is focused on the development of solid lipid nanoparticles of cefuroxime axetil (CA-SLN) for its enhanced inhibitory activity against Staphylococcus aureus produced biofilm. CA-SLN was prepared by solvent emulsification/evaporation method using single lipid (stearic acid (SA)) and binary lipids (SA and tristearin (TS)). Process variables such as volume of dispersion medium, concentration of surfactant, homogenization speed and time were optimized. The prepared SLN were characterized for encapsulation efficiency, drug polymer interaction studies (DSC and FT-IR), shape and surface morphology (SEM and AFM), in vitro drug release, stability studies and in vitro anti biofilm activity against S. aureus biofilm. Among the process variables, increased volume of dispersion medium, homogenization speed and time led to increase in particle size whereas increase in surfactant concentration decreased the particle size. SLN prepared using binary lipids exhibited higher entrapment efficiency than the single lipid. DSC and FT-IR studies showed no incompatible interaction between drug and excipients. CA-SLN showed two folds higher anti-biofilm activity in vitro than pristine CA against S. aureus biofilm.

  10. Solid lipid nanoparticle preparation by a warm microemulsion based process: influence of microemulsion microstructure.

    PubMed

    Fadda, P; Monduzzi, M; Caboi, F; Piras, S; Lazzari, P

    2013-03-25

    Warm microemulsions (WME) containing lipids are used as starting systems to obtain solid lipid nanoparticles (SLN) in alternative processes to those based on high pressure homogenization technique. SLN characteristics can be influenced by the microemulsion composition and the specific conditions adopted in the quenching process related to the transformation of WME into nanoparticles. To establish optimized conditions for the production of SLN starting from WME, in a first step of this work we have defined the microstructure of warm microemulsions highlighted in the lecithin (LCT)/water (W)/tripalmitin (TP)/1-butanol (B)/taurocholate sodium salt (ST) phase behavior at 70°C. Moreover, we have further studied the LCT/W/TP/B system by evaluating the effect on the microemulsion area due to the LCT/B weight ratio, the replacement of 1-butanol with different alcohols (ROH), and the addition of taurocholate sodium salt (ST) at different LCT/ST weight ratios. The microstructure of the isotropic phase region obtained in the presence of ST has been characterized by both (1)H NMR PGSE measurements and electrical conductivity. The characteristics of final nanoparticles are discussed taking into account both the microstructure of the parent WME and the conditions of the quenching process leading to SLN. The present results highlight the relevance of the microstructural characteristic of WME to assure the obtainment of SLN with average diameter in the order of 100-2000 nm and narrow size distribution. PMID:23422277

  11. In Vitro and In Vivo Trypanocidal Activity of H2bdtc-Loaded Solid Lipid Nanoparticles

    PubMed Central

    Carneiro, Zumira A.; da S. Maia, Pedro I.; Sesti-Costa, Renata; Lopes, Carla D.; Pereira, Tatiana A.; Milanezi, Cristiane M.; da Silva, Marcelo A. Pereira.; Lopez, Renata F. V.; Silva, João S.; Deflon, Victor M.

    2014-01-01

    The parasite Trypanosoma cruzi causes Chagas disease, which remains a serious public health concern and continues to victimize thousands of people, primarily in the poorest regions of Latin America. In the search for new therapeutic drugs against T. cruzi, here we have evaluated both the in vitro and the in vivo activity of 5-hydroxy-3-methyl-5-phenyl-pyrazoline-1-(S-benzyl dithiocarbazate) (H2bdtc) as a free compound or encapsulated into solid lipid nanoparticles (SLN); we compared the results with those achieved by using the currently employed drug, benznidazole. H2bdtc encapsulated into solid lipid nanoparticles (a) effectively reduced parasitemia in mice at concentrations 100 times lower than that normally employed for benznidazole (clinically applied at a concentration of 400 µmol kg−1 day−1); (b) diminished inflammation and lesions of the liver and heart; and (c) resulted in 100% survival of mice infected with T. cruzi. Therefore, H2bdtc is a potent trypanocidal agent. PMID:24810753

  12. Evaluation of oral bioavailability and anticancer potential of raloxifene solid lipid nanoparticles.

    PubMed

    Battani, Somashekhar; Pawar, Harish; Suresh, Sarasija

    2014-08-01

    The objective of the present investigation was formulation of raloxifene loaded solid lipid nanoparticles (R-SLN) for oral administration and evaluation of its anticancer potential in 7,12- dimethylbenzanthracene (DMBA)-induced breast cancer in Sprague-Dawley rats. Optimized R-SLN formulation prepared by modified micro-emulsion method resulted in R-SLN of 288.0±28.5 nm size and 95.56% entrapment efficiency. R-SLN exhibited in vitro prolonged release of raloxifene for 72 h in phosphate buffered saline. R-SLN was stable in simulated gastro-intestinal (GIT) fluids consisting of pH 1.2, pH 7.4, simulated gastric fluid and simulated intestinal fluid. A two-fold increase was observed in raloxifene oral bioavailability from R-SLN. R-SLN exhibited enhanced efficacy and chemopreventive activity over pure raloxifene as indicated by evaluation of tumor burden (P < 0.001) and tumor incidence (P < 0.001). The results indicate the potential of raloxifene solid lipid nanoparticles in optimizing chemoprevention of breast cancer by R-SLN. PMID:25935981

  13. Quantitative, Qualitative and In Vitro Evaluation of Solid Lipid Nanoparticles Containing 5-Fluorouracil

    NASA Astrophysics Data System (ADS)

    Majrad, Mohamed Saleh

    The primary goal of this research work was to develop solid lipid nanoparticles (SLNs) containing 5-Flourouracil and to evaluate its effect on various cell lines. The solid lipid nanoparticles were prepared through a new temperature modulated solidification technique developed in our laboratory. Particle size analysis by dynamic light scattering (DLS) and morphology evaluation by transmission electron microscopy (TEM) demonstrated that the SLNs are nanoparticulates. Cytotoxic activity of SLN loaded 5-Fluorouracil showed a decrease in viability when compared to pure solution of 5-FU on PC-3 and Caco-2 cell line. Blank SLN showed no decrease in cell viability when the concentration increased. Biocompatibility studies of SLNs in human RBCs indicated that 5-FU SLN formulations are compatible. Bovine permeability study shows that apparent permeability for 5-FU SLN was 0.000348 cm/s and 1.339 cm/s for 5-FU solution. The preliminary results from various in vitro evaluations suggest that 5-FU loaded SLNs have the potential to be used as an anti-cancer drug delivery system.

  14. Application of Response Surface Methodology for the Technological Improvement of Solid Lipid Nanoparticles.

    PubMed

    Dal Pizzol, Carine; O'Reilly, Andre; Winter, Evelyn; Sonaglio, Diva; de Campos, Angela Machado; Creczynski-Pasa, Tânia Beatriz

    2016-02-01

    Solid lipid nanoparticles (SLN) are colloidal particles consisting of a matrix composed of solid (at room and body temperatures) lipids dispersed in aqueous emulsifier solution. During manufacture, their physicochemical properties may be affected by several formulation parameters, such as type and concentration of lipid, proportion of emulsifiers and amount of solvent. Thus, the aim of this work was to study the influence of these variables on the preparation of SLN. A D-optimal Response Surface Methodology design was used to establish a mathematical model for the optimization of SLN. A total of 30 SLN formulations were prepared using the ultrasound method, and then characterized on the basis of their physicochemical properties, including particle size, polydispersity index (PI) and Zeta Potential (s). Particle sizes ranged between 107 and 240 nm. All SLN formulations showed negative sigma and PI values below 0.28. Prediction of the optimal conditions was performed using the desirability function targeting the reduction of all responses. The optimized SLN formulation showed similar theoretical and experimental values, confirming the sturdiness and predictive ability of the mathematical model for SLN optimization. PMID:27433573

  15. Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In Vitro Drug Release and Pharmacokinetics Studies

    PubMed Central

    Gaur, Praveen Kumar; Mishra, Shikha; Bajpai, Meenakshi; Mishra, Anushika

    2014-01-01

    Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of 124.5 ± 3.2 nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6–98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C ± 2°C and 75 ± 5% relative humidity (RH) for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (Cmax⁡) and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES). PMID:24967360

  16. Comparison of drug release from liquid crystalline monoolein dispersions and solid lipid nanoparticles using a flow cytometric technique

    PubMed Central

    Dawoud, Mohamed Z.; Nasr, Mohamed

    2016-01-01

    Colloidal lipid particles such as solid lipid nanoparticles and liquid crystalline nanoparticles have great opportunities as drug carriers especially for lipophilic drugs intended for intravenous administration. In order to evaluate drug release from these nanoparticles and determine their behavior after administration, emulsion droplets were used as a lipophilic compartment to which the transfer of a model drug was measured. The detection of the model drug transferred from monoolein cubic particles and trimyristin solid lipid nanoparticles into emulsion droplets was performed using a flow cytometric technique. A higher rate and amount of porphyrin transfer from the solid lipid nanoparticles compared to the monoolein cubic particles was observed. This difference might be attributed to the formation of a highly ordered particle which leads to the expulsion of drug to the surface of the crystalline particle. Furthermore, the sponge-like structure of the monoolein cubic particles decreases the rate and amount of drug transferred. In conclusion, the flow cytometric technique is a suitable technique to study drug transfer from these carriers to large lipophilic acceptors. Monoolein cubic particles with their unique structure can be used successfully as a drug carrier with slow drug release compared with trimyristin nanoparticles. PMID:27006901

  17. Characterization and evaluation of metformin-loaded solid lipid nanoparticles for celluar and mitochondrial uptake.

    PubMed

    Xu, Qiang; Zhu, Tao; Yi, Chaoli; Shen, Qi

    2016-01-01

    Considered a popular drug for diabetes in recent years, metformin was determined to have a moderate anti-tumor effect, particularly in breast cancer. In this study, the anticancer mechanism of metformin was verified by preparing solid lipid nanoparticles (SLNs) and chitosan-modified solid lipid nanoparticles (CSLNs) containing metformin and then estimating the potential of these SLNs for uptake in cells and mitochondria. Metformin-SLNs were prepared using an emulsification and low-temperature solidification method. The mean particle size, zeta potential, entrapment efficiency, and loading efficiency of metformin-SLNs and metformin chitosan-modified SLNs were 102.3 ± 4.16 and 200.1 ± 17.69 nm, -21.25 ± 4.89 and 50.6 ± 4.09 mv, 26.25 ± 2.59% and 33.6 ± 2.21%, and 1.74 ± 0.16% and 1.46 ± 0.10%, respectively. TEM images showed that both the nanoparticles had spherical morphologies with no aggregation. Results of cellular and mitochondrial uptake showed that the metformin-SLNs were easier to uptake in cells and mitochondria than the pure drug group (that was the control group without SLN structure modification). The findings of this research provide a basis for conducting further studies on the anticancer mechanism of metformin. PMID:26288997

  18. Development of solid lipid nanoparticles as carriers for improving oral bioavailability of glibenclamide.

    PubMed

    Gonçalves, L M D; Maestrelli, F; Di Cesare Mannelli, L; Ghelardini, C; Almeida, A J; Mura, P

    2016-05-01

    A solid lipid nanoparticle (SLN) formulation was developed with the aim of improving the oral bioavailability and the therapeutic effectiveness of glibenclamide (GLI), a poorly water-soluble drug used in the treatment of type 2 diabetes. The SLN was prepared using different lipid components (Precirol® and Compritol®) and preparation procedures. Precirol-based SLN, obtained with the emulsion of solvent evaporation technique gave the best results and was selected for drug loading. Addition of lecithin to the SLN core or PEG coating was effective in increasing the nanoparticles stability in simulated gastric solution. Both such formulations were stable after one month storage at 5±3°C, exhibited the absence of in vitro cytotoxicity, and presented a similar in vitro prolonged-release, reaching 100% release after 24h. The lecithin-containing GLI-loaded SLN formulation, selected for in vivo studies in virtue of its higher EE% than the PEG-coated formulation (70.3% vs 19.6%), showed a significantly stronger hypoglycemic effect with respect to the drug alone, in terms of both shorter onset time and longer duration of the effect. These positive results indicated that the proposed SLN approach was successful in improving GLI oral bioavailability, confirming its potential as an effective delivery system for a suitable therapy of diabetes. PMID:26925503

  19. Formulation of solid lipid nanoparticles (SLN): the value of different alkyl polyglucoside surfactants.

    PubMed

    Keck, Cornelia M; Kovačević, Andjelka; Müller, Rainer H; Savić, Snežana; Vuleta, Gordana; Milić, Jela

    2014-10-20

    Alkyl polyglycosides (APGs) represent a group of nonionic tensides with excellent skin compatibility. Thus they seem to be excellent stabilizers for lipid nanoparticles for dermal application. To investigate this, different APGs were selected to evaluate their influence on the formation and characteristics of solid lipid nanoparticles (SLN). Contact angle analysis of the aqueous solutions/dispersions of the APGs on cetyl palmitate films revealed good wettability for all APG surfactants. Cetyl palmitate based SLN were prepared by hot high pressure homogenization and subjected to particle size, charge and inner structure analysis. 1% of each APG was sufficient to obtain SLN with a mean size between 150 nm and 175 nm and a narrow size distribution. The zeta potential in water was ∼ -50 mV; the values in the original medium were distinctly lower, but still sufficient high to provide good physical stability. Physical stability at different temperatures (5°C, 25°C and 40°C) was confirmed by a constant particle size over an observation period of 90 days in all dispersions. In comparison to SLN stabilized with classical surfactants, e.g., Polysorbate, APG stabilized SLN possess a smaller size, improved physical stability and contain less surfactant. Therefore, the use of APGs for the stabilization of lipid nanoparticles is superior in comparison to classical stabilizers. Further, the results indicate that the length of the alkyl chain of the APG influences the diminution efficacy, the final particle size and the crystallinity of the particles. APGs with short alkyl chain led to a faster reduction in size during high pressure homogenization, to a smaller particle size of the SLN and to a lower recrystallization index, i.e., to a lower crystallinity of the SLN. The crystallinity of the SLN increased with an increase in the alkyl chain length of APGs. Therefore, by using the tested APGs differing in the alkyl chain length, not only small sized and physically stable but

  20. Formulation of solid lipid nanoparticles (SLN): the value of different alkyl polyglucoside surfactants.

    PubMed

    Keck, Cornelia M; Kovačević, Andjelka; Müller, Rainer H; Savić, Snežana; Vuleta, Gordana; Milić, Jela

    2014-10-20

    Alkyl polyglycosides (APGs) represent a group of nonionic tensides with excellent skin compatibility. Thus they seem to be excellent stabilizers for lipid nanoparticles for dermal application. To investigate this, different APGs were selected to evaluate their influence on the formation and characteristics of solid lipid nanoparticles (SLN). Contact angle analysis of the aqueous solutions/dispersions of the APGs on cetyl palmitate films revealed good wettability for all APG surfactants. Cetyl palmitate based SLN were prepared by hot high pressure homogenization and subjected to particle size, charge and inner structure analysis. 1% of each APG was sufficient to obtain SLN with a mean size between 150 nm and 175 nm and a narrow size distribution. The zeta potential in water was ∼ -50 mV; the values in the original medium were distinctly lower, but still sufficient high to provide good physical stability. Physical stability at different temperatures (5°C, 25°C and 40°C) was confirmed by a constant particle size over an observation period of 90 days in all dispersions. In comparison to SLN stabilized with classical surfactants, e.g., Polysorbate, APG stabilized SLN possess a smaller size, improved physical stability and contain less surfactant. Therefore, the use of APGs for the stabilization of lipid nanoparticles is superior in comparison to classical stabilizers. Further, the results indicate that the length of the alkyl chain of the APG influences the diminution efficacy, the final particle size and the crystallinity of the particles. APGs with short alkyl chain led to a faster reduction in size during high pressure homogenization, to a smaller particle size of the SLN and to a lower recrystallization index, i.e., to a lower crystallinity of the SLN. The crystallinity of the SLN increased with an increase in the alkyl chain length of APGs. Therefore, by using the tested APGs differing in the alkyl chain length, not only small sized and physically stable but

  1. Improved In Vitro Antileukemic Activity of All-Trans Retinoic Acid Loaded in Cholesteryl Butyrate Solid Lipid Nanoparticles.

    PubMed

    Silva, Elton Luiz; Lima, Flávia Alves; Carneiro, Guilherme; Ramos Jonas Periera; Gomes, Dawidson Assis; de Souza-Fagundes, Elaine Maria; Ferreira, Lucas Antônio Miranda

    2016-02-01

    All-trans retinoic acid, a hydrophobic drug, has become one of the most successful examples of differentiation agents used for treatment of acute promyelocytic leukemia. On the other hand, histone deacetylase inhibitors, such as cholesteryl butyrate, present differentiating activity and.can potentiate action of drugs such as all-trans retinoic acid. Solid lipid nanoparticles represent a promising alternative for administration of hydrophobic drugs such as ATRA. This study aimed to develop, characterize, and evaluate the cytotoxicity of all-trans retinoic acid-loaded solid lipid nanoparticles for leukemia treatment. The influence of in situ formation of an ion pairing between all-trans retinoic acid and lipophilic amines on the characteristics of the particles (size, zeta potential, encapsulation efficiency) was evaluated. Cholesteryl butyrate, a butyric acid donor, was used as a component of the lipid matrix. In vitro activity on cell viability and distribution of cell cycle phases were evaluated for HL-60, Jurkat, and THP-1 cell lines. The encapsulation efficiency of all-trans retinoic acid in cholesteryl butyrate-solid lipid nanoparticles was significantly increased by the presence of the amine. Inhibition of cell viability by all-trans retinoic acid-loaded solid lipid nanoparticles was more pronounced than the free drug. Analysis of the distribution of cell cycle phases also showed increased activity for all-trans retinoic acid-loaded cholesteryl butyrate-solid lipid nanoparticles, with a clear increase in subdiploid DNA content. The ion pair formation in SLN containing cholesteryl butyrate can be explored as a simple and inexpensive strategy to improve the efficacy and bioavail-ability of ATRA in the treatment of the cancer and metabolic diseases in which this retinoid plays an important role. PMID:27433579

  2. Preparation of ultra-fine powders from polysaccharide-coated solid lipid nanoparticles and nanostructured lipid carriers by innovative nano spray drying technology.

    PubMed

    Wang, Taoran; Hu, Qiaobin; Zhou, Mingyong; Xue, Jingyi; Luo, Yangchao

    2016-09-10

    In this study, five polysaccharides were applied as natural polymeric coating materials to prepare solid lipid nanoparticles (SLN) and nanostructure lipid carriers (NLC), and then the obtained lipid colloidal particles were transformed to solid powders by the innovative nano spray drying technology. The feasibility and suitability of this new technology to generate ultra-fine lipid powder particles were evaluated and the formulation was optimized. The spray dried SLN powder exhibited the aggregated and irregular shape and dimension, but small, uniform, well-separated spherical powder particles of was obtained from NLC. The optimal formulation of NLC was prepared by a 20-30% oleic acid content with carrageenan or pectin as coating material. Therefore, nano spray drying technology has a potential application to produce uniform, spherical, and sub-microscale lipid powder particles when the formulation of lipid delivery system is appropriately designed.

  3. Solid Lipid Nanoparticles of Atovaquone Based on 24 Full-Factorial Design

    PubMed Central

    Mohtar, Noratiqah; A. K. Khan, Nurzalina; Darwis, Yusrida

    2015-01-01

    Solid lipid nanoparticles of atovaquone (ATQ-SLN) were prepared by high shear homogenization method using tripalmitin, trilaurin, and Compritol 888 ATO as the lipid matrices and Phospholipon 90H, Tween 80, and poloxamer 188 as the surfactants. Optimization of the formulations was conducted using 6 sets of 24 full-factorial design based on four independent variables that were the number of homogenizing cycles, concentration of the lipid, concentration of the co-surfactant, and concentration of the main surfactant. The dependent variables were particle size and polydispersity index (PdI). The homogenizing cycles showed a negative influence on the dependent variables which reduced both the particle size and the PdI value. Moreover, a combination of certain percentages of the main surfactant and co-surfactant also showed a negative influence that reduced both the particle size and PdI value. Selected formulations from each design were further characterized for the entrapment efficiency and yield. The optimised formulation of ATQ-SLN consisted of trilaurin, Phospholipon 90H and Tween 80 with a particle size of 89.4 ± 0.2 nm and entrapment efficiency of 83.0 ± 1.7%. The in-vitro release evaluation of the formulation showed a complete and immediate release of ATQ from the SLN that could be a solution to improve the poor aqueous solubility and hence poor bioavailability of the drug. PMID:26664366

  4. Preparation of solid lipid nanoparticles from W/O/W emulsions: preliminary studies on insulin encapsulation.

    PubMed

    Gallarate, Marina; Trotta, Michele; Battaglia, Luigi; Chirio, Daniela

    2009-08-01

    A method to produce solid lipid nanoparticles (SLN) from W/O/W multiple emulsions was developed applying the solvent-in-water emulsion-diffusion technique. Insulin was chosen as hydrophilic peptide drug to be dissolved in the acidic inner aqueous phase of multiple emulsions and to be consequently carried in SLN. Several partially water-miscible solvents with low toxicity were screened in order to optimize emulsions and SLN composition, after assessing that insulin did not undergo any chemical modification in the presence of the different solvents and under the production process conditions. SLN of spherical shape and with mean diameters in the 600-1200 nm range were obtained by simple water dilution of the W/O/W emulsion. Best results, in terms of SLN mean diameter and encapsulation efficiencies, were obtained using glyceryl monostearate as lipid matrix, butyl lactate as a solvent, and soy lecithin and Pluronic F68 as surfactants. Encapsulation efficiencies up to 40% of the loaded amount were obtained, owing to the actual multiplicity of the system; the use of multiple emulsion-derived SLN can be considered a useful strategy to encapsulate a hydrophilic drug in a lipid matrix.

  5. Indomethacin-Loaded Solid Lipid Nanoparticles for Ocular Delivery: Development, Characterization, and In Vitro Evaluation

    PubMed Central

    Hippalgaonkar, Ketan; Adelli, Goutham R.; Hippalgaonkar, Kanchan; Repka, Michael A.

    2013-01-01

    Abstract Purpose The goal of this study was to develop and characterize indomethacin-loaded solid lipid nanoparticles (IN-SLNs; 0.1% w/v) for ocular delivery. Methods Various lipids, homogenization pressures/cycles, Tween 80 fraction in the mixture of surfactants (Poloxamer 188 and Tween 80; total surfactant concentration at 1% w/v), and pH were investigated in the preparation of the IN-SLNs. Compritol® 888 ATO was selected as the lipid phase for the IN-SLNs, as indomethacin exhibited a highest distribution coefficient and solubility in this phase. Results Homogenization at 15,000 psi for 6 cycles resulted in the smallest particle size. Increase in the Poloxamer 188 fraction resulted in decrease in the entrapment efficiency (EE). The mean particle size, polydispersity index, zeta-potential, and EE of the optimized formulation were 140 nm, 0.16, −21 mV, and 72.0%, respectively. IN-SLNs were physically stable post-sterilization and on storage for a period of 1 month (last timepoint tested). A dramatic increase in the chemical stability and in vitro corneal permeability of indomethacin was observed with the IN-SLN formulation in comparison to the indomethacin solution- (0.1% w/v) and indomethacin hydroxypropyl-beta-cyclodextrin-based formulations (0.1% w/v). Conclusion Results from this study suggest that topical IN-SLNs could significantly improve ocular bioavailability of indomethacin. PMID:23421502

  6. Preparation and characterization of solid lipid nanoparticles loaded with frankincense and myrrh oil.

    PubMed

    Shi, Feng; Zhao, Ji-Hui; Liu, Ying; Wang, Zhi; Zhang, Yong-Tai; Feng, Nian-Ping

    2012-01-01

    The aim of the present study was to prepare solid lipid nanoparticles (SLNs) for the oral delivery of frankincense and myrrh essential oils (FMO). Aqueous dispersions of SLNs were successfully prepared by a high-pressure homogenization method using Compritol 888 ATO as the solid lipid and soybean lecithin and Tween 80 as the surfactants. The properties of the SLNs such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE) were investigated. The morphology of SLNs was observed by transmission electron microscopy (TEM). The crystallinity of the formulation was analyzed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). In addition, drug evaporation release and antitumor activity were also studied. Round SLNs with a mean size of 113.3 ± 3.6 nm, a ZP of -16.8 ± 0.4 mV, and an EE of 80.60% ± 1.11% were obtained. DSC and XRD measurements revealed that less ordered structures were formed in the inner cores of the SLN particles. Evaporation loss of the active components in FMO could be reduced in the SLNs. Furthermore, the SLN formulation increased the antitumor efficacy of FMO in H22-bearing Kunming mice. Hence, the presented SLNs can be used as drug carriers for hydrophobic oil drugs extracted from traditional Chinese medicines. PMID:22619540

  7. Preparation and characterization of solid lipid nanoparticles loaded with frankincense and myrrh oil

    PubMed Central

    Shi, Feng; Zhao, Ji-Hui; Liu, Ying; Wang, Zhi; Zhang, Yong-Tai; Feng, Nian-Ping

    2012-01-01

    The aim of the present study was to prepare solid lipid nanoparticles (SLNs) for the oral delivery of frankincense and myrrh essential oils (FMO). Aqueous dispersions of SLNs were successfully prepared by a high-pressure homogenization method using Compritol 888 ATO as the solid lipid and soybean lecithin and Tween 80 as the surfactants. The properties of the SLNs such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE) were investigated. The morphology of SLNs was observed by transmission electron microscopy (TEM). The crystallinity of the formulation was analyzed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). In addition, drug evaporation release and antitumor activity were also studied. Round SLNs with a mean size of 113.3 ± 3.6 nm, a ZP of −16.8 ± 0.4 mV, and an EE of 80.60% ± 1.11% were obtained. DSC and XRD measurements revealed that less ordered structures were formed in the inner cores of the SLN particles. Evaporation loss of the active components in FMO could be reduced in the SLNs. Furthermore, the SLN formulation increased the antitumor efficacy of FMO in H22-bearing Kunming mice. Hence, the presented SLNs can be used as drug carriers for hydrophobic oil drugs extracted from traditional Chinese medicines. PMID:22619540

  8. Preparation and characterization of catalase-loaded solid lipid nanoparticles protecting enzyme against proteolysis.

    PubMed

    Qi, Ce; Chen, Yan; Jing, Qing-Zhe; Wang, Xing-Guo

    2011-01-01

    Catalase-loaded solid lipid nanoparticles (SLNs) were prepared by the double emulsion method (w/o/w) and solvent evaporation techniques, using acetone/methylene chloride (1:1) as an organic solvent, lecithin and triglyceride as oil phase and Poloxmer 188 as a surfactant. The optimized SLN was prepared by lecithin: triglyceride ratio (5%), 20-second + 30-second sonication, and 2% Poloxmer 188. The mean particle size of SLN was 296.0 ± 7.0 nm, polydispersity index range and zeta potential were 0.322-0.354 and -36.4 ± 0.6, respectively, and the encapsulation efficiency reached its maximum of 77.9 ± 1.56. Catalase distributed between the solid lipid and inner aqueous phase and gradually released from Poloxmer coated SLNs up to 20% within 20 h. Catalase-loaded SLN remained at 30% of H(2)O(2)-degrading activity after being incubated with Proteinase K for 24 h, while free catalase lost activity within 1 h.

  9. Formulation and optimization of raloxifene-loaded solid lipid nanoparticles to enhance oral bioavailability.

    PubMed

    Tran, Tuan Hiep; Ramasamy, Thiruganesh; Cho, Hyuk Jun; Kim, Yong Il; Poudel, Bijay Kumar; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2014-07-01

    The main aim of this study was to improve the oral bioavailability of raloxifene (RXF), a selective estrogen receptor modulator, by incorporation into solid lipid nanoparticles (SLN). RXF-loaded SLN was prepared by homogenization-sonication technique and characterized through physicochemical, pharmacokinetic, and cytotoxicity studies. The optimized SLN formulation exhibited a spherical shape with average size around 140 nm, easing its transport across the lymphatic system. Augmentation in the profiles of C(max) (308%) and AUC (270%) indicated a significant enhancement in the rate and extent of bioavailability by SLN formulations compared to free drug. In vitro cytotoxicity study performed in NIH-3T3 cells revealed that RXF-SLN was cytocompatible, and SLN remained unchanged during the freeze-drying process. Furthermore, the optimized formulation was quite stable at room temperature for more than two months, exemplifying its superior performance. In conclusion, SLN provides a promising platform for the pronounced enhancement of RXF bioavailability. PMID:24757949

  10. Solid lipid nanoparticles for potential doxorubicin delivery in glioblastoma treatment: preliminary in vitro studies.

    PubMed

    Battaglia, Luigi; Gallarate, Marina; Peira, Elena; Chirio, Daniela; Muntoni, Elisabetta; Biasibetti, Elena; Capucchio, Maria Teresa; Valazza, Alberto; Panciani, Pier Paolo; Lanotte, Michele; Schiffer, Davide; Annovazzi, Laura; Caldera, Valentina; Mellai, Marta; Riganti, Chiara

    2014-07-01

    The major obstacle to glioblastoma pharmacological therapy is the overcoming of the blood-brain barrier (BBB). In literature, several strategies have been proposed to overcome the BBB: in this experimental work, solid lipid nanoparticles (SLN), prepared according to fatty acid coacervation technique, are proposed as the vehicle for doxorubicin (Dox), to enhance its permeation through an artificial model of BBB. The in vitro cytotoxicity of Dox-loaded SLN has been measured on three different commercial and patient-derived glioma cell lines. Dox was entrapped within SLN thanks to hydrophobic ion pairing with negatively charged surfactants, used as counterions. Results indicate that Dox entrapped in SLN maintains its cytotoxic activity toward glioma cell lines; moreover, its permeation through hCMEC/D3 cell monolayer, assumed as a model of the BBB, was increased when the drug was entrapped in SLN. In conclusion, SLN proved to be a promising vehicle for the delivery of Dox to the brain in glioblastoma treatment.

  11. Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives

    PubMed Central

    Üner, Melike; Yener, Gülgün

    2007-01-01

    Solid lipid nanoparticles (SLN) have been reported to be an alternative system to emulsions, liposomes, microparticles and their polymeric counterparts for various application routes since the early 1990s due to their advantages. Various research groups have also increasingly focused on improving their stability in body fluids after administration by coating of particles with hydrophilic molecules such as poly(ethylene)glycol (PEG) derivatives. Altering surface characteristics by coating SLN with hydrophilic molecules improves plasma stability and biodistribution, and subsequent bioavailability of drugs entrapped. Their storage stability is also increased. This paper basicly reviews types of SLN, principles of drug loading and models of drug incorporation. The influence of PEG coating on particle size and surface characteristics is discussed followed by alteration in pharmacokinetics and bioavailability of drugs in order to target the site of action via SLN. The future direction of research and clinical implications of SLN is also considered. PMID:18019829

  12. Effect of environment pH on the photophysics of fisetin in solid lipid nanoparticles.

    PubMed

    Das, Shrabanti; Maity, Arnab; Purkayastha, Pradipta

    2015-12-01

    Photophysical modulation of fisetin has been extensively studied in bulk aqueous as well as solid lipid nanoparticles (SLN) by varying the pH of the medium. The solution pH was varied from 5 to 9 to mimic biological environments. Neutral and anionic forms of fisetin coexist in ground state in both acidic and alkaline conditions. However, in the excited state and at low pH, the anionic form of fisetin predominates over the proton transferred form, whereas in SLNs, the proton transferred form is the major emitting species. Higher pH showed enhancement in anionic emission to different extent in the two types of environments. Limited percolation of H(+) and OH(-) ions inside the SLNs that host fisetin molecules controls their photophysics. The experimental results encourage usage of fisetin as a drug depending on the ratio of the neutral and anionic as well as the proton transferred forms under various pH conditions.

  13. Solid lipid nanoparticles as attractive drug vehicles: Composition, properties and therapeutic strategies.

    PubMed

    Geszke-Moritz, Małgorzata; Moritz, Michał

    2016-11-01

    This work briefly reviews up-to-date developments in solid lipid nanoparticles (SLNs) as effective nanocolloidal system for drug delivery. It summarizes SLNs in terms of their preparation, surface modification and properties. The application of SLNs as a carrier system enables to improve the therapeutic efficacy of drugs from various therapeutic groups. Present uses of SLNs include cancer therapy, dermatology, bacterial infections, brain targeting and eye disorders among others. The usage of SLNs provides enhanced pharmacokinetic properties and modulated release of drugs. SLN ubiquitous application results from their specific features such as possibility of surface modification, increased permeation through biological barriers, resistance to chemical degradation, possibility of co-delivery of various therapeutic agents or stimuli-responsiveness. This paper will be useful to the scientists working in the domain of SLN-based drug delivery systems. PMID:27524099

  14. Enhanced in Vitro Anti-Tumor Activity of 5-Azacytidine by Entrapment into Solid Lipid Nanoparticles

    PubMed Central

    Jahanfar, Farhad; Hasani, Akbar; Shanebandi, Dariush; Rahmati, Mohammad; Hamishehkar, Hamed

    2016-01-01

    Purpose: In this study the effectiveness of encapsulating of 5-azacytidine into the lipid nanoparticles was investigated and in vitro effect of encapsulated 5-azacytidine studied on MCF-7 cell lines Methods: 5-azacytidine -loaded solid lipid nanoparticles were produced by double emulsification (w/o/w) method by using stearic acid as lipid matrix, soy lecithin and poloxamer 407 as surfactant and co-surfactant respectively. Particle size, zeta potential, surface morphology, entrapment efficiency and kinetic of drug release were studied. In vitro effect of 5-azacytidine on MCF-7 cell line studied by MTT assay, DAPI staining, Rhodamine B relative uptake, and also Real time RT-PCR was performed for studying difference effect of free and encapsulated drug on expression of RARß2 gene. Results: The formulation F5 with 55.84±0.46 % of entrapment efficiency shows zero order kinetic of drug release and selected for in vitro studies; the cytotoxicity of free drug and encapsulated drug in 48 h of incubation have significant difference. DAPI staining shows morphology of apoptotic nucleus in both free and encapsulated drug, Rhodamine B labeled SLNs show time dependency and accumulation of SLNs in cytoplasm. Real time qRT-PCR doesn’t show any significant difference (p>0.05) in expression of RARß2 gene in both cells treated with free or encapsulated drug. Conclusion: The results of the present study indicated that the entrapment of 5-azacytidine into SLNs enhanced its cytotoxicity performance and may pave a way for the future design of a desired dosage form for 5-azacytidine. PMID:27766220

  15. Lipid nanoparticles for parenteral delivery of actives.

    PubMed

    Joshi, Medha D; Müller, Rainer H

    2009-02-01

    The present review compiles the applications of lipid nanoparticles mainly solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and lipid drug conjugates (LDC) in parenteral delivery of pharmaceutical actives. The attempts to incorporate anticancer agents, imaging agents, antiparasitics, antiarthritics, genes for transfection, agents for liver, cardiovascular and central nervous system targeting have been summarized. The utility of lipid nanoparticles as adjuvant has been discussed separately. A special focus of this review is on toxicity caused by these kinds of lipid nanoparticles with a glance on the fate of lipid nanoparticles after their parenteral delivery in vivo viz the protein adsorption patterns. PMID:18824097

  16. Evidence does not support absorption of intact solid lipid nanoparticles via oral delivery

    NASA Astrophysics Data System (ADS)

    Hu, Xiongwei; Fan, Wufa; Yu, Zhou; Lu, Yi; Qi, Jianping; Zhang, Jian; Dong, Xiaochun; Zhao, Weili; Wu, Wei

    2016-03-01

    Whether and to what extent solid lipid nanoparticles (SLNs) can be absorbed integrally via oral delivery should be clarified because it is the basis for elucidation of absorption mechanisms. To address this topic, the in vivo fate of SLNs as well as their interaction with biomembranes is investigated using water-quenching fluorescent probes that can signal structural variations of lipid-based nanocarriers. Live imaging indicates prolonged retention of SLNs in the stomach, whereas in the intestine, SLNs can be digested quickly. No translocation of intact SLNs to other organs or tissues can be observed. The in situ perfusion study shows bioadhesion of both SLNs and simulated mixed micelles (SMMs) to intestinal mucus, but no evidence of penetration of integral nanocarriers. Both SLNs and SMMs exhibit significant cellular uptake, but fail to penetrate cell monolayers. Confocal laser scanning microscopy reveals that nanocarriers mainly concentrate on the surface of the monolayers, and no evidence of penetration of intact vehicles can be obtained. The mucous layer acts as a barrier to the penetration of both SLNs and SMMs. Both bile salt-decoration and SMM formulation help to strengthen the interaction with biomembranes. It is concluded that evidence does not support absorption of intact SLNs via oral delivery.Whether and to what extent solid lipid nanoparticles (SLNs) can be absorbed integrally via oral delivery should be clarified because it is the basis for elucidation of absorption mechanisms. To address this topic, the in vivo fate of SLNs as well as their interaction with biomembranes is investigated using water-quenching fluorescent probes that can signal structural variations of lipid-based nanocarriers. Live imaging indicates prolonged retention of SLNs in the stomach, whereas in the intestine, SLNs can be digested quickly. No translocation of intact SLNs to other organs or tissues can be observed. The in situ perfusion study shows bioadhesion of both SLNs and

  17. Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe Vera in glioma cells.

    PubMed

    K S, Joshy; Sharma, Chandra P; Kalarikkal, Nandakumar; Sandeep, K; Thomas, Sabu; Pothen, Laly A

    2016-09-01

    Zidovudine loaded solid lipid nanoparticles of stearic acid modified with Aloe Vera (AV) have been prepared via simple emulsion solvent evaporation method which showed excellent stability at room temperature and refrigerated condition. The nanoparticles were examined by Fourier transform infrared spectroscopy (FT-IR), which revealed the overlap of the AV absorption peak with the absorption peak of modified stearic acid nanoparticles. The inclusion of AV to stearic acid decreased the crystallinity and improved the hydrophilicity of lipid nanoparticles and thereby improved the drug loading efficacy of lipid nanoparticles. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging revealed that, the average particle size of unmodified (bare) nanoparticles was 45.66±12.22nm and modified solid lipid nanoparticles showed an average size of 265.61±80.44nm. Solid lipid nanoparticles with well-defined morphology were tested in vitro for their possible application in drug delivery. Cell culture studies using C6 glioma cells on the nanoparticles showed enhanced growth and proliferation of cells without exhibiting any toxicity. In addition, normal cell morphology and improved uptake were observed by fluorescence microscopy images of rhodamine labeled modified solid lipid nanoparticles compared with unmodified nanoparticles. The cellular uptake study suggested that these nanoparticles could be a promising drug delivery system to enhance the uptake of antiviral drug by brain cells and it could be a suitable drug carrier system for the treatment of HIV. PMID:27207037

  18. Development and evaluation of solid lipid nanoparticles of mometasone furoate for topical delivery

    PubMed Central

    Madan, Jyotsana R; Khude, Priyanka A; Dua, Kamal

    2014-01-01

    Introduction: Solid lipid nanoparticles (SLNs) are the new generation of submicron sized lipid emulsions where liquid lipid (oil) has been substituted by solid lipid. Lipids used in the formulation are safe, stable and biodegradable in nature. SLNs offer various advantages for topical drug delivery like ability of deposition into skin with the reduced systemic exposure and reduced local side-effects along with providing sustained release of drug. Mometasone furoate (MF) is a topical glucocorticoid having anti-inflammatory, anti-pruritic, anti-hyper proliferative activity. Owing to these properties it is recommended in chronic inflammation and psoriasis. In market, MF cream and lotion (0.1%) are available, which show slight skin irritation, burning and common side-effects due to steroids. Experimental: To overcome the shortcomings of conventional formulations, there is a need to develop a novel formulation that can reduce these side-effects and show maximum desired effects. Thus, SLN of MF can be prepared, which would help in increasing skin deposition as well as provide sustained release. In this study, SLNs were prepared by solvent - injection method. Results: The F8 batch had shown maximum entrapment up to55.59% and sustained drug release for more than 8 h. The skin permeability of SLN loaded gel was found to be 15.21times more than that of marketed cream. SLN loaded gel showed 83.52% of skin deposition which was 2.67 times more than marketed cream and 20 times more than plain drug loaded gel. The scanning electron microscopy and zeta potential study showed formation of good SLN dispersion. The stability study showed successful formation of stable SLNs. Thus, SLNs proved the potential for topical delivery of corticosteroid drug over the conventional formulations. Experimental: To overcome the shortcomings of conventional formulations, there is a need to develop a novel formulation that can reduce these side-effects and show maximum desired effects. Thus, SLN of

  19. Solid Lipid Nanoparticles Improve the Diclofenac Availability in Vitreous after Intraocular Injection

    PubMed Central

    Abrishami, Majid; Vakili Ahrari Roodi, Mohammad

    2016-01-01

    Purpose. In order to improve the drug availability after intravitreal administration, solid lipid nanoparticles (SLNs) containing diclofenac were prepared. Methods. In this experimental study, 18 albino rabbits were included. In right and left eyes of all rabbits, SLNs containing diclofenac and commercial form of diclofenac (0.3 mg drug) were intravitreally injected, respectively. One, four, twelve, twenty-four, and forty-eight hours after injection, vitreous and aqueous humor samples were obtained in all cases. Then, the concentration of diclofenac sodium was evaluated in all samples. Results. Size of nanoparticles was around 170 nm after preparation. Drug concentration in eyes injected with SLNs was significantly higher than left eyes injected with commercial formulation up to 4 hours after intravitreal injection (p < 0.05). Diclofenac was quantified in samples up to 48 hours after intraocular injection. Four hours after intravitreal injection, the concentration of diclofenac in vitreous and aqueous humor of eyes receiving SLNs was, respectively, 2.5 and 6.5 times higher than eyes injected with commercial form of drug. Conclusions. Here, we demonstrate the potential of SLNs as a carrier of diclofenac for intraocular injection in order to prevent the systemic effects of the drug, increase the injection intervals, and improve the patient compliance. PMID:27803815

  20. Solid lipid nanoparticles induced hematological changes and inflammatory response in mice.

    PubMed

    Silva, Adny Henrique; Locatelli, Claudriana; Filippin-Monteiro, Fabíola Branco; Zanetti-Ramos, Betina G; Conte, Aline; Creczynski-Pasa, Tânia Beatriz

    2014-03-01

    Solid lipid nanoparticles (SLNs) are an alternative drug delivery system compared to emulsions, liposomes and polymeric nanoparticles. Due to their unique sizes and properties, SLNs offer possibility to develop new therapeutic approaches. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could be used for drug targeting. However, toxicity of these new formulations has not been investigated thus far. In this study, we carried out an in vivo toxicity study. For that mice were divided into three groups and treated intraperitoneally with triestearin-based SLNs (TN), natural wax-based SLNs (VN) or vehicle for 10 days. After that, necropsies, histopathological and hematological analysis, as well as hepatic and renal functions were performed. Our results indicated that both TN and VN were absorbed post-exposure and induced an inflammatory response in adipose tissue. However, histopathological analysis demonstrated the absence of toxicity in both treated groups. In addition, the body weights were similar among the groups and low toxicity was also indicated by the unchanged serum biochemical parameters. This study provides a preliminary data for toxicological studies of two different SLNs in long-term in vivo exposure. However, further studies should be conducted in order to investigate the inflammatory response in order to establish the safety of these SLNs. PMID:23451884

  1. Solid lipid nanoparticles induced hematological changes and inflammatory response in mice.

    PubMed

    Silva, Adny Henrique; Locatelli, Claudriana; Filippin-Monteiro, Fabíola Branco; Zanetti-Ramos, Betina G; Conte, Aline; Creczynski-Pasa, Tânia Beatriz

    2014-03-01

    Solid lipid nanoparticles (SLNs) are an alternative drug delivery system compared to emulsions, liposomes and polymeric nanoparticles. Due to their unique sizes and properties, SLNs offer possibility to develop new therapeutic approaches. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could be used for drug targeting. However, toxicity of these new formulations has not been investigated thus far. In this study, we carried out an in vivo toxicity study. For that mice were divided into three groups and treated intraperitoneally with triestearin-based SLNs (TN), natural wax-based SLNs (VN) or vehicle for 10 days. After that, necropsies, histopathological and hematological analysis, as well as hepatic and renal functions were performed. Our results indicated that both TN and VN were absorbed post-exposure and induced an inflammatory response in adipose tissue. However, histopathological analysis demonstrated the absence of toxicity in both treated groups. In addition, the body weights were similar among the groups and low toxicity was also indicated by the unchanged serum biochemical parameters. This study provides a preliminary data for toxicological studies of two different SLNs in long-term in vivo exposure. However, further studies should be conducted in order to investigate the inflammatory response in order to establish the safety of these SLNs.

  2. Tumor-targeted delivery of paclitaxel using low density lipoprotein-mimetic solid lipid nanoparticles.

    PubMed

    Kim, Jin-Ho; Kim, Youngwook; Bae, Ki Hyun; Park, Tae Gwan; Lee, Jung Hee; Park, Keunchil

    2015-04-01

    Water-insoluble anticancer drugs, including paclitaxel, present severe clinical side effects when administered to patients, primarily associated with the toxicity of reagents used to solubilize the drugs. In efforts to develop alternative formulations of water-insoluble anticancer drugs suitable for intravenous administration, we developed biocompatible anticancer therapeutic solid lipid nanoparticles (SLNs), mimicking the structure and composition of natural particles, low-density lipoproteins (LDLs), for tumor-targeted delivery of paclitaxel. These therapeutic nanoparticles contained water-insoluble paclitaxel in the core with tumor-targeting ligand covalently conjugated on the polyethylene glycol (PEG)-modified surface (targeted PtSLNs). In preclinical human cancer xenograft mouse model studies, the paclitaxel-containing tumor-targeting SLNs exhibited pronounced in vivo stability and enhanced biocompatibility. Furthermore, these SLNs had superior antitumor activity to in-class nanoparticular therapeutics in clinical use (Taxol and Genexol-PM) and yielded long-term complete responses. The in vivo targeted antitumor activities of the SLN formulations in a mouse tumor model suggest that LDL-mimetic SLN formulations can be utilized as a biocompatible, tumor-targeting platform for the delivery of various anticancer therapeutics.

  3. Sesamol-loaded solid lipid nanoparticles for treatment of skin cancer.

    PubMed

    Geetha, T; Kapila, Meenakshi; Prakash, Om; Deol, Parneet Kaur; Kakkar, Vandita; Kaur, Indu Pal

    2015-02-01

    Abstract Role of reactive oxygen species (ROS) in skin carcinogenesis is well documented. Natural molecules, like sesamol, with marked antioxidant potential can be useful in combating skin cancers. In vitro antiproliferative (using MTT assay) and DNA fragmentation studies in HL 60 cell lines, confirmed the apoptotic nature of sesamol. However, it showed a significant flux across the mice skin upon topical application, such that its local availability in skin is limited. Former is attributed mainly to its properties like small size, low molecular weight (138.28), and a sufficient lipid and water solubility (log P 1.29; solubility 38.8 mg/ml). To achieve its maximum epicutaneous delivery, packaging it into a suitable carrier system is thus indicated. Sesamol-loaded solid lipid nanoparticles (S-SLN) were thus prepared with particle size of 127.9 nm (PI: 0.256) and entrapment efficiency of 88.21%. Topical application of S-SLN in a cream base indicated significant retention in the skin with minimal flux across skin as confirmed by the in-vivo skin retention and ex-vivo skin permeation studies. In vivo anticancer studies performed on TPA-induced and benzo(a)pyrene initiated tumour production (ROS mediated) in mouse epidermis showed the normalization (in histology studies) of skin cancers post their induction, upon treatment with S-SLN. PMID:25268273

  4. In vitro cytotoxicity and bioavailability of solid lipid nanoparticles containing tamoxifen citrate.

    PubMed

    Hashem, Fahima M; Nasr, Mohamed; Khairy, Ahmed

    2014-11-01

    The objective of this study was to evaluate the influence of solid lipid nanoparticles (SLN) loaded with the poorly water-soluble drug tamoxifen citrate (TC) on the in vitro antitumor activity and bioavailability of the drug. TC-loaded SLN were prepared by solvent injection method using glycerol monostearate (GMS) or stearic acid (SA) as lipid matrix. Poloxamer 188 or tween 80 were used as stabilizers. TC-loaded SLN (F3 and F4) prepared using GMS and stabilized by poloxamer 188 showed highest entrapment efficiency % (86.07 ± 1.74 and 90.40 ± 1.22%) and reasonable mean particle sizes (130.40 ± 9.45 and 243.80 ± 12.33 nm), respectively. The in vitro release of TC from F3 and F4 exhibited an initial burst effect followed by a sustained drug release. In vitro cytotoxicity of F3 against human breast cancer cell line MCF-7 showed comparable antitumor activity to free drug. Moreover, the results of bioavailability evaluation of TC-loaded SLN in rats compared to free TC indicated that 160.61% increase in the oral bioavailability of TC. The obtained results suggest that incorporation of the poorly water-soluble drug TC in SLN preserves the in vitro antitumor activity and significantly enhance oral bioavailability of TC in rats. PMID:24032414

  5. A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles.

    PubMed

    Wissing, S A; Müller, R H

    2001-08-01

    Solid lipid nanoparticles (SLN) have been introduced as a novel carrier system for drugs and cosmetics. It has been found that SLN possess characteristics of physical UV-blockers on their own, thus offering the possibility of developing a more effective sunscreen system with reduced side-effects. Incorporation of the chemical sunscreen tocopherol acetate into SLN prevents chemical degradation and increases the UV-blocking capacity. Aqueous SLN dispersions were produced and incorporated into gels, followed by particle size examination, stability testing upon storage and thermoanalytical examination. Investigation of the UV-blocking capacity using different in vitro techniques revealed that the SLN dispersions produced in this study are at least twice as effective as their reference emulsions (conventional emulsions with identical lipid content). Placebo SLN even show greater UV-blocking efficacy than emulsions containing tocopherol acetate as the molecular sunscreen. Incorporation of tocopherol acetate into SLN leads to an overadditive UV-blocking effect. Furthermore, film formation of SLN on the skin and occlusivity were examined. The obtained data show that incorporation of tocopherol acetate into SLN leads to an improved sunscreen and skin care formulation.

  6. Solid lipid nanoparticles loaded with lipoyl-memantine codrug: preparation and characterization.

    PubMed

    Laserra, Sara; Basit, Abdul; Sozio, Piera; Marinelli, Lisa; Fornasari, Erika; Cacciatore, Ivana; Ciulla, Michele; Türkez, Hasan; Geyikoglu, Fatime; Di Stefano, Antonio

    2015-05-15

    Solid lipid nanoparticles (SLNs) are considered very attractive drug-delivery systems (DDS) able to enhance the efficacy of some therapeutic agents in several pathologies difficult to treat in a conventional way. Starting from these evidences, this study describes the preparation, physicochemical characterization, release, and in vitro cytotoxicity of stealth SLNs as innovative approach to improve solubility and absorption through the gastrointestinal tract of lipoyl-memantine (LA-MEM), a potential anti-Alzheimer codrug. Physico-chemical properties of LA-MEM loaded SLNs have been intensively investigated. Differential scanning calorimetry (DSC) was used to clarify the state and crystalline structure of the formulation. The results obtained from particles size analysis, polydispersity (PDI), and zeta potential measurements allowed the identification of the optimized formulation, which was characterized by a drug-lipid ratio 1:5, an average intensity diameter of 170nm, a PDI of 0.072, a zeta potential of -33.8mV, and an entrapment efficiency of 88%. Moreover, in vitro stability and release studies in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF), and preliminary in vitro cytotoxicity studies revealed that LA-MEM loaded SLNs could represent potential candidate for an in vivo investigation as DDS for the brain since it resulted devoid of citotoxicity and able to release the free codrug.

  7. Sesamol-loaded solid lipid nanoparticles for treatment of skin cancer.

    PubMed

    Geetha, T; Kapila, Meenakshi; Prakash, Om; Deol, Parneet Kaur; Kakkar, Vandita; Kaur, Indu Pal

    2015-02-01

    Abstract Role of reactive oxygen species (ROS) in skin carcinogenesis is well documented. Natural molecules, like sesamol, with marked antioxidant potential can be useful in combating skin cancers. In vitro antiproliferative (using MTT assay) and DNA fragmentation studies in HL 60 cell lines, confirmed the apoptotic nature of sesamol. However, it showed a significant flux across the mice skin upon topical application, such that its local availability in skin is limited. Former is attributed mainly to its properties like small size, low molecular weight (138.28), and a sufficient lipid and water solubility (log P 1.29; solubility 38.8 mg/ml). To achieve its maximum epicutaneous delivery, packaging it into a suitable carrier system is thus indicated. Sesamol-loaded solid lipid nanoparticles (S-SLN) were thus prepared with particle size of 127.9 nm (PI: 0.256) and entrapment efficiency of 88.21%. Topical application of S-SLN in a cream base indicated significant retention in the skin with minimal flux across skin as confirmed by the in-vivo skin retention and ex-vivo skin permeation studies. In vivo anticancer studies performed on TPA-induced and benzo(a)pyrene initiated tumour production (ROS mediated) in mouse epidermis showed the normalization (in histology studies) of skin cancers post their induction, upon treatment with S-SLN.

  8. Design and Evaluation of Voriconazole Loaded Solid Lipid Nanoparticles for Ophthalmic Application.

    PubMed

    Khare, Anubha; Singh, Inderbir; Pawar, Pravin; Grover, Kanchan

    2016-01-01

    Voriconazole is a second-generation antifungal agent with excellent broad spectrum of antifungal activity commercially available for oral and intravenous administration. Systemic administration of voriconazole is associated with side effects including visual and hepatic abnormalities. This study assessed the feasibility of using solid lipid nanoparticles for ocular delivery of voriconazole adopting stearic acid as lipidic material, tween 80 as a stabilizer, and Carbopol 934 as controlled release agent and for increasing the precorneal residence time in eye. The systems were prepared using two different methods, that is, ultrasonication method and microemulsion technique. The results indicated that the larger particle size of SLNs was found with microemulsion technique (308 ± 3.52 nm to 343 ± 3.51) compared to SLN prepared with ultrasonication method (234 ± 3.52 nm to 288 ± 4.58 nm). The polydispersity index values were less than 0.3 for all formulations and zeta potential of the prepared formulations by these two methods varied from -22.71 ± 0.63 mV to -28.86 ± 0.58 mV. Powder X-ray diffraction and differential scanning calorimetry indicated decrease in crystallinity of drug. The in vitro release study and the SLN formulations prepared with ultrasonication method demonstrated sustained release up to 12 hours. This study demonstrated that SLN prepared by ultrasonication method is more suitable than microemulsion technique without causing any significant effect on corneal hydration level. PMID:27293896

  9. Solid lipid nanoparticles loaded with lipoyl-memantine codrug: preparation and characterization.

    PubMed

    Laserra, Sara; Basit, Abdul; Sozio, Piera; Marinelli, Lisa; Fornasari, Erika; Cacciatore, Ivana; Ciulla, Michele; Türkez, Hasan; Geyikoglu, Fatime; Di Stefano, Antonio

    2015-05-15

    Solid lipid nanoparticles (SLNs) are considered very attractive drug-delivery systems (DDS) able to enhance the efficacy of some therapeutic agents in several pathologies difficult to treat in a conventional way. Starting from these evidences, this study describes the preparation, physicochemical characterization, release, and in vitro cytotoxicity of stealth SLNs as innovative approach to improve solubility and absorption through the gastrointestinal tract of lipoyl-memantine (LA-MEM), a potential anti-Alzheimer codrug. Physico-chemical properties of LA-MEM loaded SLNs have been intensively investigated. Differential scanning calorimetry (DSC) was used to clarify the state and crystalline structure of the formulation. The results obtained from particles size analysis, polydispersity (PDI), and zeta potential measurements allowed the identification of the optimized formulation, which was characterized by a drug-lipid ratio 1:5, an average intensity diameter of 170nm, a PDI of 0.072, a zeta potential of -33.8mV, and an entrapment efficiency of 88%. Moreover, in vitro stability and release studies in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF), and preliminary in vitro cytotoxicity studies revealed that LA-MEM loaded SLNs could represent potential candidate for an in vivo investigation as DDS for the brain since it resulted devoid of citotoxicity and able to release the free codrug. PMID:25747452

  10. Formulation of Tenofovir-Loaded Functionalized Solid Lipid Nanoparticles Intended for HIV Prevention

    PubMed Central

    ALUKDA, DIMA; STURGIS, TIMOTHY; YOUAN, BI-BOTTI C.

    2011-01-01

    The objective of this study is to engineer polylysine–heparin functionalized solid lipid nanoparticles (fSLNs) for the use of a vaginal microbicide delivery template for HIV prevention. The fSLNs are prepared using a modified phase-inversion technique followed by a layer-by-layer deposition method. The Box–Behnken experimental design is used to analyze the influence of three factors (X1 = bovine serum albumin concentration, X2 = pH of the aqueous phase, and X3 = lipid amount) on the particle mean diameter (PMD) measured by dynamic light scattering (DLS). Tenofovir is used as a model anti-HIV microbicide. The SLNs are also characterized for morphology, zeta potential (ζ), percent drug encapsulation efficiency (EE%), and cytotoxicity on a human vaginal epithelial cell line by electron microscopy, DLS, ultraviolet, and fluorescence spectroscopy, respectively. The statistical model predicts particle size (Y) with 90% confidence and the Y values are significantly affected by X1 and X2. The produced fSLNs appear noncytotoxic and exhibit a platelet-like shape with respective PMD, EE%, and ζ value of 153 nm, 8.3%, and −51mV. These fSLNs intended to be administered topically have the potential to enhance cellular uptake of hydrophobic microbicides and outdistance the virus during the HIV/AIDS infection process, possibly leading to more effective prevention of the disease transmission. PMID:21437910

  11. Preparation, characterization, and optimization of primaquine-loaded solid lipid nanoparticles.

    PubMed

    Omwoyo, Wesley Nyaigoti; Ogutu, Bernhards; Oloo, Florence; Swai, Hulda; Kalombo, Lonji; Melariri, Paula; Mahanga, Geoffrey Maroa; Gathirwa, Jeremiah Waweru

    2014-01-01

    Primaquine (PQ) is one of the most widely used antimalarial drugs and is the only available drug that combats the relapsing form of malaria. PQ use in higher doses is limited by severe tissue toxicity including hematological- and gastrointestinal-related side effects. Nanoformulation of drugs in an appropriate drug carrier system has been extensively studied and shown to have the potential to improve bioavailability, thereby enhancing activity, reducing dose frequency, and subsequently reducing toxicity. The aim of this work was to design, synthesize, and characterize PQ-loaded solid lipid nanoparticles (SLNs) (PQ-SLNs) as a potential drug-delivery system. SLNs were prepared by a modified solvent emulsification evaporation method based on a water-in-oil-in-water (w/o/w) double emulsion. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the PQ-SLNs were 236 nm, +23 mV, 14%, and 75%, respectively. The zeta potential of the SLNs changed dramatically, from -6.54 mV to +23.0 mV, by binding positively charged chitosan as surface modifier. A spherical morphology of PQ-SLNs was seen by scanning electron microscope. In vitro, release profile depicted a steady drug release over 72 hours. Differential scanning calorimeter thermograms demonstrated presence of drug in drug-loaded nanoparticles along with disappearance of decomposition exotherms, suggesting increased physical stability of drug in prepared formulations. Negligible changes in characteristic peaks of drug in Fourier transform infrared spectra indicated absence of any interaction among the various components entrapped in the nanoparticle formulation. The nanoformulated PQ was 20% more effective as compared with conventional oral dose when tested in Plasmodium berghei-infected Swiss albino mice. This study demonstrated an efficient method of forming a nanomedicine delivery system for antimalarial drugs.

  12. Preparation, characterization, and optimization of primaquine-loaded solid lipid nanoparticles

    PubMed Central

    Omwoyo, Wesley Nyaigoti; Ogutu, Bernhards; Oloo, Florence; Swai, Hulda; Kalombo, Lonji; Melariri, Paula; Mahanga, Geoffrey Maroa; Gathirwa, Jeremiah Waweru

    2014-01-01

    Primaquine (PQ) is one of the most widely used antimalarial drugs and is the only available drug that combats the relapsing form of malaria. PQ use in higher doses is limited by severe tissue toxicity including hematological- and gastrointestinal-related side effects. Nanoformulation of drugs in an appropriate drug carrier system has been extensively studied and shown to have the potential to improve bioavailability, thereby enhancing activity, reducing dose frequency, and subsequently reducing toxicity. The aim of this work was to design, synthesize, and characterize PQ-loaded solid lipid nanoparticles (SLNs) (PQ-SLNs) as a potential drug-delivery system. SLNs were prepared by a modified solvent emulsification evaporation method based on a water-in-oil-in-water (w/o/w) double emulsion. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the PQ-SLNs were 236 nm, +23 mV, 14%, and 75%, respectively. The zeta potential of the SLNs changed dramatically, from −6.54 mV to +23.0 mV, by binding positively charged chitosan as surface modifier. A spherical morphology of PQ-SLNs was seen by scanning electron microscope. In vitro, release profile depicted a steady drug release over 72 hours. Differential scanning calorimeter thermograms demonstrated presence of drug in drug-loaded nanoparticles along with disappearance of decomposition exotherms, suggesting increased physical stability of drug in prepared formulations. Negligible changes in characteristic peaks of drug in Fourier transform infrared spectra indicated absence of any interaction among the various components entrapped in the nanoparticle formulation. The nanoformulated PQ was 20% more effective as compared with conventional oral dose when tested in Plasmodium berghei-infected Swiss albino mice. This study demonstrated an efficient method of forming a nanomedicine delivery system for antimalarial drugs. PMID:25143734

  13. Formulation and Physicochemical Characterization of Lycopene-Loaded Solid Lipid Nanoparticles

    PubMed Central

    Nazemiyeh, Elham; Eskandani, Morteza; Sheikhloie, Hossein; Nazemiyeh, Hossein

    2016-01-01

    Purpose: Lycopene belongs to the carotenoids that shows good pharmacological properties including antioxidant, anti-inflammatory and anticancer. However, as a result of very low aqueous solubility, it has a limited systemic absorption, following oral administration. Methods: Here, we prepared a stable lycopene-loaded solid lipid nanoparticles using Precirol® ATO5, Compritol 888 ATO and myristic acid by hot homogenization method with some modification. The size and morphological characteristics of nanoparticles were evaluated using Scanning Electron Microscopy (SEM). Moreover, zeta potential and dispersity index (DI) were measured using zeta sizer. In addition, encapsulation efficiency (EE%), drug loading (DL) and cumulative drug release were quantified. Results: The results showed that the size and DI of particles was generally smaller in the case of SLNs prepared with precirol when compared to SLNs prepared with compritol. Scanning electron microscopy (SEM) and particle size analyses showed spherical SLNs (125 ± 3.89 nm), monodispersed distribution, and zeta potential of −10.06 ± 0.08 mV. High EE (98.4 ± 0.5 %) and DL (44.8 ± 0.46 mg/g) were achieved in the case of nanoparticles prepared by precirol. The stability study of the lycopene-SLNs in aqueous medium (4 °C) was showed that after 2 months there is no significant differences seen in size and DI compared with the fresh formulation. Conclusion: Conclusively, in this investigation we prepared a stable lycopene-SLNs with good physicochemical characteristic which candidate it for the future in vivo trials in nutraceutical industries. PMID:27478786

  14. Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box-Behnken design.

    PubMed

    Wang, Fengzhen; Chen, Li; Jiang, Sunmin; He, Jun; Zhang, Xiumei; Peng, Jin; Xu, Qunwei; Li, Rui

    2014-09-01

    The purpose of the present study was to optimize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLNs) which were used as topical eye drops by evaluating the relationship between design factors and experimental data. A three factor, three-level Box-Behnken design (BBD) was used for the optimization procedure, choosing the amount of GMS, the amount of phospholipid, the concentration of surfactant as the independent variables. The chosen dependent variables were entrapment efficiency, dosage loading, and particle size. The generated polynomial equations and response surface plots were used to relate the dependent and independent variables. The optimal nanoparticles were formulated with 100 mg GMS, 150 mg phospholipid, and 1% Tween80 and PEG 400 (1:1, w/v). A new formulation was prepared according to these levels. The observed responses were close to the predicted values of the optimized formulation. The particle size was 197.8 ± 4.9 nm. The polydispersity index of particle size was 0.239 ± 0.01 and the zeta potential was 32.7 ± 2.6 mV. The entrapment efficiency and dosage loading were about 68.39% and 2.49%, respectively. Fourier transform infrared spectroscopy (FT-IR) study indicated that the drug was entrapped in nanoparticles. The optimized formulation showed a sustained release followed the Peppas model. MTZ-SLNs showed significant prolonged decreasing intraocular pressure effect comparing with MTZ solution in vivo pharmacodynamics studies. The results of acute eye irritation study indicated that MTZ-SLNs and AZOPT both had no eye irritation. Furthermore, the MTZ-SLNs were suitable to be stored at low temperature (4 °C).

  15. Surface-active solid lipid nanoparticles as Pickering stabilizers for oil-in-water emulsions.

    PubMed

    Gupta, Renuka; Rousseau, Dérick

    2012-03-01

    Oil-in-water (O/W) emulsions solely stabilized by surface-active solid lipid nanoparticles (SLNs) were developed. The SLNs were generated by quench-cooling hot O/W nanoemulsions consisting of 7.5% glyceryl stearyl citrate (GSC) dispersed in water. Their initial volume-weighted mean particle diameter (∼152 nm) and zeta potential (ca.-49 mV) remained unchanged for 24 weeks. O/W emulsions (oil phase volume fraction: 0.2) containing 7.5% (w/w) GSC SLNs in the aqueous phase were kinetically-stable for 12 weeks and did not visually phase-separate over 24 weeks. The O/W emulsions generated with solid-state GSC SLNs had a volume-weighted mean oil droplet diameter of ∼459 nm and a zeta potential of ca.-43 mV. Emulsion microstructure evaluated with TEM revealed dispersed oil droplets sparsely covered with adsorbed Pickering-type SLNs as well aggregated SLNs present in the continuous phase. Gradual emulsion destabilization resulted from GSC SLN dissolution during the experimental timeframe. Overall, surface-active SLNs developed via nanoemulsions effectively kinetically stabilized O/W emulsions.

  16. Effect of Palm or Coconut Solid Lipid Nanoparticles (SLNs) on Growth of Lactobacillus plantarum in Milk.

    PubMed

    Jo, Yeon-Ji; Choi, Mi-Jung; Kwon, Yun-Joong

    2015-01-01

    This study was performed to investigate the effect of palm or coconut solid lipid nanoparticles (PO-SLNs or CO-SLNs) on growth of Lactobacillus plantarum (L. plantarum) in milk during storage period. The PO or CO (0.1% or 1.0%) was dispersed both in distilled water (DW) and ultra high temperature milk (UHTM), and subsequently emulsified with Tween(®) 80 by ultrasonication (30% power, 2 min). Increase in particle size and encapsulation efficiency (EE%) in DW was observed with an increase in oil concentration, whereas a decrease in ζ-potential of SLNs was noted with an increment in oil concentration. Moreover, the CO-SLNs exhibited relatively smaller particle size and higher EE% than PO-SLNs. The CO-SLNs were found to be more stable than PO-SLNs. Higher lipid oxidation of PO or CO-SLNs in UHTM was observed during the storage test, when compared to PO or CO-SLNs in DW. However, there was no remarkable difference in lipid oxidation during storage period (p>0.05). In the growth test, the viability of L. plantarum in control (without PO or CO-SLNs in DW) exhibited a dramatic decrease with increasing storage period. In addition, viability of L. plantarum of PO or CO-SLNs in UHTM was higher than that of SLNs in DW. Based on the present study, production of SLNs containing PO or CO in UHTM is proposed, which can be used in lactobacilli fortified beverages in food industry. PMID:26761828

  17. Nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) for retinyl palmitate: effect on skin permeation.

    PubMed

    Clares, Beatriz; Calpena, Ana C; Parra, Alexander; Abrego, Guadalupe; Alvarado, Helen; Fangueiro, Joana F; Souto, Eliana B

    2014-10-01

    The aim of this study was to develop biocompatible lipid-based nanocarriers for retinyl palmitate (RP) to improve its skin delivery, photostability and biocompatibility, and to avoid undesirable topical side effects. RP loaded nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) were characterized in terms of size, surface electrical charge, pH, drug encapsulation efficiency and morphology. Spherical-shaped nanocarriers with a negatively charged surface (>|40|mV) and mean size lower than 275 nm were produced with adequate skin compatibility. The rheological properties showed that aqueous dispersions of SLNs followed a non-Newtonian behavior, pseudoplastic fluid adjusted to Herschel-Bulkley equation, whereas LPs and NEs exhibited a Newtonian behavior. SLNs offered significantly better photoprotection than LPs and NEs for RP. The cumulative amount of drug permeated through human skin at the end of 38 h was 6.67 ± 1.58 μg, 4.36 ± 0.21 μg and 3.64 ± 0.28 μg for NEs, LPs and SLNs, respectively. NEs flux was significantly higher than SLNs and LPs: NEs (0.37 ± 0.12 μg/h) > LPs (0.15 ± 0.09 μg/h) > SLNs (0.10 ± 0.05 μg/h). LPs offered significant higher skin retention than NEs and SLNs. Finally, even though all developed nanocarriers were found to be biocompatible, according to histological studies, NE was the system that most disrupted the skin. These encouraging findings can guide in proper selection of topical carriers among the diversity of available lipid-based nanocarriers, especially when a dermatologic or cosmetic purpose is desired. PMID:25102113

  18. Effect of Palm or Coconut Solid Lipid Nanoparticles (SLNs) on Growth of Lactobacillus plantarum in Milk

    PubMed Central

    Jo, Yeon-Ji; Choi, Mi-Jung

    2015-01-01

    This study was performed to investigate the effect of palm or coconut solid lipid nanoparticles (PO-SLNs or CO-SLNs) on growth of Lactobacillus plantarum (L. plantarum) in milk during storage period. The PO or CO (0.1% or 1.0%) was dispersed both in distilled water (DW) and ultra high temperature milk (UHTM), and subsequently emulsified with Tween® 80 by ultrasonication (30% power, 2 min). Increase in particle size and encapsulation efficiency (EE%) in DW was observed with an increase in oil concentration, whereas a decrease in ζ-potential of SLNs was noted with an increment in oil concentration. Moreover, the CO-SLNs exhibited relatively smaller particle size and higher EE% than PO-SLNs. The CO-SLNs were found to be more stable than PO-SLNs. Higher lipid oxidation of PO or CO-SLNs in UHTM was observed during the storage test, when compared to PO or CO-SLNs in DW. However, there was no remarkable difference in lipid oxidation during storage period (p>0.05). In the growth test, the viability of L. plantarum in control (without PO or CO-SLNs in DW) exhibited a dramatic decrease with increasing storage period. In addition, viability of L. plantarum of PO or CO-SLNs in UHTM was higher than that of SLNs in DW. Based on the present study, production of SLNs containing PO or CO in UHTM is proposed, which can be used in lactobacilli fortified beverages in food industry. PMID:26761828

  19. Nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) for retinyl palmitate: effect on skin permeation.

    PubMed

    Clares, Beatriz; Calpena, Ana C; Parra, Alexander; Abrego, Guadalupe; Alvarado, Helen; Fangueiro, Joana F; Souto, Eliana B

    2014-10-01

    The aim of this study was to develop biocompatible lipid-based nanocarriers for retinyl palmitate (RP) to improve its skin delivery, photostability and biocompatibility, and to avoid undesirable topical side effects. RP loaded nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) were characterized in terms of size, surface electrical charge, pH, drug encapsulation efficiency and morphology. Spherical-shaped nanocarriers with a negatively charged surface (>|40|mV) and mean size lower than 275 nm were produced with adequate skin compatibility. The rheological properties showed that aqueous dispersions of SLNs followed a non-Newtonian behavior, pseudoplastic fluid adjusted to Herschel-Bulkley equation, whereas LPs and NEs exhibited a Newtonian behavior. SLNs offered significantly better photoprotection than LPs and NEs for RP. The cumulative amount of drug permeated through human skin at the end of 38 h was 6.67 ± 1.58 μg, 4.36 ± 0.21 μg and 3.64 ± 0.28 μg for NEs, LPs and SLNs, respectively. NEs flux was significantly higher than SLNs and LPs: NEs (0.37 ± 0.12 μg/h) > LPs (0.15 ± 0.09 μg/h) > SLNs (0.10 ± 0.05 μg/h). LPs offered significant higher skin retention than NEs and SLNs. Finally, even though all developed nanocarriers were found to be biocompatible, according to histological studies, NE was the system that most disrupted the skin. These encouraging findings can guide in proper selection of topical carriers among the diversity of available lipid-based nanocarriers, especially when a dermatologic or cosmetic purpose is desired.

  20. Effect of Palm or Coconut Solid Lipid Nanoparticles (SLNs) on Growth of Lactobacillus plantarum in Milk.

    PubMed

    Jo, Yeon-Ji; Choi, Mi-Jung; Kwon, Yun-Joong

    2015-01-01

    This study was performed to investigate the effect of palm or coconut solid lipid nanoparticles (PO-SLNs or CO-SLNs) on growth of Lactobacillus plantarum (L. plantarum) in milk during storage period. The PO or CO (0.1% or 1.0%) was dispersed both in distilled water (DW) and ultra high temperature milk (UHTM), and subsequently emulsified with Tween(®) 80 by ultrasonication (30% power, 2 min). Increase in particle size and encapsulation efficiency (EE%) in DW was observed with an increase in oil concentration, whereas a decrease in ζ-potential of SLNs was noted with an increment in oil concentration. Moreover, the CO-SLNs exhibited relatively smaller particle size and higher EE% than PO-SLNs. The CO-SLNs were found to be more stable than PO-SLNs. Higher lipid oxidation of PO or CO-SLNs in UHTM was observed during the storage test, when compared to PO or CO-SLNs in DW. However, there was no remarkable difference in lipid oxidation during storage period (p>0.05). In the growth test, the viability of L. plantarum in control (without PO or CO-SLNs in DW) exhibited a dramatic decrease with increasing storage period. In addition, viability of L. plantarum of PO or CO-SLNs in UHTM was higher than that of SLNs in DW. Based on the present study, production of SLNs containing PO or CO in UHTM is proposed, which can be used in lactobacilli fortified beverages in food industry.

  1. Uniformity of drug payload and its effect on stability of solid lipid nanoparticles containing an ester prodrug.

    PubMed

    Kim, Jin-Ki; Howard, Melissa D; Dziubla, Thomas D; Rinehart, John J; Jay, Michael; Lu, Xiuling

    2011-01-25

    Nanocarrier systems are frequently characterized by their size distribution, while drug encapsulation in nanocarriers is generally characterized in terms of an entire population, assuming that drug distribution is uniform. Careful characterization of nanocarriers and assessment of their behavior in biological environments are essential for adequate prediction of the fate of the nanoparticles in vivo. Solid lipid nanoparticles containing [(3)H]-dexamethasone palmitate (an ester prodrug) and [(14)C]-stearyl alcohol (a component of the nanoparticle matrix) were prepared using the nanotemplate engineering method for bioresponsive tumor delivery to overcome interstitial fluid pressure gradients, a physiological barrier to tumor uptake of chemotherapeutic agents. While particle size analysis indicated a uniform size distribution of 93.2 ± 0.5 nm, gel filtration chromatography (GFC) revealed two nanoparticle populations. Drug encapsulation efficiency was 97%, but it distributed differently in the two populations, with average drug/lipid ratios of 0.04 and 0.25, respectively. The difference in surface properties resulted in distinguishing protein adsorption features of the two populations. GFC and HPLC profiles of the mixture of nanoparticles and human serum albumin (HSA) showed that no HSA was adsorbed to the first population of nanoparticles, but minor amounts were adsorbed to the second population. After 24 h incubation in 50% human plasma, ≥80% of the [(3)H]-dexamethasone palmitate was associated with nanoparticles. Thus, characterization of solid lipid nanoparticles produced by this method may be challenging from a regulatory perspective, but the strong association of the drug with the nanoparticles in plasma indicates that this nanocarrier system has the potential for in vivo application. PMID:21158414

  2. Development of cationic solid lipid nanoparticles with factorial design-based studies for topical administration of doxorubicin.

    PubMed

    Taveira, Stephânia F; Araújo, Luciana M P de Campos; de Santana, Danielle C A S; Nomizo, Auro; de Freitas, Luiz Alexandre P; Lopez, Renata F V

    2012-04-01

    Topical chemotherapy using doxorubicin, a powerful anticancer drug, can be used as an alternative with reduced systemic toxicity when treating skin cancer. The aim of the present work was to use factorial design-based studies to develop cationic solid lipid nanoparticles containing doxorubicin; further investigations into the influence of these particles on the drug's cytotoxicity and cellular uptake in B16F10 murine melanoma cells were performed. A 32 full factorial design was applied for two different lipid phases; one phase used stearic acid and the other used a 1:2 mixture of stearic acid and glyceryl behenate. The two factors investigated included the ratio between the lipid and the water phase and the ratio between the surfactant (poloxamer) and the co-surfactant (cetylpyridinium chloride). It was observed that the studied factors did not affect the mean diameter or the polydispersity of the obtained nanoparticles; however, they did significantly affect the zeta potential values. Optimised formulations with particle sizes ranging from 251 to 306 nm and positive zeta potentials were selected for doxorubicin incorporation. High entrapment efficiencies were achieved (97%) in formulations with higher amounts of stearic acid, suggesting that cationic charges on doxorubicin molecules may interact with the negative charges in stearic acid. Melanoma culture cell experiments showed that cationic solid lipid nanoparticles without drug were not cytotoxic to melanoma cells. The encapsulation of doxorubicin significantly increased cytotoxicity, indicating the potential of these nanoparticles for the treatment of skin cancer.

  3. Alendronate Sodium as Enteric Coated Solid Lipid Nanoparticles; Preparation, Optimization, and In Vivo Evaluation to Enhance Its Oral Bioavailability

    PubMed Central

    Hosny, Khaled Mohamed

    2016-01-01

    Treatment of osteoporosis with alendronate sodium has several challenges. The first challenge is the low bioavailability. The second main challenge is side effects, which include oesophageal ulceration. The aim of this research was to reformulate alendronate sodium as enteric coated solid lipid nanoparticles in order to enhance its bioavailability, and preventing the free alendronate sodium from coming into direct contact with the gastrointestinal mucosa, and thereby reducing the possibility of side effects. Enteric coated solid lipid nanoparticles were prepared according to the Box-Behnken design employing Design expert® software, and characterized for size, morphology, and entrapment efficiency. The optimized formula was coated with an Eudragit S100 and evaluated for drug release in acidic and basic media, stability studies and pharmacokinetic evaluations on rabbits. The results indicated that, using Derringer's desirability functional tool for optimization, the highest entrapment efficiency value of 74.3% and the smallest size value of 98 nm were predicted under optimum conditions with a desirability value of 0.917. The optimized nanoparticles released alendronate sodium only at an alkaline pH. The pharmacokinetic evaluation revealed that alendronate sodium bioavailability was enhanced by more than 7.4-fold in rabbits. In conclusion, enteric coated solid lipid nanoparticles is a promising formula for the delivery of alendronate sodium, eliminating its oesophageal side effects and enhancing its bioavailability. PMID:27148747

  4. Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

    SciTech Connect

    Ying, Bo; Campbell, Robert B.

    2014-04-04

    Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carrier systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of

  5. Intracellular trafficking of solid lipid nanoparticles and their distribution between cells through tunneling nanotubes.

    PubMed

    Kristl, Julijana; Plajnšek, Karmen Teskač; Kreft, Mateja Erdani; Janković, Biljana; Kocbek, Petra

    2013-09-27

    The intracellular fate of nanosized drug delivery systems is still not well understood. Various internalization pathways have been discovered, but knowledge of their intracellular trafficking is still incomplete. The aim of this study was to examine the internalization, pathways, and positioning taken by solid lipid nanoparticles (SLNs) in cells. SLNs were fluorescence labeled with a newly synthesized fluorescent probe, 14-DACA. The probe was strongly incorporated into the nanoparticle core under the influence of its long lipophilic chain, enabling superior visualization of SLNs under complex and dynamic intracellular conditions. The intracellular distribution of SLNs was studied qualitatively using a co-localization technique and quantitatively using fluorescence intensity profiles. SLNs were seen inside the cells as distinct bright blue dots that underwent dynamic movement and were finally positioned in the proximity of the nucleus. A few SLNs were shown to be present in mitochondria and between actin filaments, but none in the cell nucleus or lysosomes. SLNs are here reported to be present in tunneling nanotubes (TNTs), which could be a new route of SLN transfer between cells. More TNTs were observed in cells treated with SLNs. The presence of TNTs was additionally confirmed by atomic force microscopy analysis, which indicated that treated cells were more rough than control cells. Detailed investigation of the subcellular localization of SLNs and the evidence for their transfer and distribution via TNTs to the cells, which are not in direct contact with the source of SLNs, are important for understanding the mechanism of targeted drug delivery. Understanding the possible intercellular distribution of SLNs via TNTs can significantly influence approaches to treating organelle-specific diseases.

  6. Brain targeted solid lipid nanoparticles for brain ischemia: preparation and in vitro characterization.

    PubMed

    Morsi, Nadia M; Ghorab, Dalia M; Badie, Hany A

    2013-01-01

    This study aims at formulating solid lipid nanoparticles (SLNs) of Vinpocetine (VIN) to be used as a brain targeted sustained drug-delivery system. VIN is a derivative of vincamine alkaloid, used for chronic cerebral vascular ischemia. However, it suffers from low bioavailability and short half-life. Its oral bioavailability is recorded to be between 7 and 55%. Its elimination half-life is 1-2 h so it would be a good candidate for a sustained drug-delivery system. VIN SLNs were prepared using modified high shear homogenization followed by ultrasonication technique. The effect of incorporating different lipids at different concentrations of various surfactants was investigated. The VIN SLNs were characterized by entrapment efficiency percent (EE%), particle size distribution, zeta-potential, and cumulative released percent after 96 h. The EE% ranged between 83.34% ± 0.95-94.56% ± 0.11 due to the lipophilic character of VIN. The mean particle size measured ranged from 123 nm-464 nm. The cumulative released percent after 96 h ranged from 23.55% to 75.67% showing a controlled release profile. Formula (F32) composed of 5% glyceryl monostearate (GMS) and stabilized by 2% surfactant mixture [Tween 80, Pluronic F 68 (1:1)] was the most appropriate formula for brain delivery having EE% of 89.09% ± 1.49, zero-order release kinetics with cumulative released percent of 72.12% after 96 h, zeta-potential of -11.3 ± 0.97 mV. It showed a unimodal size distribution with particle size ≈ 90 nm and polydispersity index of 0.121. The formula of choice in this study exhibited a zero-order sustained release profile and met the requirement for a brain targeted SLN so it could be a promising formula to deliver VIN to the brain.

  7. Development and Evaluation of Solid Lipid Nanoparticles of N-6-Furfuryl Adenine for Prevention of Photoaging.

    PubMed

    Goindi, Shishu; Guleria, Ankita; Aggarwal, Nidhi

    2015-10-01

    N-6-furfuryl adenine (N6FA) also known as "kinetin" is a biologically active natural phytochemical. It belongs to the category of cytokinins, the natural plant growth hormones that promote cell division and play role in cell differentiation. Overall, N6FA aids in increasing the plant's life span. Human cells also contain.small quantities of N6FA. Scientists are trying to understand its function in humans. N6FA is being investigated for its properties such as antiplatelet, antioxidant, antiproliferative and anti-aging effects on human cells. The aim of the present investigation was to prepare solid lipid nanoparticle (SLN) based topical formulations of N6FA and to evaluate its efficacy against ultraviolet (UV) radiation induced skin photodamage. SLNs were prepared by hot microemulsion technique and optimized for the type and concentration of lipid and surfactant(s). The optimized SLN formulation was characterized in terms of particle size, drug entrapment efficiency, zeta potential and pH; evaluated for stability, spreadability, ex-vivo skin permeation and photoprotective effects against UV induced skin damage. The cumulative amount of drug permeated through mice skin using SLNs was 3 folds higher than from conventional cream base. The results of biochemical and histopathological investigations of skin treated with N6FA loaded SLNs clearly demonstrated the efficacy of optimized formulation in preventing photodamage (lesions, ulcers and changes in skin integrity) due to chronic UV exposure. The effects were comparable with widely used marketed formulation, Garnier wrinkle lift anti-aging cream. Results suggested that N6FA incorporated into SLNs may provide therapeutic as well as cosmeceutical benefits. PMID:26502637

  8. Design and Evaluation of Voriconazole Loaded Solid Lipid Nanoparticles for Ophthalmic Application

    PubMed Central

    Khare, Anubha; Singh, Inderbir; Pawar, Pravin; Grover, Kanchan

    2016-01-01

    Voriconazole is a second-generation antifungal agent with excellent broad spectrum of antifungal activity commercially available for oral and intravenous administration. Systemic administration of voriconazole is associated with side effects including visual and hepatic abnormalities. This study assessed the feasibility of using solid lipid nanoparticles for ocular delivery of voriconazole adopting stearic acid as lipidic material, tween 80 as a stabilizer, and Carbopol 934 as controlled release agent and for increasing the precorneal residence time in eye. The systems were prepared using two different methods, that is, ultrasonication method and microemulsion technique. The results indicated that the larger particle size of SLNs was found with microemulsion technique (308 ± 3.52 nm to 343 ± 3.51) compared to SLN prepared with ultrasonication method (234 ± 3.52 nm to 288 ± 4.58 nm). The polydispersity index values were less than 0.3 for all formulations and zeta potential of the prepared formulations by these two methods varied from −22.71 ± 0.63 mV to −28.86 ± 0.58 mV. Powder X-ray diffraction and differential scanning calorimetry indicated decrease in crystallinity of drug. The in vitro release study and the SLN formulations prepared with ultrasonication method demonstrated sustained release up to 12 hours. This study demonstrated that SLN prepared by ultrasonication method is more suitable than microemulsion technique without causing any significant effect on corneal hydration level. PMID:27293896

  9. Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E

    NASA Astrophysics Data System (ADS)

    Rute Neves, Ana; Fontes Queiroz, Joana; Weksler, Babette; Romero, Ignacio A.; Couraud, Pierre-Olivier; Reis, Salette

    2015-12-01

    Nanotechnology can be an important tool to improve the permeability of some drugs for the blood-brain barrier. In this work we created a new system to enter the brain by functionalizing solid lipid nanoparticles with apolipoprotein E, aiming to enhance their binding to low-density lipoprotein receptors on the blood-brain barrier endothelial cells. Solid lipid nanoparticles were successfully functionalized with apolipoprotein E using two distinct strategies that took advantage of the strong interaction between biotin and avidin. Transmission electron microscopy images revealed spherical nanoparticles, and dynamic light scattering gave a Z-average under 200 nm, a polydispersity index below 0.2, and a zeta potential between -10 mV and -15 mV. The functionalization of solid lipid nanoparticles with apolipoprotein E was demonstrated by infrared spectroscopy and fluorimetric assays. In vitro cytotoxic effects were evaluated by MTT and LDH assays in the human cerebral microvascular endothelial cells (hCMEC/D3) cell line, a human blood-brain barrier model, and revealed no toxicity up to 1.5 mg ml-1 over 4 h of incubation. The brain permeability was evaluated in transwell devices with hCMEC/D3 monolayers, and a 1.5-fold increment in barrier transit was verified for functionalized nanoparticles when compared with non-functionalized ones. The results suggested that these novel apolipoprotein E-functionalized nanoparticles resulted in dynamic stable systems capable of being used for an improved and specialized brain delivery of drugs through the blood-brain barrier.

  10. Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E.

    PubMed

    Neves, Ana Rute; Queiroz, Joana Fontes; Weksler, Babette; Romero, Ignacio A; Couraud, Pierre-Olivier; Reis, Salette

    2015-12-11

    Nanotechnology can be an important tool to improve the permeability of some drugs for the blood-brain barrier. In this work we created a new system to enter the brain by functionalizing solid lipid nanoparticles with apolipoprotein E, aiming to enhance their binding to low-density lipoprotein receptors on the blood-brain barrier endothelial cells. Solid lipid nanoparticles were successfully functionalized with apolipoprotein E using two distinct strategies that took advantage of the strong interaction between biotin and avidin. Transmission electron microscopy images revealed spherical nanoparticles, and dynamic light scattering gave a Z-average under 200 nm, a polydispersity index below 0.2, and a zeta potential between -10 mV and -15 mV. The functionalization of solid lipid nanoparticles with apolipoprotein E was demonstrated by infrared spectroscopy and fluorimetric assays. In vitro cytotoxic effects were evaluated by MTT and LDH assays in the human cerebral microvascular endothelial cells (hCMEC/D3) cell line, a human blood-brain barrier model, and revealed no toxicity up to 1.5 mg ml(-1) over 4 h of incubation. The brain permeability was evaluated in transwell devices with hCMEC/D3 monolayers, and a 1.5-fold increment in barrier transit was verified for functionalized nanoparticles when compared with non-functionalized ones. The results suggested that these novel apolipoprotein E-functionalized nanoparticles resulted in dynamic stable systems capable of being used for an improved and specialized brain delivery of drugs through the blood-brain barrier.

  11. Bevacizumab loaded solid lipid nanoparticles prepared by the coacervation technique: preliminary in vitro studies

    NASA Astrophysics Data System (ADS)

    Battaglia, Luigi; Gallarate, Marina; Peira, Elena; Chirio, Daniela; Solazzi, Ilaria; Giordano, Susanna Marzia Adele; Gigliotti, Casimiro Luca; Riganti, Chiara; Dianzani, Chiara

    2015-06-01

    Glioblastoma, the most common primary brain tumor in adults, has an inauspicious prognosis, given that overcoming the blood-brain barrier is the major obstacle to the pharmacological treatment of brain tumors. As neoangiogenesis plays a key role in glioblastoma growth, the US Food and Drug Administration approved bevacizumab (BVZ), an antivascular endothelial growth factor antibody for the treatment of recurrent glioblastoma in patients whose the initial therapy has failed. In this experimental work, BVZ was entrapped in solid lipid nanoparticles (SLNs) prepared by the fatty-acid coacervation technique, thanks to the formation of a hydrophobic ion pair. BVZ activity, which was evaluated by means of four different in vitro tests on HUVEC cells, increased by 100- to 200-fold when delivered in SLNs. Moreover, SLNs can enhance the permeation of fluorescently labelled BVZ through an hCMEC/D3 cell monolayer—an in vitro model of the blood brain barrier. These results are promising, even if further in vivo studies are required to evaluate the effective potential of BVZ-loaded SLNs in glioblastoma treatment.

  12. Transport of stearic acid-based solid lipid nanoparticles (SLNs) into human epithelial cells.

    PubMed

    Shah, Rohan M; Rajasekaran, Dhivya; Ludford-Menting, Mandy; Eldridge, Daniel S; Palombo, Enzo A; Harding, Ian H

    2016-04-01

    Development of drug delivery systems, as much as the drug molecule itself, is an important consideration for improving drug absorption and bioavailability. The mechanisms by which drug carriers enter target cells can differ depending on their size, surface properties and components. Solid lipid nanoparticles (SLNs) have gained an increased attention in recent years and are the drug carriers of interest in this paper. They are known to breach the cell-membrane barrier and have been actively sought to transport biomolecules. Previous studies by our group, and also other groups, provided an extensive characterization of SLNs. However, few studies have investigated the uptake of SLNs and these have had limited mechanistic focus. The aim of this work was to investigate the pathway of uptake of SLNs by human epithelial cells i.e., lung A549 and cervical HeLa cells. To the best of our knowledge, this is first study that investigates the cellular uptake of SLNs by human epithelial cells. The mechanism of cellular uptake was deciphered using pharmacologic inhibitors (sucrose, potassium-free buffer, filipin and cytochalasin B). Imaging techniques and flow assisted cell sorting (FACS) were used to assess the cellular uptake of SLNs loaded with rhodamine 123 as a fluorescent probe. This study provided evidence that the cellular uptake of SLNs was energy-dependent, and the endocytosis of SLNs was mainly dependent on clathrin-mediated mechanisms. The establishment of entry mechanism of SLNs is of fundamental importance for future facilitation of SLNs as biological or drug carriers.

  13. Solid lipid nanoparticles modified with stearic acid-octaarginine for oral administration of insulin.

    PubMed

    Zhang, Zhen-Hai; Zhang, Yin-Long; Zhou, Jian-Ping; Lv, Hui-Xia

    2012-01-01

    The aim of this study was to design and characterize solid lipid nanoparticles (SLNs) modified with stearic acid-octaarginine (SA-R₈) as carriers for oral administration of insulin (SA-R₈-Ins-SLNs). The SLNs were prepared by spontaneous emulsion solvent diffusion methods. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the SA-R₈-Ins-SLNs were 162 nm, 29.87 mV, 3.19%, and 76.54%, respectively. The zeta potential of the SLNs changed dramatically, from -32.13 mV to 29.87 mV, by binding the positively charged SA-R₈. Morphological studies of SA-R₈-Ins-SLNs using transmission electron microscopy showed that they were spherical. In vitro, a degradation experiment by enzymes showed that SLNs and SA-R₈ could partially protect insulin from proteolysis. Compared to the insulin solution, the SA-R₈-Ins-SLNs increased the Caco-2 cell's internalization by up to 18.44 times. In the in vivo studies, a significant hypoglycemic effect in diabetic rats over controls was obtained, with a SA-R₈-Ins-SLN pharmacological availability value of 13.86 ± 0.79. These results demonstrate that SA-R₈-modified SLNs promote the oral absorption of insulin.

  14. Wound dressings based on silver sulfadiazine solid lipid nanoparticles for tissue repairing.

    PubMed

    Sandri, Giuseppina; Bonferoni, Maria Cristina; D'Autilia, Francesca; Rossi, Silvia; Ferrari, Franca; Grisoli, Pietro; Sorrenti, Milena; Catenacci, Laura; Del Fante, Claudia; Perotti, Cesare; Caramella, Carla

    2013-05-01

    The management of difficult to heal wounds can considerably reduce the time required for tissue repairing and promote the healing process, minimizing the risk of infection. Silver compounds, especially silver sulfadiazine (AgSD), are often used to prevent or to treat wound colonization, also in presence of antibiotic-resistant bacteria. However, AgSD has been shown to be cytotoxic in vitro toward fibroblasts and keratinocytes and consequently to retard wound healing in vivo. Recently, platelet lysate (PL) has been proposed in clinical practice for the healing of persistent lesions. The aim of the present work was the development of wound dressings based on AgSD loaded in solid lipid nanoparticles (SLNs), to be used in association with PL for the treatment for skin lesions. SLN were based on chondroitin sulfate and sodium hyaluronate, bioactive polymers characterized by well-known tissue repairing properties. The encapsulation of AgSD in SLN aimed at preventing the cytotoxic effect of the drug on normal human dermal fibroblasts (NHDFs) and at enabling the association of the drug with PL. SLN were loaded in wound dressings based on hydroxypropylmethyl cellulose (HPMC) or chitosan glutamate (CS glu). These polymers were chosen to obtain a sponge matrix with suitable elasticity and softness and, moreover, with good bioadhesive behavior on skin lesions. Dressings based on chitosan glutamate showed antimicrobial activity with and without PL. Even though further in vivo evaluation could be envisaged, chitosan based dressings demonstrated to be a suitable prototype for the treatment for skin lesions.

  15. Positive-charged solid lipid nanoparticles as paclitaxel drug delivery system in glioblastoma treatment.

    PubMed

    Chirio, Daniela; Gallarate, Marina; Peira, Elena; Battaglia, Luigi; Muntoni, Elisabetta; Riganti, Chiara; Biasibetti, Elena; Capucchio, Maria Teresa; Valazza, Alberto; Panciani, Pierpaolo; Lanotte, Michele; Annovazzi, Laura; Caldera, Valentina; Mellai, Marta; Filice, Gaetano; Corona, Silvia; Schiffer, Davide

    2014-11-01

    Paclitaxel loaded solid lipid nanoparticles (SLN) of behenic acid were prepared with the coacervation technique. Generally, spherical shaped SLN with mean diameters in the range 300–600 nm were obtained. The introduction of charged molecules, such as stearylamine and glycol chitosan into the formulation allowed to obtain positive SLN with Zeta potential in the 8-20 mV range and encapsulation efficiency in the 25–90% range.Blood–brain barrier (BBB) permeability, tested in vitro through hCMEC/D3 cells monolayer, showed a significantly increase in the permeation of Coumarin-6, used as model drug, when vehicled in SLN. Positive-charged SLN do not seem to enhance permeation although stearylamine-positive SLN resulted the best permeable formulation after 24 h.Cytotoxicity studies on NO3 glioblastoma cell line demonstrated the maintenance of cytotoxic activity of all paclitaxel-loaded SLN that was always unmodified or greater compared with free drug. No difference in cytotoxicity was noted between neutral and charged SLN.Co-culture experiments with hCMEC/D3 and different glioblastoma cells evidenced that, when delivered in SLN, paclitaxel increased its cytotoxicity towards glioblastoma cells.

  16. Safranal-loaded solid lipid nanoparticles: evaluation of sunscreen and moisturizing potential for topical applications

    PubMed Central

    Khameneh, Bahman; Halimi, Vahid; Jaafari, Mahmoud Reza; Golmohammadzadeh, Shiva

    2015-01-01

    Objective(s): In the current study, sunscreen and moisturizing properties of solid lipid nanoparticle (SLN)-safranal formulations were evaluated. Materials and Methods: Series of SLN were prepared using glyceryl monostearate, Tween 80 and different amounts of safranal by high shear homogenization, and ultrasound and high-pressure homogenization (HPH) methods. SLN formulations were characterized for size, zeta potential, morphology, thermal properties, and encapsulation efficacy. The Sun Protection Factor (SPF) of the products was determined in vitro using transpore tape. The moisturizing activity of the products was also evaluated by corneometer. Results: The SPF of SLN-safranal formulations was increased when the amount of safranal increased. Mean particle size for all formulas was approximately 106 nm by probe sonication and 233 nm using HPH method. The encapsulation efficiency of safranal was around 70% for all SLN-safranal formulations. Conclusion: The results conclude that SLN-safranal formulations were found to be effective for topical delivery of safranal and succeeded in providing appropriate sunscreen properties. PMID:25810877

  17. Solid lipid nanoparticles prepared by solvent diffusion method in a nanoreactor system.

    PubMed

    Yuan, Hong; Huang, Ling-Fei; Du, Yong-Zhong; Ying, Xiao-Ying; You, Jian; Hu, Fu-Qiang; Zeng, Su

    2008-02-15

    In this study, water-in-oil (W/O) miniemulsion was used as nanoreactor to prepare solid lipid nanoparticles (SLN) by solvent diffusion method. n-Hexane, Tween 80 and Span 80 were used as the oil phase and surfactant combination for preparation of W/O miniemulsion, respectively. The stable miniemulsion with the particle size of 27.1+/-7.6 nm was obtained when the composition of water/Tween 80/Span 80/n-hexane was 1 ml/18 mg/200 mg/10 ml. Clobetasol propionate (CP) was used as a model drug. The physicochemical properties of the SLN, such as particle size, zeta potential, surface morphology, drug entrapment efficiency, drug loading capacity and in vitro drug release behaviors were investigated, comparing with those of SLN prepared by conventional aqueoethod. The SLN prepared by the novel method displayed smaller particles size and higher dus solvent diffusion mrug entrapment efficiency than those of SLN prepared by the conventional method. The drug entrapment efficiency decreased with increasing of charged amount of drug, and 15.9% of drug loading was achieved as the charged amount of drug was 20%. The in vitro drug release tests indicated that the drug release rate was faster than that of SLN prepared by the conventional method, and the drug content in SLN did not affect the in vitro drug release profile.

  18. Solid lipid nanoparticles as carrier for sunscreens: in vitro release and in vivo skin penetration.

    PubMed

    Wissing, S A; Müller, R H

    2002-06-17

    The aim of this study was the comparison of two different formulations (solid lipid nanoparticles (SLN) and conventional o/w emulsion) as carrier systems for the molecular sunscreen oxybenzone. The influence of the carrier on the rate of release was studied in vitro with a membrane-free model. The release rate could be decreased by up to 50% with the SLN formulation. Further in vitro measurements with static Franz diffusion cells were performed. In vivo, penetration of oxybenzone into stratum corneum on the forearm was investigated by the tape stripping method. It was shown that the rate of release is strongly dependent upon the formulation and could be decreased by 30-60% in SLN formulations. In all test models, oxybenzone was released and penetrated into human skin more quickly and to a greater extent from the emulsions. The rate of release also depends upon the total concentration of oxybenzone in the formulation. In vitro-in vivo correlations could be made qualitatively.

  19. Solid lipid nanoparticles (SLN)--a novel carrier for UV blockers.

    PubMed

    Wissing, S A; Müller, R H

    2001-10-01

    The formulation of safe sunscreen products is of high importance due to their increasing use because of the diminishing ozone layer. Solid lipid nanoparticles (SLN) are introduced as the new generation of carriers for cosmetics, especially for UV blockers for the use on human skin and/or hair and production thereof is described. The crystalline cetylpalmitate SLN particles have the ability of reflecting and scattering UV radiation on their own thus leading to photoprotection without the need for molecular sunscreens. An in vitro assay showed that a placebo cetyl palmitate SLN formulation is twice to three times as potent in absorbing UV radiation as a conventional emulsion. Incorporation of sunscreens into SLN lead to a synergistic photoprotection, i.e. higher than the additive effect of UV scattering caused by the SLN and UV absorption by the sunscreen. The photoprotective effect after incorporation of the molecular sunscreen 2-hydroxy-4-methoxybenzophenone (Eusolex 4360) into the SLN dispersion was observed to be increased threefold compared to a reference emulsion. Further, film formation on the skin was investigated by scanning electron microscopy, showing particle fusion due to water evaporation and formation of a dense film.

  20. Comet assay reveals no genotoxicity risk of cationic solid lipid nanoparticles.

    PubMed

    Doktorovova, Slavomira; Silva, Amélia M; Gaivão, Isabel; Souto, Eliana B; Teixeira, João P; Martins-Lopes, Paula

    2014-04-01

    Cationic solid lipid nanoparticles (cSLN) are colloidal carriers for genes or drugs, particularly lipophilic drugs. Several reports exist on their high efficiency, but only a few studies report the effect of cSLNs on living cells. In the present work, internalization, cell viability (alamar blue assay) and genotoxic potential (alkaline comet assay) of three cSLN formulations (A-C) were evaluated in HepG2 and Caco-2 cells. cSLN showed an average hydrodynamic diameter (z-ave) of 141-222 nm, zeta-potential of 55.0-72.5 mV and polidispersity indices (PdI) of 0.336-0.421. Dispersion in physiological buffers increased z-ave and PdI. 0.01 mg ml(-1) cSLN unaffected cell viability, but 1.0 mg ml(-1) significantly decreased it, being cSLN-C (Compritol-based) the most toxic and HepG2 the most affected. DNA damage was not significantly increased by 0.1 mg ml(-1) cSLN but damage was observed at 1.0 mg ml(-1) cSLN-C. Thus, no genotoxicity is to be expected at concentrations that do not reduce cell viability.

  1. α-Tocopherol succinate improves encapsulation and anticancer activity of doxorubicin loaded in solid lipid nanoparticles.

    PubMed

    Oliveira, Mariana S; Mussi, Samuel V; Gomes, Dawidson A; Yoshida, Maria Irene; Frezard, Frederic; Carregal, Virgínia M; Ferreira, Lucas A M

    2016-04-01

    This work aimed to develop solid lipid nanoparticles (SLN) co-loaded with doxorubicin and α-tocopheryl succinate (TS), a succinic acid ester of α-tocopherol that exhibits anticancer actions, evaluating the influence of TS on drug encapsulation efficiency. The SLN were characterized for size, zeta potential, entrapment efficiency (EE), and drug release. Studies of in vitro anticancer activity were also conducted. The EE was significantly improved from 30 ± 1% to 96 ± 2% for SLN without and with TS at 0.4%, respectively. In contrast, a reduction in particle size from 298 ± 1 to 79 ± 1 nm was observed for SLN without and with TS respectively. The doxorubicin release data show that SLN provide a controlled drug release. The in vitro studies showed higher cytotoxicity for doxorubicin-TS-loaded SLN than for free doxorubicin in breast cancer cells. These findings suggest that TS-doxorubicin-loaded SLN is a promising alternative for the treatment of cancer. PMID:26764108

  2. Formulation and evaluation of voriconazole ophthalmic solid lipid nanoparticles in situ gel

    PubMed Central

    Pandurangan, Dinesh Kumar; Bodagala, Prathima; Palanirajan, Vijayaraj Kumar; Govindaraj, Saravanan

    2016-01-01

    In the present investigation, solid lipid nanoparticles (SLNs)-loaded in situ gel with voriconazole drug was formulated. Further, the formulation was characterized for pH, gelling capacity, entrapment efficiency, in vitro drug release, drug content, and viscosity. Voriconazole is an antifungal drug used to treat various infections caused by yeast or other types of fungi. Film hydration technique was used to prepared SLNs from lecithin and cholesterol. Based on the entrapment efficiency 67.2-97.3% and drug release, the optimized formulation NF1 of SLNs was incorporated into in situ gels. The in situ gels were prepared using viscosity-enhancing polymers such as Carbopol and (hydroxypropyl)methyl cellulose (HPMC). Formulated SLN in situ gel formulations were characterized, which showed pH 4.9-7.1, drug content 65.69-96.3%, and viscosity (100 rpm) 120-620 cps. From the characterizations given above, F6 was optimized and evaluated for microbial assay and ocular irritation studies. Microbial assay was conducted by the cup-plate method using Candida albicans as the test organism. An ocular irritation study was conducted on albino rabbits. The results revealed that there was no ocular damage to the cornea, conjunctiva, or iris. Stability studies were carried out on the F6 formulation for 3 months, which showed that the formulation had good stability. These results indicate that the studied SLNs-loaded in situ gel is a promising vehicle for ocular delivery. PMID:27014620

  3. Galantamine-loaded solid-lipid nanoparticles for enhanced brain delivery: preparation, characterization, in vitro and in vivo evaluations.

    PubMed

    Misra, Shubham; Chopra, Kanwaljit; Sinha, V R; Medhi, Bikash

    2016-05-01

    Galantamine hydrobromide, a promising acetylcholinesterase inhibitor is reported to be associated with cholinergic side effects. Its poor brain penetration results in lower bioavailability to the target site. With an aim to overcome these limitations, solid-lipid nanoparticulate formulation of galantamine hydrobromide was developed employing biodegradable and biocompatible components. The selected galantamine hydrobromide-loaded solid-lipid nanoparticles offered nanocolloidal with size lower than 100 nm and maximum drug entrapment 83.42 ± 0.63%. In vitro drug release from these spherical drug-loaded nanoparticles was observed to be greater than 90% for a period of 24 h in controlled manner. In vivo evaluations demonstrated significant memory restoration capability in cognitive deficit rats in comparison with naive drug. The developed carriers offered approximately twice bioavailability to that of plain drug. Hence, the galantamine hydrobromide-loaded solid-lipid nanoparticles can be a promising vehicle for safe and effective delivery especially in disease like Alzheimer's. PMID:26405825

  4. Influence of selected variables on fabrication of Triamcinolone acetonide loaded solid lipid nanoparticles for topical treatment of dermal disorders.

    PubMed

    Pradhan, Madhulika; Singh, Deependra; Singh, Manju Rawat

    2016-01-01

    Aim of the study was to develop solid lipid nanoparticles (SLN) of triamcinolone acetonide (TA) and to study the effect of various process variables in order to optimize the formulation for effective delivery. Drug loaded SLNs were successfully prepared and characterized by TEM, XRD and DSC study. Process variables like surfactant concentration, drug concentration, lipid concentration etc. showed significant effect on the particle size and entrapment efficiency. SLNs exhibited prolonged drug release following Higuchi release kinetics (R(2) = 0.9909). In vitro skin distribution study demonstrated systemic escape of drug from TA loaded SLNs which might eliminate side effects associated with systemic exposure.

  5. Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity

    PubMed Central

    Yuan, Qing; Han, Jing; Cong, Wenshu; Ge, Ying; Ma, Dandan; Dai, Zhaoxia; Li, Yaping; Bi, Xiaolin

    2014-01-01

    Docetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors; however, its toxicity and side effects limit its clinical efficacy. Herein, docetaxel-loaded solid lipid nanoparticles (DSNs) were developed to reduce systemic toxicity of docetaxel while still keeping its anticancer activity. To evaluate its anticancer activity and toxicity, and to understand the molecular mechanisms of DSNs, different cellular, molecular, and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel (Taxotere®) and induced more apoptosis at 24 hours after treatment in vitro. DSNs can cause the treated cancer cells to arrest in the G2/M phase in a dose-dependent manner similar to Taxotere. They can also suppress tumor growth very effectively in a mice model with human xenograft breast cancer. Systemic analysis of gene expression profiles by microarray and subsequent verification experiments suggested that both DSNs and Taxotere regulate gene expression and gene function, including DNA replication, DNA damage response, cell proliferation, apoptosis, and cell cycle regulation. Some of these genes expressed differentially at the protein level although their messenger RNA expression level was similar under Taxotere and DSN treatment. Moreover, DSNs improved the main side effect of Taxotere by greatly lowering myelosuppression toxicity to bone marrow cells from mice. Taken together, these results expound the antitumor efficacy and the potential working mechanisms of DSNs in its anticancer activity and toxicity, which provide a theoretical foundation to develop and apply a more efficient docetaxel formulation to treat cancer patients. PMID:25378924

  6. Formulation and characterization of hydrophilic drug diclofenac sodium-loaded solid lipid nanoparticles based on phospholipid complexes technology.

    PubMed

    Liu, Dongfei; Chen, Li; Jiang, Sunmin; Zhu, Shuning; Qian, Yong; Wang, Fengzhen; Li, Rui; Xu, Qunwei

    2014-03-01

    To successfully prepare the diclofenac sodium (DS)-loaded solid lipid nanoparticles (SLNs), phospholipid complexes (PCs) technology was applied here to improve the liposolubility of DS. Solid lipid nanoparticles (SLNs) loaded with phospholipid complexes (PCs) were prepared by the modified emulsion/solvent evaporation method. DS could be solubilized effectively in the organic solvents with the existence of phospholipid and apparent partition coefficient of DS in PCs increased significantly. X-ray diffraction analysis suggested that DS in PCs was either molecularly dispersed or in an amorphous form. However, no significant difference was observed between the Fourier transform infrared spectroscopy (FT-IR) spectra of physical mixture and that of PCs. Particles with small sizes, narrow polydispersity indexes and high entrapment efficiencies could be obtained with the addition of PCs. Furthermore, according to the transmission electron microscopy, a core-shell structure was likely to be formed. The presence of PCs caused the change of zeta potential and retarded the drug release of SLNs, which indicated that phospholipid formed multilayers around the solid lipid core of SLNs. Both FT-IR and differential scanning calorimetry analysis also illustrated that some weak interactions between DS and lipid materials might take place during the preparation of SLNs. In conclusion, the model hydrophilic drug-DS can be formulated into the SLNs with the help of PCs. PMID:24236407

  7. Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm

    PubMed Central

    Xie, Shuyu; Pan, Baoliang; Shi, Baoxin; Zhang, Zhuangzhi; Zhang, Xu; Wang, Ming; Zhou, Wenzhong

    2011-01-01

    Hydatid disease caused by tapeworm is an increasing public health and socioeconomic concern. In order to enhance the therapeutic efficacy of praziquantel (PZQ) against tapeworm, PZQ-loaded hydrogenated castor oil solid lipid nanoparticle (PZQ-HCO-SLN) suspension was prepared by a hot homogenization and ultrasonication method. The stability of the suspension at 4°C and room temperature was evaluated by the physicochemical characteristics of the nanoparticles and in-vitro release pattern of the suspension. Pharmacokinetics was studied after subcutaneous administration of the suspension in dogs. The therapeutic effect of the novel formulation was evaluated in dogs naturally infected with Echinococcus granulosus. The results showed that the drug recovery of the suspension was 97.59% ± 7.56%. Nanoparticle diameter, polydispersivity index, and zeta potential were 263.00 ± 11.15 nm, 0.34 ± 0.06, and −11.57 ± 1.12 mV, respectively and showed no significant changes after 4 months of storage at both 4°C and room temperature. The stored suspensions displayed similar in-vitro release patterns as that of the newly prepared one. SLNs increased the bioavailability of PZQ 5.67-fold and extended the mean residence time of the drug from 56.71 to 280.38 hours. Single subcutaneous administration of PZQ-HCO-SLN suspension obtained enhanced therapeutic efficacy against tapeworm in infected dogs. At the dose of 5 mg/kg, the stool-ova reduction and negative conversion rates and tapeworm removal rate of the suspension were 100%, while the native PZQ were 91.55%, 87.5%, and 66.7%. When the dose reduced to 0.5 mg/kg, the native drug showed no effect, but the suspension still got the same therapeutic efficacy as that of the 5 mg/kg native PZQ. These results demonstrate that the PZQ-HCO-SLN suspension is a promising formulation to enhance the therapeutic efficacy of PZQ. PMID:22072873

  8. Ethyl oleate-containing nanostructured lipid carriers improve oral bioavailability of trans-ferulic acid ascompared with conventional solid lipid nanoparticles.

    PubMed

    Zhang, Yongtai; Li, Zhe; Zhang, Kai; Yang, Gang; Wang, Zhi; Zhao, Jihui; Hu, Rongfeng; Feng, Nianping

    2016-09-10

    trans-Ferulic acid (TFA) has antioxidative, anti-inflammatory, and cardioprotective effects, but its poor solubility in water results in unsatisfactory oral bioavailability when administered conventionally at a standard dosage. However, the limited bioavailability of TFA can be overcome by delivering it in nanostructured lipid carriers (NLCs). In this study, a microemulsion (ME)-based method was used to prepare NLCs with ethyl oleate as the liquid lipid component and glyceryl behenate as the solid lipid component. These NLCs and solid lipid nanoparticles (SLNs) were then used as vehicles for TFA. Their entrapment efficiencies (EE), stability during storage, in vitro release profiles, and in vivo pharmacokinetics were compared. The NLC formulation afforded a drug entrapment efficiency that was significantly greater than that of the SLN formulation, which was made using a single solid lipid. Furthermore, the TFA that was dispersed in the disordered binary lipid matrix of the NLC formulation was more stable than that in the SLN formulation, and thus showed less expulsion from the vehicle during storage. In in vivo pharmacokinetic studies, the NLC TFA formulation yielded a greater Cmax and AUC than that produced by the SLN formulation and an aqueous TFA suspension. This showed that the oral bioavailability of TFA was markedly improved by packaging in NLCs. NLCs are thus a promising vehicle for oral TFA administration, with significant advantages over SLNs. PMID:27374194

  9. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: I. Effect of formulation variables on the physicochemical properties, drug release and stability of clotrimazole-loaded nanoparticles

    NASA Astrophysics Data System (ADS)

    Das, Surajit; Kiong Ng, Wai; Tan, Reginald B. H.

    2014-03-01

    The objective of this study was to develop and evaluate solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) utilizing sucrose ester as a stabilizer/emulsifier for the controlled release of drug/active. Both SLNs and NLCs were prepared using different sugar esters to screen out the most suitable stabilizer. Clotrimazole was used as a model active/drug. The effect of different formulation variables on the particle size, polydispersity index and drug encapsulation efficiency of SLNs and NLCs was evaluated and compared. SLNs and NLCs were physicochemically characterized and compared using Cryo-SEM, DSC and XRD. Furthermore, a drug release study of SLNs and NLCs was conducted. Finally, physicochemical stability (size, PI, ZP, EE) of the SLNs and NLCs was checked at 25 ± 2 °C and at 2-8 °C. Among the sucrose esters, D-1216 was found to be most suitable for both SLNs and NLCs. Formulation variables exhibited a significant impact on size, PI and EE of the nanoparticles. SLNs with ˜120 nm size, ˜0.23 PI, ˜I26I mV ZP, ˜87% EE and NLCs with ˜160 nm size, 0.15 PI, ˜I26I mV ZP, ˜88% EE were produced. Cryo-SEM revealed spherical particles with a smooth surface but did not exhibit any difference in surface morphology between SLNs and NLCs. DSC and XRD results demonstrated the disappearance of clotrimazole peak(s) in drug-loaded SLNs and NLCs. Faster drug release was observed from SLNs than NLCs. NLCs were found to be more stable than SLNs in terms of size, PI, EE and drug release. The results indicated that both SLNs and NLCs stabilized with sucrose ester D-1216 can be used as controlled release carriers although NLCs have an edge over SLNs.

  10. A comparative histological study on the skin occlusion performance of a cream made of solid lipid nanoparticles and Vaseline.

    PubMed

    Hamishehkar, Hamed; Same, Saeideh; Adibkia, Khosro; Zarza, Kamyar; Shokri, Javad; Taghaee, Mehran; Kouhsoltani, Maryam

    2015-01-01

    The water content of the epidermis is a main factor in maintaining skin smoothness and elasticity and preventing skin dryness. Occlusive products can greatly affect skin hydration by forming a barrier on the skin following the topical administration of oil-based formulations. These products repair the skin barrier by restoring the skin lipids as well. Solid lipid nanoparticles (SLNs) have recently been introduced as a novel carrier with several benefits in pharmaceutics and cosmeceutics. It has been suggested that SLNs may have an occlusive effect following topical application. In this study, the occlusion effects of lipidic particles in different size ranges were investigated in vitro, ex vivo, and in vivo, and the results were compared with the positive (vaseline) and negative (blank) controls. Although larger lipidic particles showed better occlusion properties than nanoparticles in vitro, but ex vivo experiments confirmed the benefits of nanoparticles (almost 30% higher occlusion factor for particles in the range of 170 nm than ones in the range of 600 and 1800 nm). The superiority of SLN formulation to Vaseline as a positive reference was confirmed by the in vivo study. SLN formulation resulted in much thicker stratum corneum than Vaseline. It was indicated that in vitro and ex vivo study methods may not be a good reflective of the in vivo method for determining the occlusive properties of nanoparticulate systems. It was concluded that formulations containing SLNs can be used as efficient skin moisturizer products. PMID:26752986

  11. A comparative histological study on the skin occlusion performance of a cream made of solid lipid nanoparticles and Vaseline

    PubMed Central

    Hamishehkar, Hamed; Same, Saeideh; Adibkia, Khosro; Zarza, Kamyar; Shokri, Javad; Taghaee, Mehran; Kouhsoltani, Maryam

    2015-01-01

    The water content of the epidermis is a main factor in maintaining skin smoothness and elasticity and preventing skin dryness. Occlusive products can greatly affect skin hydration by forming a barrier on the skin following the topical administration of oil-based formulations. These products repair the skin barrier by restoring the skin lipids as well. Solid lipid nanoparticles (SLNs) have recently been introduced as a novel carrier with several benefits in pharmaceutics and cosmeceutics. It has been suggested that SLNs may have an occlusive effect following topical application. In this study, the occlusion effects of lipidic particles in different size ranges were investigated in vitro, ex vivo, and in vivo, and the results were compared with the positive (vaseline) and negative (blank) controls. Although larger lipidic particles showed better occlusion properties than nanoparticles in vitro, but ex vivo experiments confirmed the benefits of nanoparticles (almost 30% higher occlusion factor for particles in the range of 170 nm than ones in the range of 600 and 1800 nm). The superiority of SLN formulation to Vaseline as a positive reference was confirmed by the in vivo study. SLN formulation resulted in much thicker stratum corneum than Vaseline. It was indicated that in vitro and ex vivo study methods may not be a good reflective of the in vivo method for determining the occlusive properties of nanoparticulate systems. It was concluded that formulations containing SLNs can be used as efficient skin moisturizer products. PMID:26752986

  12. Pharmacokinetics study of arteether loaded solid lipid nanoparticles: an improved oral bioavailability in rats.

    PubMed

    Dwivedi, Pankaj; Khatik, Renuka; Khandelwal, Kiran; Taneja, Isha; Raju, Kanumuri Siva Rama; Wahajuddin; Paliwal, Sarvesh Kumar; Dwivedi, Anil Kumar; Mishra, Prabhat Ranjan

    2014-05-15

    Arteether (ART), an artemisinin derivative, is a life saving drug for multiple drug resistant malaria. It has a deliverance effect in Falciparum malaria and cerebral malaria. We have prepared solid lipid nanoparticles (SLN) by high pressure homogenization (HPH) technique. ART-loaded SLN (ART-SLN) has been produced reproducibly with homogeneous particle size. ART-SLN was characterized for their size measured by Zetasizer Nano-ZS, Malvern, UK and by high resolution transmission electron microscopy (HR-TEM) and which was found to be 100 ± 11.2 nm. The maximum percentage entrapment efficiency (%EE) determined with the high-performance liquid chromatography (HPLC) has been found to be 69 ± 4.2% in ART-SLN-3. The release pattern from ART-SLN revealed that the release of ART is slow but time-dependent manner, which is desirable as it will help to protect the acid degradation of ART in stomach. The percentage cytotoxicity of blank SLN has been found within the acceptable range. The pharmacokinetics results indicated that ART-SLN-3 absorption has been significantly enhanced in comparison to ART in aqueous suspension and ART in ground nut oil (GNO) in rats. The % relative bioavailability (RB%) of ART-SLN to the ART in GNO and ART in aqueous suspension in rats was 169.99% and 7461%, respectively which was found to be significantly high in both the cases. From the results, it can be concluded that ART-SLN offers a new approach to improve the oral bioavailability of ART.

  13. Solid lipid nanoparticles of clotrimazole silver complex: An efficient nano antibacterial against Staphylococcus aureus and MRSA.

    PubMed

    Kalhapure, Rahul S; Sonawane, Sandeep J; Sikwal, Dhiraj R; Jadhav, Mahantesh; Rambharose, Sanjeev; Mocktar, Chunderika; Govender, Thirumala

    2015-12-01

    New and effective strategies to transform current antimicrobials are required to address the increasing issue of microbial resistance and declining introduction of new antibiotic drugs. In this context, metal complexes of known drugs and nano delivery systems for antibiotics are proving to be promising strategies. The aim of the study was therefore to synthesize a silver complex of clotrimazole and formulate it into a nano delivery system for enhanced and sustained antibacterial activity against susceptible and resistant Staphylococcus aureus. A silver complex of clotrimazole was synthesized, characterized and further encapsulated into solid lipid nanoparticles to evaluate its antibacterial activity against S. aureus and methicillin-resistant S. aureus (MRSA). An in vitro cytotoxicity study was performed on HepG2 cell lines to assess the overall biosafety of the synthesized clotrimazole silver complex to mammalian cells, and was found to be non-toxic to mammalian cells (cell viability >80%). The minimum inhibitory concentrations (MIC) of clotrimazole and clotrimazole-silver were 31.25 and 9.76 μg/mL against S. aureus, and 31.25 and 15.62 against MRSA, respectively. Clotrimazole SLNs exhibited MIC values of 104 and 208 μg/mL against both MSSA and MRSA at the end of 18 and 36 h, respectively, but thereafter completely lost its antibacterial activity. Clotrimazole-silver SLNs had an MIC value of 52 μg/mL up to 54 h, after which the MIC value was 104 μg/mL against both strains at the end of 72 h. Thus, clotrimazole-silver SLNs was found to be an efficient nanoantibiotic.

  14. Amsacrine analog-loaded solid lipid nanoparticle to resolve insolubility for injection delivery: characterization and pharmacokinetics

    PubMed Central

    Fang, Yi-Ping; Chuang, Chih-Hung; Wu, Pao-Chu; Huang, Yaw-Bin; Tzeng, Cherng-Chyi; Chen, Yeh-Long; Liu, Ya-Ting; Tsai, Yi-Hung; Tsai, Ming-Jun

    2016-01-01

    Amsacrine analog is a novel chemotherapeutic agent that provides potentially broad antitumor activity when compared to traditional amsacrine. However, the major limitation of amsacrine analog is that it is highly lipophilic, making it nonconductive to intravenous administration. The aim of this study was to utilize solid lipid nanoparticles (SLN) to resolve the delivery problem and to investigate the biodistribution of amsacrine analog-loaded SLN. Physicochemical characterizations of SLN, including particle size, zeta potential, entrapment efficiency, and stability, were evaluated. In vitro release behavior was also measured by the dialysis method. In vivo pharmacokinetics and biodistribution behavior of amsacrine analog were investigated and incorporated with a non invasion in vivo imaging system to confirm the localization of SLN. The results showed that amsacrine analog-loaded SLN was 36.7 nm in particle size, 0.37 in polydispersity index, and 34.5±0.047 mV in zeta potential. More than 99% of amsacrine analog was successfully entrapped in the SLN. There were no significant differences in the physicochemical properties after storage at room temperature (25°C) for 1 month. Amsacrine analog-loaded SLN maintained good stability. An in vitro release study showed that amsacrine analog-loaded SLN sustained a release pattern and followed the zero equation. An in vivo pharmacokinetics study showed that amsacrine analog was rapidly distributed from the central compartment to the tissue compartments after intravenous delivery of amsacrine analog-loaded SLN. The biodistribution behavior demonstrated that amsacrine analog mainly accumulated in the lungs. Noninvasion in vivo imaging system images also confirmed that the drug distribution was predominantly localized in the lungs when IR-780-loaded SLN was used. PMID:27019595

  15. Solid Lipid Nanoparticles Loaded with Edaravone for Inner Ear Protection After Noise Exposure

    PubMed Central

    Gao, Gang; Liu, Ya; Zhou, Chang-Hua; Jiang, Ping; Sun, Jian-Jun

    2015-01-01

    Background: Antioxidants and the duration of treatment after noise exposure on hearing recovery are important. We investigated the protective effects of an antioxidant substance, edaravone, and its slow-release dosage form, edaravone solid lipid nanoparticles (SLNs), in steady noise-exposed guinea pigs. Methods: SLNs loaded with edaravone were produced by an ultrasound technique. Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1st day of noise exposure. Guinea pigs were exposed to 110 dB sound pressure level (SPL) noise, centered at 0.25–4.0 kHz, for 4 days at 2 h/d. After noise exposure, the guinea pigs underwent auditory brainstem response (ABR) threshold measurements, reactive oxygen species (ROS) were detected in their cochleas with electron spin resonance (ESR), and outer hair cells (OHCs) were counted with silvernitrate (AgNO3) staining at 1, 4, and 6 days. Results: The ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7%. Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea. Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment, especially in the edaravone SLN intratympanic injection group. Conclusions: Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL). PMID:25591563

  16. Formulation optimization and in vitro skin penetration of spironolactone loaded solid lipid nanoparticles.

    PubMed

    Kelidari, H R; Saeedi, M; Akbari, J; Morteza-Semnani, K; Gill, P; Valizadeh, H; Nokhodchi, A

    2015-04-01

    The aim of the current investigation was to prepare and evaluate the potential use of solid lipid nanoparticles for the dermal delivery of spironolactone (SP). The spironolactone loaded SLN (SP-SLN) was prepared by emulsion-solvent evaporation method followed by ultrasonication. The properties of obtained SLNs were characterized by photon correlation spectroscopy (PCS), scanning tunneling microscopy (STM) and differential scanning calorimetry. FT-IR was also used to investigate any interaction between SP and excipients in the molecular level during the preparation of SLNs. The performance of the formulations was investigated in terms of drug release, skin permeation and also the retention of drug by the skin. The SP-SLNs presented spherical shape with the mean diameter, zeta potential and entrapment efficiency of 88.9 nm, -23.9 mV and 59.86%, respectively. DSC study showed that SP alone encapsulated in SLNs was in the amorphous form. FT-IR analysis revealed that there were hydrogen bond interactions between the SP alone and SLN components. The dissolution results revealed that the drug release from SP-SLNs was at least 4.9 times faster than original SP within the first 30 min. The cumulative amount of SP penetrated through rat skin from SP-SLNs was almost twofold that of the SP alone in 24h after the administration. In vitro permeation studies indicated that SP-SLN may be a promising vector for use in the topical treatment. It can be concluded that SLNs provide good skin permeation for SP and may be a promising carrier for topical delivery of spironolactone offering the biphasic release pattern that might be interesting for topical application resulting in an effective treatment for skin disorders such as acne.

  17. Cholesteryl butyrate solid lipid nanoparticles inhibit the adhesion and migration of colon cancer cells

    PubMed Central

    Minelli, R; Serpe, L; Pettazzoni, P; Minero, V; Barrera, G; Gigliotti, CL; Mesturini, R; Rosa, AC; Gasco, P; Vivenza, N; Muntoni, E; Fantozzi, R; Dianzani, U; Zara, GP; Dianzani, C

    2012-01-01

    BACKGROUND AND PURPOSE Cholesteryl butyrate solid lipid nanoparticles (cholbut SLN) provide a delivery system for the anti-cancer drug butyrate. These SLN inhibit the adhesion of polymorphonuclear cells to the endothelium and may act as anti-inflammatory agents. As cancer cell adhesion to endothelium is crucial for metastasis dissemination, here we have evaluated the effect of cholbut SLN on adhesion and migration of cancer cells. EXPERIMENTAL APPROACH Cholbut SLN was incubated with a number of cancer cell lines or human umbilical vein endothelial cells (HUVEC) and adhesion was quantified by a computerized micro-imaging system. Migration was detected by the scratch ‘wound-healing’ assay and the Boyden chamber invasion assay. Expression of ERK and p38 MAPK was analysed by Western blot. Expression of the mRNA for E-cadherin and claudin-1 was measured by RT-PCR. KEY RESULTS Cholbut SLN inhibited HUVEC adhesiveness to cancer cell lines derived from human colon–rectum, breast, prostate cancers and melanoma. The effect was concentration and time-dependent and exerted on both cancer cells and HUVEC. Moreover, these SLN inhibited migration of cancer cells and substantially down-modulated ERK and p38 phosphorylation. The anti-adhesive effect was additive to that induced by the triggering of B7h, which is another stimulus inhibiting both ERK and p38 phosphorylation, and cell adhesiveness. Furthermore, cholbut SLN induced E-cadherin and inhibited claudin-1 expression in HUVEC. CONCLUSION AND IMPLICATIONS These results suggest that cholbut SLN could act as an anti-metastastic agent and they add a new mechanism to the anti-tumour activity of this multifaceted preparation of butyrate. PMID:22049973

  18. Lactoferrin-appended solid lipid nanoparticles of paclitaxel for effective management of bronchogenic carcinoma.

    PubMed

    Pandey, Vikas; Gajbhiye, Kavita Rai; Soni, Vandana

    2015-02-01

    Lung cancer is a dreadful disease which claims to be more life threatening as compared to total sum up of colon, prostate and breast cancers. Thus, there is an urgent need to develop an effective delivery approach for its management. Paclitaxel (PTX) is one of the well-known choice as antineoplasitic agent used for the treatment of different types of human cancers such as non-small-cell lung, head and neck cancers, leukemia, breast, ovarian and melanoma. Lactoferrin (Lf), a "multifunctional protein" is crucial for natural immunity which is secreted by exocrine glands. Lf receptors are expressed on the apical surface on bronchial epithelial cells. These over-expressed LF receptors can be utilized for the transportation of Lf-conjugated drug or nanocarrier devices. The present study was aimed to develop PTX-loaded Lf-coupled solid lipid nanoparticles (SLNs) for the treatment of lung cancer. PTX-loaded SLNs were prepared, characterized and then coupled with Lf using carbodiimide chemistry. The formulations were characterized by transmission electron microscopy, particle size, polydispersity index and zeta potential, whereas Lf conjugation was confirmed by FT-IR and ¹H NMR and efficiency of prepared system was evaluated by in vitro, ex vivo and in vivo evaluations. The ex vivo cytotoxicity studies on human bronchial epithelial cell lines, BEAS-2B, revealed superior anticancer activity of Lf-coupled SLNs than plain SLNs and free PTX. In vivo biodistribution studies showed higher concentrations of PTX accumulated in lungs via Lf-coupled SLNs than plain SLNs and free PTX. These studies suggested that Lf-coupled PTX-loaded SLNs could be used as potential targeting carrier for delivering anticancer drug to the lungs with the minimal side effects.

  19. Solid lipid nanoparticles of clotrimazole silver complex: An efficient nano antibacterial against Staphylococcus aureus and MRSA.

    PubMed

    Kalhapure, Rahul S; Sonawane, Sandeep J; Sikwal, Dhiraj R; Jadhav, Mahantesh; Rambharose, Sanjeev; Mocktar, Chunderika; Govender, Thirumala

    2015-12-01

    New and effective strategies to transform current antimicrobials are required to address the increasing issue of microbial resistance and declining introduction of new antibiotic drugs. In this context, metal complexes of known drugs and nano delivery systems for antibiotics are proving to be promising strategies. The aim of the study was therefore to synthesize a silver complex of clotrimazole and formulate it into a nano delivery system for enhanced and sustained antibacterial activity against susceptible and resistant Staphylococcus aureus. A silver complex of clotrimazole was synthesized, characterized and further encapsulated into solid lipid nanoparticles to evaluate its antibacterial activity against S. aureus and methicillin-resistant S. aureus (MRSA). An in vitro cytotoxicity study was performed on HepG2 cell lines to assess the overall biosafety of the synthesized clotrimazole silver complex to mammalian cells, and was found to be non-toxic to mammalian cells (cell viability >80%). The minimum inhibitory concentrations (MIC) of clotrimazole and clotrimazole-silver were 31.25 and 9.76 μg/mL against S. aureus, and 31.25 and 15.62 against MRSA, respectively. Clotrimazole SLNs exhibited MIC values of 104 and 208 μg/mL against both MSSA and MRSA at the end of 18 and 36 h, respectively, but thereafter completely lost its antibacterial activity. Clotrimazole-silver SLNs had an MIC value of 52 μg/mL up to 54 h, after which the MIC value was 104 μg/mL against both strains at the end of 72 h. Thus, clotrimazole-silver SLNs was found to be an efficient nanoantibiotic. PMID:26492156

  20. Dual drugs (microRNA-34a and paclitaxel)-loaded functional solid lipid nanoparticles for synergistic cancer cell suppression.

    PubMed

    Shi, Sanjun; Han, Lu; Deng, Li; Zhang, Yanling; Shen, Hongxin; Gong, Tao; Zhang, Zhirong; Sun, Xun

    2014-11-28

    A co-delivery system that can transport cancer related microRNAs and chemotherapeutics to their distinct targets in the tumors is an attractive strategy to eliminate tumor relapse in lung cancer therapy. In this study, we developed a dual-drug delivery system for an endogenous microRNA (miR-34a) and paclitaxel (PTX) for synergistic cancer therapy. PTX (a meiotic inhibitor) and miR-34a were loaded into cationic solid lipid nanoparticles (miSLNs-34a/PTX) which were used to treat murine B16F10-CD44(+) melanoma metastasized to the lungs of mice. This nanoparticle system demonstrated good protection for miR-34a and PTX from degradation in the serum, and had an average size of approximately 220 nm by photon correlation spectroscopy (PCS). In vitro, the parallel activity of PTX and miR-34a show synergistic anticancer efficacy. In vivo, miSLNs-34a/PTX showed passive targetability to the tumor-bearing lung tissues, and was demonstrated to be much more potent in inhibition of B16F10-bearing tumor growth and elimination of cancer cell populations in the lung than single drug-loaded solid lipid nanoparticles. It has been shown that such co-delivery of miR-34a and PTX is promising for enhanced cancer therapy to reduce tumor relapse.

  1. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics

    PubMed Central

    Ji, Peng; Yu, Tong; Liu, Ying; Jiang, Jie; Xu, Jie; Zhao, Ying; Hao, Yanna; Qiu, Yang; Zhao, Wenming; Wu, Chao

    2016-01-01

    Naringenin (NRG), a flavonoid compound, had been reported to exhibit extensive pharmacological effects, but its water solubility and oral bioavailability are only~46±6 µg/mL and 5.8%, respectively. The purpose of this study is to design and develop NRG-loaded solid lipid nanoparticles (NRG-SLNs) to provide prolonged and sustained drug release, with improved stability, involving nontoxic nanocarriers, and increase the bioavailability by means of pulmonary administration. Initially, a group contribution method was used to screen the best solid lipid matrix for the preparation of SLNs. NRG-SLNs were prepared by an emulsification and low-temperature solidification method and optimized using an orthogonal experiment approach. The morphology was examined by transmission electron microscopy, and the particle size and zeta potential were determined by photon correlation spectroscopy. The total drug content of NRG-SLNs was measured by high-performance liquid chromatography, and the encapsulation efficiency (EE) was determined by Sephadex gel-50 chromatography and high-performance liquid chromatography. The in vitro NRG release studies were carried out using a dialysis bag. The best cryoprotectant to prepare NRG-SLN lyophilized powder for future structural characterization was selected using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The short-term stability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, cellular uptake, and pharmacokinetics in rats were studied after pulmonary administration of NRG-SLN lyophilized powder. Glycerol monostearate was selected to prepare SLNs, and the optimal formulation of NRG-SLNs was spherical in shape, with a particle size of 98 nm, a polydispersity index of 0.258, a zeta potential of −31.4 mV, a total drug content of 9.76 mg, an EE of 79.11%, and a cumulative drug release of 80% in 48 hours with a sustained profile. In addition, 5% mannitol (w

  2. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics.

    PubMed

    Ji, Peng; Yu, Tong; Liu, Ying; Jiang, Jie; Xu, Jie; Zhao, Ying; Hao, Yanna; Qiu, Yang; Zhao, Wenming; Wu, Chao

    2016-01-01

    Naringenin (NRG), a flavonoid compound, had been reported to exhibit extensive pharmacological effects, but its water solubility and oral bioavailability are only~46±6 µg/mL and 5.8%, respectively. The purpose of this study is to design and develop NRG-loaded solid lipid nanoparticles (NRG-SLNs) to provide prolonged and sustained drug release, with improved stability, involving nontoxic nanocarriers, and increase the bioavailability by means of pulmonary administration. Initially, a group contribution method was used to screen the best solid lipid matrix for the preparation of SLNs. NRG-SLNs were prepared by an emulsification and low-temperature solidification method and optimized using an orthogonal experiment approach. The morphology was examined by transmission electron microscopy, and the particle size and zeta potential were determined by photon correlation spectroscopy. The total drug content of NRG-SLNs was measured by high-performance liquid chromatography, and the encapsulation efficiency (EE) was determined by Sephadex gel-50 chromatography and high-performance liquid chromatography. The in vitro NRG release studies were carried out using a dialysis bag. The best cryoprotectant to prepare NRG-SLN lyophilized powder for future structural characterization was selected using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The short-term stability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, cellular uptake, and pharmacokinetics in rats were studied after pulmonary administration of NRG-SLN lyophilized powder. Glycerol monostearate was selected to prepare SLNs, and the optimal formulation of NRG-SLNs was spherical in shape, with a particle size of 98 nm, a polydispersity index of 0.258, a zeta potential of -31.4 mV, a total drug content of 9.76 mg, an EE of 79.11%, and a cumulative drug release of 80% in 48 hours with a sustained profile. In addition, 5% mannitol (w

  3. The effective encapsulation of a hydrophobic lipid-insoluble drug in solid lipid nanoparticles using a modified double emulsion solvent evaporation method.

    PubMed

    Nabi-Meibodi, Mohsen; Vatanara, Alireza; Najafabadi, Abdolhossein Rouholamini; Rouini, Mohammad Reza; Ramezani, Vahid; Gilani, Kambiz; Etemadzadeh, Seyed Mohammad Hossein; Azadmanesh, Kayhan

    2013-12-01

    Raloxifene HCl (RH), a selective estrogen receptor modulator (SERM), is indicated for the prophylaxis or treatment of postmenopausal osteoporosis. RH shows extremely poor bioavailability due to limited solubility and an extensive intestinal/hepatic first-pass metabolism. Solid lipid nanoparticles (SLNs) are valuable carriers that can enhance drug bioavailability. However, in the case of RH, the encapsulation of the drug in SLNs remains a challenge because of its poor solubility in both water and lipids. In this study, a series of RH-containing SLNs (RH-SLNs) were generated using a modified double emulsion solvent evaporation (DESE) method. Briefly, RH with various drug/lipid ratios was solubilized in the inner core of a double emulsion using different water/organic solvent mixtures. Our best formulation was achieved with the formation of negatively charged nanoparticles, 180nm in diameter, with an encapsulation and loading efficiency of 85% and 4.5%, respectively. It also showed a Fickian mechanism of the drug release in the basic dissolution media. Thermal analysis revealed a distinct decrease in the crystallinity of lipids and RH in comparison with the unprocessed materials. The results of a cell viability assay also showed a better antiproliferative effect of the drug-loaded SLNs versus the free drug solution. Thus, these results indicated that the modified DESE method could be proposed for the effective encapsulation of RH in SLNs with appropriate physicochemical and biological properties. PMID:24036624

  4. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

    PubMed

    Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

    2016-01-01

    Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. PMID:27536103

  5. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

    PubMed Central

    Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

    2016-01-01

    Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. PMID:27536103

  6. Active Targeting of Sorafenib: Preparation, Characterization, and In Vitro Testing of Drug-Loaded Magnetic Solid Lipid Nanoparticles.

    PubMed

    Grillone, Agostina; Riva, Eugenio Redolfi; Mondini, Alessio; Forte, Claudia; Calucci, Lucia; Innocenti, Claudia; de Julian Fernandez, Cesar; Cappello, Valentina; Gemmi, Mauro; Moscato, Stefania; Ronca, Francesca; Sacco, Rodolfo; Mattoli, Virgilio; Ciofani, Gianni

    2015-08-01

    Sorafenib is an anticancer drug approved by the Food and Drug Administration for the treatment of hepatocellular and advanced renal carcinoma. The clinical application of sorafenib is promising, yet limited by its severe toxic side effects. The aim of this study is to develop sorafenib-loaded magnetic nanovectors able to enhance the drug delivery to the disease site with the help of a remote magnetic field, thus enabling cancer treatment while limiting negative effects on healthy tissues. Sorafenib and superparamagnetic iron oxide nanoparticles are encapsulated in solid lipid nanoparticles by a hot homogenization technique using cetyl palmitate as lipid matrix. The obtained nanoparticles (Sor-Mag-SLNs) have a sorafenib loading efficiency of about 90% and are found to be very stable in an aqueous environment. Plain Mag-SLNs exhibit good cytocompatibility, whereas an antiproliferative effect against tumor cells (human hepatocarcinoma HepG2) is observed for drug-loaded Sor-Mag-SLNs. The obtained results show that it is possible to prepare stable Sor-Mag-SLNs able to inhibit cancer cell proliferation through the sorafenib cytotoxic action, and to enhance/localize this effect in a desired area thanks to a magnetically driven accumulation of the drug. Moreover, the relaxivity properties observed in water suspensions hold promise for Sor-Mag-SLN tracking through clinical magnetic resonance imaging.

  7. Active Targeting of Sorafenib: Preparation, Characterization, and In Vitro Testing of Drug-Loaded Magnetic Solid Lipid Nanoparticles.

    PubMed

    Grillone, Agostina; Riva, Eugenio Redolfi; Mondini, Alessio; Forte, Claudia; Calucci, Lucia; Innocenti, Claudia; de Julian Fernandez, Cesar; Cappello, Valentina; Gemmi, Mauro; Moscato, Stefania; Ronca, Francesca; Sacco, Rodolfo; Mattoli, Virgilio; Ciofani, Gianni

    2015-08-01

    Sorafenib is an anticancer drug approved by the Food and Drug Administration for the treatment of hepatocellular and advanced renal carcinoma. The clinical application of sorafenib is promising, yet limited by its severe toxic side effects. The aim of this study is to develop sorafenib-loaded magnetic nanovectors able to enhance the drug delivery to the disease site with the help of a remote magnetic field, thus enabling cancer treatment while limiting negative effects on healthy tissues. Sorafenib and superparamagnetic iron oxide nanoparticles are encapsulated in solid lipid nanoparticles by a hot homogenization technique using cetyl palmitate as lipid matrix. The obtained nanoparticles (Sor-Mag-SLNs) have a sorafenib loading efficiency of about 90% and are found to be very stable in an aqueous environment. Plain Mag-SLNs exhibit good cytocompatibility, whereas an antiproliferative effect against tumor cells (human hepatocarcinoma HepG2) is observed for drug-loaded Sor-Mag-SLNs. The obtained results show that it is possible to prepare stable Sor-Mag-SLNs able to inhibit cancer cell proliferation through the sorafenib cytotoxic action, and to enhance/localize this effect in a desired area thanks to a magnetically driven accumulation of the drug. Moreover, the relaxivity properties observed in water suspensions hold promise for Sor-Mag-SLN tracking through clinical magnetic resonance imaging. PMID:26039933

  8. Solid lipid nanoparticles formed by solvent-in-water emulsion-diffusion technique: development and influence on insulin stability.

    PubMed

    Battaglia, Luigi; Trotta, Michele; Gallarate, Marina; Carlotti, M Eugenia; Zara, Gian Paolo; Bargoni, Alessandro

    2007-11-01

    Insulin-loaded solid lipid nanoparticles (SLN), obtained by the solvent-in-water emulsion-diffusion technique, were produced using isovaleric acid (IVA) as organic phase, glyceryl mono-stearate (GMS) as lipid, soy lecithin and sodium taurodeoxycholate (TDC) as emulsifiers. IVA, a partially water-miscible solvent with low toxicity, was used to dissolve both insulin and lipids. SLN of spherical shape were obtained by simple water dilution of the O/W emulsion. Analysis of SLN content after processing showed interesting encapsulation efficiency with respect to therapeutic doses; moreover, insulin did not undergo any chemical modification within the nanoparticles and most of it remained stable after incubation of the SLN with trypsin solution. The biological activity of insulin, i.e. the ability to decrease glycemia in rats, was not negatively influenced by the SLN production process, as after subcutaneous administration of insulin extracted from SLN to animals, the blood glucose levels were quite similar to those obtained after administration of a conventional insulin suspension. Consequently, SLN seem to have interesting possibilities as delivery systems for oral administration of insulin.

  9. Multi-scale strategy to eradicate Pseudomonas aeruginosa on surfaces using solid lipid nanoparticles loaded with free fatty acids.

    PubMed

    Taylor, Erik N; Kummer, Kim M; Dyondi, Deepti; Webster, Thomas J; Banerjee, Rinti

    2014-01-21

    Infections are both frequent and costly in hospitals around the world, leading to longer hospital stays, overuse of antibiotics, and excessive costs to the healthcare system. Moreover, antibiotic resistant organisms, such as Pseudomonas aeruginosa are increasing in frequency, leading to 1.7 million infections per year in USA hospitals, and 99,000 deaths, both due to the evolution of antibiotic resistance and the formation of biofilms on medical devices. In particular, respiratory infections are costly, deadly to 4.5 million persons per year worldwide, and can spread to the lungs through the placement of endotracheal tubing. In this study, towards a reduction in infections, solid lipid nanoparticles were formulated from free fatty acids, or natural lipophilic constituents found in tissues of the body. A strategy was developed to target infections by producing coatings made of non-toxic chemistries lauric acid and oleic acid delivered by core-shell solid lipid nanoparticles that act against bacteria by multiple mechanisms at the nanoscale, including disruption of bacteria leading to DNA release, and reducing the adhesion of dead bacteria to ~1%. This is the first such study to explore an anti-infection surface relying on these multi-tier strategies at the nanoscale.

  10. Multi-scale strategy to eradicate Pseudomonas aeruginosa on surfaces using solid lipid nanoparticles loaded with free fatty acids

    NASA Astrophysics Data System (ADS)

    Taylor, Erik N.; Kummer, Kim M.; Dyondi, Deepti; Webster, Thomas J.; Banerjee, Rinti

    2013-12-01

    Infections are both frequent and costly in hospitals around the world, leading to longer hospital stays, overuse of antibiotics, and excessive costs to the healthcare system. Moreover, antibiotic resistant organisms, such as Pseudomonas aeruginosa are increasing in frequency, leading to 1.7 million infections per year in USA hospitals, and 99 000 deaths, both due to the evolution of antibiotic resistance and the formation of biofilms on medical devices. In particular, respiratory infections are costly, deadly to 4.5 million persons per year worldwide, and can spread to the lungs through the placement of endotracheal tubing. In this study, towards a reduction in infections, solid lipid nanoparticles were formulated from free fatty acids, or natural lipophilic constituents found in tissues of the body. A strategy was developed to target infections by producing coatings made of non-toxic chemistries lauric acid and oleic acid delivered by core-shell solid lipid nanoparticles that act against bacteria by multiple mechanisms at the nanoscale, including disruption of bacteria leading to DNA release, and reducing the adhesion of dead bacteria to ~1%. This is the first such study to explore an anti-infection surface relying on these multi-tier strategies at the nanoscale.

  11. Lipase degradation of Dynasan 114 and 116 solid lipid nanoparticles (SLN)--effect of surfactants, storage time and crystallinity.

    PubMed

    Olbrich, Carsten; Kayser, Oliver; Müller, Rainer H

    2002-04-26

    In vivo drug release from solid lipid nanoparticles (SLN) takes place by diffusion and degradation of the lipid matrix. SLN with different degree of crystallinity were prepared to study the effect of crystallinity on the degradation velocity. These SLN were produced by using glycerides with different length of fatty acid chains and known differences in crystallisation velocity (Dynasan 114 and 116), and using stabilisers interfering differently with the crystallisation process of the lipid matrix (cholic acid sodium salt (NaCh), Poloxamer 407 (Plx 407)). NaCh disturbs the crystallisation process, Poloxamer shows little interference. The particles were characterised by photon correlation spectroscopy (PCS) and differential scanning calorimetry (DSC), degradation velocity was determined directly after production and during storage up to 4 weeks under different storage conditions using an especially developed assay based on the NEFA Test kit. After production, SLN with a lower crystallinity matrix (Dynasan 114 and 116, NaCh) degraded faster than higher crystalline particles (all SLN with Plx 407), and showed a decrease in degradation velocity with increasing crystallinity during storage. Fast crystallising particles made from Dynasan 116 stabilised with the non-interfering Plx 407 showed no change in the degradation velocity during storage. SLN produced with a higher crystalline lipid in combination with the crystallisation-disturbing NaCh (Dynasan 116, NaCh) required a 'ripening time' to reach sufficient crystallinity. PMID:11955810

  12. Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design.

    PubMed

    Emami, J; Mohiti, H; Hamishehkar, H; Varshosaz, J

    2015-01-01

    Budesonide is a potent non-halogenated corticosteroid with high anti-inflammatory effects. The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. The aim of the present study was to develop, characterize and optimize a solid lipid nanoparticle system to deliver budesonide to the lungs. Budesonide-loaded solid lipid nanoparticles were prepared by the emulsification-solvent diffusion method. The impact of various processing variables including surfactant type and concentration, lipid content organic and aqueous volume, and sonication time were assessed on the particle size, zeta potential, entrapment efficiency, loading percent and mean dissolution time. Taguchi design with 12 formulations along with Box-Behnken design with 17 formulations was developed. The impact of each factor upon the eventual responses was evaluated, and the optimized formulation was finally selected. The size and morphology of the prepared nanoparticles were studied using scanning electron microscope. Based on the optimization made by Design Expert 7(®) software, a formulation made of glycerol monostearate, 1.2 % polyvinyl alcohol (PVA), weight ratio of lipid/drug of 10 and sonication time of 90 s was selected. Particle size, zeta potential, entrapment efficiency, loading percent, and mean dissolution time of adopted formulation were predicted and confirmed to be 218.2 ± 6.6 nm, -26.7 ± 1.9 mV, 92.5 ± 0.52 %, 5.8 ± 0.3 %, and 10.4 ± 0.29 h, respectively. Since the preparation and evaluation of the selected formulation within the laboratory yielded acceptable results with low error percent, the modeling and optimization was justified. The optimized formulation co-spray dried with lactose (hybrid microparticles) displayed desirable fine particle fraction, mass median aerodynamic diameter (MMAD), and geometric standard deviation of 49.5%, 2.06 μm, and 2.98 μm; respectively. Our results provide fundamental data for the

  13. Solid lipid nanoparticles for hydrophilic biotech drugs: optimization and cell viability studies (Caco-2 & HEPG-2 cell lines).

    PubMed

    Severino, Patrícia; Andreani, Tatiana; Jäger, Alessandro; Chaud, Marco V; Santana, Maria Helena A; Silva, Amélia M; Souto, Eliana B

    2014-06-23

    Insulin was used as model protein to developed innovative Solid Lipid Nanoparticles (SLNs) for the delivery of hydrophilic biotech drugs, with potential use in medicinal chemistry. SLNs were prepared by double emulsion with the purpose of promoting stability and enhancing the protein bioavailability. Softisan(®)100 was selected as solid lipid matrix. The surfactants (Tween(®)80, Span(®)80 and Lipoid(®)S75) and insulin were chosen applying a 2(2) factorial design with triplicate of central point, evaluating the influence of dependents variables as polydispersity index (PI), mean particle size (z-AVE), zeta potential (ZP) and encapsulation efficiency (EE) by factorial design using the ANOVA test. Therefore, thermodynamic stability, polymorphism and matrix crystallinity were checked by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD), whereas the effect of toxicity of SLNs was check in HepG2 and Caco-2 cells. Results showed a mean particle size (z-AVE) width between 294.6 nm and 627.0 nm, a PI in the range of 0.425-0.750, ZP about -3 mV, and the EE between 38.39% and 81.20%. After tempering the bulk lipid (mimicking the end process of production), the lipid showed amorphous characteristics, with a melting point of ca. 30 °C. The toxicity of SLNs was evaluated in two distinct cell lines (HEPG-2 and Caco-2), showing to be dependent on the concentration of particles in HEPG-2 cells, while no toxicity in was reported in Caco-2 cells. SLNs were stable for 24 h in in vitro human serum albumin (HSA) solution. The resulting SLNs fabricated by double emulsion may provide a promising approach for administration of protein therapeutics and antigens.

  14. Localization and reactivity of a hydrophobic solute in lecithin and caseinate stabilized solid lipid nanoparticles and nanoemulsions.

    PubMed

    Yucel, Umut; Elias, Ryan J; Coupland, John N

    2013-03-15

    The distribution and reactivity of the lipophilic spin probe 4-phenyl-2,2,5,5-tetramethyl-3-imidazoline-1-oxyl nitroxide (PTMIO) in tetradecane (C14)- and eicosane (C20)-in-water emulsions and solid lipid nanoparticles (SLN) respectively, were investigated by electron paramagnetic resonance (EPR) spectroscopy. The lipid phase (10 wt% C14 or C20) was emulsified into either caseinate solutions (1 wt%) or lecithin+bile salt dispersions (2.4 wt%+0.6 wt%) at 70-75 °C. In C14 emulsions stabilized with lecithin+bile salt, three populations of PTMIO were observed: a population in the lipid phase (~60%, a(N)~13.9 G), an aqueous phase population (~20%, a(N)~15.4 G) with high mobility, and an immobilized surface layer population (~20%, a(N)~14.2 G) with low mobility. However, in C14 emulsions stabilized by caseinate, only two distinct populations of PTMIO were seen: a lipid phase population (~70%, a(N)~13.8 G) and an aqueous phase population (~30%, a(N)~15.5 G) with high mobility. In C20 SLN stabilized with either lecithin+bile salt or caseinate, PTMIO was excluded from the lipid phase. In lecithin+bile salt-stabilized C20 SLN, the majority of the probe (~77%) was in the interfacial layer. For both surfactant systems the rate of PTMIO reduction by aqueous iron/ascorbate was greater for C20 SLN than C14 emulsions. Lecithin affects the properties of emulsions and SLN as delivery systems by providing a distinct environment for small molecules. PMID:23352869

  15. Berberine-loaded solid lipid nanoparticles are concentrated in the liver and ameliorate hepatosteatosis in db/db mice

    PubMed Central

    Xue, Mei; Zhang, Liang; Yang, Ming-xing; Zhang, Wei; Li, Xiu-min; Ou, Zhi-min; Li, Zhi-peng; Liu, Su-huan; Li, Xue-jun; Yang, Shu-yu

    2015-01-01

    Berberine (BBR) shows very low plasma levels after oral administration due to its poor absorption by the gastrointestinal tract. We have previously demonstrated that BBR showed increased gastrointestinal absorption and enhanced antidiabetic effects in db/db mice after being entrapped into solid lipid nanoparticles (SLNs). However, whether BBR-loaded SLNs (BBR-SLNs) also have beneficial effects on hepatosteatosis is not clear. We investigated the effects of BBR-SLNs on lipid metabolism in the liver using histological staining and reverse transcription polymerase chain reaction analysis. The results showed that oral administration of BBR-SLNs inhibited the increase of body weight and decreased liver weight in parallel with the reduction of serum alanine transaminase and liver triglyceride levels in db/db mice. The maximum drug concentration in the liver was 20-fold higher than that in the blood. BBR-SLNs reduced fat accumulation and lipid droplet sizes significantly in the liver, as indicated by hematoxylin and eosin and Oil Red O staining. The expression of lipogenic genes, including fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD1), and sterol regulatory element-binding protein 1c (SREBP1c) were downregulated, while lipolytic gene carnitine palmitoyltransferase-1 (CPT1) was upregulated in BBR-SLN-treated livers. In summary, we have uncovered an unexpected effect of BBR-SLNs on hepatosteatosis treatment through the inhibition of lipogenesis and the induction of lipolysis in the liver of db/db mice. PMID:26346310

  16. Cationic solid lipid nanoparticles with primary and quaternary amines for release of saquinavir and biocompatibility with endothelia.

    PubMed

    Kuo, Yung-Chih; Wang, Cheng-Chin

    2013-01-01

    Application of cationic solid lipid nanoparticles (CSLNs), comprising complex internal matrix and lipid-regulated external surface, is an intriguing issue in current bionanotechnology. This study presents dissolution kinetics of saquinavir (SQV) from CSLNs with cholesterol-mediated esterquat 1 (EQ 1) and biocompatibility of SQV-loaded CSLNs with human brain-microvascular endothelial cells (HBMECs). CSLNs with SQV in lipid cores containing cholesterol were dissolved and incubated with HBMECs. The results revealed that an increase in the weight percentage of EQ 1 reduced the entrapment efficiency of SQV. In addition, the entrapment efficiency of SQV enhanced, when the weight percentage of cholesterol increased from 0% to 25% (w/w). The reverse was true when cholesterol increased from 0% to 75% (w/w). The dissolution profiles demonstrated that the mediation of cholesterol favored the sustained release of SQV. When the weight percentage of EQ 1 increased, the viability of HBMECs enhanced. An increase in the weight percentage of cholesterol, however, reduced the viability of HBMECs. The innovated CSLNs containing cholesterol can be effective in controlled release of SQV without inducing significant endothelial toxicity. PMID:22796778

  17. Formation of solid lipid nanoparticle (SLN)-gene vector complexes for transfection of mammalian cells in vitro.

    PubMed

    Rudolph, Carsten; Rosenecker, Joseph

    2012-03-01

    Solid lipid nanoparticles (SLNs) offer several technological advantages over standard DNA carriers such as cationic lipids or cationic polymers. However, in the absence of endosomolytic agents such as chloroquine, gene-transfer efficiency mediated by SLN-derived gene vectors consisting of optimized lipid composition remains lower compared to those achieved with standard transfection agents. This protocol describes the incorporation of a dimeric human immunodeficiency virus type-1 (HIV-1) TAT peptide into SLN gene vectors to increase gene-transfer efficiency. This results in higher transfection rates than for standard transfection agents in vitro; the ternary SLN-gene vector complexes usually result in transfection levels equal to or higher than those observed with gene vector complexes formulated with branched polyethylenimine (PEI) 25 kDa. One significant advantage of using this method is the low cytotoxicity of the SLN gene vectors. The application of the gene-transfer technique is limited to relatively low plasmid DNA (pDNA) concentrations of the resulting complexes (10 µg/mL). At higher concentrations, the particles tend to aggregate and precipitate. Therefore, their use for in vivo application, which generally requires high pDNA concentrations, is limited.

  18. Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity

    PubMed Central

    Aljaeid, Bader Mubarak; Hosny, Khaled Mohamed

    2016-01-01

    Background and objective Miconazole is a broad-spectrum antifungal drug that has poor aqueous solubility (<1 µg/mL); as a result, a reduction in its therapeutic efficacy has been reported. The aim of this study was to formulate and evaluate miconazole-loaded solid lipid nanoparticles (MN-SLNs) for oral administration to find an innovative way to alleviate the disadvantages associated with commercially available capsules. Methods MN-SLNs were prepared by hot homogenization/ultrasonication. The solubility of miconazole in different solid lipids was measured. The effect of process variables, such as surfactant types, homogenization and ultrasonication times, and the charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release, antifungal activity against Candida albicans, and in vivo pharmacokinetics were studied in rabbits. Results The MN-SLN, consisting of 1.5% miconazole, 2% Precirol ATO5, 2.5% Cremophor RH40, 0.5% Lecinol, and 0.1% Dicetylphosphate, had an average diameter of 23 nm with a 90.2% entrapment efficiency. Furthermore, the formulation of MN-SLNs enhanced the antifungal activity compared with miconazole capsules. An in vivo pharmacokinetic study revealed that the bioavailability was enhanced by >2.5-fold. Conclusion MN-SLN was more efficient in the treatment of candidiasis with enhanced oral bioavailability and could be a promising carrier for the oral delivery of miconazole. PMID:26869787

  19. Solid Lipid Nanoparticle-Based Calix[n]arenes and Calix-Resorcinarenes as Building Blocks: Synthesis, Formulation and Characterization

    PubMed Central

    Montasser, Imed; Shahgaldian, Patrick; Perret, Florent; Coleman, Anthony W.

    2013-01-01

    Solid lipid nanoparticles (SLNs) have attracted increasing attention during recent years. This paper presents an overview about the use of calix[n]arenes and calix-resorcinarenes in the formulation of SLNs. Because of their specific inclusion capability both in the intraparticle spaces and in the host cavities as well as their capacity for functionalization, these colloidal nanostructures represent excellent tools for the encapsulation of different active pharmaceutical ingredients (APIs) in the area of drug targeting, cosmetic additives, contrast agents, etc. Various synthetic routes to the supramolecular structures will be given. These various routes lead to the formulation of the corresponding SLNs. Characterization, properties, toxicological considerations as well as numerous corresponding experimental studies and analytical methods will be also exposed and discussed. PMID:24196356

  20. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    NASA Astrophysics Data System (ADS)

    Anantachaisilp, Suranan; Meejoo Smith, Siwaporn; Treetong, Alongkot; Pratontep, Sirapat; Puttipipatkhachorn, Satit; Rungsardthong Ruktanonchai, Uracha

    2010-03-01

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812® as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance (1H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

  1. Distribution of a model bioactive within solid lipid nanoparticles and nanostructured lipid carriers influences its loading efficiency and oxidative stability.

    PubMed

    Pan, Yuanjie; Tikekar, Rohan V; Nitin, N

    2016-09-10

    The overall goal of this study was to characterize the distribution of a model bioactive encapsulant in the lipid domain of SLNs and NLCs and its relationship with loading efficiency and reactivity of the model encapsulant with oxidative stress agents. Distribution of a model bioactive (beta-carotene) was compared to that of a fluorescent dye (Nile red) in SLNs, 10% NLC, 30% NLC, 50% NLC, 70% NLC (the number represents the percentage of liquid lipid within the total lipid amount) and emulsions. Fluorescence imaging shows that the distribution of Nile red in the lipid domain of colloidal carriers was similar to that of beta-carotene in all formulations. Based on the combination of imaging observations and loading efficiency measurements, the results demonstrate that beta-carotene was excluded from the lipid domain in both SLNs and NLCs. The extent of exclusion decreased, while uniformity in the distribution of encapsulant in the lipid domain of colloidal carrier increased with an increase in percentage of liquid lipid content of NLCs. Oxidative stability of the encapsulated beta-carotene in SLN and NLCs (at least until 30% liquid lipid composition) was significantly lower compared to that in emulsion. Only for the NLCs with 50 and 70% liquid lipid content, oxidative stability of the encapsulated compound was significantly higher than that in emulsions. Overall, the results demonstrate that differences in loading efficiency and oxidative stability of beta-carotene in SLNs and NLCs may be explained by the differences in the distribution of beta-carotene. PMID:27418566

  2. New methods for lipid nanoparticles preparation.

    PubMed

    Corrias, Francesco; Lai, Francesco

    2011-09-01

    Lipid nanoparticles have attracted many researchers during recent years due to the excellent tolerability and advantages compared to liposomes and polymeric nanoparticles. High pressure homogenization is the main technique used to prepare solid lipid nanoparticles (SLN) encapsulating different type of drugs, however this method involves some critical process parameters. For this reason and in order to overcome patented methods, different production techniques for lipid nanoparticles have been widely investigated in recent years (last decade). The paper reviews new methods for lipid nanoparticles preparation, and their recent applications in pharmaceutical field, especially focusing on coacervation, microemulsions templates, supercritical fluid technology, phase-inversion temperature (PIT) techniques. References of the most relevant literature and patents published by various research groups on these fields are provided. PMID:21834772

  3. Enhancement of antibacterial activity of tilmicosin against Staphylococcus aureus by solid lipid nanoparticles in vitro and in vivo.

    PubMed

    Wang, X F; Zhang, S L; Zhu, L Y; Xie, S Y; Dong, Z; Wang, Y; Zhou, W Z

    2012-01-01

    This study aimed to enhance the antibacterial activity of tilmicosin by solid lipid nanoparticles (SLN). Tilmicosin-loaded hydrogenated castor oil (HCO)-SLN was prepared using a hot homogenisation and ultrasonication method. The physicochemical characteristics of SLN were investigated by scanning electron microscopy (SEM) and photon correlation spectroscopy (PCS). The antibacterial activity of tilmicosin-SLN against Staphylococcus aureus was evaluated by growth inhibition and colony-counting method. A therapeutic study of tilmicosin-SLN was conducted by subcutaneous injection in a mouse mastitis model infected with S. aureus by teat canal infusion. Therapeutic efficacy was assessed by physical appearance of the mammary gland and measurement of colony-forming units (CFU) per gland. The results showed that the diameter, polydispersivity index, zeta potential, encapsulation efficiency and loading capacity of the nanoparticles were 343±26 nm, 0.33±0.08, -7.9±0.4 mV, 60.4±3.3% and 11.2±0.47%, respectively. Tilmicosin-SLN showed a sustained-release effect and sustained and enhanced antibacterial activity in vitro. SLN significantly enhanced the therapeutic efficacy of tilmicosin determined by lower CFU counts and a decreased degree of inflammation. These results demonstrated that the HCO-SLN is an effective carrier to enhance the antibacterial activity of tilmicosin.

  4. Novel formulation and evaluation of a Q10-loaded solid lipid nanoparticle cream: in vitro and in vivo studies.

    PubMed

    Farboud, Effat Sadat; Nasrollahi, Saman Ahmad; Tabbakhi, Zahra

    2011-01-01

    Solid lipid nanoparticles (SLNs) of coenzyme Q10 (CoQ10) were formulated by a high-pressure homogenization method. The best formulation of SLN dispersion consisted of 13% lipid (cetyl palmitate or stearic acid), 8% surfactant (Tween 80 or Tego Care 450), and water. Stability tests, particle size analysis, differential scanning calorimetry, transmission electron microscopy, and release study were conducted to find the best formulation. A simple cream of CoQ10 and a cream containing CoQ10-loaded SLNs were prepared and compared on volunteers aged 20-30 years. SLNs with particle size between 50 nm and100 nm exhibited the most suitable stability. In vitro release profiles of CoQ10 from simple cream, SLN alone, and CoQ10-loaded SLN cream showed prolonged release for SLNs compared with the simple cream, whereas there was no significant difference between SLN alone and SLN in cream. In vitro release studies also demonstrated that CoQ10-loaded SLN and SLN cream possessed a biphasic release pattern in comparison with simple cream. In vivo skin hydration and elasticity studies on 25 volunteers suggested good dermal penetration and useful activity of Q10 on skin as a hydratant and antiwrinkle cream.

  5. Solid Lipid Nanoparticle Formulations of Docetaxel Prepared with High Melting Point Triglycerides: In Vitro and in Vivo Evaluation

    PubMed Central

    2015-01-01

    Docetaxel (DCX) is a second generation taxane. It is approved by the U.S. Food and Drug Administration for the treatment of various types of cancer, including breast, non-small cell lung, and head and neck cancers. However, side effects, including those related to Tween 80, an excipient in current DCX formulations, can be severe. In the present study, we developed a novel solid lipid nanoparticle (SLN) composition of DCX. Trimyristin was selected from a list of high melting point triglycerides as the core lipid component of the SLNs, based on the rate at which the DCX was released from the SLNs and the stability of the SLNs. The trimyristin-based, PEGylated DCX-incorporated SLNs (DCX-SLNs) showed significantly higher cytotoxicity against various human and murine cancer cells in culture, as compared to DCX solubilized in a Tween 80/ethanol solution. Moreover, in a mouse model with pre-established tumors, the new DCX-SLNs were significantly more effective than DCX solubilized in a Tween 80/ethanol solution in inhibiting tumor growth without toxicity, likely because the DCX-SLNs increased the concentration of DCX in tumor tissues, but decreased the levels of DCX in major organs such as liver, spleen, heart, lung, and kidney. DCX-incorporated SLNs prepared with one or more high-melting point triglycerides may represent an improved DCX formulation. PMID:24621456

  6. Solid lipid nanoparticles for transdermal delivery of diclofenac sodium: preparation, characterization and in vitro studies.

    PubMed

    Liu, Dongfei; Ge, Yifan; Tang, Yue; Yuan, Yubing; Zhang, Qing; Li, Rui; Xu, Qunwei

    2010-01-01

    The aim of this study was to prepare diclofenac sodium (DNa) solid lipid nanoparticles (SLNs) by a modified emulsion/solvent evaporation method for transdermal delivery. Five independent processing parameters including the lipid matrix, emulsifiers, co-emulsifiers, water-dispersed phase and organic phase were assessed systematically to enhance the entrapment of DNa. The SLNs produced by optimal formulation were submicrometre size with low polydispersity index, the entrapment efficiency was about 89% and the drug loading was about 9.5%. Shape and surface morphology were determined by transmission electron microscopy, which revealed the fairly spherical and core-shell shapes of the SLNs. The in vitro release of SLNs showed a two-step release pattern: one initial burst release followed by a second slow-release phase. In the in vitro cutaneous permeation studies, value of flux obtained for DNa solution was higher than that of SLNs suspension. SLNs had also been shown to improve the dermal localization of DNa.

  7. Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin.

    PubMed

    Jenning, V; Gysler, A; Schäfer-Korting, M; Gohla, S H

    2000-05-01

    To evaluate the potential use of solid lipid nanoparticles (SLN) in dermatology and cosmetics, glyceryl behenate SLN loaded with vitamin A (retinol and retinyl palmitate) and incorporated in a hydrogel and o/w-cream were tested with respect to their influence on drug penetration into porcine skin. Conventional formulations served for comparison. Excised full thickness skin was mounted in Franz diffusion cells and the formulations were applied for 6 and 24 h, respectively. Vitamin A concentrations in the skin tissue suggested a certain drug localizing effect. High retinol concentrations were found in the upper skin layers following SLN preparations, whereas the deeper regions showed only very low vitamin A levels. Because of a polymorphic transition of the lipid carrier with subsequent drug expulsion following the application to the skin, the drug localizing action appears to be limited for 6-24 h. Best results were obtained with retinol SLN incorporated in the oil-in-water (o/w) cream retarding drug expulsion. The penetration of the occlusion sensitive drug retinyl palmitate was even more influenced by SLN incorporation. Transepidermal water loss (TEWL) and the influence of drug free SLN on retinyl palmitate uptake exclude pronounced occlusive effects. Therefore enhanced retinyl palmitate uptake should derive from specific SLN effects and is not due to non-specific occlusive properties.

  8. Solid lipid nanoparticle formulations of docetaxel prepared with high melting point triglycerides: in vitro and in vivo evaluation.

    PubMed

    Naguib, Youssef Wahib; Rodriguez, B Leticia; Li, Xinran; Hursting, Stephen D; Williams, Robert O; Cui, Zhengrong

    2014-04-01

    Docetaxel (DCX) is a second generation taxane. It is approved by the U.S. Food and Drug Administration for the treatment of various types of cancer, including breast, non-small cell lung, and head and neck cancers. However, side effects, including those related to Tween 80, an excipient in current DCX formulations, can be severe. In the present study, we developed a novel solid lipid nanoparticle (SLN) composition of DCX. Trimyristin was selected from a list of high melting point triglycerides as the core lipid component of the SLNs, based on the rate at which the DCX was released from the SLNs and the stability of the SLNs. The trimyristin-based, PEGylated DCX-incorporated SLNs (DCX-SLNs) showed significantly higher cytotoxicity against various human and murine cancer cells in culture, as compared to DCX solubilized in a Tween 80/ethanol solution. Moreover, in a mouse model with pre-established tumors, the new DCX-SLNs were significantly more effective than DCX solubilized in a Tween 80/ethanol solution in inhibiting tumor growth without toxicity, likely because the DCX-SLNs increased the concentration of DCX in tumor tissues, but decreased the levels of DCX in major organs such as liver, spleen, heart, lung, and kidney. DCX-incorporated SLNs prepared with one or more high-melting point triglycerides may represent an improved DCX formulation.

  9. Stability of paclitaxel-loaded solid lipid nanoparticles in the presence of 2-hydoxypropyl-β-cyclodextrin.

    PubMed

    Baek, Jong-Suep; Kim, Bo-Sik; Puri, Anu; Kumar, K; Cho, Cheong-Weon

    2016-06-01

    Paclitaxel (PTX)-loaded solid lipid nanoparticles without hydroxyl-β-cyclodextrin (PS) or with hydroxypropyl-β-cyclodextrin (PSC) were prepared by hot-melted sonication. Biocompatible and biodegradable stearic acid was used to produce the solid matrix. The stability of PS and PSC was assessed at different temperatures. Drug stability, as assessed by encapsulation efficiency (EE; %), particle size, and the polydispersity index (PDI), was examined and in vitro release of PTX from PS or PSC for up to 180 days was assessed. After 180 days of storage at 25 °C, no significant change in particle size, PDI, or EE of PS or PSC was observed. PS and PSC displayed similar sustained PTX release patterns. The particle size, PDI, EE, PTX release profile, and cytotoxicity of PS changed significantly with increasing incubation time, whereas those of PSC showed no significant change, when samples were stored at 40 ± 2 °C. PSC was more stable than PS in plasma with regard to particle size and PDI. These results demonstrate that PSC could be a promising formulation to increase drug stability. PMID:27146520

  10. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products.

    PubMed

    Pardeike, Jana; Hommoss, Aiman; Müller, Rainer H

    2009-01-21

    Solid lipid nanoparticles (SLN) are distinguishable from nanostructured lipid carriers (NLC) by the composition of the solid particle matrix. Both are an alternative carrier system to liposomes and emulsions. This review paper focuses on lipid nanoparticles for dermal application. Production of lipid nanoparticles and final products containing lipid nanoparticles is feasible by well-established production methods. SLN and NLC exhibit many features for dermal application of cosmetics and pharmaceutics, i.e. controlled release of actives, drug targeting, occlusion and associated with it penetration enhancement and increase of skin hydration. Due to the production of lipid nanoparticles from physiological and/or biodegradable lipids, this carrier system exhibits an excellent tolerability. The lipid nanoparticles are a "nanosafe" carrier. Furthermore, an overview of the cosmetic products currently on the market is given and the improvement of the benefit/risk ratio of the topical therapy is shown. PMID:18992314

  11. Distribution of Fullerene Nanoparticles between Water and Solid Supported Lipid Membranes: Thermodynamics and Effects of Membrane Composition on Distribution.

    PubMed

    Ha, Yeonjeong; Katz, Lynn E; Liljestrand, Howard M

    2015-12-15

    The distribution coefficient (Klipw) of fullerene between solid supported lipid membranes (SSLMs) and water was examined using different lipid membrane compositions. Klipw of fullerene was significantly higher with a cationic lipid membrane compared to that with a zwitterionic or anionic lipid membrane, potentially due to the strong interactions between negative fullerene dispersions and positive lipid head groups. The higher Klipw for fullerene distribution to ternary lipid mixture membranes was attributed to an increase in the interfacial surface area of the lipid membrane resulting from phase separation. These results imply that lipid composition can be a critical factor that affects bioconcentration of fullerene. Distribution of fullerene into zwitterionic unsaturated lipid membranes was dominated by the entropy contribution (ΔS) and the process was endothermic (ΔH > 0). This result contrasts the partitioning thermodynamics of highly and moderately hydrophobic chemicals indicating that the lipid-water distribution mechanism of fullerene may be different from that of molecular level chemicals. Potential mechanisms for the distribution of fullerene that may explain these differences include adsorption on the lipid membrane surfaces and partitioning into the center of lipid membranes (i.e., absorption).

  12. Design and evaluation of solid lipid nanoparticles modified with peptide ligand for oral delivery of protein drugs.

    PubMed

    Fan, Tingting; Chen, Chunhui; Guo, Han; Xu, Juan; Zhang, Jian; Zhu, Xi; Yang, Yang; Zhou, Zhou; Li, Lian; Huang, Yuan

    2014-10-01

    Designing feasible and effective peptide ligand modified solid lipid nanoparticles (SLNs) to improve oral bioavailability of protein drugs and evaluating the influence of mucus remains important. In the present work, two kinds of peptide ligand modified SLNs loaded with salmon calcitonin (sCT), namely, sCT CSK-SLNs and sCT IRQ-SLNs, were prepared by coupling the peptide ligand CSKSSDYQC (CSK) which was reported to show affinity with goblet cells, or IRQRRRR (IRQ), a cell penetrating peptide, to polyoxyethylene (40) stearate (SA-PEG2000). Compared with unmodified SLNs, CSK or IRQ modified SLNs with better drug protection ability could facilitate the internalization of drug on Caco-2/HT29-MTX co-cultured cells and permeation in excised rat duodenum mucosa. The internalization mechanism of two kinds of peptide ligand modified SLNs was mainly active transport via both clathrin- and caveolae-dependent endocytosis. Although mucus was an impediment to the transport of SLNs, the peptide ligand modified SLNs still showed improved drug absorption. The absolute bioavailability of sCT CSK-SLNs (12.41 ± 3.65%) and sCT IRQ-SLNs (10.05 ± 5.10%) raised to 2.45-fold and 1.98-fold compared with unmodified SLNs (5.07 ± 0.54%), implying the feasibility and effectiveness of CSK and IRQ peptide modification for the enhancement of the oral bioavailability of protein drugs. In summary, the nanoparticles modified with CSK or IRQ peptide ligand could be the potential carriers for the transport of protein drugs across intestinal barriers.

  13. In vitro characterization of 6-Coumarin loaded solid lipid nanoparticles and their uptake by immunocompetent fish cells.

    PubMed

    Trapani, Adriana; Mandracchia, Delia; Di Franco, Cinzia; Cordero, Héctor; Morcillo, Patricia; Comparelli, Roberto; Cuesta, Alberto; Esteban, Maria Angeles

    2015-03-01

    The primary aim of the present work was to evaluate the in vitro uptake of 6-Coumarin (6COUM) loaded solid lipid nanoparticles (SLN) by two gilthead seabream (Sparus aurata L.) cell types: an established cell line (SAF-1 cells) and the primary cultures of head-kidney (HK)-the main haemopoietic organ in fish, equivalent to mammalian bone marrow-leucocytes. For this purpose, after the physicochemical characterization of SLN, the uptake by those immunocompetent fish cells was evaluated using flow cytometry and confocal microscopy. Concomitantly, the uptake of 6-COUM loaded SLN was compared with that achieved with 6-COUM loaded pectin microparticles (MPs), which were selected as a competitor of the delivery carriers. After SLN and MP physicochemical characterization, the results demonstrated that SAF-1 cells were able to internalize high percentages of 6-COUM SLNs when incubated for 4, 8 and 24h, with the highest SLN concentration tested (10 μg/ml). The ability of HK leucocytes to internalize SLN was also found to vary depending on both incubation time and SLN concentration. The highest values of HK leucocytes internalizing SLN particles (around 16%) were detected at the maximum SLN concentration (20 μg/ml) at incubation times of 4 or 8h. Conversely, HK leucocytes were unable to internalize MPs at any tested concentration and incubation time. A possible mechanism explaining the uptake into cells is proposed. The present work constitutes the first approximation to consider SLN as nanocarriers for delivering biologically active substances to fish.

  14. Core-shell microcapsules of solid lipid nanoparticles and mesoporous silica for enhanced oral delivery of curcumin.

    PubMed

    Kim, Sanghoon; Diab, Roudayna; Joubert, Olivier; Canilho, Nadia; Pasc, Andreea

    2016-04-01

    Newly designed microcapsules (MC) combining a core of solid lipid nanoparticle (SLN) and a mesoporous silica shell have been developed and explored as oral delivery system of curcumin (CU). CU-loaded MC (MC-CU) are 2 μm sized and have a mesoporous silica shell of 0.3 μm thickness with a wormlike structure as characterized by small angle X-ray scattering (SAXS), nitrogen adsorption/desorption and transmission electron microscopy (TEM) measurements. It was found that SLN acts as reservoir of curcumin while the mesoporous shell insures the protection and the controlled release of the drug. MC-CU displayed a pH-dependent in vitro release profile with marked drug retention at pH 2.8. Neutral red uptake assay together with confocal laser scanning microscopy (CLSM) showed a good cell tolerance to MC-CU at relatively high concentration of inert materials. Besides, the cell-uptake test revealed that fluorescent-MC were well internalized into Caco-2 cells, confirming the possibility to use MC for gut cells targeting. These findings suggest that organic core-silica shell microcapsules are promising drug delivery systems with enhanced bioavailability for poorly soluble drugs. PMID:26752213

  15. Preparation of oridonin-loaded solid lipid nanoparticles and studies on them in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Zhang, Dianrui; Tan, Tianwei; Gao, Lei

    2006-12-01

    Oridonin, a lipophilic Chinese medicine, has very low oral bioavailability due to its poor solubility. Solid lipid nanoparticle (SLN) delivery systems of oridonin have been formed using stearic acid, soybean lecithin and pluronic F68 in our studies to overcome this problem. Emulsion evaporation-solidification at low temperature was used to prepare SLN dispersions. The particle size and morphology were examined by transmission electron microscopy (TEM), and the zeta potential was measured by a television micro-electrophoresis apparatus. Process and formulation variables have been studied and optimized on the basis of entrapment efficiency. Differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD) studies were performed to characterize the state of the drug. In vitro release studies were performed in phosphate-buffer solution (PBS) (pH 7.4). The tissue distribution in mice and the pharmacokinetics in rabbits were studied to evaluate the tissue targeted property of SLNs. Stable SLN formulations of oridonin having a mean size range of 15-35 nm and mean zeta potential -45.07 mV were developed. More than 40% oridonin was entrapped in SLNs. DSC and PXRD analysis showed that oridonin is dispersed in SLNs in an amorphous state. The release pattern of the drug was analysed and found to follow the Higuchi equations. In vivo studies demonstrated that oridonin-loaded SLNs obviously increased the concentration of oridonin in liver, lung and spleen, while its distribution in heart and kidney decreased.

  16. Brain targeted delivery of carmustine using solid lipid nanoparticles modified with tamoxifen and lactoferrin for antitumor proliferation.

    PubMed

    Kuo, Yung-Chih; Cheng, Shih-Jue

    2016-02-29

    Solid lipid nanoparticles (SLNs) conjugated with tamoxifen (TX) and lactoferrin (Lf) were applied to carry anticancer carmustine (BCNU) across the blood-brain barrier (BBB) for enhanced antiproliferation against glioblastoma multiforme (GBM). BCNU-loaded SLNs with modified TX and Lf (TX-Lf-BCNU-SLNs) were used to penetrate a monolayer of human brain-microvascular endothelial cells (HBMECs) and human astrocytes and to target malignant U87MG cells. The surface TX and Lf on TX-Lf-BCNU-SLNs improved the characteristics of sustained release for BCNU. When compared with BCNU-loaded SLNs, TX-Lf-BCNU-SLNs increased the BBB permeability coefficient for BCNU about ten times. In addition, TX-BCNU-SLNs considerably promoted the fluorescent intensity of intracellular acetomethoxy derivative of calcein (calcein-AM) in HBMECs via endocytosis. However, the conjugated Lf could only slightly increase the fluorescence of calcein-AM. Moreover, the order of formulation in the inhibition to U87MG cells was TX-Lf-BCNU-SLNs>TX-BCNU-SLNs>Lf-BCNU-SLNs>BCNU-SLNs. TX-Lf-BCNU-SLNs can be effective in infiltrating the BBB and delivering BCNU to GBM for future chemotherapy application. PMID:26721730

  17. Preparation and brain delivery of nasal solid lipid nanoparticles of quetiapine fumarate in situ gel in rat model of schizophrenia

    PubMed Central

    Li, Jian-Chun; Zhang, Wen-Jing; Zhu, Jin-Xiu; Zhu, Na; Zhang, Hong-Min; Wang, Xiu; Zhang, Jin; Wang, Qing-Qing

    2015-01-01

    To investigate the brain delivery in rat by nasal Quetiapine fumarate (QF) loaded with solid lipid nanoparticles in situ gel (QF-SLN-gel). QF-SLN-gel was prepared through micro-emulsion technique. The rat model of schizophrenia was established by intraperitoneal injection of (+)-MK-801, evaluated by stereotypic behavior, Mori’s Water Maze (MWM) test and hematoxylin and eosin (HE) staining of hippocampus. The animals were administrated with QF via oral, nasal or tail vein approach and the concentration of QF in blood and brain was determined using high performance liquid chromatography (HPLC). The QF-SLN-gel was even and transparent, having size of 117.8±2.67 d.nm, potential of 57.2±0.24 mV and EF of 97.6±0.58%. After administration of QF-SLN-gel, the concentration of QF in blood and brain of rats in nasal QF-SLN-gel group was similar with that of rats in tail vein QF group, but significantly higher than that of rats in oral QF group. The hippocampal morphology changes induced by (+)-MK-801 were ameliorated by QF, with advantage of nasal QF-SLN-gel over tail vein QF. The nasal QF-SLN-gel had stable and good brain delivery and could ameliorate the damages in rat model of schizophrenia induced by (+)-MK-801. PMID:26770349

  18. Skin Delivery and in Vitro Biological Evaluation of Trans-Resveratrol-Loaded Solid Lipid Nanoparticles for Skin Disorder Therapies.

    PubMed

    Rigon, Roberta B; Fachinetti, Naiara; Severino, Patrícia; Santana, Maria H A; Chorilli, Marlus

    2016-01-20

    The aim of this study was to evaluate the skin delivery and in vitro biological activity of trans-resveratrol (RES)-loaded solid lipid nanoparticles (SLNs). The SLNs were composed of stearic acid, poloxamer 407, soy phosphatidylcholine (SPC), an aqueous phase and 0.1% RES. The particle size, polydispersity index (PdI) and zeta potential were analyzed by dynamic light scattering (DLS). The SLNs were analyzed by scanning electron microscopy (SEM-FEG) and differential scanning calorimetry (DSC). In vitro RES-SLN skin permeation/retention assays were conducted, and their tyrosinase inhibitory activity was evaluated. An MTT reduction assay was performed on HaCat keratinocytes to determine in vitro cytotoxicity. The formulations had average diameter lower than 200 nm, the addition of SPC promoted increases in PdI in the RES-SLNs, but decreases PdI in the RES-free SLNs and the formulations exhibited zeta potentials smaller than -3 mV. The DSC analysis of the SLNs showed no endothermic peak attributable to RES. Microscopic analysis suggests that the materials formed had nanometric size distribution. Up to 45% of the RES permeated through the skin after 24 h. The RES-loaded SLNs were more effective than kojic acid at inhibiting tyrosinase and proved to be non-toxic in HaCat keratinocytes. The results suggest that the investigated RES-loaded SLNs have potential use in skin disorder therapies.

  19. Cationic solid-lipid nanoparticles are as efficient as electroporation in DNA vaccination against visceral leishmaniasis in mice.

    PubMed

    Saljoughian, N; Zahedifard, F; Doroud, D; Doustdari, F; Vasei, M; Papadopoulou, B; Rafati, S

    2013-12-01

    The use of an appropriate delivery system has recently emerged as a promising approach for the development of effective vaccination against visceral leishmaniasis (VL). Here, we compare two vaccine delivery systems, namely electroporation and cationic solid-lipid nanoparticle (cSLN) formulation, to administer a DNA vaccine harbouring the L. donovani A2 antigen along with L. infantum cysteine proteinases [CPA and CPB without its unusual C-terminal extension (CPB(-CTE) )] and evaluate their potential against L. infantum challenge. Prime-boost administration of the pcDNA-A2-CPA-CPB(-CTE) delivered by either electroporation or cSLN formulation protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-γ and lower levels of IL-10 production, leading to a strong Th1 immune response. At all time points, the ratio of IFN-γ: IL-10 induced upon restimulation with rA2-rCPA-rCPB and F/T antigens was significantly higher in vaccinated animals. Moreover, Th2-efficient protection was elicited through a high humoral immune response. Nitric oxide production, parasite burden and histopathological analysis were also in concordance with other findings. Overall, these data indicate that similar to the electroporation delivery system, cSLNs as a nanoscale vehicle of Leishmania antigens could improve immune response, hence indicating the promise of these strategies against visceral leishmaniasis.

  20. Multi criteria decision making to select the best method for the preparation of solid lipid nanoparticles of rasagiline mesylate using analytic hierarchy process.

    PubMed

    Kunasekaran, Viveksarathi; Krishnamoorthy, Kannan

    2014-07-01

    The objective of this study was to select best method for the development of rasagiline mesylate (RM) loaded nanoscale solid lipid particles using analytic hierarchy process (AHP). Improper method selection may lead to waste of time, loss of material and financial resources. One of the possibilities to overcome these difficulties, AHP was employed to find the suitable method. In the AHP, a decision of hierarchy was constructed with a goal, criteria, sub-criteria, and alternatives. After constructing the AHP, the expert choice software was used to compute the overall priority of criteria, sub-criteria and alternatives. The best alternative selected was based on the highest priority. Nanoscale solid lipid particles of RM was formulated by the selected microemulsion method (M4) and it shows the particle size, polydispersity index and zeta potential were within acceptable limits. Drug content and entrapment efficiency of the RM-solid lipid nanoparticles were 97.26% and 86.57%, respectively. This study concludes that the AHP was viable and effective tool for selecting a most suitable method for the fabrication of RM loaded nanoscale solid lipid particles. PMID:25126532

  1. Multi criteria decision making to select the best method for the preparation of solid lipid nanoparticles of rasagiline mesylate using analytic hierarchy process.

    PubMed

    Kunasekaran, Viveksarathi; Krishnamoorthy, Kannan

    2014-07-01

    The objective of this study was to select best method for the development of rasagiline mesylate (RM) loaded nanoscale solid lipid particles using analytic hierarchy process (AHP). Improper method selection may lead to waste of time, loss of material and financial resources. One of the possibilities to overcome these difficulties, AHP was employed to find the suitable method. In the AHP, a decision of hierarchy was constructed with a goal, criteria, sub-criteria, and alternatives. After constructing the AHP, the expert choice software was used to compute the overall priority of criteria, sub-criteria and alternatives. The best alternative selected was based on the highest priority. Nanoscale solid lipid particles of RM was formulated by the selected microemulsion method (M4) and it shows the particle size, polydispersity index and zeta potential were within acceptable limits. Drug content and entrapment efficiency of the RM-solid lipid nanoparticles were 97.26% and 86.57%, respectively. This study concludes that the AHP was viable and effective tool for selecting a most suitable method for the fabrication of RM loaded nanoscale solid lipid particles.

  2. Multi criteria decision making to select the best method for the preparation of solid lipid nanoparticles of rasagiline mesylate using analytic hierarchy process

    PubMed Central

    Kunasekaran, Viveksarathi; Krishnamoorthy, Kannan

    2014-01-01

    The objective of this study was to select best method for the development of rasagiline mesylate (RM) loaded nanoscale solid lipid particles using analytic hierarchy process (AHP). Improper method selection may lead to waste of time, loss of material and financial resources. One of the possibilities to overcome these difficulties, AHP was employed to find the suitable method. In the AHP, a decision of hierarchy was constructed with a goal, criteria, sub-criteria, and alternatives. After constructing the AHP, the expert choice software was used to compute the overall priority of criteria, sub-criteria and alternatives. The best alternative selected was based on the highest priority. Nanoscale solid lipid particles of RM was formulated by the selected microemulsion method (M4) and it shows the particle size, polydispersity index and zeta potential were within acceptable limits. Drug content and entrapment efficiency of the RM-solid lipid nanoparticles were 97.26% and 86.57%, respectively. This study concludes that the AHP was viable and effective tool for selecting a most suitable method for the fabrication of RM loaded nanoscale solid lipid particles. PMID:25126532

  3. Cosmetic features and applications of lipid nanoparticles (SLN, NLC).

    PubMed

    Souto, E B; Müller, R H

    2008-06-01

    A detailed review of the literature is presented in attempts to emphasize several advantages of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for cosmetic applications. Examples of several actives are given and the main features of the solid core of SLN and NLC for topical delivery of cosmetics are discussed. Lipid nanoparticles have been more and more explored in pharmaceutical technology, showing superior advantages for topical purposes over conventional colloidal carriers. PMID:18452432

  4. A novel method to produce solid lipid nanoparticles using n-butanol as an additional co-surfactant according to the o/w microemulsion quenching technique.

    PubMed

    Mojahedian, Mohammad M; Daneshamouz, Saeid; Samani, Soliman Mohammadi; Zargaran, Arman

    2013-09-01

    Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are novel medicinal carriers for controlled drug release and drug targeting in different roots of administration such as parenteral, oral, ophthalmic and topical. These carriers have some benefits such as increased drug stability, high drug payload, the incorporation of lipophilic and hydrophilic drugs, and no biotoxicity. Therefore, due to the cost-efficient, proportionally increasable, and reproducible preparation of SLN/NLC and the avoidance of organic solvents used, the warm microemulsion quenching method was selected from among several preparation methods for development in this research. To prepare the warm O/W microemulsion, lipids (distearin, stearic acid, beeswax, triolein alone or in combination with others) were melted at a temperature of 65°C. After that, different ratios of Tween60 (10-22.5%) and glyceryl monostearate (surfactant and co-surfactant) and water were added, and the combination was stirred. Then, 1-butanol (co-surfactant) was added dropwise until a clear microemulsion was formed and titration continued to achieve cloudiness (to obtain the microemulsion zone). The warm o/w microemulsions were added dropwise into 4°C water (1:5 volume ratio) while being stirred at 400 or 600 rpm. Lipid nanosuspensions were created upon the addition of the warm o/w microemulsion to the cold water. The SLN were obtained over a range of concentrations of co-surfactants and lipids and observed for microemulsion stability (clearness). For selected preparations, characterization involved also determination of mean particle size, polydispersity and shape. According to the aim of this study, the optimum formulations requiring the minimum amounts of 1-butanol (1.2%) and lower temperatures for creation were selected. Mono-disperse lipid nanoparticles were prepared in the size range 77 ± 1 nm to 124 ± 21 nm according to a laser diffraction particle size analyzer and transmission electron

  5. Solid lipid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation

    PubMed Central

    Yasir, Mohd; Sara, Udai Vir Singh

    2014-01-01

    In the present study, haloperidol (HP)-loaded solid lipid nanoparticles (SLNs) were prepared to enhance the uptake of HP to brain via intranasal (i.n.) delivery. SLNs were prepared by a modified emulsification–diffusion technique and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release, and stability. All parameters were found to be in an acceptable range. In vitro drug release was found to be 94.16±4.78% after 24 h and was fitted to the Higuchi model with a very high correlation coefficient (R2=0.9941). Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography. The brain/blood ratio at 0.5 h for HP-SLNs i.n., HP sol. i.n. and HP sol. i.v. was 1.61, 0.17 and 0.031, respectively, indicating direct nose-to-brain transport, bypassing the blood–brain barrier. The maximum concentration (Cmax) in brain achieved from i.n. administration of HP-SLNs (329.17±20.89 ng/mL, Tmax 2 h) was significantly higher than that achieved after i.v. (76.95±7.62 ng/mL, Tmax 1 h), and i.n. (90.13±6.28 ng/mL, Tmax 2 h) administration of HP sol. The highest drug-targeting efficiency (2362.43%) and direct transport percentage (95.77%) was found with HP-SLNs as compared to the other formulations. Higher DTE (%) and DTP (%) suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations. PMID:26579417

  6. Development of "all natural" layer-by-layer redispersible solid lipid nanoparticles by nano spray drying technology.

    PubMed

    Wang, Taoran; Hu, Qiaobin; Zhou, Mingyong; Xia, Yan; Nieh, Mu-Ping; Luo, Yangchao

    2016-10-01

    Solid lipid nanoparticles (SLNs) have gained tremendous attraction as carriers for controlled drug delivery. Despite numerous advances in the field, one long-standing historical challenge for their practical applications remains unmet: redispersibility after drying. In this work, a novel design of SLNs using a layer-by-layer (LbL) technique was developed and the formulations were optimized by surface response methodology (Box-Behnken design). To the best of our knowledge, this is the first study reporting the fabrication of SLNs from all natural ingredients in the absence of any synthetic surfactants or coatings. The SLNs were prepared by a combined solvent-diffusion and hot homogenization method, with soy lecithin as natural emulsifier (first layer), followed by the subsequent coating with sodium caseinate (second layer) and pectin (third layer), both of which are natural food biopolymers. The adsorption of pectin coating onto caseinate was reinforced by hydrophobic and electrostatic interactions induced by a pH-driven process along with thermal treatment. The innovative nano spray drying technology was further explored to obtain ultra-fine powders of SLNs. Compared to uncoated or single-layer coated SLNs powders, which showed severe aggregation after spray drying, the well-separated particles with spherical shape and smooth surface were obtained for layer-by-layer (LbL) SLNs, which were redispersible into water without variation of dimension, shape and morphology. The SLNs were characterized by Fourier transform infrared and high-performance differential scanning calorimetry for their physical properties. The LbL-coated SLNs based on all natural ingredients have promising features for future applications as drug delivery systems, overcoming the major obstacles in conventional spray drying and redispersing SLNs-based formulations. PMID:27470922

  7. 15d-PGJ2-Loaded Solid Lipid Nanoparticles: Physicochemical Characterization and Evaluation of Pharmacological Effects on Inflammation.

    PubMed

    de Melo, Nathalie Ferreira Silva; de Macedo, Cristina Gomes; Bonfante, Ricardo; Abdalla, Henrique Ballassini; da Silva, Camila Morais Gonçalves; Pasquoto, Tatiane; de Lima, Renata; Fraceto, Leonardo Fernandes; Clemente-Napimoga, Juliana Trindade; Napimoga, Marcelo Henrique

    2016-01-01

    15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has physiological properties including pronounced anti-inflammatory activity, though it binds strongly to serum albumin. The use of solid lipid nanoparticles (SLN) can improve therapeutic properties increasing drug efficiency and availability. 15d-PGJ2-SLN was therefore developed and investigated in terms of its immunomodulatory potential. 15d-PGJ2-SLN and unloaded SLN were physicochemically characterized and experiments in vivo were performed. Animals were pretreated with 15d-PGJ2-SLN at concentrations of 3, 10 or 30 μg·kg-1 before inflammatory stimulus with carrageenan (Cg), lipopolysaccharide (LPS) or mBSA (immune response). Interleukins (IL-1β, IL-10 and IL-17) levels were also evaluated in exudates. The 15d-PGJ2-SLN system showed good colloidal parameters and encapsulation efficiency of 96%. The results showed that the formulation was stable for up to 120 days with low hemolytic effects. The 15d-PGJ2-SLN formulation was able to reduce neutrophil migration in three inflammation models tested using low concentrations of 15d-PGJ2. Additionally, 15d-PGJ2-SLN increased IL-10 levels and reduced IL-1β as well as IL-17 in peritoneal fluid. The new 15d-PGJ2-SLN formulation highlights perspectives of a potent anti-inflammatory system using low concentrations of 15d-PGJ2. PMID:27575486

  8. 15d-PGJ2-Loaded Solid Lipid Nanoparticles: Physicochemical Characterization and Evaluation of Pharmacological Effects on Inflammation

    PubMed Central

    da Silva, Camila Morais Gonçalves; Pasquoto, Tatiane; de Lima, Renata; Fraceto, Leonardo Fernandes

    2016-01-01

    15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has physiological properties including pronounced anti-inflammatory activity, though it binds strongly to serum albumin. The use of solid lipid nanoparticles (SLN) can improve therapeutic properties increasing drug efficiency and availability. 15d-PGJ2-SLN was therefore developed and investigated in terms of its immunomodulatory potential. 15d-PGJ2-SLN and unloaded SLN were physicochemically characterized and experiments in vivo were performed. Animals were pretreated with 15d-PGJ2-SLN at concentrations of 3, 10 or 30 μg·kg-1 before inflammatory stimulus with carrageenan (Cg), lipopolysaccharide (LPS) or mBSA (immune response). Interleukins (IL-1β, IL-10 and IL-17) levels were also evaluated in exudates. The 15d-PGJ2-SLN system showed good colloidal parameters and encapsulation efficiency of 96%. The results showed that the formulation was stable for up to 120 days with low hemolytic effects. The 15d-PGJ2-SLN formulation was able to reduce neutrophil migration in three inflammation models tested using low concentrations of 15d-PGJ2. Additionally, 15d-PGJ2-SLN increased IL-10 levels and reduced IL-1β as well as IL-17 in peritoneal fluid. The new 15d-PGJ2-SLN formulation highlights perspectives of a potent anti-inflammatory system using low concentrations of 15d-PGJ2. PMID:27575486

  9. Improved oral delivery of resveratrol from N-trimethyl chitosan-g-palmitic acid surface-modified solid lipid nanoparticles.

    PubMed

    Ramalingam, Prakash; Ko, Young Tag

    2016-03-01

    Despite the therapeutic effects of resveratrol, its clinical application is restricted by its poor oral bioavailability, low water solubility, and instability. Solid lipid nanoparticles (SLNs)-based drug delivery systems have been shown to provide excellent support for the delivery of hydrophobic drugs. The poor stability and burst release behavior in stomach acidic pH conditions of SLNs result in increased aggregation of the particles in the gastrointestinal environment, limiting the success of these particles as an oral delivery system for hydrophobic drugs. N-trimethyl chitosan (TMC) graft palmitic acid (PA) (TMC-g-PA) mucoadhesive copolymer was hypothesized to be a promising candidate for the surface modification of PA-decorated resveratrol-loaded SLNs to stabilize SLNs and circumvent all the above mentioned obstacles. TMC and TMC-g-PA copolymers were therefore synthesized and characterized by (1)H-nuclear magnetic resonance ((1)H NMR) and Fourier-transformed infra-red (FT-IR) spectroscopy. Resveratrol-loaded SLNs (SLRNs) that comprised Precirol ATO 5, PA, Gelucire 50/13, Tween 80, and resveratrol as well as TMC-g-PA SLRNs were formulated and characterized in terms of physicochemical properties, stability, cytotoxicity, and in vitro and in vivo effects. The in vitro release studies of TMC-g-PA SLRNs demonstrated negligible release of resveratrol in simulated gastric and sustained release in simulated intestinal conditions and the relative bioavailability of resveratrol was furthermore found to be 3.8-fold higher from TMC-g-PA SLRNs than that from resveratrol suspension. Overall, the findings reported here indicate that TMC-g-PA SLRNs represent a potential oral drug delivery system for resveratrol.

  10. Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles

    PubMed Central

    Wang, Wenrui; Zhu, Rongrong; Xie, Qian; Li, Ang; Xiao, Yu; Li, Kun; Liu, Hui; Cui, Daxiang; Chen, Yihan; Wang, Shilong

    2012-01-01

    Curcumin has shown considerable pharmacological activity, including anti-inflammatory, but its poor bioavailability and rapid metabolization have limited its application. The purpose of the present study was to formulate curcumin-solid lipid nanoparticles (curcumin-SLNs) to improve its therapeutic efficacy in an ovalbumin (OVA)-induced allergic rat model of asthma. A solvent injection method was used to prepare the curcumin-SLNs. Physiochemical properties of curcumin-SLNs were characterized, and release experiments were performed in vitro. The pharmacokinetics in tissue distribution was studied in mice, and the therapeutic effect of the formulation was evaluated in the model. The prepared formulation showed an average size of 190 nm with a zeta potential value of −20.7 mV and 75% drug entrapment efficiency. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The release profile of curcumin-SLNs was an initial burst followed by sustained release. The curcumin concentrations in plasma suspension were significantly higher than those obtained with curcumin alone. Following administration of the curcumin-SLNs, all the tissue concentrations of curcumin increased, especially in lung and liver. In the animal model of asthma, curcumin-SLNs effectively suppressed airway hyperresponsiveness and inflammatory cell infiltration and also significantly inhibited the expression of T-helper-2-type cytokines, such as interleukin-4 and interleukin-13, in bronchoalveolar lavage fluid compared to the asthma group and curcumin-treated group. These observations implied that curcumin-SLNs could be a promising candidate for asthma therapy. PMID:22888226

  11. Development of "all natural" layer-by-layer redispersible solid lipid nanoparticles by nano spray drying technology.

    PubMed

    Wang, Taoran; Hu, Qiaobin; Zhou, Mingyong; Xia, Yan; Nieh, Mu-Ping; Luo, Yangchao

    2016-10-01

    Solid lipid nanoparticles (SLNs) have gained tremendous attraction as carriers for controlled drug delivery. Despite numerous advances in the field, one long-standing historical challenge for their practical applications remains unmet: redispersibility after drying. In this work, a novel design of SLNs using a layer-by-layer (LbL) technique was developed and the formulations were optimized by surface response methodology (Box-Behnken design). To the best of our knowledge, this is the first study reporting the fabrication of SLNs from all natural ingredients in the absence of any synthetic surfactants or coatings. The SLNs were prepared by a combined solvent-diffusion and hot homogenization method, with soy lecithin as natural emulsifier (first layer), followed by the subsequent coating with sodium caseinate (second layer) and pectin (third layer), both of which are natural food biopolymers. The adsorption of pectin coating onto caseinate was reinforced by hydrophobic and electrostatic interactions induced by a pH-driven process along with thermal treatment. The innovative nano spray drying technology was further explored to obtain ultra-fine powders of SLNs. Compared to uncoated or single-layer coated SLNs powders, which showed severe aggregation after spray drying, the well-separated particles with spherical shape and smooth surface were obtained for layer-by-layer (LbL) SLNs, which were redispersible into water without variation of dimension, shape and morphology. The SLNs were characterized by Fourier transform infrared and high-performance differential scanning calorimetry for their physical properties. The LbL-coated SLNs based on all natural ingredients have promising features for future applications as drug delivery systems, overcoming the major obstacles in conventional spray drying and redispersing SLNs-based formulations.

  12. Ion pairing with linoleic acid simultaneously enhances encapsulation efficiency and antibacterial activity of vancomycin in solid lipid nanoparticles.

    PubMed

    Kalhapure, Rahul S; Mocktar, Chunderika; Sikwal, Dhiraj R; Sonawane, Sandeep J; Kathiravan, Muthu K; Skelton, Adam; Govender, Thirumala

    2014-05-01

    Ion pairing of a fatty acid with an antibiotic may be an effective strategy for formulation optimization of a nanoantibiotic system. The aim of this study was therefore to explore the potential of linoleic acid (LA) as an ion pairing agent to simultaneously enhance encapsulation efficiency and antibacterial activity of triethylamine neutralized vancomycin (VCM) in solid lipid nanoparticles (SLNs). The prepared VCM-LA2 conjugate was characterized by Fourier transform-infrared (FT-IR) spectroscopy, logP and binding energy calculations. The shifts in the FT-IR frequencies of COOH, NH2 and CO functionalities, an increase in logP value (1.37) and a lower interaction energy between LA and VCM (-125.54 kcal/mol) confirmed the formation of the conjugate. SLNs were prepared by a hot homogenization and ultrasonication method, and characterized for size, polydispersity index (PI), zeta potential (ZP), entrapment efficiency (%EE), surface morphology and physical stability. In vitro antibacterial activity studies against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) were conducted. Size, PI and ZP for VCM-LA2_SLNs were 102.7±1.01, 0.225±0.02 and -38.8±2.1 (mV) respectively. SLNs were also stable at 4 °C for 3 months. %EE for VCM-HCl_SLNs and VCM-LA2_SLNs were 16.81±3.64 and 70.73±5.96 respectively, indicating a significant improvement in encapsulation of the drug through ion pairing with LA. Transmission electron microscopy images showed spherical nanoparticles with sizes in the range of 95-100 nm. After 36 h, VCM-HCl showed no activity against MRSA. However, the minimum inhibitory concentration for VCM-HCl_SLNs and VCM-LA2_SLNs were 250 and 31.25 μg/ml respectively against S. aureus, while against MRSA it was 500 and 15.62 μg/ml respectively. This confirms the enhanced antibacterial activity of VCM-LA2_SLNs over VCM-HCl_SLNs. These findings therefore suggest that VCM-LA2_SLNs is a promising nanoantibiotic system for effective treatment against both

  13. Antihyperglycemic activities of extracts of the mistletoes Plicosepalus acaciae and P. curviflorus in comparison to their solid lipid nanoparticle suspension formulations.

    PubMed

    Aldawsari, Hibah M; Hanafy, Abeer; Labib, Gihan S; Badr, Jihan M

    2014-01-01

    The antihyperglycemic activity of the extracts and preparations of solid lipid nanoparticle suspensions of two mistletoes growing in Saudi Arabia, Plicosepalus acaciae and P. curviflorus, as well as their possible antioxidant effect were investigated in a type 2 diabetic animal model. Type 2 diabetes was induced in adult male Wistar rats by a high-fat diet followed by injection of streptozotocin (STZ). The diabetic rats were treated in parallel with pioglitazone hydrochloride (PIO), non-toxic extracts of P. acaciae and P. curviflorus, as well as three different solid lipid nanoparticle (SLN) suspension formulations prepared from each of the two extracts. Blood glucose level, insulin resistance, oxidative stress parameters, and antioxidant markers were determined. The total extracts of P. acaciae and P. curviflorus as well as the SLN formulations exhibited a significant blood glucose-lowering effect associated with antioxidant effects in the diabetic rats. The SLN preparation with the highest lipid content gave the best result. Reduction of hyperglycemia and insulin resistance in the diabetic rats was, at least partly, due to the antioxidant activities of the extracts and their SLN formulations.

  14. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers. II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations.

    PubMed

    Das, Surajit; Ng, Wai Kiong; Tan, Reginald B H

    2014-03-14

    This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs. PMID:24531828

  15. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations

    NASA Astrophysics Data System (ADS)

    Das, Surajit; Kiong Ng, Wai; Tan, Reginald B. H.

    2014-03-01

    This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs.

  16. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers. II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations.

    PubMed

    Das, Surajit; Ng, Wai Kiong; Tan, Reginald B H

    2014-03-14

    This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs.

  17. Effect of Variable Solvents on Particle Size of Geranium Oil-Loaded Solid Lipid Nanoparticle (Ge-SLN) For Mosquito Repellent Applications

    NASA Astrophysics Data System (ADS)

    Asnawi, Syalwati; Aziz, Azila A.; Aziz, Ramlan A.

    2009-06-01

    A new delivery system for insect repellent is proposed by the incorporation of geranium oil into solid lipid nanoparticle (SLN). A variety of solvents which act as co-surfactants, were introduced to increase the particle size of GE-SLN. Ethanol, which has a high boiling point and a long chain alcohol produced larger particle than dichloromethane. The structure of SLN was not stable when methanol and acetone were used as co-solvents. Concentration of solvents can also influence the size of SLN. In vitro release experiments showed that SLN was able to reduce the rapid evaporation of geranium oil.

  18. Lipid nanoparticle interactions and assemblies

    NASA Astrophysics Data System (ADS)

    Preiss, Matthew Ryan

    Novel liposome-nanoparticle assemblies (LNAs) provide a biologically inspired route for designing multifunctional bionanotheranostics. LNAs combine the benefits of lipids and liposomes to encapsulate, transport, and protect hydrophilic and hydrophobic therapeutics with functional nanoparticles. Functional nanoparticles endow LNAs with additional capabilities, including the ability to target diseases, triggered drug release, controlled therapeutic output, and diagnostic capabilities to produce a drug delivery system that can effectively and efficiently deliver therapeutics while reducing side effects. Not only could LNAs make existing drugs better, they could also provide an avenue to allow once promising non-approved drugs (rejected due to harmful side effects, inadequate pharmacokinetics, and poor efficacy) to be safely used through targeted and controlled delivery directly to the diseased site. LNAs have the potential to be stimuli responsive, delivering drugs on command by external (ultrasound, RF heating, etc.) or internal (pH, blood sugar, heart rate, etc.) stimuli. Individually, lipids and nanoparticles have been clinically approved for therapy, such as Doxil (a liposomal doxorubicin for cancer treatment), and diagnosis, such as Feridex (an iron oxide nanoparticle an MRI contrast enhancement agent for liver tumors). In order to engineer these multifunctional LNAs for theranostic applications, the interactions between nanoparticles and lipids must be better understood. This research sought to explore the formation, design, structures, characteristics, and functions of LNAs. To achieve this goal, different types of LNAs were formed, specifically magnetoliposomes, bilayer decorated LNAs (DLNAs), and lipid-coated magnetic nanoparticles (LMNPs). A fluorescent probe was embedded in the lipid bilayer of magnetoliposomes allowing the local temperature and membrane fluidity to be observed. When subjected to an electromagnetic field that heated the encapsulated iron

  19. Lipid nanoparticles for the topical delivery of retinoids and derivatives.

    PubMed

    Morales, Javier O; Valdés, Karina; Morales, Javier; Oyarzun-Ampuero, Felipe

    2015-01-01

    Retinoids are lipophilic compounds that are highly used in cosmetics/therapeutics for skin disorders. Conventional formulations are limited by poor water solubility, high chemical/photochemical instability and the irritation of retinoids. Interestingly, lipid nanoparticles enable the administration of retinoids in aqueous media, providing drug stabilization and controlled release. Recently, it has been demonstrated that retinoids in solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules can decrease degradation, improve targeting and enhance efficacy for the treatment of skin disorders. This article focuses on the formulation, fabrication, characterization and in vitro/in vivo evaluation of solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules loaded with retinoids for skin administration. Furthermore, the incorporation of these lipid nanoparticles into secondary vehicles is discussed. PMID:25600970

  20. Lipid nanoparticles for dermal drug delivery.

    PubMed

    Kakadia, Pratibha G; Conway, Barbara R

    2015-01-01

    Lipid based drug delivery systems have been widely studied and reported over the past decade and offer a useful alternative to other colloidal drug delivery systems. Skin is a popular route of drug delivery for locally and systemically acting drugs and nanoparticles are reported as a potential formulation strategy for dermal delivery. Although the skin acts as a natural physical barrier against penetration of foreign materials, including particulates, opportunities exist for the delivery of therapeutic nanoparticles, especially in diseased and damaged skin and via appendageal routes such as the openings of hair follicles. The extent and ability of nanoparticles to penetrate into the underlying viable tissue is still the subject of debate although recent studies have identified the follicular route as the most likely route of entry; this influences the potential applications of these dosage forms as a drug delivery strategy. This paper reviews present state of art of lipid-based nanocarriers focussing on solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions, their production methods, potential advantages and applications in dermal drug delivery. PMID:25925115

  1. Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea

    PubMed Central

    Wei, Lili; Yang, Yunfang; Shi, Kun; Wu, Jun; Zhao, Wei; Mo, Jingxin

    2016-01-01

    The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a high ratio rate of lipid to drug) and LPM-SLN-2 (LPM-SLN with a low ratio rate of lipid to drug), were prepared by the solvent evaporation method. A change in the lipid concentration affects the characteristics of LPM-SLNs. The average sizes of the LPM-SLNs were 303 ± 18 nm and 519 ± 36 nm, separately, as analyzed by dynamic light scattering. The LPM-SLNs were found to be round with a smooth surface, as observed using a transmission electron microscope and a scanning electron microscope. The average encapsulation efficiencies were 87 ± 3.78% w/w and 84 ± 5.17%, accordingly. In the in vitro release experiments, LPM-SLNs showed a continuous release profile of LPM without any burst release. The oral bioavailability of LPM-SLNs was analyzed using Wistar rats. The relative bioavailabilities of LPM-SLNs were 227 and 153%, respectively, as compared that of the LPM tablet. There was no difference in the Tmax between LPM-SLN-2 and the LPM tablet. In conclusion, LPM-SLN-1 significantly improved the oral bioavailability of LPM, while LPM-SLN-2 having the same swift action as the LPM tablet. These results demonstrate the potential of LPM-SLNs in the oral delivery of LPM to treat different types of diarrhea. PMID:27708583

  2. The Effect of Particle Size on the Deposition of Solid Lipid Nanoparticles in Different Skin Layers: A Histological Study

    PubMed Central

    Mardhiah Adib, Zahra; Ghanbarzadeh, Saeed; Kouhsoltani, Maryam; Yari Khosroshahi, Ahmad; Hamishehkar, Hamed

    2016-01-01

    Purpose: In the present study the effect of particle size, as a substantial parameters in skin penetration, on the deposition depth and rate of SLNs in different layers of skin was explored. Methods: SLNs in different particle size ranges (80, 333 and 971 nm) made of Precirol as solid lipid were prepared using hot melt homogenization technique and pigmented by Rhodamine B to be able to be tracked in the skin under inspection of fluorescent microscopy. After 0.5 h, 3 h, 6 h and 24 h of SLNs administration on rat skin, animals were sacrificed and exercised skins were sliced by a freeze microtome. SLNs were monitored in the skin structure under fluorescence microscope. Results: The size of SLNs played a crucial role in the penetration to deep skin layers. The sub100 nm size range of SLNs showed the most promising skin penetration rate and depth mainly via hair follicles. Conclusion: The results of the present study indicated that the selection of an appropriate size of particles may be a valuable factor impacting the therapeutic outcomes of dermal drug administration. PMID:27123415

  3. Antidepressant effects of curcumin and HU-211 coencapsulated solid lipid nanoparticles against corticosterone-induced cellular and animal models of major depression

    PubMed Central

    He, Xiaolie; Zhu, Yanjing; Wang, Mei; Jing, Guoxin; Zhu, Rongrong; Wang, Shilong

    2016-01-01

    Major depression is a complex neuropsychiatric disorder with few treatment approaches. The use of nontargeted antidepressants induced many side effects with their low efficacy. A more precise targeting strategy is to develop nanotechnology-based drug delivery systems; hence, we employed solid lipid nanoparticles (SLNs) to encapsulate HU-211 and curcumin (Cur). The antidepressant effects of the dual-drug nanoparticles (Cur/SLNs-HU-211) for major depression treatment were investigated in corticosterone-induced cellular and animal models of major depression. Cur/SLNs-HU-211 can effectively protect PC12 cells from corticosterone-induced apoptosis and can release more dopamine, which may be associated with the higher uptake of Cur/SLNs-HU-211 shown by cellular uptake behavior analysis. Additionally, Cur/SLNs-HU-211 significantly reduced the immobility time in forced swim test, enhanced fall latency in rotarod test, and improved the level of dopamine in mice blood. Cur/SLNs-HU-211 can deliver more Cur to the brain and thus produce a significant increase in neurotransmitters level in brain tissue, especially in the hippocampus and striatum. The results of Western blot and immunofluorescence revealed that Cur/SLNs-HU-211 can significantly enhance the expression of CB1, p-MEK1, and p-ERK1/2. Our study suggests that Cur/SLNs-HU-211 may have great potential for major depression treatment. PMID:27757031

  4. Drug release and skin penetration from solid lipid nanoparticles and a base cream: a systematic approach from a comparison of three glucocorticoids.

    PubMed

    Schlupp, P; Blaschke, T; Kramer, K D; Höltje, H-D; Mehnert, W; Schäfer-Korting, M

    2011-01-01

    Solid lipid nanoparticles (SLNs) can enhance drug penetration into the skin, yet the mechanism of the improved transport is not known in full. To unravel the influence of the drug-particle interaction on penetration enhancement, 3 glucocorticoids (GCs), prednisolone (PD), the diester prednicarbate (PC) and the monoester betamethasone 17-valerate (BMV), varying in structure and lipophilicity, were loaded onto SLNs. Theoretical permeability coefficients (cm/s) of the agents rank BMV (-6.38) ≥ PC (-6.57) > PD (-7.30). GC-particle interaction, drug release and skin penetration were investigated including a conventional oil-in-water cream for reference. Both with SLN and cream, PD release was clearly superior to PC release which exceeded BMV release. With the cream, the rank order did not change when studying skin penetration, and skin penetration is thus predominantly influenced by drug release. Yet, the penetration profile for the GCs loaded onto SLNs completely changed, and differences between the steroids were almost lost. Thus, SLNs influence skin penetration by an intrinsic mechanism linked to a specific interaction of the drug-carrier complex and the skin surface, which becomes possible by the lipid nature and nanosize of the carrier and appears not to be derived by testing drug release. Interestingly, PC and PD uptake from SLN even resulted in epidermal targeting. Thus, SLNs are not only able to improve skin penetration of topically applied drugs, but may also be of particular interest when specifically aiming to influence epidermal dysfunction.

  5. Preservation of anthocyanins in solid lipid nanoparticles: Optimization of a microemulsion dilution method using the Placket-Burman and Box-Behnken designs.

    PubMed

    Ravanfar, Raheleh; Tamaddon, Ali Mohammad; Niakousari, Mehrdad; Moein, Mahmoud Reza

    2016-05-15

    Anthocyanins are the main polyphenol components from red cabbage (Brassica oleracea L. Var. Capitata f. Rubra) extracts that have inherent antioxidant activities. Anthocyanins are effectively stable in acidic gastric digestion conditions, with nearly 100% phenol content recovery. However, the total phenol content recovery after simulated pancreatic digestion was approximately 25%. To protect anthocyanins against harsh environmental conditions (e.g., pH and temperature), solid lipid nanoparticles were prepared by the dilution of water in oil (w/o) microemulsions containing anthocyanins in aqueous media. The formulations were characterized for particle size and encapsulation efficiency. The formulation parameters (e.g., volume of the internal aqueous phase, homogenization time and the percentages of total lipid, total surfactant or stabilizer) were optimized using the Placket-Burman and Box-Behnken experimental designs. Entrapment efficiency (89.2 ± 0.3%) was calculated when the mean particle size was 455 ± 2 nm. A scanning electron microscopy study revealed the spherical morphology of the particles. PMID:26776010

  6. Part I: Development and optimization of solid-lipid nanoparticles using Box-Behnken statistical design for ocular delivery of gatifloxacin.

    PubMed

    Abul Kalam, Mohd; Sultana, Yasmin; Ali, Asgar; Aqil, Mohd; Mishra, Anil K; Aljuffali, Ibrahim A; Alshamsan, Aws

    2013-06-01

    This study aims to improve gatifloxacin bioavailability to the eye using solid-lipid nanoparticles (SLN). Cationic SLNs were prepared by o/w-microemulsion method using stearylamine. The generated formulations were optimized by three-factor, three-level Box-Behnken statistical design. The independent variables were the lipid(mix) concentration (X1), poloxamers-188 (X2), and sodium-taurocholate (X3), while the dependent variables were drug release (Y1), encapsulation efficiency (EE) (Y2), and particle size (Y3 ) with applied constraints of maximizing drug release and EE and minimizing particle size. Response surface plots were drawn, statistical validity of the polynomials was established, optimized formulations were selected by feasibility and grid search, and the optimization process was validated. Particle size, polydispersity index, and zeta-potentials were measured by photon correlation spectroscopy. Particle's morphology was evaluated by transmission electron microscopy. Differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WXRD) studies were performed to characterize state of drug and lipid modification. SLN size was (250-305 nm) and zeta-potential (29-36 mV) after 3-month storage. Entrapment efficiencies were 46.58 and 78.55%, and loading efficiencies were 29.60 and 20.70 for SLN-C and SLN-D, respectively. DSC and WXRD analyses showed low-crystalline SLN and amorphous drug dispersion in SLN. In vitro release data were fitted to release kinetics equations, where the release pattern was found to follow Korsmeyer-Peppas model.

  7. Pearling of lipid vesicles induced by nanoparticles.

    PubMed

    Yu, Yan; Granick, Steve

    2009-10-14

    We show that cationic nanoparticles encapsulated within vesicles of phosphocholine lipid can induce pearling. The dynamic process occurs as two stages: formation of tubular protrusions followed by pearling instability. The breakup into individual vesicles can be controlled by nanoparticle concentration.

  8. Application of Box-Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity.

    PubMed

    Baig, Mirza Salman; Ahad, Abdul; Aslam, Mohammed; Imam, Syed Sarim; Aqil, Mohd; Ali, Asgar

    2016-04-01

    The aim of the present study was to develop and optimize levofloxacin loaded solid lipid nanoparticles for the treatment of conjunctivitis. Box-Behnken experimental design was applied for optimization of solid lipid nanoparticles. The independent variables were stearic acid as lipid (X1), Tween 80 as surfactant (X2) and sodium deoxycholate as co-surfactant (X3) while particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Further in vitro release and antibacterial activity in vitro were also performed. The optimized formulation of levofloxacin provides particle size of 237.82 nm and showed 78.71% entrapment efficiency and achieved flux 0.2,493 μg/cm(2)/h across excised goat cornea. In vitro release study showed prolonged drug release from the optimized formulation following Korsmeyer-Peppas model. Antimicrobial study revealed that the developed formulation possesses antibacterial activity against Staphylococcus aureus, and Escherichia coli equivalent to marketed eye drops. HET-CAM test demonstrated that optimized formulation was found to be non-irritant and safe for topical ophthalmic use. Our results concluded that solid lipid nanoparticles are an efficient carrier for ocular delivery of levofloxacin and other drugs.

  9. pH-Responsive therapeutic solid lipid nanoparticles for reducing P-glycoprotein-mediated drug efflux of multidrug resistant cancer cells.

    PubMed

    Chen, Hsin-Hung; Huang, Wen-Chia; Chiang, Wen-Hsuan; Liu, Te-I; Shen, Ming-Yin; Hsu, Yuan-Hung; Lin, Sung-Chyr; Chiu, Hsin-Cheng

    2015-01-01

    In this study, a novel pH-responsive cholesterol-PEG adduct-coated solid lipid nanoparticles (C-PEG-SLNs) carrying doxorubicin (DOX) capable of overcoming multidrug resistance (MDR) breast cancer cells is presented. The DOX-loaded SLNs have a mean hydrodynamic diameter of ~100 nm and a low polydispersity index (under 0.20) with a high drug-loading efficiency ranging from 80.8% to 90.6%. The in vitro drug release profiles show that the DOX-loaded SLNs exhibit a pH-controlled drug release behavior with the maximum and minimum unloading percentages of 63.4% at pH 4.7 and 25.2% at pH 7.4, respectively. The DOX-loaded C-PEG-SLNs displayed a superior ability in inhibiting the proliferation of MCF-7/MDR cells. At a DOX concentration of 80 μM, the cell viabilities treated with C-PEG-SLNs were approximately one-third of the group treated with free DOX. The inhibition activity of C-PEG-SLNs could be attributed to the transport of C-PEG to cell membrane, leading to the change of the composition of the cell membrane and thus the inhibition of permeability glycoprotein activity. This hypothesis is supported by the confocal images showing the accumulation of DOX in the nuclei of cancer cells and the localization of C-PEG on the cell membranes. The results of in vivo study further demonstrated that the DOX delivered by the SLNs accumulates predominantly in tumor via enhanced permeability and retention effect, the enhanced passive tumor accumulation due to the loose intercellular junctions of endothelial cells lining inside blood vessels at tumor site, and the lack of lymphatic drainage. The growth of MCF-7/MDR xenografted tumor on Balb/c nude mice was inhibited to ~400 mm(3) in volume as compared with the free DOX treatment group, 1,140 mm(3), and the group treated with 1,2 distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] solid lipid nanoparticles, 820 mm(3). Analysis of the body weight of nude mice and the histology of organs and tumor after the

  10. pH-Responsive therapeutic solid lipid nanoparticles for reducing P-glycoprotein-mediated drug efflux of multidrug resistant cancer cells

    PubMed Central

    Chen, Hsin-Hung; Huang, Wen-Chia; Chiang, Wen-Hsuan; Liu, Te-I; Shen, Ming-Yin; Hsu, Yuan-Hung; Lin, Sung-Chyr; Chiu, Hsin-Cheng

    2015-01-01

    In this study, a novel pH-responsive cholesterol-PEG adduct-coated solid lipid nanoparticles (C-PEG-SLNs) carrying doxorubicin (DOX) capable of overcoming multidrug resistance (MDR) breast cancer cells is presented. The DOX-loaded SLNs have a mean hydrodynamic diameter of ~100 nm and a low polydispersity index (under 0.20) with a high drug-loading efficiency ranging from 80.8% to 90.6%. The in vitro drug release profiles show that the DOX-loaded SLNs exhibit a pH-controlled drug release behavior with the maximum and minimum unloading percentages of 63.4% at pH 4.7 and 25.2% at pH 7.4, respectively. The DOX-loaded C-PEG-SLNs displayed a superior ability in inhibiting the proliferation of MCF-7/MDR cells. At a DOX concentration of 80 μM, the cell viabilities treated with C-PEG-SLNs were approximately one-third of the group treated with free DOX. The inhibition activity of C-PEG-SLNs could be attributed to the transport of C-PEG to cell membrane, leading to the change of the composition of the cell membrane and thus the inhibition of permeability glycoprotein activity. This hypothesis is supported by the confocal images showing the accumulation of DOX in the nuclei of cancer cells and the localization of C-PEG on the cell membranes. The results of in vivo study further demonstrated that the DOX delivered by the SLNs accumulates predominantly in tumor via enhanced permeability and retention effect, the enhanced passive tumor accumulation due to the loose intercellular junctions of endothelial cells lining inside blood vessels at tumor site, and the lack of lymphatic drainage. The growth of MCF-7/MDR xenografted tumor on Balb/c nude mice was inhibited to ~400 mm3 in volume as compared with the free DOX treatment group, 1,140 mm3, and the group treated with 1,2 distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] solid lipid nanoparticles, 820 mm3. Analysis of the body weight of nude mice and the histology of organs and tumor after the

  11. pH-Responsive therapeutic solid lipid nanoparticles for reducing P-glycoprotein-mediated drug efflux of multidrug resistant cancer cells.

    PubMed

    Chen, Hsin-Hung; Huang, Wen-Chia; Chiang, Wen-Hsuan; Liu, Te-I; Shen, Ming-Yin; Hsu, Yuan-Hung; Lin, Sung-Chyr; Chiu, Hsin-Cheng

    2015-01-01

    In this study, a novel pH-responsive cholesterol-PEG adduct-coated solid lipid nanoparticles (C-PEG-SLNs) carrying doxorubicin (DOX) capable of overcoming multidrug resistance (MDR) breast cancer cells is presented. The DOX-loaded SLNs have a mean hydrodynamic diameter of ~100 nm and a low polydispersity index (under 0.20) with a high drug-loading efficiency ranging from 80.8% to 90.6%. The in vitro drug release profiles show that the DOX-loaded SLNs exhibit a pH-controlled drug release behavior with the maximum and minimum unloading percentages of 63.4% at pH 4.7 and 25.2% at pH 7.4, respectively. The DOX-loaded C-PEG-SLNs displayed a superior ability in inhibiting the proliferation of MCF-7/MDR cells. At a DOX concentration of 80 μM, the cell viabilities treated with C-PEG-SLNs were approximately one-third of the group treated with free DOX. The inhibition activity of C-PEG-SLNs could be attributed to the transport of C-PEG to cell membrane, leading to the change of the composition of the cell membrane and thus the inhibition of permeability glycoprotein activity. This hypothesis is supported by the confocal images showing the accumulation of DOX in the nuclei of cancer cells and the localization of C-PEG on the cell membranes. The results of in vivo study further demonstrated that the DOX delivered by the SLNs accumulates predominantly in tumor via enhanced permeability and retention effect, the enhanced passive tumor accumulation due to the loose intercellular junctions of endothelial cells lining inside blood vessels at tumor site, and the lack of lymphatic drainage. The growth of MCF-7/MDR xenografted tumor on Balb/c nude mice was inhibited to ~400 mm(3) in volume as compared with the free DOX treatment group, 1,140 mm(3), and the group treated with 1,2 distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] solid lipid nanoparticles, 820 mm(3). Analysis of the body weight of nude mice and the histology of organs and tumor after the

  12. Immunostimulatory Lipid Nanoparticles from Herbal Medicine

    PubMed Central

    Hasson, Tal H.; Takaoka, Anna; de la Rica, Roberto; Matsui, Hiroshi; Smeureanu, Gabriela; Drain, Charles M.; Kawamura, Akira

    2014-01-01

    Reproducibility is an important issue in biological characterization of drug candidates and natural products. It is not uncommon to encounter cases in which supposedly the same sample exhibits very different biological activities. During our characterization of macrophage-stimulatory lipids from herbal medicine, it was found that the potency of these lipids could vary substantially from experiment to experiment. Further analysis of this reproducibility issue led to the discovery of solvent-dependent nanoparticle formation by these lipids. While larger nanoparticles (approximately 100 nm) of these lipids showed modest macrophage-stimulatory activity, smaller nanoparticles (<10 nm) of the same lipids exhibited substantially higher potency. Thus, the study revealed an unexpected link between nanoparticle formation and macrophage-stimulatory activity of plant lipids. Although nanoparticles have been extensively studied in the context of vehicles for drug delivery, our finding indicates that drugs themselves can form nanoassemblies, and their biological properties may be altered by the way they assemble. PMID:24495243

  13. Novel dual-reverse thermosensitive solid lipid nanoparticle-loaded hydrogel for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect.

    PubMed

    Din, Fakhar Ud; Mustapha, Omer; Kim, Dong Wuk; Rashid, Rehmana; Park, Jong Hyuck; Choi, Ju Yeon; Ku, Sae Kwang; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

    2015-08-01

    The purpose of this study was to develop novel solid lipid nanoparticle (SLN)-loaded dual-reverse thermosensitive hydrogel (DRTH) for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect. The flurbiprofen-loaded SLNs were prepared by hot homogenisation technique, after optimising the amounts of lipid mixture (tricaprin and triethanolamine in 8:2 weight ratio), drug and surfactant. The flurbiprofen-loaded thermosensitive SLN composed of drug, lipid mixture and surfactant at a weight ratio of 10/15/1.3 was a solid at room temperature, and changed to liquid form at physiological temperature due to its melting point of about 32°C. This SLN gave the mean particle size of about 190nm and entrapment efficiency of around 90%. The DRTHs were prepared by adding this flurbiprofen-loaded thermosensitive SLN in various poloxamer solutions. Their rheological characterisation, release and stability were investigated while a morphological and pharmacokinetic study was performed after its rectal administration to rats compared with the drug and hydrogel. Poloxamer 188 and SLN decreased the gelation temperature and gelation time, but increased the viscosity at 25°C, gel strength and mucoadhesive force of DRTHs. In particular, the DRTH composed of [SLN/P 407/P 188 (10%/15%/25%)] with the gelation temperature of about 35°C existed as liquid at room temperature, but gelled at 30-36°C, leading to opposite reversible property of SLN. Thus, it was easy to administer rectally, and it gelled rapidly inside the body. This DRTH gave a significantly increased dissolution rate of the drug as compared to the flurbiprofen, but significantly retarded as compared to the hydrogel, including the initial dissolution rate. Moreover, this DRTH gave significantly higher plasma concentration and 7.5-fold AUC values compared to the drug, and lower initial plasma concentration and Cmax value compared to the hydrogel due to reduced initial burst effect. No

  14. Novel dual-reverse thermosensitive solid lipid nanoparticle-loaded hydrogel for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect.

    PubMed

    Din, Fakhar Ud; Mustapha, Omer; Kim, Dong Wuk; Rashid, Rehmana; Park, Jong Hyuck; Choi, Ju Yeon; Ku, Sae Kwang; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

    2015-08-01

    The purpose of this study was to develop novel solid lipid nanoparticle (SLN)-loaded dual-reverse thermosensitive hydrogel (DRTH) for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect. The flurbiprofen-loaded SLNs were prepared by hot homogenisation technique, after optimising the amounts of lipid mixture (tricaprin and triethanolamine in 8:2 weight ratio), drug and surfactant. The flurbiprofen-loaded thermosensitive SLN composed of drug, lipid mixture and surfactant at a weight ratio of 10/15/1.3 was a solid at room temperature, and changed to liquid form at physiological temperature due to its melting point of about 32°C. This SLN gave the mean particle size of about 190nm and entrapment efficiency of around 90%. The DRTHs were prepared by adding this flurbiprofen-loaded thermosensitive SLN in various poloxamer solutions. Their rheological characterisation, release and stability were investigated while a morphological and pharmacokinetic study was performed after its rectal administration to rats compared with the drug and hydrogel. Poloxamer 188 and SLN decreased the gelation temperature and gelation time, but increased the viscosity at 25°C, gel strength and mucoadhesive force of DRTHs. In particular, the DRTH composed of [SLN/P 407/P 188 (10%/15%/25%)] with the gelation temperature of about 35°C existed as liquid at room temperature, but gelled at 30-36°C, leading to opposite reversible property of SLN. Thus, it was easy to administer rectally, and it gelled rapidly inside the body. This DRTH gave a significantly increased dissolution rate of the drug as compared to the flurbiprofen, but significantly retarded as compared to the hydrogel, including the initial dissolution rate. Moreover, this DRTH gave significantly higher plasma concentration and 7.5-fold AUC values compared to the drug, and lower initial plasma concentration and Cmax value compared to the hydrogel due to reduced initial burst effect. No

  15. In vitro antitumor efficacy of berberine: solid lipid nanoparticles against human HepG2, Huh7 and EC9706 cancer cell lines

    NASA Astrophysics Data System (ADS)

    Meng, Xiang-Ping; Wang, Xiao; Wang, Huai-ling; Chen, Tong-sheng; Wang, Yi-fei; Wang, Zhi-ping

    2016-03-01

    Hepatocarcinoma and esophageal squamous cell carcinomas threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma and esophageal carcinoma to chemotherapy. Berberine (Ber), an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma and antiesophageal carcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Ber loaded solid lipid nanoparticles (Ber-SLN) was prepared by hot melting and then high pressure homogenization technique. The in vitro anti-hepatocarcinoma and antiesophageal carcinoma effects of Ber-SLN relative to efficacy of bulk Ber were evaluated. The particle size and zeta potential of Ber-SLN were 154.3 ± 4.1 nm and -11.7 ± 1.8 mV, respectively. MTT assay showed that Ber-SLN effectively inhibited the proliferation of human HepG2 and Huh7 and EC9706 cells, and the corresponding IC50 value was 10.6 μg/ml, 5.1 μg/ml, and 7.3 μg/ml (18.3μg/ml, 6.5μg/ml, and 12.4μg/ml μg/ml of bulk Ber solution), respectively. These results suggest that the delivery of Ber-SLN is a promising approach for treating tumors.

  16. A retinyl palmitate-loaded solid lipid nanoparticle system: effect of surface modification with dicetyl phosphate on skin permeation in vitro and anti-wrinkle effect in vivo.

    PubMed

    Jeon, Ho Seong; Seo, Jo Eun; Kim, Min Soo; Kang, Mean Hyung; Oh, Dong Ho; Jeon, Sang Ok; Seong Hoon Jeong; Choi, Young Wook; Lee, Sangkil

    2013-08-16

    Surface-modified solid lipid nanoparticles (SLNs) containing retinyl palmitate (Rpal) were prepared by the hot-melt method using Gelucire 50/13(®) and Precirol ATO5(®). Dicetyl phosphate (DCP) was added to negatively charge the surfaces of the SLNs and thereby enhance the skin distribution properties of Rpal. In vitro skin permeation and in vivo anti-aging studies were performed using SLNs dispersed in a hydrogel. The SLNs were under 100 nm in size with an even polydispersity index (PDI), and the high absolute zeta-potential value was sufficient to maintain the colloidal stability of the SLNs. DCP-modified negative SLNs (DCPmod-SLNs) enhanced the skin distribution of Rpal 4.8-fold and delivered Rpal to a greater depth than did neutral SLNs. The in vivo anti-wrinkle effect of the DCPmod-SLN formulation was Rpal dose-dependent. However, the anti-wrinkle effects of the DCPmod-SLN formulations were significantly different from that of the negative control and effectively prevented the reduction of elastin and superoxide dismutase by UV irradiation. In conclusion, the DCPmod-SLN system presented is a good candidate for topical Rpal delivery. PMID:23702002

  17. Enhanced delivery of etoposide across the blood-brain barrier to restrain brain tumor growth using melanotransferrin antibody- and tamoxifen-conjugated solid lipid nanoparticles.

    PubMed

    Kuo, Yung-Chih; Wang, I-Hsin

    2016-08-01

    Melanotransferrin antibody (MA) and tamoxifen (TX) were conjugated on etoposide (ETP)-entrapped solid lipid nanoparticles (ETP-SLNs) to target the blood-brain barrier (BBB) and glioblastom multiforme (GBM). MA- and TX-conjugated ETP-SLNs (MA-TX-ETP-SLNs) were used to infiltrate the BBB comprising a monolayer of human astrocyte-regulated human brain-microvascular endothelial cells (HBMECs) and to restrain the proliferation of malignant U87MG cells. TX-grafted ETP-SLNs (TX-ETP-SLNs) significantly enhanced the BBB permeability coefficient for ETP and raised the fluorescent intensity of calcein-AM when compared with ETP-SLNs. In addition, surface MA could increase the BBB permeability coefficient for ETP about twofold. The viability of HBMECs was higher than 86%, suggesting a high biocompatibility of MA-TX-ETP-SLNs. Moreover, the efficiency in antiproliferation against U87MG cells was in the order of MA-TX-ETP-SLNs  >  TX-ETP-SLNs  >  ETP-SLNs  >  SLNs. The capability of MA-TX-ETP-SLNs to target HBMECs and U87MG cells during internalization was verified by immunochemical staining of expressed melanotransferrin. MA-TX-ETP-SLNs can be a potent pharmacotherapy to deliver ETP across the BBB to GBM. PMID:26768307

  18. A retinyl palmitate-loaded solid lipid nanoparticle system: effect of surface modification with dicetyl phosphate on skin permeation in vitro and anti-wrinkle effect in vivo.

    PubMed

    Jeon, Ho Seong; Seo, Jo Eun; Kim, Min Soo; Kang, Mean Hyung; Oh, Dong Ho; Jeon, Sang Ok; Seong Hoon Jeong; Choi, Young Wook; Lee, Sangkil

    2013-08-16

    Surface-modified solid lipid nanoparticles (SLNs) containing retinyl palmitate (Rpal) were prepared by the hot-melt method using Gelucire 50/13(®) and Precirol ATO5(®). Dicetyl phosphate (DCP) was added to negatively charge the surfaces of the SLNs and thereby enhance the skin distribution properties of Rpal. In vitro skin permeation and in vivo anti-aging studies were performed using SLNs dispersed in a hydrogel. The SLNs were under 100 nm in size with an even polydispersity index (PDI), and the high absolute zeta-potential value was sufficient to maintain the colloidal stability of the SLNs. DCP-modified negative SLNs (DCPmod-SLNs) enhanced the skin distribution of Rpal 4.8-fold and delivered Rpal to a greater depth than did neutral SLNs. The in vivo anti-wrinkle effect of the DCPmod-SLN formulation was Rpal dose-dependent. However, the anti-wrinkle effects of the DCPmod-SLN formulations were significantly different from that of the negative control and effectively prevented the reduction of elastin and superoxide dismutase by UV irradiation. In conclusion, the DCPmod-SLN system presented is a good candidate for topical Rpal delivery.

  19. Cellular uptake of beta-carotene from protein stabilized solid lipid nano-particles prepared by homogenization-evaporation method

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Using a homogenization-evaporation method, beta-carotene (BC) loaded nano-particles were prepared with different ratios of food-grade sodium caseinate (SC), whey protein isolate (WPI), or soy protein isolate (SPI) to BC and evaluated for their physiochemical stability, in vitro cytotoxicity, and cel...

  20. Polystyrene Nanoparticles Perturb Lipid Membranes.

    PubMed

    Rossi, Giulia; Barnoud, Jonathan; Monticelli, Luca

    2014-01-01

    Polystyrene is abundant in marine debris. Like most synthetic polymers, it degrades very slowly, producing smaller and smaller particles easily ingested by wildlife. The presence of plastic microscopic particles in fish and marine wildlife is massive and well documented, but its impact on cellular activity is not understood. Biological activity generally requires interaction with biological membranes, but this is difficult to study at the molecular scale in vivo. Here we use coarse-grained molecular simulations to determine the effect of nanosized polystyrene (PS) particles on the properties of model biological membranes. We find that PS nanoparticles permeate easily into lipid membranes. Dissolved in the membrane core, PS chains alter membrane structure, significantly reduce molecular diffusion, and soften the membrane. Moreover, PS severely affects membrane lateral organization by stabilizing raft-like domains. Changes in membrane properties and lateral organization can severely affect the activity of membrane proteins and thereby cellular function.

  1. Lamellar crystalline self-assembly behaviour and solid lipid nanoparticles of a palmityl prodrug analogue of Capecitabine—A chemotherapy agent

    SciTech Connect

    Gong, Xiaojuan; Moghaddam, Minoo J.; Sagnella, Sharon M.; Conn, Charlotte E.; Danon, Stephen J.; Waddington, Lynne J.; Drummond, Calum J.

    2014-09-24

    An amphiphile prodrug, 5'-deoxy-5-fluoro-N4-(palmityloxycarbonyl) cytidine or 5'-deoxy-5-fluoro-N4-(hexadecanaloxycarbonyl) cytidine (5-FCPal), consisting of the same head group as the commercially available chemotherapeutic agent Capecitabine, linked to a palmityl hydrocarbon chain via a carbamate bond is reported. Thermal analysis of this prodrug indicates that it melts at ~115 °C followed quickly by degradation beginning at ~120 °C. The neat solid 5-FCPal amphiphile acquires a lamellar crystalline arrangement with a d-spacing of 28.6 ± 0.3 Å, indicating interdigitation of the hydrocarbon chains. Under aqueous conditions, solid 5-FCPal is non-swelling and no lyotropic liquid crystalline phase formation is observed. In order to assess the in vitro toxicity and in vivo efficacy in colloidal form, solid lipid nanoparticles (SLNs) with an average size of ~700 nm were produced via high pressure homogenization. The in vitro toxicity of the 5-FCPal SLNs against several different cancer and normal cell types was assessed over a 48 h period, and IC50 values were comparable to those observed for Capecitabine. The in vivo efficacy of the 5-FCPal SLNs was then assessed against the highly aggressive mouse 4T1 breast cancer model. To do so, the prodrug SLNs were administered orally at 3 different dosages (0.1, 0.25, 0.5 mmol/mouse/day) and compared to Capecitabine delivered at the same dosages. After 21 days of receiving the treatments, the 0.5 mmol dose of 5-FCPal exhibited the smallest average tumour volume. Since 5-FCPal is activated in a similar manner to Capecitabine via a 3 step enzymatic pathway with the final step occurring preferentially at the tumour site, formulation of the prodrug into SLNs combines the advantage of selective, localized activation with the sustained release properties of nanostructured amphiphile self-assembly and multiple payload materials thereby potentially creating a more effective anticancer agent.

  2. Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice.

    PubMed

    Thakkar, Arvind; Chenreddy, Sushma; Thio, Astrid; Khamas, Wael; Wang, Jeffrey; Prabhu, Sunil

    2016-01-01

    Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer. PMID:27499621

  3. Sodium alginate-cross-linked polymyxin B sulphate-loaded solid lipid nanoparticles: Antibiotic resistance tests and HaCat and NIH/3T3 cell viability studies.

    PubMed

    Severino, Patrícia; Chaud, Marco V; Shimojo, Andrea; Antonini, Danilo; Lancelloti, Marcelo; Santana, Maria Helena A; Souto, Eliana B

    2015-05-01

    Polymyxins are a group of antibiotics with a common structure of a cyclic peptide with a long hydrophobic tail. Polymyxin B sulphate (PLX) has cationic charge, which is an obstacle for the efficient loading into Solid Lipid Nanoparticles (SLN). In the present paper, we describe an innovative method to load PLX into SLN to achieve the sustained release of the drug. PLX was firstly cross-linked with sodium alginate (SA) at different ratios (1:1, 1:2 and 1:3 SA/PLX), and loaded into SLN produced by high pressure homogenization (HPH). Optimized SLN were produced applying 500bar pressure and 5 homogenization cycles. The best results were obtained with SA/PLX (1:1), recording 99.08±1.2% for the association efficiency of the drug with SA, 0.99±10g for the loading capacity and 212.07±5.84% degree of swelling. The rheological profile of aqueous SA solution followed the typical behaviour of concentrated polymeric solutions, whereas aqueous SA/PLX solution exhibited a gel-like dynamic behaviour. Micrographs show that SA/PLX depicted a porous and discontinuous amorphous phase in different ratios. The encapsulation efficiency of SA/PLX (1:1) in SLN, the mean particle diameter, polydispersity index and zeta potential were, respectively, 82.7±5.5%; 439.5±20.42nm, 0.241±0.050 and -34.8±0.55mV. The effect of SLN on cell viability was checked in HaCat and NIH/3T3 cell lines, and the minimal inhibitory concentrations (MIC) were determined in Pseudomonas aeruginosa strains. SA/PLX-loaded SLN were shown to be less toxic than free PLX. Minimal inhibitory concentrations (MIC) showed the presence of the cross-linker polymer-drug complex, and SLN were shown to enhance MIC in the evaluated strains.

  4. Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice

    PubMed Central

    Thakkar, Arvind; Chenreddy, Sushma; Thio, Astrid; Khamas, Wael; Wang, Jeffrey; Prabhu, Sunil

    2016-01-01

    Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer. PMID:27499621

  5. Optimization of process variables of zanamivir-loaded solid lipid nanoparticles and the prediction of their cellular transport in Caco-2 cell model.

    PubMed

    Shi, Li-Li; Cao, Yue; Zhu, Xiao-Yin; Cui, Jing-Hao; Cao, Qing-Ri

    2015-01-15

    The aim of this study was to optimize the process variables of zanamivir-loaded solid lipid nanoparticles (SLNs) and to predict their cellular transport across Caco-2 cell monolayers. Zanamivir-loaded SLNs were prepared by a double emulsion solvent evaporation method. The effects of process variables on the mean particle size and zeta potential of SLNs were investigated and the physicochemical properties of SLNs were characterized. In addition, the cytotoxicity and transport ability of SLNs were also studied in Caco-2 cell model. The mean particle size of drug-loaded SLNs was significantly affected by the process variables. The SLNs were prepared using glyceryl monosterate (1% polyvinyl alcohol (PVA) or 1.5% poloxamer 188 as surfactant) had a regular shape with a relatively lower mean particle size (324.2 and 224.9 nm, respectively), higher encapsulation efficacy (55.7 and 42.4%, respectively) and sustained drug release over 12h. The crystalline form of drug had been partly changed and no physicochemical interaction had occurred between drug and carriers in SLNs. The cell viability was approximately 100% even at a high concentration of blank SLNs. There was no remarkable difference in drug permeation between drug-loaded SLNs and drug solution at 2h, while drug-loaded SLNs showed a significant decrease in drug permeation compared with the drug solution at 4h. The process variables of zanamivir-loaded SLNs were successfully optimized in this study. However, these SLNs significantly reduced the transport ability of zanamivir across Caco-2 cell monolayers. Further studies are needed to fully understand the real absorption mechanism of developed SLNs.

  6. [Cytological Study in vitro on Co-delivery of siRNA and Paclitaxel within Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Tumors].

    PubMed

    Huang, Rui; Yao, Xinyu; Chen, Yuan; Sun, Xun; Lin, Yunzhu

    2016-02-01

    Multidrug resistance (MDR) remains the major obstacle to the success of clinical cancer chemotherapy. P-glycoprotein (P-gp), encoded by the MDR1, is an important part with complex mechanisms associated with the MDR. In order to overcome the MDR of tumors, we in the present experimental design incorporated small interfering RNA (siRNA) targeting MDR1 gene and anticancer drug paclitaxel (PTX) into the solid lipid nanoparticles (SLNs) to achieve the combinational therapeutic effects of genetherapy and chemotherapy. In this study, siRNA-PTX-SLNs were successfully prepared. The cytotoxicity of blank SLNs and siRNA-PTX-SLNs in MCF-7 cells and MCF-7/ADR cells were detected by MTT; and the uptake efficiency of PTX in MCF-7/ADR cells were detected via HPLC method; quantitative real-time PCR and flow cytometry were performed to investigate the silencing effect of siRNA-PTX- SLNs on MDR1 gene in MCF-7/ADR cells. The results showed that PTX loaded SLNs could significantly inhibit the growth of tumor cells, and more importantly, the MDR tumor cells treated with siRNA-PTX-SLNs showed the lowest viability. HPLC study showed that SLNs could enhance the cellular uptake for PTX. Meanwhile, siRNA delivered by SLNs significantly decreased the P-gp expression in MDR tumor cells, thus increased the cellular accumulation of rhodamine123 as a P-gp substrate. In conclusion, the MDR1 gene could be silenced by siRNA-PTX-SLNs, which could promote the growth inhibition efficiency of PTX on tumor cells, leading to synergetic effect on MDR tumor therapy. PMID:27382749

  7. Methazolamide-loaded solid lipid nanoparticles modified with low-molecular weight chitosan for the treatment of glaucoma: vitro and vivo study.

    PubMed

    Wang, Fengzhen; Chen, Li; Zhang, Dongsheng; Jiang, Sunmin; Shi, Kun; Huang, Yuan; Li, Rui; Xu, Qunwei

    2014-11-01

    The aims of this study were to design and characterize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLN) with and without modification of low molecular weight chitosan (CS) and compare their potentials for ocular drug delivery. Low molecular weight CS was obtained via a modified chemical oxidative degradation method. SLN with CS (CS-SLN-MTZ) and without CS (SLN-MTZ) were prepared according to a modified emulsion-solvent evaporation method. SLN-MTZ and CS-SLN-MTZ were 199.4 ± 2.8 nm and 252.8 ± 4.0 nm in particle size, -21.3 ± 1.9 mV and +31.3 ± 1.7 mV in zeta potential, respectively. Physical stability studies demonstrated that CS-SLN-MTZ remained stable for at least 4 months at 4 °C, while SLN-MTZ no more than 2 months. A prolonged in vitro release profile of MTZ from CS-SLN-MTZ was obtained compared with SLN-MTZ. Furthermore, CS-SLN-MTZ presented a better permeation property in excised rabbit cornea. In vivo studies indicated that the intraocular pressure lowering effect of CS-SLN-MTZ (245.75 ± 18.31 mmHg × h) was significantly better than both SLN-MTZ (126.74 ± 17.73 mmHg × h) and commercial product Brinzolamide Eye Drops AZOPT® (171.17 ± 16.45 mmHg × h). The maximum percentage decrease in IOP of CS-SLN-MTZ (42.78 ± 7.71%) was higher than SLN-MTZ (27.82 ± 4.15%) and was comparable to AZOPT (38.06 ± 1.25%). CS-SLN-MTZ showed no sign of ocular irritancy according to the Draize method and the histological examination.

  8. Nanoparticle-lipid bilayer interactions studied with lipid bilayer arrays.

    PubMed

    Lu, Bin; Smith, Tyler; Schmidt, Jacob J

    2015-05-01

    The widespread environmental presence and commercial use of nanoparticles have raised significant health concerns as a result of many in vitro and in vivo assays indicating toxicity of a wide range of nanoparticle species. Many of these assays have identified the ability of nanoparticles to damage cell membranes. These interactions can be studied in detail using artificial lipid bilayers, which can provide insight into the nature of the particle-membrane interaction through variation of membrane and solution properties not possible with cell-based assays. However, the scope of these studies can be limited because of the low throughput characteristic of lipid bilayer platforms. We have recently described an easy to use, parallel lipid bilayer platform which we have used to electrically investigate the activity of 60 nm diameter amine and carboxyl modified polystyrene nanoparticles (NH2-NP and COOH-NP) with over 1000 lipid bilayers while varying lipid composition, bilayer charge, ionic strength, pH, voltage, serum, particle concentration, and particle charge. Our results confirm recent studies finding activity of NH2-NP but not COOH-NP. Detailed analysis shows that NH2-NP formed pores 0.3-2.3 nm in radius, dependent on bilayer and solution composition. These interactions appear to be electrostatic, as they are regulated by NH2-NP surface charge, solution ionic strength, and bilayer charge. The ability to rapidly measure a large number of nanoparticle and membrane parameters indicates strong potential of this bilayer array platform for additional nanoparticle bilayer studies.

  9. Antibiotic-free nanotherapeutics: ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors.

    PubMed

    Nafee, Noha; Husari, Ayman; Maurer, Christine K; Lu, Cenbin; de Rossi, Chiara; Steinbach, Anke; Hartmann, Rolf W; Lehr, Claus-Michael; Schneider, Marc

    2014-10-28

    Cystic fibrosis (CF) is a genetic disease mainly manifested in the respiratory tract. Pseudomonas aeruginosa (P. aeruginosa) is the most common pathogen identified in cultures of the CF airways, however, its eradication with antibiotics remains challenging as it grows in biofilms that counterwork human immune response and dramatically decrease susceptibility to antibiotics. P. aeruginosa regulates pathogenicity via a cell-to-cell communication system known as quorum sensing (QS) involving the virulence factor (pyocyanin), thus representing an attractive target for coping with bacterial pathogenicity. The first in vivo potent QS inhibitor (QSI) was recently developed. Nevertheless, its lipophilic nature might hamper its penetration of non-cellular barriers such as mucus and bacterial biofilms, which limits its biomedical application. Successful anti-infective inhalation therapy necessitates proper design of a biodegradable nanocarrier allowing: 1) high loading and prolonged release, 2) mucus penetration, 3) effective pulmonary delivery, and 4) maintenance of the anti-virulence activity of the QSI. In this context, various pharmaceutical lipids were used to prepare ultra-small solid lipid nanoparticles (us-SLNs) by hot melt homogenization. Plain and QSI-loaded SLNs were characterized in terms of colloidal properties, drug loading, in vitro release and acute toxicity on Calu-3 cells. Mucus penetration was studied using a newly-developed confocal microscopy technique based on 3D-time-lapse imaging. For pulmonary application, nebulization efficiency of SLNs and lung deposition using next generation impactor (NGI) were performed. The anti-virulence efficacy was investigated by pyocyanin formation in P. aeruginosa cultures. Ultra-small SLNs (<100nm diameter) provided high encapsulation efficiency (68-95%) according to SLN composition, high burst in phosphate buffer saline compared to prolonged release of the payload over >8h in simulated lung fluid with minor burst. All

  10. Curcuminoids-loaded lipid nanoparticles: novel approach towards malaria treatment.

    PubMed

    Nayak, Aditya P; Tiyaboonchai, Waree; Patankar, Swati; Madhusudhan, Basavaraj; Souto, Eliana B

    2010-11-01

    In the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. For the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy (SEM) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta potential of the particles ranged between -28 and -45 mV depending on the nature of the lipid matrix produced, which also influenced the entrapment efficiency (EE) and drug loading capacity (LC) found to be in the range of 80-94% and 1.62-3.27%, respectively. The LC increased reciprocally on increasing the amount of MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses revealed that increasing imperfections within the lipid matrix allowed for increasing encapsulation parameters. Nanoparticles were further sterilized by filtration process which was found to be superior over autoclaving in preventing thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic activity revealed 2-fold increase in antimalarial activity of curcuminoids entrapped in lipid nanoparticles when compared to free curcuminoids at the tested dosage level.

  11. Nanoparticles: Neither solid nor liquid

    NASA Astrophysics Data System (ADS)

    Aguado, Andrés

    2016-09-01

    Nanoparticles of gallium deposited on a sapphire substrate, which are now shown to remain stable in a state of solid/liquid coexistence across a temperature window wider than 600 K, may prove useful for studying the properties of solid/liquid interfaces and in plasmonic or catalytic applications.

  12. Lipid-based colloidal carriers for peptide and protein delivery – liposomes versus lipid nanoparticles

    PubMed Central

    Martins, Susana; Sarmento, Bruno; Ferreira, Domingos C; Souto, Eliana B

    2007-01-01

    This paper highlights the importance of lipid-based colloidal carriers and their pharmaceutical implications in the delivery of peptides and proteins for oral and parenteral administration. There are several examples of biomacromolecules used nowadays in the therapeutics, which are promising candidates to be delivered by means of liposomes and lipid nanoparticles, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). Several production procedures can be applied to achieve a high association efficiency between the bioactives and the carrier, depending on the physicochemical properties of both, as well as on the production procedure applied. Generally, this can lead to improved bioavailability, or in case of oral administration a more consistent temporal profile of absorption from the gastrointestinal tract. Advantages and drawbacks of such colloidal carriers are also pointed out. This article describes strategies used for formulation of peptides and proteins, methods used for assessment of association efficiency and practical considerations regarding the toxicological concerns. PMID:18203427

  13. Lipid-based colloidal carriers for peptide and protein delivery--liposomes versus lipid nanoparticles.

    PubMed

    Martins, Susana; Sarmento, Bruno; Ferreira, Domingos C; Souto, Eliana B

    2007-01-01

    This paper highlights the importance of lipid-based colloidal carriers and their pharmaceutical implications in the delivery of peptides and proteins for oral and parenteral administration. There are several examples of biomacromolecules used nowadays in the therapeutics, which are promising candidates to be delivered by means of liposomes and lipid nanoparticles, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). Several production procedures can be applied to achieve a high association efficiency between the bioactives and the carrier, depending on the physicochemical properties of both, as well as on the production procedure applied. Generally, this can lead to improved bioavailability, or in case of oral administration a more consistent temporal profile of absorption from the gastrointestinal tract. Advantages and drawbacks of such colloidal carriers are also pointed out. This article describes strategies used for formulation of peptides and proteins, methods used for assessment of association efficiency and practical considerations regarding the toxicological concerns. PMID:18203427

  14. Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery

    PubMed Central

    Fang, Yi-Ping; Wu, Pao-Chu; Huang, Yaw-Bin; Tzeng, Cherng-Chyi; Chen, Yeh-Long; Hung, Yu-Han; Tsai, Ming-Jun; Tsai, Yi-Hung

    2012-01-01

    Background The synthetic potential chemotherapeutic agent 3-Chloro-4-[(4-methoxyphenyl) amino]furo[2,3-b]quinoline (PK-L4) is an analog of amsacrine. The half-life of PK-L4 is longer than that of amsacrine; however, PK-L4 is difficult to dissolve in aqueous media, which is problematic for administration by intravenous injection. Aims To utilize solid lipid nanoparticles (SLNs) modified with polyethylene glycol (PEG) to improve the delivery of PK-L4 and investigate its biodistribution behavior after intravenous administration. Results The particle size of the PK-L4-loaded SLNs was 47.3 nm and the size of the PEGylated form was smaller, at 28 nm. The entrapment efficiency (EE%) of PK-L4 in SLNs with and without PEG showed a high capacity of approximately 100% encapsulation. Results also showed that the amount of PK-L4 released over a prolonged period from SLNs both with and without PEG was comparable to the non-formulated group, with 16.48% and 30.04%, respectively, of the drug being released, which fit a zero-order equation. The half-maximal inhibitory concentration values of PK-L4-loaded SLNs with and those without PEG were significantly reduced by 45%–64% in the human lung carcinoma cell line (A549), 99% in the human breast adenocarcinoma cell line with estrogen receptor (MCF7), and 95% in the human breast adenocarcinoma cell line (MDA-MB-231). The amount of PK-L4 released by SLNs with PEG was significantly higher than that from the PK-L4 solution (P < 0.05). After intravenous bolus of the PK-L4-loaded SLNs with PEG, there was a marked significant difference in half-life alpha (0.136 ± 0.046 hours) when compared with the PK-L4 solution (0.078 ± 0.023 hours); also the area under the curve from zero to infinity did not change in plasma when compared to the PK-L4 solution. This demonstrated that PK-L4-loaded SLNs were rapidly distributed from central areas to tissues and exhibited higher accumulation in specific organs. The highest deposition of PK-L4-loaded SLNs

  15. Nanoparticle-lipid bilayer interactions studied with lipid bilayer arrays

    NASA Astrophysics Data System (ADS)

    Lu, Bin; Smith, Tyler; Schmidt, Jacob J.

    2015-04-01

    The widespread environmental presence and commercial use of nanoparticles have raised significant health concerns as a result of many in vitro and in vivo assays indicating toxicity of a wide range of nanoparticle species. Many of these assays have identified the ability of nanoparticles to damage cell membranes. These interactions can be studied in detail using artificial lipid bilayers, which can provide insight into the nature of the particle-membrane interaction through variation of membrane and solution properties not possible with cell-based assays. However, the scope of these studies can be limited because of the low throughput characteristic of lipid bilayer platforms. We have recently described an easy to use, parallel lipid bilayer platform which we have used to electrically investigate the activity of 60 nm diameter amine and carboxyl modified polystyrene nanoparticles (NH2-NP and COOH-NP) with over 1000 lipid bilayers while varying lipid composition, bilayer charge, ionic strength, pH, voltage, serum, particle concentration, and particle charge. Our results confirm recent studies finding activity of NH2-NP but not COOH-NP. Detailed analysis shows that NH2-NP formed pores 0.3-2.3 nm in radius, dependent on bilayer and solution composition. These interactions appear to be electrostatic, as they are regulated by NH2-NP surface charge, solution ionic strength, and bilayer charge. The ability to rapidly measure a large number of nanoparticle and membrane parameters indicates strong potential of this bilayer array platform for additional nanoparticle bilayer studies.The widespread environmental presence and commercial use of nanoparticles have raised significant health concerns as a result of many in vitro and in vivo assays indicating toxicity of a wide range of nanoparticle species. Many of these assays have identified the ability of nanoparticles to damage cell membranes. These interactions can be studied in detail using artificial lipid bilayers, which

  16. Intravenous administration to rabbits of non-stealth and stealth doxorubicin-loaded solid lipid nanoparticles at increasing concentrations of stealth agent: pharmacokinetics and distribution of doxorubicin in brain and other tissues.

    PubMed

    Zara, Gian Paolo; Cavalli, Roberta; Bargoni, Alessandro; Fundarò, Anna; Vighetto, Daniela; Gasco, Maria Rosa

    2002-06-01

    The pharmacokinetics and tissue distribution of doxorubicin incorporated in non-stealth solid lipid nanoparticles (SLN) and in stealth solid lipid nanoparticles (SSLN) (three formulations at increasing concentrations of stearic acid-PEG 2000 as stealth agent) after intravenous administration to conscious rabbits have been studied. The control was the commercial doxorubicin solution. The experiments lasted 6 h and blood samples were collected at fixed times after the injections. In all samples, the concentration of doxorubicin and doxorubicinol were determined. Doxorubicin AUC increased as a function of the amount of stealth agent present in the SLN. Doxorubicin was still present in the blood 6 h after the injection of SLN or SSLN, while no doxorubicin was detectable after the i.v. injection of doxorubicin solution. Tissue distribution of doxorubicin was determined 30 min, 2 and 6 h after the administration of the five formulations. Doxorubicin was present in the brain only after the SLN administration. The increase in the stealth agent affected the doxorubicin transported into the brain; 6 h after injection, doxorubicin was detectable in the brain only with the SSLN at the highest amount of stealth agent. In the other rabbit tissues (liver, lungs, spleeen, heart and kidneys) the amount of doxorubicin present was always lower after the injection of any of the four types of SLN than after the commercial solution. In particular, all SLN formulations significantly decreased heart and liver concentrations of doxorubicin.

  17. Iontophoretic delivery of lipophilic and hydrophilic drugs from lipid nanoparticles across human skin.

    PubMed

    Charoenputtakun, Ponwanit; Li, S Kevin; Ngawhirunpat, Tanansait

    2015-11-10

    The combined effects of iontophoresis and lipid nanoparticles on drug delivery across human epidermal membrane (HEM) were investigated. The delivery of lipophilic and hydrophilic drugs, all trans-retinoic acid (ATRA), salicylate (SA), and acyclovir (ACV), across HEM from lipid nanoparticles, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), was compared in passive and iontophoresis experiments in vitro. Iontophoresis experiments were also performed with synthetic Nuclepore membrane for comparison. Drug distribution in the skin after iontophoretic delivery with the lipid nanoparticles was examined using a model probe rhodamine B base (RhoB). The drug-loaded lipid nanoparticles had average sizes of ∼ 118-169 nm and a negative zeta potential. Iontophoresis did not enhance the delivery of ATRA across HEM from SLN and NLC. However, HEM distribution study of RhoB suggested that lipophilic drugs could be delivered into the deeper layer of the skin following iontophoretic delivery of the drugs from the lipid nanoparticles. Iontophoresis enhanced the delivery of hydrophilic drug SA with the lipid nanoparticles. Similarly, iontophoresis enhanced the delivery of ACV when it was loaded in SLN. These results suggest that lipid nanoparticles are a promising drug delivery method that can be combined with iontophoresis to improve skin delivery of hydrophilic drugs. PMID:26325320

  18. Iontophoretic delivery of lipophilic and hydrophilic drugs from lipid nanoparticles across human skin.

    PubMed

    Charoenputtakun, Ponwanit; Li, S Kevin; Ngawhirunpat, Tanansait

    2015-11-10

    The combined effects of iontophoresis and lipid nanoparticles on drug delivery across human epidermal membrane (HEM) were investigated. The delivery of lipophilic and hydrophilic drugs, all trans-retinoic acid (ATRA), salicylate (SA), and acyclovir (ACV), across HEM from lipid nanoparticles, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), was compared in passive and iontophoresis experiments in vitro. Iontophoresis experiments were also performed with synthetic Nuclepore membrane for comparison. Drug distribution in the skin after iontophoretic delivery with the lipid nanoparticles was examined using a model probe rhodamine B base (RhoB). The drug-loaded lipid nanoparticles had average sizes of ∼ 118-169 nm and a negative zeta potential. Iontophoresis did not enhance the delivery of ATRA across HEM from SLN and NLC. However, HEM distribution study of RhoB suggested that lipophilic drugs could be delivered into the deeper layer of the skin following iontophoretic delivery of the drugs from the lipid nanoparticles. Iontophoresis enhanced the delivery of hydrophilic drug SA with the lipid nanoparticles. Similarly, iontophoresis enhanced the delivery of ACV when it was loaded in SLN. These results suggest that lipid nanoparticles are a promising drug delivery method that can be combined with iontophoresis to improve skin delivery of hydrophilic drugs.

  19. Delivery of lipophilic bioactives: assembly, disassembly, and reassembly of lipid nanoparticles.

    PubMed

    Yao, Mingfei; Xiao, Hang; McClements, David Julian

    2014-01-01

    The oral bioavailability of lipophilic bioactive molecules can be greatly increased by encapsulating them within engineered lipid nanoparticles (ELNs), such as micelles, microemulsions, nanoemulsions, or solid lipid nanoparticles (SLNs). After ingestion, these ELNs are disassembled in the gastrointestinal tract (GIT) and then reassembled into biological lipid nanoparticles (mixed micelles) in the small intestine. These mixed micelles solubilize and transport lipophilic bioactive components to the epithelial cells. The mixed micelles are then disassembled and reassembled into yet another form of biological lipid nanoparticle [chylomicrons (CMs)] within the enterocyte cells. The CMs carry the bioactive components into the systemic (blood) circulation via the lymphatic system, thereby avoiding first-pass metabolism. This article provides an overview of the various physicochemical and physiological processes responsible for the assembly and disassembly of lipid nanoparticles outside and inside the GIT. This knowledge can be used to design food-grade delivery systems to improve the oral bioavailability of encapsulated lipophilic bioactive components. PMID:24328432

  20. Interactions of Lipidic Cubic Phase Nanoparticles with Lipid Membranes.

    PubMed

    Jabłonowska, Elżbieta; Nazaruk, Ewa; Matyszewska, Dorota; Speziale, Chiara; Mezzenga, Raffaele; Landau, Ehud M; Bilewicz, Renata

    2016-09-20

    The interactions of liquid-crystalline monoolein (GMO) cubic phase nanoparticles with various model lipid membranes spread at the air-solution interface by the Langmuir technique were investigated. Cubosomes have attracted attention as potential biocompatible drug delivery systems, and thus understanding their mode of interaction with membranes is of special interest. Cubosomes spreading at the air-water interface as well as interactions with a monolayer of 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) compressed to different surface pressures were studied by monitoring surface pressure-time dependencies at constant area. Progressive incorporation of the nanoparticles was shown to lead to mixed monolayer formation. The concentration of cubosomes influenced the mechanism of incorporation, as well as the fluidity and permeability of the resulting lipid membranes. Brewster angle microscopy images reflected the dependence of the monolayer structure on the cubosomes presence in the subphase. A parameter Csat was introduced to indicate the point of saturation of the lipid membrane with the cubosomal material. This parameter was found to depend on the surface pressure showing that the cubosomes disintegrate in prolonged contact with the membrane, filling available voids in the lipid membrane. At highest surface pressures when the layer is most compact, the penetration of cubosomal material is not possible and only some exchange with the membrane lipid becomes the route of including GMO into the layer. Finally, comparative studies of the interactions between lipids with various headgroup charges with cubosomes suggest that at high surface pressure an exchange of lipid component between the monolayer and the cubosome in its intact form may occur. PMID:27550742

  1. Interactions of Lipidic Cubic Phase Nanoparticles with Lipid Membranes.

    PubMed

    Jabłonowska, Elżbieta; Nazaruk, Ewa; Matyszewska, Dorota; Speziale, Chiara; Mezzenga, Raffaele; Landau, Ehud M; Bilewicz, Renata

    2016-09-20

    The interactions of liquid-crystalline monoolein (GMO) cubic phase nanoparticles with various model lipid membranes spread at the air-solution interface by the Langmuir technique were investigated. Cubosomes have attracted attention as potential biocompatible drug delivery systems, and thus understanding their mode of interaction with membranes is of special interest. Cubosomes spreading at the air-water interface as well as interactions with a monolayer of 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) compressed to different surface pressures were studied by monitoring surface pressure-time dependencies at constant area. Progressive incorporation of the nanoparticles was shown to lead to mixed monolayer formation. The concentration of cubosomes influenced the mechanism of incorporation, as well as the fluidity and permeability of the resulting lipid membranes. Brewster angle microscopy images reflected the dependence of the monolayer structure on the cubosomes presence in the subphase. A parameter Csat was introduced to indicate the point of saturation of the lipid membrane with the cubosomal material. This parameter was found to depend on the surface pressure showing that the cubosomes disintegrate in prolonged contact with the membrane, filling available voids in the lipid membrane. At highest surface pressures when the layer is most compact, the penetration of cubosomal material is not possible and only some exchange with the membrane lipid becomes the route of including GMO into the layer. Finally, comparative studies of the interactions between lipids with various headgroup charges with cubosomes suggest that at high surface pressure an exchange of lipid component between the monolayer and the cubosome in its intact form may occur.

  2. Lipid-Based Nanoparticles as Pharmaceutical Drug Carriers: From Concepts to Clinic

    PubMed Central

    Puri, Anu; Loomis, Kristin; Smith, Brandon; Lee, Jae-Ho; Yavlovich, Amichai; Heldman, Eli; Blumenthal, Robert

    2010-01-01

    In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nano-emulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We

  3. Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic.

    PubMed

    Puri, Anu; Loomis, Kristin; Smith, Brandon; Lee, Jae-Ho; Yavlovich, Amichai; Heldman, Eliahu; Blumenthal, Robert

    2009-01-01

    In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nanoemulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We

  4. Modelling encapsulation of gold and silver nanoparticles inside lipid nanotubes

    NASA Astrophysics Data System (ADS)

    Baowan, Duangkamon; Thamwattana, Ngamta

    2014-02-01

    Lipid nanotubes are of particular interest for use as a template to create various one-dimensional nanostructures and as a carrier for drug and gene delivery. Understanding the encapsulation process is therefore crucial for such development. This paper models the interactions between lipid nanotubes and spheres of gold and silver nanoparticles and determines the critical dimension of lipid nanotubes that maximises the interaction with the nanoparticles. Our results confirm the acceptance of gold and silver nanoparticles inside lipid nanotubes. Further, we find that the lipid nanotube of radius approximately 10.23 nm is most favourable to encapsulate both types of nanoparticles.

  5. Method of fabricating lipid bilayer membranes on solid supports

    NASA Technical Reports Server (NTRS)

    Cho, Nam-Joon (Inventor); Frank, Curtis W. (Inventor); Glenn, Jeffrey S. (Inventor); Cheong, Kwang Ho (Inventor)

    2012-01-01

    The present invention provides a method of producing a planar lipid bilayer on a solid support. With this method, a solution of lipid vesicles is first deposited on the solid support. Next, the lipid vesicles are destabilized by adding an amphipathic peptide solution to the lipid vesicle solution. This destabilization leads to production of a planar lipid bilayer on the solid support. The present invention also provides a supported planar lipid bilayer, where the planar lipid bilayer is made of naturally occurring lipids and the solid support is made of unmodified gold or titanium oxide. Preferably, the supported planar lipid bilayer is continuous. The planar lipid bilayer may be made of any naturally occurring lipid or mixture of lipids, including, but not limited to phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinsitol, cardiolipin, cholesterol, and sphingomyelin.

  6. Lipid nanoparticles for the delivery of biopharmaceuticals.

    PubMed

    Silva, Ana C; Amaral, Maria H; Lobo, Jose M S; Lopes, Carla M

    2015-01-01

    Biopharmaceuticals comprise therapeutic protein-based, nucleic acids and cell-based products. According to their therapeutic success, the clinical use of these products has been growing. Therefore, the development of efficient biopharmaceuticals delivery systems, which overcome their limitations for administration, remains an excellent prospect for pharmaceutical technologists. In this area, lipid nanoparticles have been increasingly recognized as one of the most promising delivery systems, due to their exclusive advantages. However, no clinical biopharmaceutical lipid nanoparticle-based products are yet available. This fact could be explained by the lack or failure of in vivo studies, regarding stability and toxicological concerns, and also by the complex regulatory issues that must be accomplished. The present review article focuses on the different classes of biopharmaceuticals, their characteristics and limitations for administration. A state of the art regarding the use of lipid nanoparticles to improve biopharmaceuticals delivery is presented and a critical prospect of the future directions that should be addressed by pharmaceutical technologists is also discussed.

  7. Lipid nanoparticles: effect on bioavailability and pharmacokinetic changes.

    PubMed

    Souto, Eliana B; Müller, Rainer H

    2010-01-01

    The main aim of pharmaceutical technology research is the design of successful formulations for effective therapy, taking into account several issues including therapeutic requirements and patient compliance. In this regard, several achievements have been reported with colloidal carriers, in particular with lipid nanoparticles, due to their unique physicochemical properties. For several years these carriers have been showing potential success for several administration routes, namely oral, dermal, parenteral, and, more recently, for pulmonary and brain targeting. The present chapter provides a review of the use of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) to modify the release profile and the pharmacokinetic parameters of active pharmaceutical ingredients (APIs) incorporated in these lipid matrices, aiming to modify the API bioavailability, either upwards or downwards depending on the therapeutic requirement. Definitions of the morphological characteristics, surface properties, and polymorphic structures will also be given, emphasizing their influence on the incorporation parameters of the API, such as yield of production, loading capacity, and encapsulation efficiency. PMID:20217528

  8. Lipid nanoparticles as drug/gene delivery systems to the retina.

    PubMed

    del Pozo-Rodríguez, Ana; Delgado, Diego; Gascón, Alicia R; Solinís, Maria Ángeles

    2013-03-01

    This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patient's vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market. PMID:23286300

  9. Solid Lipid Nanoparticle assemblies (SLNas) for an anti-TB inhalation treatment-A Design of Experiments approach to investigate the influence of pre-freezing conditions on the powder respirability.

    PubMed

    Maretti, Eleonora; Rustichelli, Cecilia; Romagnoli, Marcello; Balducci, Anna Giulia; Buttini, Francesca; Sacchetti, Francesca; Leo, Eliana; Iannuccelli, Valentina

    2016-09-10

    For direct intramacrophagic antitubercular therapy, pulmonary administration through Dry Powder Inhaler (DPI) devices is a reasonable option. For the achievement of efficacious aerosolisation, rifampicin-loaded Solid Lipid Nanoparticle assemblies (SLNas) were developed using the melt emulsifying technique followed by freeze-drying. Indeed, this drying method can cause freezing or drying stresses compromising powder respirability. It is the aim of this research to offer novel information regarding pre-freezing variables. These included type and concentration of cryoprotectants, pre-freezing temperature, and nanoparticle concentration in the suspension. In particular, the effects of such variables were observed at two main levels. First of all, on SLNas characteristics - i.e., size, polydispersity index, zeta-potential, circularity, density, and drug loading. Secondly, on powder respirability, taking into account aerodynamic diameter, emitted dose, and respirable fraction. Considering the complexity of the factors involved in a successful respirable powder, a Design of Experiments (DoE) approach was adopted as a statistical tool for evaluating the effect of pre-freezing conditions. Interestingly, the most favourable impact on powder respirability was exerted by quick-freezing combined with a certain grade of sample dilution before the pre-freezing step without the use of cryoprotectants. In such conditions, a very high SLNas respirable fraction (>50%) was achieved, along with acceptable yields in the final dry powder as well as a reduction of powder mass to be introduced into DPI capsules with benefits in terms of administered drug dose feasibility. PMID:27473279

  10. Silencing of hepatitis C virus replication by a non-viral vector based on solid lipid nanoparticles containing a shRNA targeted to the internal ribosome entry site (IRES).

    PubMed

    Torrecilla, Josune; Del Pozo-Rodríguez, Ana; Solinís, María Ángeles; Apaolaza, Paola S; Berzal-Herranz, Beatriz; Romero-López, Cristina; Berzal-Herranz, Alfredo; Rodríguez-Gascón, Alicia

    2016-10-01

    Gene silencing mediated by RNAi has gained increasing interest as an alternative for the treatment of infectious diseases such as refractory hepatitis C virus (HCV) infection. In this work we have designed and evaluated a non-viral vector based on solid lipid nanoparticles (SLN) bearing hyaluronic acid, protamine and a short hairpin RNA (shRNA74) targeted to the Internal Ribosome Entry Site (IRES) of the HCV. The vector was able to inhibit the expression of the HCV IRES in Huh-7 cells, with the inhibition level dependent on the shRNA74 to SLN ratio and on the shRNA74 dose added to the culture cells. The nanocarrier was also able to inhibit the replication in human hepatoma cells supporting a subgenomic HCV replicon (Huh-7 NS3-3'). The vector was quickly and efficiently internalized by the cells, and endocytosis was the most productive uptake mechanism for silencing. Clathrin-mediated endocytosis and to a lesser extent caveolae/lipid raft-mediated endocytosis were identified as endocytic mechanisms involved in the cell uptake. Internalization via the CD44 receptor was also involved, although this entry route seems to be less productive for silencing than endocytosis. The vector did not induce either hemolysis or agglutination of red cells in vitro, which was indicative of good biocompatibility. In summary, we have shown for the first time the ability of a non-viral SLN-based vector to silence a HCV replicon.

  11. Silencing of hepatitis C virus replication by a non-viral vector based on solid lipid nanoparticles containing a shRNA targeted to the internal ribosome entry site (IRES).

    PubMed

    Torrecilla, Josune; Del Pozo-Rodríguez, Ana; Solinís, María Ángeles; Apaolaza, Paola S; Berzal-Herranz, Beatriz; Romero-López, Cristina; Berzal-Herranz, Alfredo; Rodríguez-Gascón, Alicia

    2016-10-01

    Gene silencing mediated by RNAi has gained increasing interest as an alternative for the treatment of infectious diseases such as refractory hepatitis C virus (HCV) infection. In this work we have designed and evaluated a non-viral vector based on solid lipid nanoparticles (SLN) bearing hyaluronic acid, protamine and a short hairpin RNA (shRNA74) targeted to the Internal Ribosome Entry Site (IRES) of the HCV. The vector was able to inhibit the expression of the HCV IRES in Huh-7 cells, with the inhibition level dependent on the shRNA74 to SLN ratio and on the shRNA74 dose added to the culture cells. The nanocarrier was also able to inhibit the replication in human hepatoma cells supporting a subgenomic HCV replicon (Huh-7 NS3-3'). The vector was quickly and efficiently internalized by the cells, and endocytosis was the most productive uptake mechanism for silencing. Clathrin-mediated endocytosis and to a lesser extent caveolae/lipid raft-mediated endocytosis were identified as endocytic mechanisms involved in the cell uptake. Internalization via the CD44 receptor was also involved, although this entry route seems to be less productive for silencing than endocytosis. The vector did not induce either hemolysis or agglutination of red cells in vitro, which was indicative of good biocompatibility. In summary, we have shown for the first time the ability of a non-viral SLN-based vector to silence a HCV replicon. PMID:27451369

  12. Polymer-coated echogenic lipid nanoparticles with dual release triggers.

    PubMed

    Nahire, Rahul; Haldar, Manas K; Paul, Shirshendu; Mergoum, Anaas; Ambre, Avinash H; Katti, Kalpana S; Gange, Kara N; Srivastava, D K; Sarkar, Kausik; Mallik, Sanku

    2013-03-11

    Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer-coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 min simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin-loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging.

  13. Lipid-enveloped hybrid nanoparticles for drug delivery

    NASA Astrophysics Data System (ADS)

    Tan, Songwei; Li, Xu; Guo, Yajun; Zhang, Zhiping

    2013-01-01

    Recent advances in nanotechnology and material sciences have promoted the development of nanomedicine. Among the formulations developed, novel lipid-enveloped hybrid nanoparticles have attracted more attention because of their special structure, properties and clinical applicability. The hybrid nanoparticles are composed of a hydrophilic PEG shell, a nano-sized polymeric or inorganic core and a lipid mono- or bi-layer between the core and PEG shell. This kind of nanoparticle possesses both the characteristics of liposomes and nanoparticles which endows it with many advantages like long circulation, high drug loading efficiency, high stability and biocompatibility, controlled release properties, and drug cocktail delivery. This review describes the recent developments of lipid-enveloped hybrid nanoparticles in cancer treatment, including the fabrication methods, formulations and applications of these hybrid nanoparticles. We expect that the continuing development of lipid-based nanomedicine will greatly improve cancer treatment.

  14. Lipid-enveloped hybrid nanoparticles for drug delivery.

    PubMed

    Tan, Songwei; Li, Xu; Guo, Yajun; Zhang, Zhiping

    2013-02-01

    Recent advances in nanotechnology and material sciences have promoted the development of nanomedicine. Among the formulations developed, novel lipid-enveloped hybrid nanoparticles have attracted more attention because of their special structure, properties and clinical applicability. The hybrid nanoparticles are composed of a hydrophilic PEG shell, a nano-sized polymeric or inorganic core and a lipid mono- or bi-layer between the core and PEG shell. This kind of nanoparticle possesses both the characteristics of liposomes and nanoparticles which endows it with many advantages like long circulation, high drug loading efficiency, high stability and biocompatibility, controlled release properties, and drug cocktail delivery. This review describes the recent developments of lipid-enveloped hybrid nanoparticles in cancer treatment, including the fabrication methods, formulations and applications of these hybrid nanoparticles. We expect that the continuing development of lipid-based nanomedicine will greatly improve cancer treatment.

  15. Cellular uptake and transcytosis of lipid-based nanoparticles across the intestinal barrier: Relevance for oral drug delivery.

    PubMed

    Neves, Ana Rute; Queiroz, Joana Fontes; Costa Lima, Sofia A; Figueiredo, Francisco; Fernandes, Rui; Reis, Salette

    2016-02-01

    Oral administration is the preferred route for drug delivery and nanosystems represent a promising tool for protection and transport of hardly soluble, chemically unstable and poorly permeable drugs through the intestinal barrier. In the present work, we have studied lipid nanoparticles cellular uptake, internalization pathways and transcytosis routes through Caco-2 cell monolayers. Both lipid nanosystems presented similar size (∼180nm) and surface charge (-30mV). Nanostructured lipid carriers showed a higher cellular uptake and permeability across the barrier, but solid lipid nanoparticles could enter cells faster than the former. The internalization of lipid nanoparticles occurs mainly through a clathrin-mediated endocytosis mechanism, although caveolae-mediated endocytosis is also involved in the uptake. Both lipid nanoparticles were able to cross the intestinal barrier by a preferential transcellular route. This work contributed to a better knowledge of the developed nanosystems for the oral delivery of a wide spectrum of drugs.

  16. Solid lipid nanodispersions containing mixed lipid core and a polar heterolipid: characterization.

    PubMed

    Attama, A A; Schicke, B C; Paepenmüller, T; Müller-Goymann, C C

    2007-08-01

    This paper describes the characterization of solid lipid nanodispersions (SLN) prepared with a 1:1 mixture of theobroma oil and goat fat as the main lipid matrix and Phospholipon 90G (P90G) as a stabilizer heterolipid, using polysorbate 80 as the mobile surfactant, with a view to applying the SLN in drug delivery. The 1:1 lipid mixture and P90G constituting the lipid matrix was first homogeneously prepared by fusion. Thereafter, the SLN were formulated with a gradient of polysorbate 80 and constant lipid matrix concentration by melt-high pressure homogenisation. The SLN were characterized by time-resolved particle size analysis, zeta potential and osmotic pressure measurements, differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD). Transmission electron microscopy (TEM) and isothermal heat conduction microcalorimetry (IMC) which monitors the in situ crystallization were also carried out on the SLN containing P90G and 1.0 % w/w of polysorbate 80. The results obtained in these studies were compared with SLN prepared with theobroma oil with and without phospholipid. Particle size analysis of SLN indicated reduction in size with increase in concentration of mobile surfactant and was in the lower nanometer range after 3 months except SLN prepared without P90G or polysorbate 80. The lipid nanoparticles had negative potentials after 3 months. WAXD and DSC studies revealed low crystalline SLN after 3 months of storage except in WAXD of SLN formulated with 1.0 % w/w polysorbate 80. TEM micrograph of the SLN containing 1.0 % w/w polysorbate 80 revealed discrete particles whose sizes were in consonance with the static light scattering measurement. In situ crystallization studies in IMC revealed delayed crystallization of the SLN with 1.0 % w/w polysorbate 80. Results indicate lipid mixtures produced SLN with lower crystallinity and higher particle sizes compared with SLN prepared with theobroma oil alone with or without P90G, and would lead to higher

  17. Solid lipid nanoparticles co-loaded with doxorubicin and α-tocopherol succinate are effective against drug-resistant cancer cells in monolayer and 3-D spheroid cancer cell models.

    PubMed

    Oliveira, Mariana S; Aryasomayajula, Bhawani; Pattni, Bhushan; Mussi, Samuel V; Ferreira, Lucas A M; Torchilin, Vladmir P

    2016-10-15

    This work aimed to develop solid lipid nanoparticles (SLN) co-loaded with doxorubicin and α-tocopherol succinate (TS) and to evaluate its potential to overcome drug resistance and to increase antitumoral effect in MCF-7/Adr and NCI/Adr cancer cell lines. The SLN were prepared by a hot homogenization method and characterized for size, zeta potential, entrapment efficiency (EE), and drug loading (DL). The cytotoxicity of SLN or penetration was evaluated in MCF-7/Adr and NCI/adr as a monolayer or spheroid cancer cell model. The SLN showed a size in the range of 74-80nm, negative zeta potential, EE of 99%, and DL of 67mg/g. The SLN co-loaded with Dox and TS showed a stronger cytotoxicity against MCF-7/Adr and NCI/Adr cells. In the monolayer model, the doxorubicin co-localization as a free and encapsulated form was higher for the encapsulated drug in MCF-7/Adr and NCI/adr, suggesting a bypassing of P-glycoprotein bomb efflux. For cancer cell spheroids, the SLN co-loaded with doxorubicin and TS showed a prominent cytotoxicity and a greater penetration of doxorubicin. PMID:27568499

  18. Asymmetric heat transfer from nanoparticles in lipid bilayers

    NASA Astrophysics Data System (ADS)

    Potdar, Dipti; Sammalkorpi, Maria

    2015-12-01

    Here, we use molecular dynamics simulations to characterize the heat transfer properties of lipid bilayer - gold nanoparticle systems in which the nanoparticle acts as a heat source. The focus is on dipalmitoylphosphatidylcholine (DPPC) lipid bilayers and thiolated alcohol and alkyl functionalized nanoparticles as prototype hydrophilic and hydrophobic nanoparticles. We find hydrophilic nanoparticles which are partly in contact with the surrounding water environment are more efficient in transferring heat to the system than hydrophobic ones which reside surrounded by the membrane. This is because of the hydrogen bonding capability of the hydroxy pentanethiol and the more efficient heat conductivity through water than the lipid bilayer. Additionally, we find the heat conductance is strongly asymmetric and has a discontinuity between the bilayer leaflets. In total, the findings provide understanding on heat transport from localized heat sources in lipid bilayers and could bear significance, e.g., in engineering and controlling photoactivated triggering of liposomal systems.

  19. Development and Evaluation of Lipid Nanoparticles for Drug Delivery: Study of Toxicity In, Vitro and In Vivo.

    PubMed

    Winter, Evelyn; Dal Pizzol, Carine; Locatelli, Claudriana; Crezkynski-Pasa, Tânia Beatriz

    2016-02-01

    Lipid nanoparticles have received considerable attention in the field of drug delivery, due their ability to incorporate lipophilic drugs and to allow controlled drug release. Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE) are three different lipid nanostructured systems presenting intrinsically physical properties, which have been widely studied in recent years. Despite the extensive applicability of lipid nanoparticles, the toxicity of these systems has not been sufficiently investigated thus far. It is generally believed that lipids are biocompatible. However, it is known that materials structured in nanoscale might have their intrinsic physicochemical properties modified. Thus, the aim of this study was to evaluate the cytotoxicity of these three nanoparticle systems. To this end, in vitro and in vivo toxicity studies were carried out. Our results indicate that nanoparticles containing the solid lipid GMS (SLN and NLC) induced an important cytotoxicity in vitro, but showed minimal toxicity in vivo--evidenced by the body weight analysis. The NE did not induce in vitro toxicity and did not induce body weight alteration. On the contrary, the SLN and NLC possibly induce an inflammatory process in vivo. All nanoparticle systems induced lipid peroxidation in the animals' livers, but only SLN and NLC induced a decrease of antioxidant defences indicating that the main mechanism of toxicity is the induction of oxidative stress in liver. The higher toxicity induced by SLN and NLC indicates that the solid lipid GMS could be the responsible for this effect. Nevertheless, this study provides important insights for toxicological studies of different lipid nanoparticles systems. PMID:27433582

  20. Development and Evaluation of Lipid Nanoparticles for Drug Delivery: Study of Toxicity In, Vitro and In Vivo.

    PubMed

    Winter, Evelyn; Dal Pizzol, Carine; Locatelli, Claudriana; Crezkynski-Pasa, Tânia Beatriz

    2016-02-01

    Lipid nanoparticles have received considerable attention in the field of drug delivery, due their ability to incorporate lipophilic drugs and to allow controlled drug release. Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE) are three different lipid nanostructured systems presenting intrinsically physical properties, which have been widely studied in recent years. Despite the extensive applicability of lipid nanoparticles, the toxicity of these systems has not been sufficiently investigated thus far. It is generally believed that lipids are biocompatible. However, it is known that materials structured in nanoscale might have their intrinsic physicochemical properties modified. Thus, the aim of this study was to evaluate the cytotoxicity of these three nanoparticle systems. To this end, in vitro and in vivo toxicity studies were carried out. Our results indicate that nanoparticles containing the solid lipid GMS (SLN and NLC) induced an important cytotoxicity in vitro, but showed minimal toxicity in vivo--evidenced by the body weight analysis. The NE did not induce in vitro toxicity and did not induce body weight alteration. On the contrary, the SLN and NLC possibly induce an inflammatory process in vivo. All nanoparticle systems induced lipid peroxidation in the animals' livers, but only SLN and NLC induced a decrease of antioxidant defences indicating that the main mechanism of toxicity is the induction of oxidative stress in liver. The higher toxicity induced by SLN and NLC indicates that the solid lipid GMS could be the responsible for this effect. Nevertheless, this study provides important insights for toxicological studies of different lipid nanoparticles systems.

  1. Encapsulation of ethylhexyl methoxycinnamate, a light-sensitive UV filter, in lipid nanoparticles.

    PubMed

    Durand, L; Habran, N; Henschel, V; Amighi, K

    2010-01-01

    The aim of this study was to encapsulate ethylhexyl methoxycinnamate (EMC), a commonly used UVB filter, in a solid lipid matrix in order to obtain microparticles and then nanoparticles to reduce its photo-instability under UV light exposure. Glyceryl behenate, rice bran wax and ozokerite were investigated for encapsulating EMC. The suspensions of nanoparticles contained 70% encapsulated EMC (relative to the lipid mass). The absorbance level at 310 nm of suspensions containing nanoparticles was more than twice that of those containing microparticles. So, decreasing the size of particles improved the efficiency of light protection, regardless of the lipid material used. Moreover, free EMC presented a 30% loss of its efficiency after 2 h of irradiation, whereas the three NLC formulations showed a loss of absorbency between 10% and 21%. The in vitro cutaneous penetration test did not show a higher potential penetration for EMC contained in nanosuspensions compared to free EMC. PMID:21034364

  2. Encapsulation of ethylhexyl methoxycinnamate, a light-sensitive UV filter, in lipid nanoparticles.

    PubMed

    Durand, L; Habran, N; Henschel, V; Amighi, K

    2010-01-01

    The aim of this study was to encapsulate ethylhexyl methoxycinnamate (EMC), a commonly used UVB filter, in a solid lipid matrix in order to obtain microparticles and then nanoparticles to reduce its photo-instability under UV light exposure. Glyceryl behenate, rice bran wax and ozokerite were investigated for encapsulating EMC. The suspensions of nanoparticles contained 70% encapsulated EMC (relative to the lipid mass). The absorbance level at 310 nm of suspensions containing nanoparticles was more than twice that of those containing microparticles. So, decreasing the size of particles improved the efficiency of light protection, regardless of the lipid material used. Moreover, free EMC presented a 30% loss of its efficiency after 2 h of irradiation, whereas the three NLC formulations showed a loss of absorbency between 10% and 21%. The in vitro cutaneous penetration test did not show a higher potential penetration for EMC contained in nanosuspensions compared to free EMC.

  3. Lipid nanoparticles for improved topical application of drugs for skin diseases.

    PubMed

    Schäfer-Korting, Monika; Mehnert, Wolfgang; Korting, Hans-Christian

    2007-07-10

    Due to the lower risk of systemic side effects topical treatment of skin disease appears favourable, yet the stratum corneum counteracts the penetration of xenobiotics into viable skin. Particulate carrier systems may mean an option to improve dermal penetration. Since epidermal lipids are found in high amounts within the penetration barrier, lipid carriers attaching themselves to the skin surface and allowing lipid exchange between the outermost layers of the stratum corneum and the carrier appear promising. Besides liposomes, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied intensively. Here we describe the potential of these carrier systems and compare the dermal uptake from SLN and NLC to the one of alternative vehicle systems. A special focus is upon the interactions of active ingredients and the lipid matrix as well as the quantification of dermal penetration. PMID:17544165

  4. Solid lipid nanoparticle-based vectors intended for the treatment of X-linked juvenile retinoschisis by gene therapy: In vivo approaches in Rs1h-deficient mouse model.

    PubMed

    Apaolaza, P S; Del Pozo-Rodríguez, A; Torrecilla, J; Rodríguez-Gascón, A; Rodríguez, J M; Friedrich, U; Weber, B H F; Solinís, M A

    2015-11-10

    X-linked juvenile retinoschisis (XLRS), which results from mutations in the gene RS1 that encodes the protein retinoschisin, is a retinal degenerative disease affecting between 1/5000 and 1/25,000 people worldwide. Currently, there is no cure for this disease and the treatment is based on the application of low-vision aids. The aim of the present work was the in vitro and in vivo evaluation of two different non-viral vectors based on solid lipid nanoparticles (SLNs), protamine and two anionic polysaccharides, hyaluronic acid (HA) or dextran (DX), for the treatment of XLRS. First, the vectors containing a plasmid which encodes both the reporter green fluorescent protein (GFP) and the therapeutic protein retinoschisin, under the control of CMV promoters, were characterized in vitro. Then, the vectors were subretinally or intravitreally administrated to C57BL/6 wild type mice. One week later, GFP was detected in all treated mice and in all retinal layers except in the Outer Nuclear Layer (ONL) and the Inner Nuclear Layer (INL), regardless of the administration route and the vector employed. Finally, two weeks after subretinal or intravitreal injection to Rs1h-deficient mice, GFP and retinoschisin expression was detected in all retinal layers, except in the ONL, which was maintained for at least two months after subretinal administration. The structural analysis of the treated Rs1h-deficient eyes showed a partial recovery of the retina related to the production of retinoschisin. This work shows for the first time a successful RS1 gene transfer to Rs1h-deficient animals using non-viral nanocarriers, with promising results that point to non-viral gene therapy as a feasible future therapeutic tool for retinal disorders. PMID:26400864

  5. Nanoparticle ligand presentation for targeting solid tumors.

    PubMed

    Duskey, Jason T; Rice, Kevin G

    2014-10-01

    Among the many scientific advances to come from the study of nanoscience, the development of ligand-targeted nanoparticles to eliminate solid tumors is predicted to have a major impact on human health. There are many reports describing novel designs and testing of targeted nanoparticles to treat cancer. While the principles of the technology are well demonstrated in controlled lab experiments, there are still many hurdles to overcome for the science to mature into truly efficacious targeted nanoparticles that join the arsenal of agents currently used to treat cancer in humans. One of these hurdles is overcoming unwanted biodistribution to the liver while maximizing delivery to the tumor. This almost certainly requires advances in both nanoparticle stealth technology and targeting. Currently, it continues to be a challenge to control the loading of ligands onto polyethylene glycol (PEG) to achieve maximal targeting. Nanoparticle cellular uptake and subcellular targeting of genes and siRNA also remain a challenge. This review examines the types of ligands that have been most often used to target nanoparticles to solid tumors. As the science matures over the coming decade, careful control over ligand presentation on nanoparticles of precise size, shape, and charge will likely play a major role in achieving success.

  6. Nanoparticle ligand presentation for targeting solid tumors.

    PubMed

    Duskey, Jason T; Rice, Kevin G

    2014-10-01

    Among the many scientific advances to come from the study of nanoscience, the development of ligand-targeted nanoparticles to eliminate solid tumors is predicted to have a major impact on human health. There are many reports describing novel designs and testing of targeted nanoparticles to treat cancer. While the principles of the technology are well demonstrated in controlled lab experiments, there are still many hurdles to overcome for the science to mature into truly efficacious targeted nanoparticles that join the arsenal of agents currently used to treat cancer in humans. One of these hurdles is overcoming unwanted biodistribution to the liver while maximizing delivery to the tumor. This almost certainly requires advances in both nanoparticle stealth technology and targeting. Currently, it continues to be a challenge to control the loading of ligands onto polyethylene glycol (PEG) to achieve maximal targeting. Nanoparticle cellular uptake and subcellular targeting of genes and siRNA also remain a challenge. This review examines the types of ligands that have been most often used to target nanoparticles to solid tumors. As the science matures over the coming decade, careful control over ligand presentation on nanoparticles of precise size, shape, and charge will likely play a major role in achieving success. PMID:24927668

  7. Roxithromycin-loaded lipid nanoparticles for follicular targeting.

    PubMed

    Wosicka-Frąckowiak, Hanna; Cal, Krzysztof; Stefanowska, Justyna; Główka, Eliza; Nowacka, Magdalena; Struck-Lewicka, Wiktoria; Govedarica, Biljana; Pasikowska, Monika; Dębowska, Renata; Jesionowski, Teofil; Srčič, Stane; Markuszewski, Michał Jan

    2015-11-30

    Particulate drug carriers e.g. nanoparticles (NPs) have been shown to penetrate and accumulate preferentially in skin hair follicles creating high local concentration of a drug. In order to develop such a follicle targeting system we obtained and characterized solid lipid nanoparticles (SLN) loaded with roxithromycin (ROX). The mean particle size (172±2 nm), polydisperisty index (0.237±0.007), zeta potential (-31.68±3.10 mV) and incorporation efficiency (82.1±3.0%) were measured. The long term stability of ROX-loaded SLN suspensions was proved up to 26 weeks. In vitro drug release study was performed using apparatus 4 dialysis adapters. Skin irritation test conducted using the EpiDerm™ tissue model demonstrated no irritation potential for ROX-loaded SLN. Ex vivo human skin penetration studies, employing rhodamine B hexyl ester perchlorate (RBHE) as a fluorescent dye to label the particles, revealed fluorescence deep in the skin, specifically around the hair follicles up to over 1mm depth. The comparison of fluorescence intensities after application of RBHE solution and RBHE-labelled ROX-loaded SLN was done. Then cyanoacrylate follicular biopsies were obtained in vivo and analyzed for ROX content, proving the possibility of penetration to human pilosebaceous units and delivering ROX by using SLN with the size below 200 nm. PMID:26456292

  8. Roxithromycin-loaded lipid nanoparticles for follicular targeting.

    PubMed

    Wosicka-Frąckowiak, Hanna; Cal, Krzysztof; Stefanowska, Justyna; Główka, Eliza; Nowacka, Magdalena; Struck-Lewicka, Wiktoria; Govedarica, Biljana; Pasikowska, Monika; Dębowska, Renata; Jesionowski, Teofil; Srčič, Stane; Markuszewski, Michał Jan

    2015-11-30

    Particulate drug carriers e.g. nanoparticles (NPs) have been shown to penetrate and accumulate preferentially in skin hair follicles creating high local concentration of a drug. In order to develop such a follicle targeting system we obtained and characterized solid lipid nanoparticles (SLN) loaded with roxithromycin (ROX). The mean particle size (172±2 nm), polydisperisty index (0.237±0.007), zeta potential (-31.68±3.10 mV) and incorporation efficiency (82.1±3.0%) were measured. The long term stability of ROX-loaded SLN suspensions was proved up to 26 weeks. In vitro drug release study was performed using apparatus 4 dialysis adapters. Skin irritation test conducted using the EpiDerm™ tissue model demonstrated no irritation potential for ROX-loaded SLN. Ex vivo human skin penetration studies, employing rhodamine B hexyl ester perchlorate (RBHE) as a fluorescent dye to label the particles, revealed fluorescence deep in the skin, specifically around the hair follicles up to over 1mm depth. The comparison of fluorescence intensities after application of RBHE solution and RBHE-labelled ROX-loaded SLN was done. Then cyanoacrylate follicular biopsies were obtained in vivo and analyzed for ROX content, proving the possibility of penetration to human pilosebaceous units and delivering ROX by using SLN with the size below 200 nm.

  9. Lipid nanoparticles based on butyl-methoxydibenzoylmethane: in vitro UVA blocking effect.

    PubMed

    Niculae, G; Lacatusu, I; Badea, N; Meghea, A

    2012-08-10

    The aim of the present study was to obtain efficient lipid nanoparticles loaded with butyl-methoxydibenzoylmethane (BMDBM) in order to develop cosmetic formulations with enhanced UVA blocking effect. For this purpose, two adequate liquid lipids (medium chain triglycerides and squalene) have been used in combination with two solid lipids (cetyl palmitate and glyceryl stearate) in order to create appropriate nanostructured carriers with a disordered lipid network able to accommodate up to 1.5% BMDBM. The lipid nanoparticles (LNs) were characterized in terms of particle size, zeta potential, entrapment efficiency, loading capacity and in vitro UVA blocking effect. The efficiency of lipid nanoparticles in developing some cosmetic formulations has been evaluated by determining the in vitro erythemal UVA protection factor. In order to quantify the photoprotective effect, some selected cream formulations based on BMDBM-LNs and a conventional emulsion were exposed to photochemical UV irradiation at a low energy to simulate the solar energy during the midday. The results obtained demonstrated the high ability of cream formulations based on BMDBM-LNs to absorb more than 96% of UVA radiation. Moreover, the developed cosmetic formulations manifest an enhanced UVA blocking effect, the erythemal UVA protection factor being four times higher than those specific to conventional emulsions.

  10. Lipid nanoparticles based on butyl-methoxydibenzoylmethane: in vitro UVA blocking effect

    NASA Astrophysics Data System (ADS)

    Niculae, G.; Lacatusu, I.; Badea, N.; Meghea, A.

    2012-08-01

    The aim of the present study was to obtain efficient lipid nanoparticles loaded with butyl-methoxydibenzoylmethane (BMDBM) in order to develop cosmetic formulations with enhanced UVA blocking effect. For this purpose, two adequate liquid lipids (medium chain triglycerides and squalene) have been used in combination with two solid lipids (cetyl palmitate and glyceryl stearate) in order to create appropriate nanostructured carriers with a disordered lipid network able to accommodate up to 1.5% BMDBM. The lipid nanoparticles (LNs) were characterized in terms of particle size, zeta potential, entrapment efficiency, loading capacity and in vitro UVA blocking effect. The efficiency of lipid nanoparticles in developing some cosmetic formulations has been evaluated by determining the in vitro erythemal UVA protection factor. In order to quantify the photoprotective effect, some selected cream formulations based on BMDBM-LNs and a conventional emulsion were exposed to photochemical UV irradiation at a low energy to simulate the solar energy during the midday. The results obtained demonstrated the high ability of cream formulations based on BMDBM-LNs to absorb more than 96% of UVA radiation. Moreover, the developed cosmetic formulations manifest an enhanced UVA blocking effect, the erythemal UVA protection factor being four times higher than those specific to conventional emulsions.

  11. Nanoparticle-triggered release from lipid membrane vesicles.

    PubMed

    Reimhult, Erik

    2015-12-25

    Superparamagnetic iron oxide nanoparticles are used in a rapidly expanding number of research and practical applications in biotechnology and biomedicine. We highlight how recent developments in iron oxide nanoparticle design and understanding of nanoparticle membrane interactions have led to applications in magnetically triggered, liposome delivery vehicles with controlled structure. Nanoscale vesicles actuated by incorporated nanoparticles allow for controlling location and timing of compound release, which enables e.g. use of more potent drugs in drug delivery as the interaction with the right target is ensured. This review emphasizes recent results on the connection between nanoparticle design, vesicle assembly and the stability and release properties of the vesicles. While focused on lipid vesicles magnetically actuated through iron oxide nanoparticles, these insights are of general interest for the design of capsule and cell delivery systems for biotechnology controlled by nanoparticles.

  12. Novel Methods of Lipidic Nanoparticle Preparation and Drug Loading

    NASA Astrophysics Data System (ADS)

    Maitani, Y.

    2013-09-01

    In improving cancer chemotherapy, lipidic nanoparticle systems for drug delivery, such as liposomes and emulsions, have received much attention because they are capable of delivering their drug payload selectively to cancer cells and of circulating for a long period in the bloodstream. In addition, lipidic nanoparticles have been examined for use in gene delivery as a non-viral vector. Preparation methods of particles and drug loading methods are crucial for the physicochemical properties of nanoparticles, which are the key aspects for pharmaceutical applications. This review describes new preparation methods for nanoparticles and a loading method for drugs using nanotechnology, including an evaluation of nanoparticles from the point of drug release for applications in cancer therapy and gene delivery.

  13. Carbon Nanoparticles and Carbonaceous Solids

    NASA Astrophysics Data System (ADS)

    Duley, W. W.

    2015-03-01

    This paper reports on the preparation of hydrogenated amorphous carbon nano-particles whose spectral characteristics include an absorption band at 217.5 nm with the profile and characteristics of the interstellar 217.5 nm feature. Vibrational spectra of these particles also contain the features commonly observed in IR absorption and emission from dust in the diffuse interstellar medium. These materials are produced under ``slow`` deposition conditions by minimizing the flux of incident carbon atoms and by reducing surface mobility.

  14. Novel Lutein Loaded Lipid Nanoparticles on Porcine Corneal Distribution

    PubMed Central

    Liu, Chi-Hsien; Chiu, Hao-Che; Wu, Wei-Chi; Sahoo, Soubhagya Laxmi; Hsu, Ching-Yun

    2014-01-01

    Topical delivery has the advantages including being user friendly and cost effective. Development of topical delivery carriers for lutein is becoming an important issue for the ocular drug delivery. Quantification of the partition coefficient of drug in the ocular tissue is the first step for the evaluation of delivery efficacy. The objectives of this study were to evaluate the effects of lipid nanoparticles and cyclodextrin (CD) on the corneal lutein accumulation and to measure the partition coefficients in the porcine cornea. Lipid nanoparticles combined with 2% HPβCD could enhance lutein accumulation up to 209.2 ± 18 (μg/g) which is 4.9-fold higher than that of the nanoparticles. CD combined nanoparticles have 68% of drug loading efficiency and lower cytotoxicity in the bovine cornea cells. From the confocal images, this improvement is due to the increased partitioning of lutein to the corneal epithelium by CD in the lipid nanoparticles. The novel lipid nanoparticles could not only improve the stability and entrapment efficacy of lutein but also enhance the lutein accumulation and partition in the cornea. Additionally the corneal accumulation of lutein was further enhanced by increasing the lutein payload in the vehicles. PMID:25101172

  15. Spherical nanoparticle supported lipid bilayers for the structural study of membrane geometry-sensitive molecules.

    PubMed

    Fu, Riqiang; Gill, Richard L; Kim, Edward Y; Briley, Nicole E; Tyndall, Erin R; Xu, Jie; Li, Conggang; Ramamurthi, Kumaran S; Flanagan, John M; Tian, Fang

    2015-11-11

    Many essential cellular processes including endocytosis and vesicle trafficking require alteration of membrane geometry. These changes are usually mediated by proteins that can sense and/or induce membrane curvature. Using spherical nanoparticle supported lipid bilayers (SSLBs), we characterize how SpoVM, a bacterial development factor, interacts with differently curved membranes by magic angle spinning solid-state NMR. Our results demonstrate that SSLBs are an effective system for structural and topological studies of membrane geometry-sensitive molecules.

  16. Adenosine conjugated lipidic nanoparticles for enhanced tumor targeting.

    PubMed

    Swami, Rajan; Singh, Indu; Jeengar, Manish Kumar; Naidu, V G M; Khan, Wahid; Sistla, Ramakrishna

    2015-01-01

    Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonspecific targeting and inefficient penetration. Targeted delivery of anti-cancer agents solely to tumor cells introduces a smart strategy because it enhances the therapeutic index compared with untargeted drugs. The present study was performed to investigate the efficiency of adenosine (ADN) to target solid lipid nanoparticles (SLN) to over expressing adenosine receptor cell lines such as human breast cancer and prostate cancer (MCF-7 and DU-145 cells), respectively. SLN were prepared by emulsification and solvent evaporation process using docetaxel (DTX) as drug and were characterized by various techniques like dynamic light scattering, differential scanning calorimeter and transmission electron microscopy. DTX loaded SLNs were surface modified with ADN, an adenosine receptors ligand using carbodiimide coupling. Conjugation was confirmed using infrared spectroscopy and quantified using phenol-sulfuric acid method. Conjugated SLN were shown to have sustained drug release as compared to unconjugated nanoparticles and drug suspension. Compared with free DTX and unconjugated SLN, ADN conjugated SLN showed significantly higher cytotoxicity of loaded DTX, as evidenced by in vitro cell experiments. The IC50 was 0.41 μg/ml for native DTX, 0.30 μg/ml for unconjugated SLN formulation, and 0.09 μg/ml for ADN conjugated SLN formulation in MCF-7 cell lines. Whereas, in DU-145, there was 2 fold change in IC50 of ADN-SLN as compared to DTX. IC50 was found to be 0.44 μg/ml for free DTX, 0.39 μg/ml for unconjugated SLN and 0.22 μg/ml for ADN-SLN. Annexin assay and cell cycle analysis assay further substantiated the cell cytotoxicity. Fluorescent cell uptake and competitive ligand-receptor binding assay corroborated the receptor mediated endocytosis pathway indicated role of adenosine receptors in internalization of conjugated particles. Pharmacokinetic studies of lipidic

  17. Effect of Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody on regulating the levels of baicalin and amino acids during cerebral ischemia-reperfusion in rats.

    PubMed

    Liu, Zhidong; Zhang, Li; He, Qiansong; Liu, Xiaolei; Okeke, Chukwunweike Ikechukwu; Tong, Ling; Guo, Lili; Yang, Hongyun; Zhang, Qian; Zhao, Hainan; Gu, Xing

    2015-07-15

    Baicalin has many pharmacological activities, including neuroprotective function against ischemia and neurodegeneration. In our previous study, we found that Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody (OX26-PEG-CSLN) might be a promising carrier to deliver drugs across the blood-brain barrier for the treatment of brain diseases. So, the aim of this present study was to further elucidate the mechanisms of OX26-PEG-CSLN cerebral ischemia protection by monitoring the changes of extracellular amino acids. In addition, we investigated the effect of OX26-PEG-CSLN on the excitotoxic neuronal injury as well as the pharmacokinetic profiles of baicalin in cerebrospinal fluid during ischemia-reperfusion period. The cerebrospinal fluid was collected by a microdialysis technique and divided into two parts - one part for pharmacokinetic study of baicalin using LC-MS/MS method and the other for pharmacodynamic study which was done by pre- column derivatization of the amino acids and analysis using a high-performance liquid chromatography with fluorescence detector (HPLC-FLD). The pharmacokinetic study showed that the AUC value of OX26-PEG-CSLN was 5.69-fold higher than that of the baicalin solution (Sol) (P<0.05) and the Cmax value of OX26-PEG-CSLN was 6.84-fold higher than that of the Sol (P<0.05). Moreover, the extracellular levels of glutamate (Glu), aspartic acid (Asp), glycine (Gly), taurine (Tau) and γ-aminobutyric acid (GABA) were measured for monitoring the imbalance of amino acids caused by ischemia and reperfusion. The excitotoxic index (EI) was also calculated for evaluating the imbalance between excitatory amino acid and inhibitory amino acid. The pharmacodynamic study showed that OX26-PEG-CSLN had stronger effect than Sol in reducing the content of aspartic, glutamic acid and increasing the concentrations of glycine, taurine and γ-aminobutyric acid during ischemia-reperfusion period. In conclusion, OX26-PEG-CSLN improved

  18. Assay to detect lipid peroxidation upon exposure to nanoparticles.

    PubMed

    Potter, Timothy M; Neun, Barry W; Stern, Stephan T

    2011-01-01

    This chapter describes a method for the analysis of human hepatocarcinoma cells (HEP G2) for lipid peroxidation products, such as malondialdehyde (MDA), following treatment with nanoparticle formulations. Oxidative stress has been identified as a likely mechanism of nanoparticle toxicity, and cell-based in vitro systems for evaluation of nanoparticle-induced oxidative stress are widely considered to be an important component of biocompatibility screens. The products of lipid peroxidation, lipid hydroperoxides, and aldehydes, such as MDA, can be measured via a thiobarbituric acid reactive substances (TBARS) assay. In this assay, which can be performed in cell culture or in cell lysate, MDA combines with thiobarbituric acid (TBA) to form a fluorescent adduct that can be detected at an excitation wavelength of 530 nm and an emission wavelength of 550 nm. The results are then expressed as MDA equivalents, normalized to total cellular protein (determined by Bradford assay).

  19. The encapsulation effect of UV molecular absorbers into biocompatible lipid nanoparticles

    NASA Astrophysics Data System (ADS)

    Lacatusu, Ioana; Badea, Nicoleta; Murariu, Alina; Meghea, Aurelia

    2011-12-01

    The efficiency of a cosmetic product depends not only on the active ingredients, but also on the carrier system devoted to improve its bioavailability. This article aims to encapsulate two couples of UV molecular absorbers, with a blocking action on both UV-A and UV-B domains, into efficient lipid nanoparticles. The effect of encapsulation on the specific properties such as sun protection factor and photostability behaviour has been demonstrated. The lipid nanoparticles with size range 30-350 nm and a polydispersity index between 0.217 and 0.244 are obtained using a modified high shear homogenisation method. The nanoparticles had spherical shapes with a single crystallisation form of lipid matrices characteristic for the least ordered crystal structure (α-form). The in vitro determination of photoprotection has led to high SPF ratings, with values of about 20, which assure a good photoprotection and filtering about 95% of UV radiation. The photoprotection effect after irradiation stage was observed to be increased more than twice compared to initial samples as a result of isomerisation phenomena. All the results have shown that good photoprotection effect and improved photostability could be obtained using such sunscreen couples, thus demonstrating that UV absorbers-solid lipid nanoparticles are promising carriers for cosmetic formulations.

  20. Hypoxia Responsive, Tumor Penetrating Lipid Nanoparticles for Delivery of Chemotherapeutics to Pancreatic Cancer Cell Spheroids.

    PubMed

    Kulkarni, Prajakta; Haldar, Manas K; Katti, Preeya; Dawes, Courtney; You, Seungyong; Choi, Yongki; Mallik, Sanku

    2016-08-17

    Solid tumors are often poorly irrigated due to structurally compromised microcirculation. Uncontrolled multiplication of cancer cells, insufficient blood flow, and the lack of enough oxygen and nutrients lead to the development of hypoxic regions in the tumor tissues. As the partial pressure of oxygen drops below the necessary level (10 psi), the cancer cells modulate their genetic makeup to survive. Hypoxia triggers tumor progression by enhancing angiogenesis, cancer stem cell production, remodeling of the extracellular matrix, and epigenetic changes in the cancer cells. However, the hypoxic regions are usually located deep in the tumors and are usually inaccessible to the intravenously injected drug carrier or the drug. Considering the designs of the reported nanoparticles, it is likely that the drug is delivered to the peripheral tumor tissues, close to the blood vessels. In this study, we prepared lipid nanoparticles (LNs) comprising the synthesized hypoxia-responsive lipid and a peptide-lipid conjugate. We observed that the resultant LNs penetrated to the hypoxic regions of the tumors. Under low oxygen partial pressure, the hypoxia-responsive lipid undergoes reduction, destabilizing the lipid membrane, and releasing encapsulated drugs from the nanoparticles. We demonstrated the results employing spheroidal cultures of the pancreatic cancer cells BxPC-3. We observed that the peptide-decorated, drug encapsulated LNs reduced the viability of pancreatic cancer cells of the spheroids to 35% under hypoxic conditions. PMID:27391789

  1. Nanoparticles for solid rocket propulsion

    NASA Astrophysics Data System (ADS)

    Galfetti, L.; DeLuca, L. T.; Severini, F.; Meda, L.; Marra, G.; Marchetti, M.; Regi, M.; Bellucci, S.

    2006-08-01

    The characterization of several differently sized aluminium powders, by BET (specific surface), EM (electron microscopy), XRD (x-ray diffraction), and XPS (x-ray photoelectron spectroscopy), was performed in order to evaluate their application in solid rocket propellant compositions. These aluminium powders were used in manufacturing several laboratory composite solid rocket propellants, based on ammonium perchlorate (AP) as oxidizer and hydroxil-terminated polybutadiene (HTPB) as binder. The reference formulation was an AP/HTPB/Al composition with 68/17/15% mass fractions respectively. The ballistic characterization of the propellants, in terms of steady burning rates, shows better performance for propellant compositions employing nano-aluminium when compared to micro-aluminium. Results obtained in the pressure range 1-70 bar show that by increasing the nano-Al mass fraction or decreasing the nano-Al size, larger steady burning rates are measured with essentially the same pressure sensitivity.

  2. Lipid and polymer nanoparticles for drug delivery to bacterial biofilms.

    PubMed

    Forier, Katrien; Raemdonck, Koen; De Smedt, Stefaan C; Demeester, Jo; Coenye, Tom; Braeckmans, Kevin

    2014-09-28

    Biofilms are matrix-enclosed communities of bacteria that show increased antibiotic resistance and the capability to evade the immune system. They can cause recalcitrant infections which cannot be cured with classical antibiotic therapy. Drug delivery by lipid or polymer nanoparticles is considered a promising strategy for overcoming biofilm resistance. These particles are able to improve the delivery of antibiotics to the bacterial cells, thereby increasing the efficacy of the treatment. In this review we give an overview of the types of polymer and lipid nanoparticles that have been developed for this purpose. The antimicrobial activity of nanoparticle encapsulated antibiotics compared to the activity of the free antibiotic is discussed in detail. In addition, targeting and triggered drug release strategies to further improve the antimicrobial activity are reviewed. Finally, ample attention is given to advanced microscopy methods that shed light on the behavior of nanoparticles inside biofilms, allowing further optimization of the nanoformulations. Lipid and polymer nanoparticles were found to increase the antimicrobial efficacy in many cases. Strategies such as the use of fusogenic liposomes, targeting of the nanoparticles and triggered release of the antimicrobial agent ensured the delivery of the antimicrobial agent in close proximity of the bacterial cells, maximizing the exposure of the biofilm to the antimicrobial agent. The majority of the discussed papers still present data on the in vitro anti-biofilm activity of nanoformulations, indicating that there is an urgent need for more in vivo studies in this field.

  3. In vitro lipolysis tests on lipid nanoparticles: comparison between lipase/co-lipase and pancreatic extract.

    PubMed

    Jannin, Vincent; Dellera, Eleonora; Chevrier, Stéphanie; Chavant, Yann; Voutsinas, Christophe; Bonferoni, Cristina; Demarne, Frédéric

    2015-01-01

    Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLC) are lipid nanocarriers aimed to the delivery of drugs characterized by a low bioavailability, such as poorly water-soluble drugs and peptides or proteins. The oral administration of these lipid nanocarriers implies the study of their lipolysis in presence of enzymes that are commonly involved in dietary lipid digestion in the gastrointestinal tract. In this study, a comparison between two methods was performed: on one hand, the lipase/co-lipase assay, commonly described in the literature to study the digestion of lipid nanocarriers, and on the other hand, the lipolysis test using porcine pancreatic extract and the pH-stat apparatus. This pancreatic extract contains both the pancreatic lipase and carboxyl ester hydrolase (CEH) that permit to mimic in a biorelevant manner the duodenal digestive lipolysis. The test was performed by means of a pH-stat apparatus to work at constant pH, 5.5 or 6.25, representing respectively the fasted or fed state pH conditions. The evolution of all acylglycerol entities was monitored during the digestion by sampling the reaction vessel at different time points, until 60 min, and the lipid composition of the digest was analyzed by gas chromatography. SLN and NLC systems obtained with long-chain saturated acylglycerols were rapidly and completely digested by pancreatic enzymes. The pH-stat titration method appears to be a powerful technique to follow the digestibility of these solid lipid-based nanoparticles. PMID:25342478

  4. Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

    PubMed

    Tan, Angel; Rao, Shasha; Prestidge, Clive A

    2013-12-01

    The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications. PMID:23775443

  5. Incorporation of liquid lipid in lipid nanoparticles for ocular drug delivery enhancement

    NASA Astrophysics Data System (ADS)

    Shen, Jie; Sun, Minjie; Ping, Qineng; Ying, Zhi; Liu, Wen

    2010-01-01

    The present work investigates the effect of liquid lipid incorporation on the physicochemical properties and ocular drug delivery enhancement of nanostructured lipid carriers (NLCs) and attempts to elucidate in vitro and in vivo the potential of NLCs for ocular drug delivery. The CyA-loaded or fluorescein-marked nanocarriers composed of Precifac ATO 5 and Miglyol 840 (as liquid lipid) were prepared by melting-emulsion technology, and the physicochemical properties of nanocarriers were determined. The uptake of nanocarriers by human corneal epithelia cell lines (SDHCEC) and rabbit cornea was examined. Ex vivo fluorescence imaging was used to investigate the ocular distribution of nanocarriers. The in vitro cytotoxicity and in vivo acute tolerance were evaluated. The higher drug loading capacity and improved in vitro sustained drug release behavior of lipid nanoparticles was found with the incorporation of liquid lipid in lipid nanoparticles. The uptake of nanocarriers by the SDHCEC was increased with the increase in liquid lipid loading. The ex vivo fluorescence imaging of the ocular tissues indicated that the liquid lipid incorporation could improve the ocular retention and penetration of ocular therapeutics. No alternation was macroscopically observed in vivo after ocular surface exposure to nanocarriers. These results indicated that NLC was a biocompatible and potential nanocarrier for ocular drug delivery enhancement.

  6. Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics.

    PubMed

    Maier, Martin A; Jayaraman, Muthusamy; Matsuda, Shigeo; Liu, Ju; Barros, Scott; Querbes, William; Tam, Ying K; Ansell, Steven M; Kumar, Varun; Qin, June; Zhang, Xuemei; Wang, Qianfan; Panesar, Sue; Hutabarat, Renta; Carioto, Mary; Hettinger, Julia; Kandasamy, Pachamuthu; Butler, David; Rajeev, Kallanthottathil G; Pang, Bo; Charisse, Klaus; Fitzgerald, Kevin; Mui, Barbara L; Du, Xinyao; Cullis, Pieter; Madden, Thomas D; Hope, Michael J; Manoharan, Muthiah; Akinc, Akin

    2013-08-01

    In recent years, RNA interference (RNAi) therapeutics, most notably with lipid nanoparticle-based delivery systems, have advanced into human clinical trials. The results from these early clinical trials suggest that lipid nanoparticles (LNPs), and the novel ionizable lipids that comprise them, will be important materials in this emerging field of medicine. A persistent theme in the use of materials for biomedical applications has been the incorporation of biodegradability as a means to improve biocompatibility and/or to facilitate elimination. Therefore, the aim of this work was to further advance the LNP platform through the development of novel, next-generation lipids that combine the excellent potency of the most advanced lipids currently available with biodegradable functionality. As a representative example of this novel class of biodegradable lipids, the lipid evaluated in this work displays rapid elimination from plasma and tissues, substantially improved tolerability in preclinical studies, while maintaining in vivo potency on par with that of the most advanced lipids currently available.

  7. Biodegradable Lipids Enabling Rapidly Eliminated Lipid Nanoparticles for Systemic Delivery of RNAi Therapeutics

    PubMed Central

    Maier, Martin A; Jayaraman, Muthusamy; Matsuda, Shigeo; Liu, Ju; Barros, Scott; Querbes, William; Tam, Ying K; Ansell, Steven M; Kumar, Varun; Qin, June; Zhang, Xuemei; Wang, Qianfan; Panesar, Sue; Hutabarat, Renta; Carioto, Mary; Hettinger, Julia; Kandasamy, Pachamuthu; Butler, David; Rajeev, Kallanthottathil G; Pang, Bo; Charisse, Klaus; Fitzgerald, Kevin; Mui, Barbara L; Du, Xinyao; Cullis, Pieter; Madden, Thomas D; Hope, Michael J; Manoharan, Muthiah; Akinc, Akin

    2013-01-01

    In recent years, RNA interference (RNAi) therapeutics, most notably with lipid nanoparticle-based delivery systems, have advanced into human clinical trials. The results from these early clinical trials suggest that lipid nanoparticles (LNPs), and the novel ionizable lipids that comprise them, will be important materials in this emerging field of medicine. A persistent theme in the use of materials for biomedical applications has been the incorporation of biodegradability as a means to improve biocompatibility and/or to facilitate elimination. Therefore, the aim of this work was to further advance the LNP platform through the development of novel, next-generation lipids that combine the excellent potency of the most advanced lipids currently available with biodegradable functionality. As a representative example of this novel class of biodegradable lipids, the lipid evaluated in this work displays rapid elimination from plasma and tissues, substantially improved tolerability in preclinical studies, while maintaining in vivo potency on par with that of the most advanced lipids currently available. PMID:23799535

  8. Percutaneous absorption of benzophenone-3 loaded lipid nanoparticles and polymeric nanocapsules: A comparative study.

    PubMed

    Gilbert, E; Roussel, L; Serre, C; Sandouk, R; Salmon, D; Kirilov, P; Haftek, M; Falson, F; Pirot, F

    2016-05-17

    For the last years, the increase of the number of skin cancer cases led to a growing awareness of the need of skin protection against ultraviolet (UV) radiations. Chemical UV filters are widely used into sunscreen formulations as benzophenone-3 (BP-3), a usually used broad spectrum chemical UV filter that has been shown to exercise undesirable effects after topical application. Innovative sunscreen formulations are thus necessary to provide more safety to users. Lipid carriers seem to be a good alternative to formulate chemical UV filters reducing their skin penetration while maintaining good photo-protective abilities. The aim of this work was to compare percutaneous absorption and cutaneous bioavailability of BP-3 loaded into solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), nanostructured polymeric lipid carriers (NPLC) and nanocapsules (NC). Particle size, zeta potential and in vitro sun protection factor (SPF) of nanoparticle suspensions were also investigated. Results showed that polymeric lipid carriers, comprising NPLC and NC, significantly reduced BP-3 skin permeation while exhibiting the highest SPF. This study confirms the interesting potential of NPLC and NC to formulate chemical UV filters. PMID:26976501

  9. Intelligent design of multifunctional lipid-coated nanoparticle platforms for cancer therapy.

    PubMed

    Ramishetti, Srinivas; Huang, Leaf

    2012-12-01

    Nanotechnology is rapidly evolving and dramatically changing the paradigms of drug delivery. The small sizes, unique chemical properties, large surface areas, structural diversity and multifunctionality of nanoparticles prove to be greatly advantageous for combating notoriously therapeutically evasive diseases such as cancer. Multifunctional nanoparticles have been designed to enhance tumor uptake through either passive or active targeting, while also avoiding reticuloendothelial system uptake through the incorporation of PEG onto the surface. First-generation nanoparticle systems, such as liposomes, are good carriers for drugs and nucleic acid therapeutics, although they have some limitations. These lipid bilayers are now being utilized as excellent carriers for drug-loaded, solid core particles such as iron oxide, mesoporus silica and calcium phosphate. In this article, their design, as well as their multifunctional role in cancer therapy are discussed.

  10. Sticking polydisperse hydrophobic magnetite nanoparticles to lipid membranes.

    PubMed

    Paulus, Michael; Degen, Patrick; Brenner, Thorsten; Tiemeyer, Sebastian; Struth, Bernd; Tolan, Metin; Rehage, Heinz

    2010-10-19

    The formation of a layer of hydrophobic magnetite (Fe(3)O(4)) nanoparticles stabilized by lauric acid is analyzed by in situ X-ray reflectivity measurements. The data analysis shows that the nanoparticles partially disperse their hydrophobic coating. Consequently, a Langmuir layer was formed by lauric acid molecules that can be compressed into an untilted condensed phase. A majority of the nanoparticles are attached to the Langmuir film integrating lauric acid residue on their surface into the Langmuir film. Hence, the particles at the liquid-gas interface can be identified as so-called Janus beads, which are amphiphilic solids having two sides with different functionality.

  11. Sticking polydisperse hydrophobic magnetite nanoparticles to lipid membranes.

    PubMed

    Paulus, Michael; Degen, Patrick; Brenner, Thorsten; Tiemeyer, Sebastian; Struth, Bernd; Tolan, Metin; Rehage, Heinz

    2010-10-19

    The formation of a layer of hydrophobic magnetite (Fe(3)O(4)) nanoparticles stabilized by lauric acid is analyzed by in situ X-ray reflectivity measurements. The data analysis shows that the nanoparticles partially disperse their hydrophobic coating. Consequently, a Langmuir layer was formed by lauric acid molecules that can be compressed into an untilted condensed phase. A majority of the nanoparticles are attached to the Langmuir film integrating lauric acid residue on their surface into the Langmuir film. Hence, the particles at the liquid-gas interface can be identified as so-called Janus beads, which are amphiphilic solids having two sides with different functionality. PMID:20873726

  12. Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability

    PubMed Central

    Neves, Ana Rute; Lúcio, Marlene; Martins, Susana; Lima, José Luís Costa; Reis, Salette

    2013-01-01

    Introduction Resveratrol is a polyphenol found in grapes and red wines. Interest in this polyphenol has increased due to its pharmacological cardio- and neuroprotective, chemopreventive, and antiaging effects, among others. Nevertheless, its pharmacokinetic properties are less favorable, since the compound has poor bioavailability, low water solubility, and is chemically unstable. To overcome these problems, we developed two novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance resveratrol’s oral bioavailability for further use in medicines, supplements, and nutraceuticals. Methods and materials Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with resveratrol were successfully produced by a modified hot homogenization technique. These were completely characterized to evaluate the quality of the developed resveratrol-loaded nanoparticles. Results Cryo-scanning electron microscopy morphology studies showed spherical and uniform nanoparticles with a smooth surface. An average resveratrol entrapment efficiency of ~70% was obtained for both SLNs and NLCs. Dynamic light scattering measurements gave a Z-average of 150–250 nm, polydispersity index of ~0.2, and a highly negative zeta potential of around −30 mV with no statistically significant differences in the presence of resveratrol. These characteristics remained unchanged for at least 2 months, suggesting good stability. Differential scanning calorimetry studies confirmed the solid state of the SLNs and NLCs at both room and body temperatures. The NLCs had a less ordered crystalline structure conferred by the inclusion of the liquid lipid, since they had lower values for phase transition temperature, melting enthalpy, and the recrystallization index. The presence of resveratrol induced a disorder in the crystal structure of the nanoparticles, suggesting a favoring of its entrapment. The in vitro release studies on conditions of storage showed a negligible

  13. A Glu-urea-Lys Ligand-conjugated Lipid Nanoparticle/siRNA System Inhibits Androgen Receptor Expression In Vivo

    PubMed Central

    Lee, Justin B; Zhang, Kaixin; Tam, Yuen Yi C; Quick, Joslyn; Tam, Ying K; Lin, Paulo JC; Chen, Sam; Liu, Yan; Nair, Jayaprakash K; Zlatev, Ivan; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Rennie, Paul S; Cullis, Pieter R

    2016-01-01

    The androgen receptor plays a critical role in the progression of prostate cancer. Here, we describe targeting the prostate-specific membrane antigen using a lipid nanoparticle formulation containing small interfering RNA designed to silence expression of the messenger RNA encoding the androgen receptor. Specifically, a Glu-urea-Lys PSMA-targeting ligand was incorporated into the lipid nanoparticle system formulated with a long alkyl chain polyethylene glycol-lipid to enhance accumulation at tumor sites and facilitate intracellular uptake into tumor cells following systemic administration. Through these features, and by using a structurally refined cationic lipid and an optimized small interfering RNA payload, a lipid nanoparticle system with improved potency and significant therapeutic potential against prostate cancer and potentially other solid tumors was developed. Decreases in serum prostate-specific antigen, tumor cellular proliferation, and androgen receptor levels were observed in a mouse xenograft model following intravenous injection. These results support the potential clinical utility of a prostate-specific membrane antigen–targeted lipid nanoparticle system to silence the androgen receptor in advanced prostate cancer.

  14. Feasibility of lipid nanoparticles for ocular delivery of anti-inflammatory drugs.

    PubMed

    Souto, Eliana B; Doktorovova, Slavomira; Gonzalez-Mira, Elisabet; Egea, Maria Antonia; Garcia, Maria Luisa

    2010-07-01

    Due to the multiple barriers imposed by the eye against the penetration of drugs, the ocular delivery and targeting are considered difficult to achieve. A major challenge in ocular drug therapy is to improve the poor bioavailability of topically applied ophthalmic drugs by overcoming the severe constraints imposed by the eye on drug absorption. One of the promising strategies nowadays is the use of colloidal carrier systems characterized by a submicron-meter size. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) represent promising alternatives to conventional and very popular ocular carrier systems, such as the nanoemulsions, liposomes, and polymeric nanoparticles. Nevertheless, taking into account the characteristics of the eye, morphometrical properties of the colloidal systems (e.g., average particle size and polydispersion) may represent a limiting factor for topical application without induced corneal irritation, being responsible for the selected system. This review article focuses on the application of lipid nanoparticles (SLN, NLC) as carriers for both non-steroidal and steroidal anti-inflammatory drugs for the treatment of ocular inflammatory disorders. Major benefits, as well as shortcomings, of ocular inflammation conditions are described, in particular upon management of inflammation induced by ocular surgery (e.g., cataracts, refractive surgery). Particular emphasis is given to the clinical choices currently available, while examining the most recent drugs that have been approved. PMID:20597640

  15. In vivo evaluation of porous silicon and porous silicon solid lipid nanocomposites for passive targeting and imaging.

    PubMed

    Kallinen, Annukka M; Sarparanta, Mirkka P; Liu, Dongfei; Mäkilä, Ermei M; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A; Airaksinen, Anu J

    2014-08-01

    The use of nanoparticle carriers for the sustained release of cytotoxic drugs in cancer therapy can result in fewer adverse effects and can thus be of great benefit for the patient. Recently, a novel nanocomposite, prepared by the encapsulation of THCPSi nanoparticles within solid lipids (SLN), was developed and characterized as a promising drug delivery carrier in vitro. The present study describes the in vivo evaluation of unmodified THCPSi nanoparticles and THCPSi-solid lipid nanocomposites (THCPSi-SLNCs) as potential drug delivery carriers for cancer therapy by using (18)F radiolabeling for the detection of the particle biodistribution in mice. Passive tumor targeting of (18)F-THCPSis and (18)F-THCPSi-SLNCs by the enhanced permeation and retention effect was investigated in a murine breast cancer model. Encapsulation of THCPSi nanoparticles with solid lipids improved their accumulation in tumors at a 7 week time point (tumor-to-liver ratio 0.10 ± 0.08 and 0.24 ± 0.09% for (18)F-THCPSis and (18)F-THCPSi-SLNCs, respectively).

  16. Compaction of DNA with Lipid Modified Silica Nanoparticles

    NASA Astrophysics Data System (ADS)

    Savarala, Sushma; Wunder, Stephanie L.; Ilies, Marc

    2012-02-01

    There is an increasing interest in modified inorganic nanoparticles, polymers or hybrid polymer-inorganic nanoparticles for use in DNA transfection, rather than viral vectors or liposomes. Adsorption of the DNA to the nanoparticles prevents enzymatic degradation of the DNA, although the reason for this protection is not completely understood. In order to compact the negatively charged DNA, a positively charged surface is required, and for transfection applications, the nanosystems must remain stable in suspension. It is also useful to minimize the amount of cytotoxic cationic lipid needed for DNA compaction in delivery applications. Here we investigate the colloidal stability of supported lipid bilayers (SLBs) composed of mixtures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC, 14:0 PC) and 1,2-dimyristoyl-3-trimethylammonium-propane (DMTAP, 14:0 TAP), and their ability to compact plasmid DNA. Ionic strengths and DMPC/DMTAP ratios that resulted in SLB formation, no excess small unilamellar vesicles (SUVs) in the suspensions, and colloidal stability, were determined. DNA/SLB/lipid ratios that resulted in compaction were then investigated.

  17. Oscillatory characteristics of metallic nanoparticles inside lipid nanotubes

    NASA Astrophysics Data System (ADS)

    Sadeghi, Fatemeh; Ansari, Reza; Darvizeh, Mansour

    2015-12-01

    This study is concerned with the oscillatory behavior of metallic nanoparticles, and in particular silver and gold nanoparticles, inside lipid nanotubes (LNTs) using the continuum approximation along with the 6-12 Lennard-Jones (LJ) potential function. The nanoparticle is modeled as a dense sphere and the LNT is assumed to be comprised of six layers including two head groups, two intermediate layers and two tail groups. To evaluate van der Waals (vdW) interactions, analytical expressions are first derived through undertaking surface and volume integrals which are then validated by a fully numerical scheme based on the differential quadrature (DQ) technique. Using the actual force distribution between the two interacting molecules, the equation of motion is directly solved utilizing the Runge-Kutta numerical integration scheme to arrive at the time history of displacement and velocity of the inner core. Also, a semi-analytical expression incorporating both geometrical parameters and initial conditions is introduced for the precise evaluation of oscillation frequency. A comprehensive study is conducted to gain an insight into the influences of nanoparticle radius, LNT length, head and tail group thicknesses and initial conditions on the oscillatory behavior of the metallic nanoparticles inside LNTs. It is found that the escape velocity and oscillation frequency of silver nanoparticles are higher than those of gold ones. It is further shown that the oscillation frequency is less affected by the tail group thickness when compared to the head group thickness.

  18. Encapsulation of biophenolic phytochemical EGCG within lipid nanoparticles enhances its stability and cytotoxicity against cancer.

    PubMed

    Radhakrishnan, Rasika; Kulhari, Hitesh; Pooja, Deep; Gudem, Sagarika; Bhargava, Suresh; Shukla, Ravi; Sistla, Ramakrishna

    2016-06-01

    Epigallocatechin gallate (EGCG), a green tea polyphenolic catechin, has been known to possess a variety of beneficial biological activities. The in-vitro anti-cancer activity of EGCG is well documented. However, the use of EGCG in modern therapeutics is limited due to its poor bioavailability and limited stability at physiological pH. In this study, we have investigated the stability profiles of EGCG in aqueous solutions using UV-vis spectroscopy. Stability results showed very low stability profile of EGCG at physiological pH with rapid degradation under alkaline conditions. Therefore, we have encapsulated EGCG in solid lipid nanoparticles to increase its stability and evaluated for anticancer activity. The lipid core of nanoparticles not only provides an additional structural reinforcement to the nanoparticle assembly, but also makes it biologically compatible, thereby enabling a stealth vehicle for efficient drug delivery. EGCG loaded nanoparticles (EGCG-SLN) were characterized using dynamic light scattering, Fourier transform infrared spectroscopy and differential scanning calorimetry. EGCG and EGCG-SLN were evaluated for their anticancer activities by cellular proliferation. The cytotoxicity of EGCG-SLN was found to be 8.1 times higher against MDA-MB 231 human breast cancer cells and 3.8 times higher against DU-145 human prostate cancer cells than that of the pure EGCG. PMID:27234272

  19. Influence of different surfactants on the technological properties and in vivo ocular tolerability of lipid nanoparticles.

    PubMed

    Leonardi, Antonio; Bucolo, Claudio; Romano, Giovanni Luca; Platania, Chiara Bianca Maria; Drago, Filippo; Puglisi, Giovanni; Pignatello, Rosario

    2014-08-15

    Addition of one or more surfactant agents is often necessary for the production of nanostructured lipid and polymeric systems. The removal of residual surfactants is a required step for technological and toxicological reasons, especially for peculiar applications, such as the ophthalmic field. This study was planned to assess the technological properties of some surfactants, commonly used for the production of lipid nanoparticles, as well as their ocular safety profile. Stable and small-size solid lipid nanoparticles were obtained using Dynasan(®) 114 as the lipid matrix and all the tested surfactants. However, from a toxicological point of view, the nanocarriers produced using Kolliphor(®) P188 were the most valuable, showing no irritant effect on the ocular surface up to the highest tested surfactant concentration (0.4%, w/v). The SLN produced using Cremophor(®) A25 and Lipoid(®) S100 were tolerated up to a surfactant concentration of 0.2% by weight, while for Tween(®) 80 and Kolliphor(®) HS 15 a maximum concentration of 0.05% can be considered totally not-irritant.

  20. Nanoparticle-blood interactions: the implications on solid tumour targeting.

    PubMed

    Lazarovits, James; Chen, Yih Yang; Sykes, Edward A; Chan, Warren C W

    2015-02-18

    Nanoparticles are suitable platforms for cancer targeting and diagnostic applications. Typically, less than 10% of all systemically administered nanoparticles accumulate in the tumour. Here we explore the interactions of blood components with nanoparticles and describe how these interactions influence solid tumour targeting. In the blood, serum proteins adsorb onto nanoparticles to form a protein corona in a manner dependent on nanoparticle physicochemical properties. These serum proteins can block nanoparticle tumour targeting ligands from binding to tumour cell receptors. Additionally, serum proteins can also encourage nanoparticle uptake by macrophages, which decreases nanoparticle availability in the blood and limits tumour accumulation. The formation of this protein corona will also increase the nanoparticle hydrodynamic size or induce aggregation, which makes nanoparticles too large to enter into the tumour through pores of the leaky vessels, and prevents their deep penetration into tumours for cell targeting. Recent studies have focused on developing new chemical strategies to reduce or eliminate serum protein adsorption, and rescue the targeting potential of nanoparticles to tumour cells. An in-depth and complete understanding of nanoparticle-blood interactions is key to designing nanoparticles with optimal physicochemical properties with high tumour accumulation. The purpose of this review article is to describe how the protein corona alters the targeting of nanoparticles to solid tumours and explains current solutions to solve this problem.

  1. Solid-Supported Lipid Multilayers under High Hydrostatic Pressure.

    PubMed

    Nowak, Benedikt; Paulus, Michael; Nase, Julia; Salmen, Paul; Degen, Patrick; Wirkert, Florian J; Honkimäki, Veijo; Tolan, Metin

    2016-03-22

    In this work, the structure of solid-supported lipid multilayers exposed to increased hydrostatic pressure was studied in situ by X-ray reflectometry at the solid-liquid interface between silicon and an aqueous buffer solution. The layers' vertical structure was analyzed up to a maximum pressure of 4500 bar. The multilayers showed phase transitions from the fluid into different gel phases. With increasing pressure, a gradual filling of the sublayers between the hydrophilic head groups with water was observed. This process was inverted when the pressure was decreased, yielding finally smaller water layers than those in the initial state. As is commonly known, water has an abrasive effect on lipid multilayers by the formation of vesicles. We show that increasing pressure can reverse this process so that a controlled switching between multi- and bilayers is possible. PMID:26927365

  2. MOF nanoparticles coated by lipid bilayers and their uptake by cancer cells.

    PubMed

    Wuttke, Stefan; Braig, Simone; Preiß, Tobias; Zimpel, Andreas; Sicklinger, Johannes; Bellomo, Claudia; Rädler, Joachim O; Vollmar, Angelika M; Bein, Thomas

    2015-11-11

    We report the synthesis of MOF@lipid nanoparticles as a versatile and powerful novel class of nanocarriers based on metal-organic frameworks (MOFs). We show that the MOF@lipid system can effectively store dye molecules inside the porous scaffold of the MOF while the lipid bilayer prevents their premature release. Efficient uptake of the MOF@lipid nanoparticles by cancer cells makes these nanocarriers promising for drug delivery and diagnostic purposes.

  3. A Critical Review of Lipid-based Nanoparticles for Taxane Delivery

    PubMed Central

    Feng, Lan; Mumper, Russell J.

    2012-01-01

    Nano-based delivery systems have attracted a great deal of attention in the past two decades as a strategy to overcome the low therapeutic index of conventional anticancer drugs and delivery barriers in solid tumors. Myriads of preclinical studies have been focused on developing nano-based formulations to effectively deliver taxanes, one of the most important and most prescribed anticancer drug types in the clinic. Given the hydrophobic property of taxanes, lipid-based NPs, serve as a viable alternative delivery system. This critical review will provide an overview and perspective of the advancement of lipid-based nanoparticles for taxane delivery. Currently available formulations of taxanes and their drawbacks as well as criteria for idea taxane delivery system will be discussed. PMID:22796606

  4. Challenges and solutions for the delivery of biotech drugs--a review of drug nanocrystal technology and lipid nanoparticles.

    PubMed

    Muller, Rainer H; Keck, Cornelia M

    2004-09-30

    Biotechnology allows tailor-made production of biopharmaceuticals and biotechnological drugs; however, many of them require special formulation technologies to overcome drug-associated problems. Such potential challenges to solve are: poor solubility, limited chemical stability in vitro and in vivo after administration (i.e. short half-life), poor bioavailability and potentially strong side effects requiring drug enrichment at the site of action (targeting). This review describes the use of nanoparticulate carriers, developed in our research group, as one solution to overcome such delivery problems, i.e. drug nanocrystals, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and lipid-drug conjugate (LDC) nanoparticles, examples of drugs are given. As a recently developed targeting principle, the concept of differential protein adsorption is described (PathFinder Technology) using as example delivery to the brain. PMID:15380654

  5. Transdermal delivery of biomacromolecules using lipid-like nanoparticles

    NASA Astrophysics Data System (ADS)

    Bello, Evelyn A.

    The transdermal delivery of biomacromolecules, including proteins and nucleic acids, is challenging, owing to their large size and the penetration-resistant nature of the stratum corneum. Thus, an urgent need exists for the development of transdermal delivery methodologies. This research focuses on the use of cationic lipid-like nanoparticles (lipidoids) for the transdermal delivery of proteins, and establishes an in vitro model for the study. The lipidoids used were first combinatorially designed and synthesized; afterwards, they were employed for protein encapsulation in a vesicular system. A skin penetration study demonstrated that lipidoids enhance penetration depth in a pig skin model, overcoming the barrier that the stratum corneum presents. This research has successfully identified active lipidoids capable of efficiently penetrating the skin; therefore, loading proteins into lipidoid nanoparticles will facilitate the transdermal delivery of proteins. Membrane diffusion experiments were used to confirm the results. This research has confirmed that lipidoids are a suitable material for transdermal protein delivery enhancement.

  6. The metabolism of fatty alcohols in lipid nanoparticles by alcohol dehydrogenase.

    PubMed

    Dong, X; Mumper, R J

    2006-09-01

    Fatty alcohols are commonly used in lipid-based drug delivery systems including parenteral emulsions and solid lipid nanoparticles (NPs). The purpose of these studies was to determine whether horse liver alcohol dehydrogenase (HLADH), a NAD-dependent enzyme, could metabolize the fatty alcohols within the NPs and thus serve as a mechanism to degrade these NPs in the body. Solid nanoparticles (<100 nm) were engineered from oil-in-water microemulsion precursors using emulsifying wax NF as the oil phase and polyoxyethylene 20-stearyl ether (Brij 78) as the surfactant. Emulsifying wax contains both cetyl and stearyl alcohols. NPs were incubated with the enzyme and NAD+ at 37 degrees C for up to 48 h, and the concentrations of fatty alcohols were quantitatively determined over time by gas chromatography (GC). The concentrations of cetyl alcohol and stearyl alcohol within the NPs decreased to only 10-20% remaining after 15-24 h of incubation. In parallel, NP size, turbidity and the fluorescence intensity of NADH all increased over time. It was concluded that horse liver alcohol dehydrogenase/NAD+ was able to metabolize the fatty alcohols within the NPs, suggesting that NPs made of fatty alcohols may be metabolized in the body via endogenous alcohol dehydrogenase enzyme systems. PMID:16954110

  7. The metabolism of fatty alcohols in lipid nanoparticles by alcohol dehydrogenase.

    PubMed

    Dong, X; Mumper, R J

    2006-09-01

    Fatty alcohols are commonly used in lipid-based drug delivery systems including parenteral emulsions and solid lipid nanoparticles (NPs). The purpose of these studies was to determine whether horse liver alcohol dehydrogenase (HLADH), a NAD-dependent enzyme, could metabolize the fatty alcohols within the NPs and thus serve as a mechanism to degrade these NPs in the body. Solid nanoparticles (<100 nm) were engineered from oil-in-water microemulsion precursors using emulsifying wax NF as the oil phase and polyoxyethylene 20-stearyl ether (Brij 78) as the surfactant. Emulsifying wax contains both cetyl and stearyl alcohols. NPs were incubated with the enzyme and NAD+ at 37 degrees C for up to 48 h, and the concentrations of fatty alcohols were quantitatively determined over time by gas chromatography (GC). The concentrations of cetyl alcohol and stearyl alcohol within the NPs decreased to only 10-20% remaining after 15-24 h of incubation. In parallel, NP size, turbidity and the fluorescence intensity of NADH all increased over time. It was concluded that horse liver alcohol dehydrogenase/NAD+ was able to metabolize the fatty alcohols within the NPs, suggesting that NPs made of fatty alcohols may be metabolized in the body via endogenous alcohol dehydrogenase enzyme systems.

  8. Microfluidic Synthesis of Hybrid Nanoparticles with Controlled Lipid Layers: Understanding Flexibility-Regulated Cell-Nanoparticle Interaction.

    PubMed

    Zhang, Lu; Feng, Qiang; Wang, Jiuling; Zhang, Shuai; Ding, Baoquan; Wei, Yujie; Dong, Mingdong; Ryu, Ji-Young; Yoon, Tae-Young; Shi, Xinghua; Sun, Jiashu; Jiang, Xingyu

    2015-10-27

    The functionalized lipid shell of hybrid nanoparticles plays an important role for improving their biocompatibility and in vivo stability. Yet few efforts have been made to critically examine the shell structure of nanoparticles and its effect on cell-particle interaction. Here we develop a microfluidic chip allowing for the synthesis of structurally well-defined lipid-polymer nanoparticles of the same sizes, but covered with either lipid-monolayer-shell (MPs, monolayer nanoparticles) or lipid-bilayer-shell (BPs, bilayer nanoparticles). Atomic force microscope and atomistic simulations reveal that MPs have a lower flexibility than BPs, resulting in a more efficient cellular uptake and thus anticancer effect than BPs do. This flexibility-regulated cell-particle interaction may have important implications for designing drug nanocarriers.

  9. Design Principles for Nanoparticles Enveloped by a Polymer-Tethered Lipid Membrane.

    PubMed

    Hu, Mingyang; Stanzione, Francesca; Sum, Amadeu K; Faller, Roland; Deserno, Markus

    2015-10-27

    We propose the design for a nanoparticle carrier that combines three existing motifs into a single construct: a liposome is stabilized by anchoring it to an enclosed solid core via extended polymeric tethers that are chemically grafted to the core and physisorb into the surrounding lipid membrane. Such a design would exhibit several enticing properties, among them: (i) the anchoring stabilizes the liposome against a variety of external stresses, while preserving an aqueous compartment between core and membrane; (ii) the interplay of design parameters such as polymer length or grafting density enforces strong constraints on nanoparticle size and hence ensures a high degree of uniformity; and (iii) the physical and chemical characteristics of the individual constituents equip the construct with numerous functionalities that can be exploited in many ways. However, navigating the large parameter space requires a sound prior understanding for how various design features work together, and how this impacts potential pathways for synthesizing and assembling these nanoparticles. In this paper, we examine these connections in detail, using both soft matter theory and computer simulations at all levels of resolution. We thereby derive strong constraints on the experimentally relevant parameter space, and also propose potential equilibrium and nonequilibrium pathways for nanoparticle assembly.

  10. Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies

    PubMed Central

    Bhaskar, Kesavan; Anbu, Jayaraman; Ravichandiran, Velayutham; Venkateswarlu, Vobalaboina; Rao, Yamsani Madhusudan

    2009-01-01

    The aim of the study is to prepare aqueous dispersions of lipid nanoparticles – flurbiprofen solid lipid nanoparticles (FLUSLN) and flurbiprofen nanostructured lipid carriers (FLUNLC) by hot homogenization followed by sonication technique and then incorporated into the freshly prepared hydrogels for transdermal delivery. They are characterized for particle size, for all the formulations, more than 50% of the particles were below 300 nm after 90 days of storage at RT. DSC analyses were performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by TEM which revealed fairly spherical shape of the formulations. Further they were evaluated for in vitro drug release characteristics, rheological behaviour, pharmacokinetic and pharmacodynamic studies. The pharmacokinetics of flurbiprofen in rats following application of SLN gel (A1) and NLC gel (B1) for 24 h were evaluated. The Cmax of the B1 formulation was 38.67 ± 2.77 μg/ml, which was significantly higher than the A1 formulation (Cmax = 21.79 ± 2.96 μg/ml). The Cmax and AUC of the B1 formulation were 1.8 and 2.5 times higher than the A1 gel formulation respectively. The bioavailability of flurbiprofen with reference to oral administration was found to increase by 4.4 times when gel formulations were applied. Anti-inflammatory effect in the Carrageenan-induced paw edema in rat was significantly higher for B1 and A1 formulation than the orally administered flurbiprofen. Both the SLN and NLC dispersions and gels enriched with SLN and NLC possessed a sustained drug release over period of 24 h but the sustained effect was more pronounced with the SLN and NLC gel PMID:19243632

  11. Lipid-Albumin Nanoparticles (LAN) for Therapeutic Delivery of Antisense Oligonucleotide against HIF-1α.

    PubMed

    Li, Hong; Quan, Jishan; Zhang, Mengzi; Yung, Bryant C; Cheng, Xinwei; Liu, Yang; Lee, Young B; Ahn, Chang-Ho; Kim, Deog Joong; Lee, Robert J

    2016-07-01

    Lipid-albumin nanoparticles (LAN) were synthesized for delivery of RX-0047, an antisense oligonucleotide (ASO) against the hypoxia inducible factor-1 alpha (HIF-1α) to solid tumor. These lipid nanoparticles (LNs) incorporated a human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate, which is cationic and can form electrostatic complexes with negatively charged oligonucleotides. The delivery efficiency of LAN-RX-0047 was investigated in KB cells and a KB murine xenograft model. When KB cells were treated with LAN-RX-0047, significant HIF-1α downregulation and enhanced cellular uptake were observed compared to LN-RX-0047. LN-RX-0047 and LAN-RX-0047 showed similar cytotoxicity against KB cells with IC50 values of 19.3 ± 3.8 and 20.1 ± 4.2 μM, respectively. LAN-RX-0047 was shown to be taken up by the cells via the macropinocytosis and caveolae-mediated endocytosis pathways while LN-RX-0047 was taken up by cells via caveolae-mediated endocytosis. In the KB xenograft tumor model, LAN-RX-0047 exhibited tumor suppressive activity and significantly reduced intratumoral HIF-1α expression compared to LN-RX-0047. Furthermore, LAN-RX-0047 greatly increased survival time of mice bearing KB-1 xenograft tumors at doses of either 3 mg/kg or 16 mg/kg. These results indicated that LAN-RX-0047 is a highly effective vehicle for therapeutic delivery of antisense agents to tumor.

  12. Magnetic lipid nanoparticles loading doxorubicin for intracellular delivery: Preparation and characteristics

    NASA Astrophysics Data System (ADS)

    Ying, Xiao-Ying; Du, Yong-Zhong; Hong, Ling-Hong; Yuan, Hong; Hu, Fu-Qiang

    2011-04-01

    Tumor intracellular delivery is an effective route for targeting chemotherapy to enhance the curative effect and minimize the side effect of a drug. In this study, the magnetic lipid nanoparticles with an uptake ability by tumor cells were prepared dispersing ferroso-ferric oxide nanoparticles in aqueous phase using oleic acid (OA) as a dispersant, and following the solvent dispersion of lipid organic solution. The obtained nanoparticles with 200 nm volume average diameter and -30 mV surface zeta potential could be completely removed by external magnetic field from aqueous solution. Using doxorubicin (DOX) as a model drug, the drug-loaded magnetic lipid nanoparticles were investigated in detail, such as the effects of OA, drug and lipid content on volume average diameter, zeta potential, drug encapsulation efficiency, drug loading, and in vitro drug release. The drug loading capacity and encapsulation efficiency were enhanced with increasing drug or lipid content, reduced with increasing OA content. The in vitro drug release could be controlled by changing drug or lipid content. Cellular uptake by MCF-7 cells experiment presented the excellent internalization ability of the prepared magnetic lipid nanoparticles. These results evidenced that the present magnetic lipid nanoparticles have potential for targeting therapy of antitumor drugs.

  13. Electrosprayed core-shell polymer-lipid nanoparticles for active component delivery

    NASA Astrophysics Data System (ADS)

    Eltayeb, Megdi; Stride, Eleanor; Edirisinghe, Mohan

    2013-11-01

    A key challenge in the production of multicomponent nanoparticles for healthcare applications is obtaining reproducible monodisperse nanoparticles with the minimum number of preparation steps. This paper focus on the use of electrohydrodynamic (EHD) techniques to produce core-shell polymer-lipid structures with a narrow size distribution in a single step process. These nanoparticles are composed of a hydrophilic core for active component encapsulation and a lipid shell. It was found that core-shell nanoparticles with a tunable size range between 30 and 90 nm and a narrow size distribution could be reproducibly manufactured. The results indicate that the lipid component (stearic acid) stabilizes the nanoparticles against collapse and aggregation and improves entrapment of active components, in this case vanillin, ethylmaltol and maltol. The overall structure of the nanoparticles produced was examined by multiple methods, including transmission electron microscopy and differential scanning calorimetry, to confirm that they were of core-shell form.

  14. Cationic additives in nanosystems activate cytotoxicity and inflammatory response of human neutrophils: lipid nanoparticles versus polymeric nanoparticles

    PubMed Central

    Hwang, Tsong-Long; Aljuffali, Ibrahim A; Lin, Chwan-Fwu; Chang, Yuan-Ting; Fang, Jia-You

    2015-01-01

    This report compares the effect of lipid and polymeric nanoparticles upon human neutrophils in the presence of cationic surfactants. Nanostructured lipid carriers and poly(lactic-co-glycolic) acid nanoparticles were manufactured as lipid and polymeric systems, respectively. Some cytotoxic and proinflammatory mediators such as lactate dehydrogenase (LDH), elastase, O2•−, and intracellular Ca2+ were examined. The nanoparticles showed a size of 170–225 nm. Incorporation of cetyltrimethylammonium bromide or soyaethyl morpholinium ethosulfate, the cationic surfactant, converted zeta potential from a negative to a positive charge. Nanoparticles without cationic surfactants revealed a negligible change on immune and inflammatory responses. Cationic surfactants in both nanoparticulate and free forms induced cell death and the release of mediators. Lipid nanoparticles generally demonstrated a greater response compared to polymeric nanoparticles. The neutrophil morphology observed by electron microscopy confirmed this trend. Cetyltrimethylammonium bromide as the coating material showed more significant activation of neutrophils than soyaethyl morpholinium ethosulfate. Confocal microscope imaging displayed a limited internalization of nanoparticles into neutrophils. It is proposed that cationic nanoparticles interact with the cell membrane, triggering membrane disruption and the following Ca2+ influx. The elevation of intracellular Ca2+ induces degranulation and oxidative stress. The consequence of these effects is cytotoxicity and cell death. Caution should be taken when selecting feasible nanoparticulate formulations and cationic additives for consideration of applicability and toxicity. PMID:25609950

  15. Efficacy of edelfosine lipid nanoparticles in breast cancer cells.

    PubMed

    Aznar, María Ángela; Lasa-Saracíbar, Beatriz; Estella-Hermoso de Mendoza, Ander; Blanco-Prieto, María José

    2013-10-01

    Breast cancer is a heterogeneous group of neoplasms predominantly originating in the terminal duct lobular units. It represents the leading cause of cancer death in women and the survival frequencies for patients at advanced stages of the disease remain low. New treatment options need to be researched to improve these rates. The anti-tumor ether lipid edelfosine (ET) is the prototype of a novel generation of promising anticancer drugs. However, it presents several drawbacks for its use in cancer therapy, including gastrointestinal and hemolytic toxicity and low oral bioavailability. To overcome these obstacles, ET was encapsulated in Precirol ATO 5 lipid nanoparticles (ET-LN), and its anti-tumor potential was in vitro tested in breast cancer. The formulated ET-LN were more effective in inhibiting cell proliferation and notably decreased cell viability, showing that the cytotoxic effect of ET was considerably enhanced when ET was encapsulated. In addition, ET and ET-LN were able to promote cell cycle arrest at G1 phase. Moreover, although both treatments provoked an apoptotic effect in a time-dependent manner, such anti-tumor effects were noticeably improved with ET-LN treatment. Therefore, our results indicate that encapsulating ET in LN played an essential role in improving the efficacy of the drug.

  16. Bioreducible Lipid-like Nanoparticles for Intracellular Protein Delivery

    NASA Astrophysics Data System (ADS)

    Arellano, Carlos Luis

    Protein-based therapy is one of the most direct ways to manipulate cell function and treat human disease. Although protein therapeutics has made its way to clinical practice, with five of the top fifteen global pharmaceuticals being peptide or protein-based drugs, one common limitation is that the effects of protein therapy are only achieved through the targeting of cell surface receptors and intracellular domains. Due to the impermeability of the cell membrane to most foreign materials, entire classes of potentially therapeutic proteins cannot thoroughly be studied without a safe and efficient method of transporting proteins into the cytosol. We report the use of a combinatorially-designed bioreducible lipid-like material (termed "lipidoid") - based protein delivery platform for the transfection of human cancer cell lines. Lipidoid nanoparticles are synthesized through a thin film dispersion method. The degradation of the bioreducible nanoparticles was observed when exposed to glutathione, a highly reductive compound present in the cytosol. We demonstrate that the nanoparticles are capable of transfecting a dose-dependent concentration of our model protein, beta-galactosidase into HeLa cells. Furthermore, formulations of the lipidoid containing the cytotoxic proteins saporin and RNase-A are both capable of inhibiting tumor cell proliferation as observed in in vitro treatment of different human cancer cell lines. There was no observed loss in protein activity after lyophilization and long--term storage, indicating the potential of pre-clinical applications. Overall, we demonstrate an effective approach to protein formulation and intracellular delivery. We believe that our formulations will lead to the study of a whole class of previously untapped therapeutics that may generate new solutions for previously untreatable diseases.

  17. Simulated Permeation and Characterization of PEGylated Gold Nanoparticles in a Lipid Bilayer System.

    PubMed

    Oroskar, Priyanka A; Jameson, Cynthia J; Murad, Sohail

    2016-08-01

    PEGylated gold nanoparticles are considered suitable nanocarriers for use in biomedical applications and targeted drug delivery systems. In our previous investigation with the alkanethiol-functionalized gold nanoparticle, we found that permeation across a protein-free phospholipid membrane resulted in damaging effects of lipid displacement and water and ion leakage. In the present study, we carry out a series of coarse-grained molecular simulations to explore permeation of lipid bilayer systems by a PEGylated gold nanoparticle, especially at the bulk-liquid-lipid interface as well as the interface between the two lipid leaflets. Initially, we examine molecular-level details of a PEGylated gold nanoparticle (constructed from cycled annealing) in water and find a distribution of ligand configurations (from mushroom to brush states) present in nanoparticles with medium to high surface coverage. We also find that the characteristic properties of the PEGylated gold nanoparticle do not change when it is placed in a salt solution. In our permeation studies, we investigate events of water and ion penetration as well as lipid translocation while varying the ligand length, nanoparticle surface coverage, and ion concentration gradient of our system. Results from our studies show the following: (1) The number of water molecules in the interior of the membrane during ligand-coated nanoparticle permeation increases with PEGn-SH surface coverage, ligand length, and permeation velocity but is not sensitive to the ion concentration gradient. (2) Lipid molecules do not leave the membrane; instead they complete trans-bilayer lipid flip-flop with longer ligands and higher surface coverages. (3) The lack of formation of stable water pores prevents ion translocation. (4) The PEGylated nanoparticle causes less damage to the membrane overall due to favorable interactions with the lipid headgroups which may explain why experimentalists observe endocytosis of PEGylated nanocarriers in vivo.

  18. Simulated Permeation and Characterization of PEGylated Gold Nanoparticles in a Lipid Bilayer System.

    PubMed

    Oroskar, Priyanka A; Jameson, Cynthia J; Murad, Sohail

    2016-08-01

    PEGylated gold nanoparticles are considered suitable nanocarriers for use in biomedical applications and targeted drug delivery systems. In our previous investigation with the alkanethiol-functionalized gold nanoparticle, we found that permeation across a protein-free phospholipid membrane resulted in damaging effects of lipid displacement and water and ion leakage. In the present study, we carry out a series of coarse-grained molecular simulations to explore permeation of lipid bilayer systems by a PEGylated gold nanoparticle, especially at the bulk-liquid-lipid interface as well as the interface between the two lipid leaflets. Initially, we examine molecular-level details of a PEGylated gold nanoparticle (constructed from cycled annealing) in water and find a distribution of ligand configurations (from mushroom to brush states) present in nanoparticles with medium to high surface coverage. We also find that the characteristic properties of the PEGylated gold nanoparticle do not change when it is placed in a salt solution. In our permeation studies, we investigate events of water and ion penetration as well as lipid translocation while varying the ligand length, nanoparticle surface coverage, and ion concentration gradient of our system. Results from our studies show the following: (1) The number of water molecules in the interior of the membrane during ligand-coated nanoparticle permeation increases with PEGn-SH surface coverage, ligand length, and permeation velocity but is not sensitive to the ion concentration gradient. (2) Lipid molecules do not leave the membrane; instead they complete trans-bilayer lipid flip-flop with longer ligands and higher surface coverages. (3) The lack of formation of stable water pores prevents ion translocation. (4) The PEGylated nanoparticle causes less damage to the membrane overall due to favorable interactions with the lipid headgroups which may explain why experimentalists observe endocytosis of PEGylated nanocarriers in vivo

  19. Use of Solid Phase Extraction in the Biochemistry Laboratory to Separate Different Lipids

    ERIC Educational Resources Information Center

    Flurkey, William H.

    2005-01-01

    Solid-phase extraction (SPE) was used to demonstrate how various lipids and lipid classes could be separated in a biochemistry laboratory setting. Three different SPE methods were chosen on their ability to separate a lipid mixture, consisting of a combination of a either a fatty acid, a triacylglycerol, a mono- or diacylglycerol, phospholipid,…

  20. Optimization of the production of solid Witepsol nanoparticles loaded with rosmarinic acid.

    PubMed

    Campos, Débora A; Madureira, Ana Raquel; Gomes, Ana Maria; Sarmento, Bruno; Pintado, Maria Manuela

    2014-03-01

    During the last decade there has been a growing interest in the formulation of new food and nutraceutical products containing compounds with antioxidant activity. Unfortunately, due to their structure, certain compounds such as polyphenols, in particular rosmarinic acid (RA) are not stable and may interact easily with matrices in which they are incorporated. To overcome such limitations, the formulation of loaded polyphenols nanoparticles can offer an efficient solution to protect such compounds. Based on this rationale, the aim of this study was to prepare solid lipid nanoparticles (SLNs) loaded with RA using a hot melt ultrasonication method, where Witepsol H15 was used as lipid and Polysorbate 80 (Tween 80) as surfactant, following a 3(2) fractional factorial design, resulting in the use of 3 different percentages of surfactant (viz. 1, 2 and 3%, v/v) and lipid (0.5, 1.0 and 1.5%, w/v). The stability of the nanoparticles systems were tested during 28 d in aqueous solution stored at refrigeration temperature (ca. 5 °C), tracking the mean particle size of different formulations by photon correlation spectroscopy. To confirm RA entrapment, thermal analyses of the nanoparticles by DSC and FTIR were performed. The association efficiencies percentages (AE%) were determined using HPLC to quantitatively assess the RA in supernatants. Results showed that Witepsol H15 produced nanoparticles with initial mean diameters between 270 and 1000 nm, yet over time, a slight increase occurred, but without occurrence of aggregation. The AE% showed a high percentage of encapsulation (ca. 99%), which reveals low polyphenol releases from SLNs throughout storage time. In general, results showed a successful production of SLNs with properties that can be used to food applications. PMID:24413308

  1. Using RNA as a tool to modify lipid nanoparticles

    NASA Astrophysics Data System (ADS)

    Wilner, Samantha E.

    Lipid nanoparticles (LNPs) provide an attractive option for therapeutic applications because they can self-assemble and carry a diverse set of cargoes ranging from hydrophobic drugs to small interfering RNA (siRNA). Liposomes and micelles represent two classes of LNPs that have been developed for medicinal purposes; however, active targeting of LNPs to specific tissues and LNP stability in vivo remain significant challenges. We have exploited the structural characteristics and targeting ability of nucleic acids to address these obstacles. Specifically, we have introduced short nucleic acid targeting species, called aptamers, to the surface of stable nucleic acid lipid particles (SNALPs), a subset of liposomes used in siRNA delivery. In this manner, we have actively targeted SNALPs to cancer cells that overexpress the transferrin receptor (TfR). HeLa cells expressing enhanced green fluorescent protein (EGFP) were treated with SNALPs bearing an antiTfR aptamer (C2) that was identified in our lab. C2-conjugated SNALPs showed increased levels of uptake by cells by flow cytometry. More importantly, the enhanced uptake by C2-conjugated SNALPs translated to an increased level of gene knockdown when SNALPs were loaded with anti-EGFP siRNA or anti-Lamin NC siRNA. Expression of EGFP and Lamin NC decreased, respectively. These preliminary studies illustrate that aptamer-conjugated SNALPs can be designed to knock down both endogenous and exogenous genes in cancer cells with high specificity. We have also used nucleic acids to stabilize lipid micelles by introducing short quadruplex forming oligonucleotide sequences at the lipid headgroup. Micelle formation was confirmed via dynamic light scattering, transmission electron microscopy, and small angle X-ray scattering. Micelle stability was assessed using NMR and by a FRET-based assay in the presence of serum proteins. Quadruplex-stabilized micelles demonstrated enhanced stability suggesting that alterations to oligonucleotide

  2. Conformational Changes in High-Density Lipoprotein Nanoparticles Induced by High Payloads of Paramagnetic Lipids

    PubMed Central

    2016-01-01

    High-density lipoprotein (HDL) nanoparticles doped with gadolinium lipids can be used as magnetic resonance imaging diagnostic agents for atherosclerosis. In this study, HDL nanoparticles with different molar fractions of gadolinium lipids (0 < xGd-lipids < 0.33) were prepared, and the MR relaxivity values (r1 and r2) for all compositions were measured. Both r1 and r2 parameters reached a maximal value at a molar fraction of approximately xGd-lipids = 0.2. Higher payloads of gadolinium did not significantly increase relaxivity values but induced changes in the structure of HDL, increasing the size of the particles from dH = 8.2 ± 1.6 to 51.7 ± 7.3 nm. High payloads of gadolinium lipids trigger conformational changes in HDL, with potential effects on the in vivo behavior of the nanoparticles. PMID:27713933

  3. Novel lipid hybrid albumin nanoparticle greatly lowered toxicity of pirarubicin.

    PubMed

    Zhou, Jing; Zhang, Xuanmiao; Li, Mei; Wu, Wenqi; Sun, Xun; Zhang, Ling; Gong, Tao

    2013-10-01

    Pirarubicin (THP) is an effective anthracycline for the treatment of solid tumor. However, its potential side effects are prominent and clinical use is restricted. We aimed to develop a novel pirarubicin-oleic acid complex albumin nanoparticle (THP-OA-AN) in order to reduce the toxicity of THP. Oleic acid, human serum albumin (HSA), and egg yolk lecithin E80 was used to prepare THP-OA-AN. Prepared THP-OA-AN was characterized and animal experiments were conducted to assess its tumor suppression effect, distribution, and toxicity. Comparison between THP and THP-OA-AN showed that, with retained antitumor efficiency, the toxicity of THP-OA-AN is significantly reduced regarding bone marrow suppression, cardiotoxicity, renal toxicity, and gastrointestinal toxicity. This study developed a safe and effective formulation of THP, which has greater potential for clinic use in the tumor therapy.

  4. Versatile Solid Phase Syntheses of Structured Nanoparticle Hybrids

    NASA Astrophysics Data System (ADS)

    Koberstein, Jeffrey

    2011-03-01

    While it is widely recognized that nanoparticles can exhibit a wide variety of exciting size-dependent properties and responses, it is equally important to recognize that devices and systems cannot be created from bare nanoparticles alone. The potential of nanoparticles can only be achieved by proper consideration of matrices that not only provide mechanical support and integrity to the nanoparticles, but can also control various aspects of their spatial assembly such as geometry and interparticle spacing. Polymers represent a logical and robust matrix for the creation of nanocomposite assemblies, however, phenomena such as aggregation are often problematic when blending nanoparticles and homopolymers. These problems can be avoided by preparation of nanoparticle hybrids wherein all required polymers are covalently tethered to the nanoparticles prior to assembly so that a polymer matrix is not necessary. We report on a new method for covalent decoration of nanoparticles with polymers of tailored molecular design that is based upon a solid phase synthesis strategy. The modular process, much like molecular Tinker Toys, is capable of decorating nanoparticles with essentially any type of branched or copolymeric structure using only a few elementary heterobifunctional building blocks. Because end group functionality is always retained in the process, functional nanoparticles can be readily crosslinked by simple orthogonal reactions such as azide-alkyne click chemistry. The method can be used to create sophisticated hybrid nanoparticle structures important to drug delivery applications, to form highly functional crosslinkers that gel at conversions as low as a few percent, or to fabricate crosslinked matrix-free nanocomposites. Supported by grants DMR-0704054 from the NSF and W911NF-10-1-0184 from the US Army Research Office.

  5. Evaluation of Atazanavir and Darunavir Interactions with Lipids for Developing pH-responsive Anti-HIV Drug Combination Nanoparticles

    PubMed Central

    Duan, Jinghua; Freeling, Jennifer P.; Koehn, Josefin; Shu, Cuiling; Ho, Rodney J. Y.

    2014-01-01

    We evaluated two HIV protease inhibitors, atazanavir and darunavir, for pH-dependent solubility, lipid binding, and drug release from lipid nanoparticles. Both atazanavir and darunavir incorporated into lipid nanoparticles composed of pegylated and non-pegylated phospholipids with nearly 100% efficiency, but only atazanavir lipid nanoparticles formed stable lipid-drug particles and exhibited pH-dependent drug release. Darunavir lipid nanoparticles were unstable and formed mixed micelles at low drug-lipid concentrations, and thus are not suitable for lipid-drug particle development. When atazanavir lipid nanoparticles were prepared with ritonavir, a metabolic and cellular membrane exporter inhibitor, and tenofovir, an HIV reverse transcriptase inhibitor, stable, scalable, and reproducible anti-HIV drug combination lipid nanoparticles were produced. Drug incorporation efficiencies of 85.5 ± 8.2, 85.1 ± 7.1, and 6.1 ± 0.8 % for atazanavir, ritonavir, and tenofovir, respectively, were achieved. Preliminary primate pharmacokinetic studies with these pH-responsive anti-HIV drug combination lipid nanoparticles administered subcutaneously produced detectable plasma concentrations that lasted for 7 days for all three drugs. These anti-HIV lipid nanoparticles could be developed as a long-acting targeted antiretroviral therapy. PMID:24948204

  6. In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters

    PubMed Central

    2014-01-01

    Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC. PMID:25232295

  7. In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters

    NASA Astrophysics Data System (ADS)

    Hu, Yun; Ehrich, Marion; Fuhrman, Kristel; Zhang, Chenming

    2014-08-01

    Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC.

  8. Nanoparticle permeation induces water penetration, ion transport, and lipid flip-flop.

    PubMed

    Song, Bo; Yuan, Huajun; Pham, Sydney V; Jameson, Cynthia J; Murad, Sohail

    2012-12-11

    Nanoparticles are generally considered excellent candidates for targeted drug delivery. However, ion leakage and cytotoxicity induced by nanoparticle permeation is a potential problem in such drug delivery schemes because of the toxic effect of many ions. In this study, we have carried out a series of coarse-grained molecular dynamics simulations to investigate the water penetration, ion transport, and lipid molecule flip-flop in a protein-free phospholipid bilayer membrane during nanoparticle permeation. The effect of ion concentration gradient, pressure differential across the membrane, nanoparticle size, and permeation velocity have been examined in this work. Some conclusions from our studies include (1) The number of water molecules in the interior of the membrane during the nanoparticle permeation increases with the nanoparticle size and the pressure differential across the membrane but is unaffected by the nanoparticle permeation velocity or the ion concentration gradient. (2) Ion transport is sensitive to the size of nanoparticle as well as the ion concentration gradient between two sides of the membrane; no anion/cation selectivity is observed for small nanoparticle permeation, while anions are preferentially translocated through the membrane when the size of nanoparticle is large enough. (3) Incidences of lipid molecule flip-flop increases with the size of nanoparticle and ion concentration gradient and decreases with the pressure differential and the nanoparticle permeation velocity.

  9. Preparation of stabilized magnetic nanoparticles with polymerizable lipid and anchor compounds.

    PubMed

    Kang, Boram; Choi, Suk-Jung

    2014-02-01

    Although the lipid-based method for coating of magnetic nanoparticles (MNPs) is rapid and simple, the unstable state of the lipid layer is a major limitation for the practical application of this method. We devised a method to prepare stabilized MNPs by covalent modifications such as lipid polymerization and anchoring of the lipid layer. The stability of the modified lipid layer was demonstrated by the stable status of enzymes immobilized on the MNPs and the resistance of the MNPs to aggregation. We also determined the maximum ratio of nonpolymerizable lipophilic compounds that can be included in the layer without significantly reducing stability.

  10. Surface-functionalized nanoparticle permeation triggers lipid displacement and water and ion leakage.

    PubMed

    Oroskar, Priyanka A; Jameson, Cynthia J; Murad, Sohail

    2015-01-27

    Functionalized nanoparticles (NPs) are considered suitable carriers for targeted drug delivery systems. However, the ion and water leakage induced by permeation of these nanoparticles is a challenge in these drug delivery methods because of cytotoxic effects of some ions. In this study, we have carried out a series of coarse-grained molecular dynamics simulations to investigate the effect of length of ligands on permeation of a nanoparticle across a protein-free phospholipid bilayer membrane. Water and ion penetration as well as incidence of lipid flip-flop events and loss of lipid molecules from the membrane are explored in this study while varying the nanoparticle size, length of ligand, ion concentration gradient, pressure differential across the membrane, and nanoparticle permeation velocity. Some results from our studies include (1) the number of water molecules in the interior of the membrane during ligand-coated nanoparticle permeation increases with nanoparticle size, ligand length, pressure differential, and permeation velocity but is not sensitive to the ion concentration gradient; (2) some lipid molecules leave the membrane by being entangled with ligands of the NP instead of completing the flip-flop that permits them to rejoin the membrane, thereby leading to fewer flip-flop events; and (3) the formation of water columns or water "fingers" provides a mechanism of ion transport across lipid bilayer membranes, but such ion penetration events are less likely for sodium ions than chloride ions and less likely for nanoparticles with longer-ligands.

  11. Adsorption of nanoparticles at the solid-liquid interface.

    PubMed

    Brenner, Thorsten; Paulus, Michael; Schroer, Martin A; Tiemeyer, Sebastian; Sternemann, Christian; Möller, Johannes; Tolan, Metin; Degen, Patrick; Rehage, Heinz

    2012-05-15

    The adsorption of differently charged nanoparticles at liquid-solid interfaces was investigated by in situ X-ray reflectivity measurements. The layer formation of positively charged maghemite (γ-Fe(2)O(3)) nanoparticles at the aqueous solution-SiO(2) interface was observed while negatively charged gold nanoparticles show no adsorption at this interface. Thus, the electrostatic interaction between the particles and the charged surface was determined as the driving force for the adsorption process. The data analysis shows that a logarithmic particle size distribution describes the density profile of the thin adsorbed maghemite layer. The size distribution in the nanoparticle solution determined by small angle X-ray scattering shows an average particle size which is similar to that found for the adsorbed film. The formed magehemite film exhibits a rather high stability.

  12. Adsorption of nanoparticles at the solid-liquid interface.

    PubMed

    Brenner, Thorsten; Paulus, Michael; Schroer, Martin A; Tiemeyer, Sebastian; Sternemann, Christian; Möller, Johannes; Tolan, Metin; Degen, Patrick; Rehage, Heinz

    2012-05-15

    The adsorption of differently charged nanoparticles at liquid-solid interfaces was investigated by in situ X-ray reflectivity measurements. The layer formation of positively charged maghemite (γ-Fe(2)O(3)) nanoparticles at the aqueous solution-SiO(2) interface was observed while negatively charged gold nanoparticles show no adsorption at this interface. Thus, the electrostatic interaction between the particles and the charged surface was determined as the driving force for the adsorption process. The data analysis shows that a logarithmic particle size distribution describes the density profile of the thin adsorbed maghemite layer. The size distribution in the nanoparticle solution determined by small angle X-ray scattering shows an average particle size which is similar to that found for the adsorbed film. The formed magehemite film exhibits a rather high stability. PMID:22386203

  13. Effects of magnetic cobalt ferrite nanoparticles on biological and artificial lipid membranes

    PubMed Central

    Drašler, Barbara; Drobne, Damjana; Novak, Sara; Valant, Janez; Boljte, Sabina; Otrin, Lado; Rappolt, Michael; Sartori, Barbara; Iglič, Aleš; Kralj-Iglič, Veronika; Šuštar, Vid; Makovec, Darko; Gyergyek, Sašo; Hočevar, Matej; Godec, Matjaž; Zupanc, Jernej

    2014-01-01

    Background The purpose of this work is to provide experimental evidence on the interactions of suspended nanoparticles with artificial or biological membranes and to assess the possibility of suspended nanoparticles interacting with the lipid component of biological membranes. Methods 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid vesicles and human red blood cells were incubated in suspensions of magnetic bare cobalt ferrite (CoFe2O4) or citric acid (CA)-adsorbed CoFe2O4 nanoparticles dispersed in phosphate-buffered saline and glucose solution. The stability of POPC giant unilamellar vesicles after incubation in the tested nanoparticle suspensions was assessed by phase-contrast light microscopy and analyzed with computer-aided imaging. Structural changes in the POPC multilamellar vesicles were assessed by small angle X-ray scattering, and the shape transformation of red blood cells after incubation in tested suspensions of nanoparticles was observed using scanning electron microscopy and sedimentation, agglutination, and hemolysis assays. Results Artificial lipid membranes were disturbed more by CA-adsorbed CoFe2O4 nanoparticle suspensions than by bare CoFe2O4 nanoparticle suspensions. CA-adsorbed CoFe2O4-CA nanoparticles caused more significant shape transformation in red blood cells than bare CoFe2O4 nanoparticles. Conclusion Consistent with their smaller sized agglomerates, CA-adsorbed CoFe2O4 nanoparticles demonstrate more pronounced effects on artificial and biological membranes. Larger agglomerates of nanoparticles were confirmed to be reactive against lipid membranes and thus not acceptable for use with red blood cells. This finding is significant with respect to the efficient and safe application of nanoparticles as medicinal agents. PMID:24741305

  14. Cyclosporine A-loaded lipid nanoparticles in inflammatory bowel disease.

    PubMed

    Guada, Melissa; Beloqui, Ana; Alhouayek, Mireille; Muccioli, Giulio G; Dios-Viéitez, Maria del Carmen; Préat, Véronique; Blanco-Prieto, Maria J

    2016-04-30

    Cyclosporine A (CsA) is a well-known immunosuppressive agent used as rescue therapy in severe steroid-refractory ulcerative colitis (UC). However, toxicity issues associated with CsA when administered in its commercially available formulations have been reported in clinical practice. Since nanotechnology has been proposed as a promising strategy to improve safety and efficacy in the treatment of inflammatory bowel disease (IBD), the main purpose of this study was to evaluate the effect of oral administration of CsA-loaded lipid nanoparticles (LN) in the dextran sodium sulfate (DSS)-induced colitis mouse model using Sandimmune Neoral(®) as reference. The results showed that the formulations used did not decrease colon inflammation in terms of myeloperoxidase activity (MPO), tumor necrosis factor (TNF)-α expression, or histological scoring in the acute stage of the disease. However, further studies are needed in order to corroborate the efficacy of these formulations in the chronic phase of the disease. PMID:26972380

  15. Porous Silica-Supported Solid Lipid Particles for Enhanced Solubilization of Poorly Soluble Drugs.

    PubMed

    Yasmin, Rokhsana; Rao, Shasha; Bremmell, Kristen E; Prestidge, Clive A

    2016-07-01

    Low dissolution of drugs in the intestinal fluid can limit their effectiveness in oral therapies. Here, a novel porous silica-supported solid lipid system was developed to optimize the oral delivery of drugs with limited aqueous solubility. Using lovastatin (LOV) as the model poorly water-soluble drug, two porous silica-supported solid lipid systems (SSL-A and SSL-S) were fabricated from solid lipid (glyceryl monostearate, GMS) and nanoporous silica particles Aerosil 380 (silica-A) and Syloid 244FP (silica-S) via immersion/solvent evaporation. SSL particles demonstrated significantly higher rate and extent of lipolysis in comparison with the pure solid lipid, depending on the lipid loading levels and the morphology. The highest lipid digestion was observed when silica-S was loaded with 34% (w/w) solid lipid, and differential scanning calorimeter (DSC) analysis confirmed the encapsulation of up to 2% (w/w) non-crystalline LOV in this optimal SSL-S formulation. Drug dissolution under non-digesting intestinal conditions revealed a three- to sixfold increase in dissolution efficiencies when compared to the unformulated drug and a LOV-lipid suspension. Furthermore, the SSL-S provided superior drug solubilization under simulated intestinal digesting condition in comparison with the drug-lipid suspension and drug-loaded silica. Therefore, solid lipid and nanoporous silica provides a synergistic effect on optimizing the solubilization of poorly water-soluble compound and the solid lipid-based porous carrier system provides a promising delivery approach to overcome the oral delivery challenges of poorly water-soluble drugs.

  16. Porous Silica-Supported Solid Lipid Particles for Enhanced Solubilization of Poorly Soluble Drugs.

    PubMed

    Yasmin, Rokhsana; Rao, Shasha; Bremmell, Kristen E; Prestidge, Clive A

    2016-07-01

    Low dissolution of drugs in the intestinal fluid can limit their effectiveness in oral therapies. Here, a novel porous silica-supported solid lipid system was developed to optimize the oral delivery of drugs with limited aqueous solubility. Using lovastatin (LOV) as the model poorly water-soluble drug, two porous silica-supported solid lipid systems (SSL-A and SSL-S) were fabricated from solid lipid (glyceryl monostearate, GMS) and nanoporous silica particles Aerosil 380 (silica-A) and Syloid 244FP (silica-S) via immersion/solvent evaporation. SSL particles demonstrated significantly higher rate and extent of lipolysis in comparison with the pure solid lipid, depending on the lipid loading levels and the morphology. The highest lipid digestion was observed when silica-S was loaded with 34% (w/w) solid lipid, and differential scanning calorimeter (DSC) analysis confirmed the encapsulation of up to 2% (w/w) non-crystalline LOV in this optimal SSL-S formulation. Drug dissolution under non-digesting intestinal conditions revealed a three- to sixfold increase in dissolution efficiencies when compared to the unformulated drug and a LOV-lipid suspension. Furthermore, the SSL-S provided superior drug solubilization under simulated intestinal digesting condition in comparison with the drug-lipid suspension and drug-loaded silica. Therefore, solid lipid and nanoporous silica provides a synergistic effect on optimizing the solubilization of poorly water-soluble compound and the solid lipid-based porous carrier system provides a promising delivery approach to overcome the oral delivery challenges of poorly water-soluble drugs. PMID:27048207

  17. Solid lipid microparticles for enhanced dermal delivery of tetracycline HCl.

    PubMed

    Rahimpour, Yahya; Javadzadeh, Yousef; Hamishehkar, Hamed

    2016-09-01

    Acne vulgaris (commonly called acne) is a most common skin disease during adolescence, afflicting more than 85% of teenagers. Topical tetracycline (Tc) is used for mild inflammatory acne and as an adjunct to systemic treatment in more severe forms. Solid lipid microparticles (SLMs) are useful tool for topical delivery because of their biodegradable, biocompatible and low toxic characteristic accompanying with excellent skin hydration, occlusiveness and controlled release properties. The purpose of this study was to prepare Tc-loaded SLMs were produced by the spray drying technique and characterized by scanning electron microscopy, powder X-ray diffractometry and differential scanning calorimetry. In vitro and ex vivo release characteristics of Tc through SLMs and control formulations (aqueous carbopol gel) were evaluated over 24h using a vertical Franz diffusion cell through cellulose acetate membranes and exercised rat skin, respectively. SLM formulations present high encapsulation values above 97% without significant different among formulations (p<0.05). The sustained release pattern of Tc through SLMs was illustrated by in vitro release study. The ex vivo drug skin permeation study revealed that Tc dermal deposition of optimum SLMs formulation was about 7 times that of the control formulations. The enhanced skin penetration and accumulation of Tc observed for Tc-loaded SLMs may increase the efficiency of acne therapy and decrease the associated Tc side effects. PMID:27131093

  18. Comparison of the oral bioavailability of silymarin-loaded lipid nanoparticles with their artificial lipolysate counterparts: implications on the contribution of integral structure.

    PubMed

    Shangguan, Mingzhu; Qi, Jianping; Lu, Yi; Wu, Wei

    2015-07-15

    Both solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were artificially broken down into lipolysates. Their oral bioavailability, with silymarin as a model drug, was compared in dogs to highlight the contribution of their integral structure. The lipid nanoparticles were prepared using a conventional hot homogenization method, whereas the lipolysates were obtained through lipolysis in phospholipid- and bile salt-enriched simulated intestinal fluid. More than 80% of vehicle-associated drugs could be transformed into the water-soluble form of mixed micelles. Pharmacokinetics analysis in dogs showed a decrease in bioavailability of 74.86% and 59.09% for lipolysates compared to integral NLCs and SLNs, respectively. It was indicated that lipolysates contributed to a majority of drug absorption. Integral nanoparticles were superior to their lipolysate counterparts, but only marginally; if the approximately 20% of the drug that precipitated during in vitro lipolysis was deducted from the overall absorption amount, the superiority of integral nanoparticles would be significantly compromised. In conclusion, lipolysis was the predominant in vivo absorption mechanism, and the contribution of intact lipid nanoparticles was limited.

  19. Dry powder inhaler formulation of lipid-polymer hybrid nanoparticles via electrostatically-driven nanoparticle assembly onto microscale carrier particles.

    PubMed

    Yang, Yue; Cheow, Wean Sin; Hadinoto, Kunn

    2012-09-15

    Lipid-polymer hybrid nanoparticles have emerged as promising nanoscale carriers of therapeutics as they combine the attractive characteristics of liposomes and polymers. Herein we develop dry powder inhaler (DPI) formulation of hybrid nanoparticles composed of poly(lactic-co-glycolic acid) and soybean lecithin as the polymer and lipid constituents, respectively. The hybrid nanoparticles are transformed into inhalable microscale nanocomposite structures by a novel technique based on electrostatically-driven adsorption of nanoparticles onto polysaccharide carrier particles, which eliminates the drawbacks of conventional techniques based on controlled drying (e.g. nanoparticle-specific formulation, low yield). First, we engineer polysaccharide carrier particles made up of chitosan cross-linked with tripolyphosphate and dextran sulphate to exhibit the desired aerosolization characteristics and physical robustness. Second, we investigate the effects of nanoparticle to carrier mass ratio and salt inclusion on the adsorption efficiency, in terms of the nanoparticle loading and yield, from which the optimal formulation is determined. Desorption of the nanoparticles from the carrier particles in phosphate buffer saline is also examined. Lastly, we characterize aerosolization efficiency of the nanocomposite product in vitro, where the emitted dose and respirable fraction are found to be comparable to the values of conventional DPI formulations.

  20. Ultrafast Electronic Dynamics in Solid and Liquid Gallium Nanoparticles

    NASA Astrophysics Data System (ADS)

    Nisoli, M.; Stagira, S.; de Silvestri, S.; Stella, A.; Tognini, P.; Cheyssac, P.; Kofman, R.

    1997-05-01

    The electron thermalization process both in solid and liquid metallic gallium nanoparticles with radii in the range 50-90 Å is investigated by femtosecond pump-probe measurements. The results show that the temporal behavior of the electron energy relaxation is similar in both phases, with a time constant varying from ~0.6 to ~1.6 ps by increasing the nanoparticle size. We interpret the experimental data in terms of a size-dependent electron-surface interaction model and show the importance of the energy exchange with surface phonons in the electronic thermalization.

  1. Topical Skin Cancer Therapy Using Doxorubicin-Loaded Cationic Lipid Nanoparticles and lontophoresis.

    PubMed

    Huber, Lucas A; Pereira, Tatiana A; Ramos, Danielle N; Rezende, Lucas C D; Emery, Flávio S; Sobral, Lays Martin; Leopoldino, Andréia Machado; Lopez, Renata F V

    2015-11-01

    The topical administration of chemotherapeutics is a promising approach for the treatment of skin cancer; however, different pharmaceutical strategies are required to allow large amounts of drug to penetrate tumors. This work examined the potential of the anodic iontophoresis of doxorubicin-loaded cationic solid lipid nanoparticles (DOX-SLN) to increase the distribution and tumor penetration of DOX. A double-labeled cationic DOX-SLN composed of the lipids stearic acid and monoolein and a new BODIPY dye was prepared and characterized. The skin distribution and penetration of DOX were evaluated in vitro using confocal microscopy and vertical diffusion cells, respectively. The antitumor potential was evaluated in vivo through the anodic iontophoresis of DOX-SLN in squamous cell carcinoma induced in nude BALB/c mice. The encapsulation of DOX drastically altered the DOX partition coefficient and increased the distribution of DOX in the lipid matrix of the stratum corneum (SC). The association with iontophoresis created high-concentration drug reservoir zones in the follicles of the skin. Although the iontophoresis of a DOX solution increased the penetration of DOX in the viable epidermis by approximately 4-fold, the iontophoresis of cationic DOX-SLN increased the DOX penetration by approximately 50-fold. In vivo, the DOX-SLN iontophoretic treatment was effective in inhibiting tumor cell survival and tumor growth and was accompanied by an increase in keratinization and consequent cell death. These results indicate a strong and synergic effect of iontophoresis with DOX-SLN and provide a potential strategy for the treatment of skin cancer.

  2. Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

    PubMed

    Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

    2016-01-01

    Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace. PMID:26354801

  3. Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

    PubMed

    Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

    2016-01-01

    Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace.

  4. Supercritical fluid precipitation of ketoprofen in novel structured lipid carriers for enhanced mucosal delivery--a comparison with solid lipid particles.

    PubMed

    Gonçalves, V S S; Matias, A A; Rodríguez-Rojo, S; Nogueira, I D; Duarte, C M M

    2015-11-10

    Structured lipid carriers based on mixture of solid lipids with liquid lipids are the second generation of solid lipid particles, offering the advantage of improved drug loading capacity and higher storage stability. In this study, structured lipid carriers were successfully prepared for the first time by precipitation from gas saturated solutions. Glyceryl monooleate (GMO), a liquid glycerolipid, was selected in this work to be incorporated into three solid glycerolipids with hydrophilic-lipophilic balance (HLB) ranging from 1 to 13, namely Gelucire 43/01™, Geleol™ and Gelucire 50/13™. In general, microparticles with a irregular porous morphology and a wide particle size distribution were obtained. The HLB of the individual glycerolipids might be a relevant parameter to take into account during the processing of solid:liquid lipid blends. As expected, the addition of a liquid lipid into a solid lipid matrix led to increased stability of the lipid carriers, with no significant modifications in their melting enthalpy after 6 months of storage. Additionally, Gelucire 43/01™:GMO particles were produced with different mass ratios and loaded with ketoprofen. The drug loading capacity of the structured lipid carriers increased as the GMO content in the particles increased, achieving a maximum encapsulation efficiency of 97% for the 3:1 mass ratio. Moreover, structured lipid carriers presented an immediate release of ketoprofen from its matrix with higher permeation through a mucous-membrane model, while solid lipid particles present a controlled release of the drug with less permeation capacity.

  5. Lipid-polymer hybrid nanoparticles as a new generation therapeutic delivery platform: a review.

    PubMed

    Hadinoto, Kunn; Sundaresan, Ajitha; Cheow, Wean Sin

    2013-11-01

    Lipid-polymer hybrid nanoparticles (LPNs) are core-shell nanoparticle structures comprising polymer cores and lipid/lipid-PEG shells, which exhibit complementary characteristics of both polymeric nanoparticles and liposomes, particularly in terms of their physical stability and biocompatibility. Significantly, the LPNs have recently been demonstrated to exhibit superior in vivo cellular delivery efficacy compared to that obtained from polymeric nanoparticles and liposomes. Since their inception, the LPNs have advanced significantly in terms of their preparation strategy and scope of applications. Their preparation strategy has undergone a shift from the conceptually simple two-step method, involving preformed polymeric nanoparticles and lipid vesicles, to the more principally complex, yet easier to perform, one-step method, relying on simultaneous self-assembly of the lipid and polymer, which has resulted in better products and higher production throughput. The scope of LPNs' applications has also been extended beyond single drug delivery for anticancer therapy, to include combinatorial and active targeted drug deliveries, and deliveries of genetic materials, vaccines, and diagnostic imaging agents. This review details the current state of development for the LPNs preparation and applications from which we identify future research works needed to bring the LPNs closer to its clinical realization.

  6. Lipid-polymer hybrid nanoparticles as a new generation therapeutic delivery platform: a review.

    PubMed

    Hadinoto, Kunn; Sundaresan, Ajitha; Cheow, Wean Sin

    2013-11-01

    Lipid-polymer hybrid nanoparticles (LPNs) are core-shell nanoparticle structures comprising polymer cores and lipid/lipid-PEG shells, which exhibit complementary characteristics of both polymeric nanoparticles and liposomes, particularly in terms of their physical stability and biocompatibility. Significantly, the LPNs have recently been demonstrated to exhibit superior in vivo cellular delivery efficacy compared to that obtained from polymeric nanoparticles and liposomes. Since their inception, the LPNs have advanced significantly in terms of their preparation strategy and scope of applications. Their preparation strategy has undergone a shift from the conceptually simple two-step method, involving preformed polymeric nanoparticles and lipid vesicles, to the more principally complex, yet easier to perform, one-step method, relying on simultaneous self-assembly of the lipid and polymer, which has resulted in better products and higher production throughput. The scope of LPNs' applications has also been extended beyond single drug delivery for anticancer therapy, to include combinatorial and active targeted drug deliveries, and deliveries of genetic materials, vaccines, and diagnostic imaging agents. This review details the current state of development for the LPNs preparation and applications from which we identify future research works needed to bring the LPNs closer to its clinical realization. PMID:23872180

  7. Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A quality-by-design approach.

    PubMed

    Rose, Fabrice; Wern, Jeanette Erbo; Ingvarsson, Pall Thor; van de Weert, Marco; Andersen, Peter; Follmann, Frank; Foged, Camilla

    2015-07-28

    The purpose of this study was to design a novel and versatile adjuvant intended for mucosal vaccination based on biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with the cationic surfactant dimethyldioctadecylammonium (DDA) bromide and the immunopotentiator trehalose-6,6'-dibehenate (TDB) (CAF01) to tailor humoral and cellular immunity characterized by antibodies and Th1/Th17 responses. Such responses are important for the protection against diseases caused by intracellular bacteria such as Chlamydia trachomatis and Mycobacterium tuberculosis. The hybrid NPs were engineered using an oil-in-water single emulsion method and a quality-by-design approach was adopted to define the optimal operating space (OOS). Four critical process parameters (CPPs) were identified, including the acetone concentration in the water phase, the stabilizer [polyvinylalcohol (PVA)] concentration, the lipid-to-total solid ratio, and the total concentration. The CPPs were linked to critical quality attributes consisting of the particle size, polydispersity index (PDI), zeta-potential, thermotropic phase behavior, yield and stability. A central composite face-centered design was performed followed by multiple linear regression analysis. The size, PDI, enthalpy of the phase transition and yield were successfully modeled, whereas the models for the zeta-potential and the stability were poor. Cryo-transmission electron microscopy revealed that the main structural effect on the nanoparticle architecture is caused by the use of PVA, and two different morphologies were identified: i) A PLGA core coated with one or several concentric lipid bilayers, and ii) a PLGA nanoshell encapsulating lipid membrane structures. The optimal formulation, identified from the OOS, was evaluated in vivo. The hybrid NPs induced antibody and Th1/Th17 immune responses that were similar in quality and magnitude to the response induced by DDA/TDB liposomes, showing that the adjuvant

  8. Assembling nanoparticle coatings to improve the drug delivery performance of lipid based colloids

    NASA Astrophysics Data System (ADS)

    Simovic, Spomenka; Barnes, Timothy J.; Tan, Angel; Prestidge, Clive A.

    2012-02-01

    Lipid based colloids (e.g. emulsions and liposomes) are widely used as drug delivery systems, but often suffer from physical instabilities and non-ideal drug encapsulation and delivery performance. We review the application of engineered nanoparticle layers at the interface of lipid colloids to improve their performance as drug delivery systems. In addition we focus on the creation of novel hybrid nanomaterials from nanoparticle-lipid colloid assemblies and their drug delivery applications. Specifically, nanoparticle layers can be engineered to enhance the physical stability of submicron lipid emulsions and liposomes, satbilise encapsulated active ingredients against chemical degradation, control molecular transport and improve the dermal and oral delivery characteristics, i.e. increase absorption, bioavailability and facilitate targeted delivery. It is feasible that hybrid nanomaterials composed of nanoparticles and colloidal lipids are effective encapsulation and delivery systems for both poorly soluble drugs and biological drugs and may form the basis for the next generation of medicines. Additional pre-clinical research including specific animal model studies are required to advance the peptide/protein delivery systems, whereas the silica lipid hybrid systems have now entered human clinical trials for poorly soluble drugs.

  9. Assembling nanoparticle coatings to improve the drug delivery performance of lipid based colloids.

    PubMed

    Simovic, Spomenka; Barnes, Timothy J; Tan, Angel; Prestidge, Clive A

    2012-02-21

    Lipid based colloids (e.g. emulsions and liposomes) are widely used as drug delivery systems, but often suffer from physical instabilities and non-ideal drug encapsulation and delivery performance. We review the application of engineered nanoparticle layers at the interface of lipid colloids to improve their performance as drug delivery systems. In addition we focus on the creation of novel hybrid nanomaterials from nanoparticle-lipid colloid assemblies and their drug delivery applications. Specifically, nanoparticle layers can be engineered to enhance the physical stability of submicron lipid emulsions and liposomes, satbilise encapsulated active ingredients against chemical degradation, control molecular transport and improve the dermal and oral delivery characteristics, i.e. increase absorption, bioavailability and facilitate targeted delivery. It is feasible that hybrid nanomaterials composed of nanoparticles and colloidal lipids are effective encapsulation and delivery systems for both poorly soluble drugs and biological drugs and may form the basis for the next generation of medicines. Additional pre-clinical research including specific animal model studies are required to advance the peptide/protein delivery systems, whereas the silica lipid hybrid systems have now entered human clinical trials for poorly soluble drugs.

  10. Lipid nanoparticles for alkyl lysophospholipid edelfosine encapsulation: development and in vitro characterization.

    PubMed

    Estella-Hermoso de Mendoza, Ander; Rayo, Marta; Mollinedo, Faustino; Blanco-Prieto, María J

    2008-02-01

    The ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine, edelfosine (ET-18-OCH(3)) is the prototype molecule of a promising class of antitumor drugs named alkyl-lysophospholipid analogues (ALPs) or antitumor ether lipids. This drug presents a very important drawback as can be the dose dependent haemolysis when administered intravenously. Lipid nanoparticles have been lately proposed for different drug encapsulation as an alternative to other controlled release delivery systems, such as liposomes or polymeric nanoparticles. The aim of this study was to develop a lipid nanoparticulate system that would decrease systemic toxicity as well as improve the therapeutic potential of the drug. Lipids employed were Compritol 888 ATO and stearic acid. The nanoparticles were characterized by photon correlation spectroscopy for size and size distribution, and atomic force microscopy (AFM) was used for the determination of morphological properties. By both differential scanning calorimetry (DSC) and X-ray diffractometry, crystalline behaviour of lipids and drug was assessed. The drug encapsulation efficiency and the drug release kinetics under in vitro conditions were measured by HPLC-MS. It was concluded that Compritol presents advantages as a matrix material for the manufacture of the nanoparticles and for the controlled release of edelfosine. PMID:17707618

  11. The Interplay of Lung Surfactant Proteins and Lipids Assimilates the Macrophage Clearance of Nanoparticles

    PubMed Central

    Ruge, Christian A.; Schaefer, Ulrich F.; Herrmann, Jennifer; Kirch, Julian; Cañadas, Olga; Echaide, Mercedes; Pérez-Gil, Jesús; Casals, Cristina; Müller, Rolf; Lehr, Claus-Michael

    2012-01-01

    The peripheral lungs are a potential entrance portal for nanoparticles into the human body due to their large surface area. The fact that nanoparticles can be deposited in the alveolar region of the lungs is of interest for pulmonary drug delivery strategies and is of equal importance for toxicological considerations. Therefore, a detailed understanding of nanoparticle interaction with the structures of this largest and most sensitive part of the lungs is important for both nanomedicine and nanotoxicology. Astonishingly, there is still little known about the bio-nano interactions that occur after nanoparticle deposition in the alveoli. In this study, we compared the effects of surfactant-associated protein A (SP-A) and D (SP-D) on the clearance of magnetite nanoparticles (mNP) with either more hydrophilic (starch) or hydrophobic (phosphatidylcholine) surface modification by an alveolar macrophage (AM) cell line (MH-S) using flow cytometry and confocal microscopy. Both proteins enhanced the AM uptake of mNP compared with pristine nanoparticles; for the hydrophilic ST-mNP, this effect was strongest with SP-D, whereas for the hydrophobic PL-mNP it was most pronounced with SP-A. Using gel electrophoretic and dynamic light scattering methods, we were able to demonstrate that the observed cellular effects were related to protein adsorption and to protein-mediated interference with the colloidal stability. Next, we investigated the influence of various surfactant lipids on nanoparticle uptake by AM because lipids are the major surfactant component. Synthetic surfactant lipid and isolated native surfactant preparations significantly modulated the effects exerted by SP-A and SP-D, respectively, resulting in comparable levels of macrophage interaction for both hydrophilic and hydrophobic nanoparticles. Our findings suggest that because of the interplay of both surfactant lipids and proteins, the AM clearance of nanoparticles is essentially the same, regardless of different

  12. Synthesis of carbon-encapsulated iron nanoparticles via solid state reduction of iron oxide nanoparticles

    SciTech Connect

    Bystrzejewski, M.

    2011-06-15

    The encapsulation of iron nanoparticles in protective carbon cages leads to unique hybrid core-shell nanomaterials. Recent literature reports suggest that such nanocomposites can be obtained in a relatively simple process involving the solid state carbothermal reduction of iron oxide nanoparticles. This approach is very attractive because it does not require advanced equipment and consumes less energy in comparison to widely used plasma methods. The presented more-in-depth study shows that the carbothermal approach is sensitive to temperature and the process yield strongly depends on the morphology and crystallinity of the carbon material used as a reductant. - Graphical abstract: Reduction of iron oxide nanoparticles by carbon black at 1200 deg. C yields well crystallized carbon-encapsulated iron nanoparticles. Highlights: > Carbon-encapsulated iron nanoparticles were synthesized by carbothermal reduction of iron oxide nanoparticles. > The process has the highest selectivity at 1200 C. > Lower temperatures result in iron oxide nanoparticles wrapped in carbon matrix. > The encapsulation rate of Fe at 1200 deg. C was found to be 15%.

  13. Comparative biodistribution in mice of cyanine dyes loaded in lipid nanoparticles.

    PubMed

    Mérian, Juliette; Boisgard, Raphaël; Bayle, Pierre-Alain; Bardet, Michel; Tavitian, Bertrand; Texier, Isabelle

    2015-06-01

    Two near infrared cyanine dyes, DiD (1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine perchlorate) and ICG (Indocyanine Green) were loaded in lipid nanoparticles (LNP). DiD-LNP and ICG-LNP presented similar physicochemical characteristics (hydrodynamic diameter, polydispersity, zeta potential), encapsulation efficiency, and colloidal stability when stored in PBS buffer. However, whereas DiD had similar biodistribution than cholesteryl-1-(14)C-oleate ([(14)C]CHO, a constituent of the nanoparticle used as a reference radiotracer), ICG displayed a different biodistribution pattern, similar to that of the free dye, indicative of its immediate leakage from the nanovector after blood injection. NMR spectroscopy using Proton NOE (Nuclear Overhauser Effect) measurements showed that the localization of the dye in the lipid nanoparticles was slightly different: ICG, more amphiphilic than DiD, was found both inside the lipid core and at particle interface, whereas DiD, more hydrophobic, appeared exclusively located inside the particle core. The ICG release rate from the particles was 7% per 1 month under storage conditions (4 °C, dark, 10% of lipids), whereas no leakage could be detected for DiD. ICG leakage increased considerably in the presence of BSA 40 g/L (45% leakage in 24h at 100 mg/mL of lipids), because of the high affinity of the fluorophore for plasma proteins. On the contrary, no DiD leakage was observed, until high dilution of the nanoparticles which triggered their dissociation (45% leakage in 24h at 1 mg/mL of lipids). Altogether, the subtle difference in dye localization into the nanoparticles, the partial dissociation of the LNP in diluted media, and more importantly the high ICG affinity for plasma proteins, accounted for the differences observed in the fluorescence biodistribution after tail vein injection of the dye-loaded nanoparticles.

  14. Targeted lipid-polyaniline hybrid nanoparticles for photoacoustic imaging guided photothermal therapy of cancer

    NASA Astrophysics Data System (ADS)

    Wang, Jinping; Yan, Ran; Guo, Fang; Yu, Meng; Tan, Fengping; Li, Nan

    2016-07-01

    Designing a targeted and versatile photothermal agent for the integration of precise diagnosis and effective photothermal treatment of tumors is desirable but remains a great challenge. In this study, folic acid ligand conjugated lipid-coated polyaniline hybrid nanoparticles (FA-Lipid-PANI NPs) were successfully fabricated by a distinctive technology. The obtained hybrid FA-Lipid-PANI NPs with small size exhibited not only significant photoacoustic (PA) imaging signals, but also a remarkable photothermal effect for tumor treatment. With PA imaging and photothermal therapy (PTT), the tumor could be accurately positioned and thoroughly eradicated in vivo after intravenous injection of FA-Lipid-PANI NPs. These multifunctional nanoparticles could play an important role in simultaneously facilitating imaging and PTT to achieve better therapeutic efficacy.

  15. Combinatorial library strategies for synthesis of cationic lipid-like nanoparticles and their potential medical applications.

    PubMed

    Altınoglu, Sarah; Wang, Ming; Xu, Qiaobing

    2015-03-01

    The past two decades have witnessed the high efficiency and efficacy of cationic lipids and liposomal formations for drug delivery. The tedious synthesis of conventional lipids and the inefficiency in studying structure-activity relationships, however, have hindered the clinical translation of lipid nanoparticle delivery systems. Combinatorial synthesis of lipid-like nanoparticles ('lipidoids') has recently emerged as an approach to accelerate the development of these delivery platforms. Utilizing a high-throughput screening strategy, the libraries of lipidoids are sorted and prime candidates for the delivery in the intended application can be identified and optimized for the next generation. In this review, we outline methods used for combinatorial lipidoid synthesis, the application of high-throughput screening, and the current medical applications of candidate lipidoids.

  16. Fucose decorated solid-lipid nanocarriers mediate efficient delivery of methotrexate in breast cancer therapeutics.

    PubMed

    Garg, Neeraj K; Singh, Bhupinder; Jain, Ashay; Nirbhavane, Pradip; Sharma, Rajeev; Tyagi, Rajeev K; Kushwah, Varun; Jain, Sanyog; Katare, Om Prakash

    2016-10-01

    The present study is designed to engineer fucose anchored methotrexate loaded solid lipid nanoparticles (SLNs) to target breast cancer. The developed nano-carriers were characterized with respect to particle size, PDI, zeta potential, drug loading and entrapment, in-vitro release etc. The characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, biodistribution, changes in tumor volume and animal survival. The ex-vivo results showed greater cellular uptake and better cytotoxicity at lower IC50 of methotrexate in breast cancer cells. Further, we observed increased programmed cell death (apoptosis) with altered lysosomal membrane permeability and better rate of degradation of lysosomal membrane in-vitro. On the other hand, in-vivo evaluation showed maximum bioavailability and tumor targeting efficiency with minimum secondary drug distribution in various organs with formulated and anchored nano-carrier when compared with free drug. Moreover, sizeable reduction in tumor burden was estimated with fucose decorated SLNs as compared to that seen with free MTX and SLNs-MTX. Fucose decorated SLNs showed promising results to develop therapeutic interventions for breast cancer, and paved a way to explore this promising and novel nano-carrier which enables to address breast cancer. PMID:27268228

  17. Fucose decorated solid-lipid nanocarriers mediate efficient delivery of methotrexate in breast cancer therapeutics.

    PubMed

    Garg, Neeraj K; Singh, Bhupinder; Jain, Ashay; Nirbhavane, Pradip; Sharma, Rajeev; Tyagi, Rajeev K; Kushwah, Varun; Jain, Sanyog; Katare, Om Prakash

    2016-10-01

    The present study is designed to engineer fucose anchored methotrexate loaded solid lipid nanoparticles (SLNs) to target breast cancer. The developed nano-carriers were characterized with respect to particle size, PDI, zeta potential, drug loading and entrapment, in-vitro release etc. The characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, biodistribution, changes in tumor volume and animal survival. The ex-vivo results showed greater cellular uptake and better cytotoxicity at lower IC50 of methotrexate in breast cancer cells. Further, we observed increased programmed cell death (apoptosis) with altered lysosomal membrane permeability and better rate of degradation of lysosomal membrane in-vitro. On the other hand, in-vivo evaluation showed maximum bioavailability and tumor targeting efficiency with minimum secondary drug distribution in various organs with formulated and anchored nano-carrier when compared with free drug. Moreover, sizeable reduction in tumor burden was estimated with fucose decorated SLNs as compared to that seen with free MTX and SLNs-MTX. Fucose decorated SLNs showed promising results to develop therapeutic interventions for breast cancer, and paved a way to explore this promising and novel nano-carrier which enables to address breast cancer.

  18. Direct measurements of heating by electromagnetically trapped gold nanoparticles on supported lipid bilayers.

    PubMed

    Bendix, Poul M; Reihani, S Nader S; Oddershede, Lene B

    2010-04-27

    Absorption of electromagnetic irradiation results in significant heating of metallic nanoparticles, an effect which can be advantageously used in biomedical contexts. Also, metallic nanoparticles are presently finding widespread use as handles, contacts, or markers in nanometer scale systems, and for these purposes it is essential that the temperature increase associated with electromagnetic irradiation is not harmful to the environment. Regardless of whether the heating of metallic nanoparticles is desired or not, it is crucial for nanobio assays to know the exact temperature increase associated with electromagnetic irradiation of metallic nanoparticles. We performed direct measurements of the temperature surrounding single gold nanoparticles optically trapped on a lipid bilayer, a biologically relevant matrix. The lipid bilayer had incorporated fluorescent molecules which have a preference for either fluid or gel phases. The heating associated with electromagnetic radiation was measured by visualizing the melted footprint around the irradiated particle. The effect was measured for individual gold nanoparticles of a variety of sizes and for a variety of laser powers. The temperatures were highly dependent on particle size and laser power, with surface temperature increments ranging from a few to hundreds of degrees Celsius. Our results show that by a careful choice of gold nanoparticle size and strength of irradiating electromagnetic field, one can control the exact particle temperature. The method is easily applicable to any type of nanoparticle for which the photothermal effect is sought to be quantified.

  19. WO3/Pt nanoparticles promote light-induced lipid peroxidation and lysosomal instability within tumor cells.

    PubMed

    Clark, Andrea J; Petty, Howard R

    2016-02-19

    Although metal-metal oxide nanoparticles have attracted considerable interest as catalysts, they have attracted little interest in nanomedicine. This is likely due to the fact that metal oxide semiconductors generally require biologically harmful ultraviolet excitation. In contrast, this study focuses upon WO3/Pt nanoparticles, which can be excited by visible light. To optimize the nanoparticles' catalytic performance, platinization was performed at alkaline pH. These nanoparticles destroyed organic dyes, consumed dissolved oxygen and produced hydroxyl radicals. 4T1 breast cancer cells internalized WO3/Pt nanoparticles within the membrane-bound endo-lysosomal compartment as shown by electron and fluorescence microscopy. During visible light exposure, but not in darkness, WO3/Pt nanoparticles manufacture reactive oxygen species, promote lipid peroxidation, and trigger lysosomal membrane disruption. As cells of the immune system degrade organic molecules, produce reactive oxygen species, and activate the lipid peroxidation pathway within target cells, these nanoparticles mimic the chemical attributes of immune effector cells. These biomimetic nanoparticles should become useful in managing certain cancers, especially ocular cancer.

  20. WO3/Pt nanoparticles promote light-induced lipid peroxidation and lysosomal instability within tumor cells.

    PubMed

    Clark, Andrea J; Petty, Howard R

    2016-02-19

    Although metal-metal oxide nanoparticles have attracted considerable interest as catalysts, they have attracted little interest in nanomedicine. This is likely due to the fact that metal oxide semiconductors generally require biologically harmful ultraviolet excitation. In contrast, this study focuses upon WO3/Pt nanoparticles, which can be excited by visible light. To optimize the nanoparticles' catalytic performance, platinization was performed at alkaline pH. These nanoparticles destroyed organic dyes, consumed dissolved oxygen and produced hydroxyl radicals. 4T1 breast cancer cells internalized WO3/Pt nanoparticles within the membrane-bound endo-lysosomal compartment as shown by electron and fluorescence microscopy. During visible light exposure, but not in darkness, WO3/Pt nanoparticles manufacture reactive oxygen species, promote lipid peroxidation, and trigger lysosomal membrane disruption. As cells of the immune system degrade organic molecules, produce reactive oxygen species, and activate the lipid peroxidation pathway within target cells, these nanoparticles mimic the chemical attributes of immune effector cells. These biomimetic nanoparticles should become useful in managing certain cancers, especially ocular cancer. PMID:26788907

  1. Solid-phase synthesis of molecularly imprinted nanoparticles.

    PubMed

    Canfarotta, Francesco; Poma, Alessandro; Guerreiro, Antonio; Piletsky, Sergey

    2016-03-01

    Molecularly imprinted polymers (MIPs) are synthetic materials, generally based on acrylic or methacrylic monomers, that are polymerized in the presence of a specific target molecule called the 'template' and capable of rebinding selectively to this target molecule. They have the potential to be low-cost and robust alternatives to biomolecules such as antibodies and receptors. When prepared by traditional synthetic methods (i.e., with free template in solution), their usefulness has been limited by high binding site heterogeneity, the presence of residual template and the fact that the production methods are complex and difficult to standardize. To overcome some of these limitations, we developed a method for the synthesis of MIP nanoparticles (nanoMIPs) using an innovative solid-phase approach, which relies on the covalent immobilization of the template molecules onto the surface of a solid support (glass beads). The obtained nanoMIPs are virtually free of template and demonstrate high affinity for the target molecule (e.g., melamine and trypsin in our published work). Because of an affinity separation step performed on the solid phase after polymerization, poor binders and unproductive polymer are removed, so the final product has more uniform binding characteristics. The overall protocol, starting from the immobilization of the template onto the solid phase and including the purification and characterization of the nanoparticles, takes up to 1 week.

  2. Solid-phase synthesis of molecularly imprinted nanoparticles.

    PubMed

    Canfarotta, Francesco; Poma, Alessandro; Guerreiro, Antonio; Piletsky, Sergey

    2016-03-01

    Molecularly imprinted polymers (MIPs) are synthetic materials, generally based on acrylic or methacrylic monomers, that are polymerized in the presence of a specific target molecule called the 'template' and capable of rebinding selectively to this target molecule. They have the potential to be low-cost and robust alternatives to biomolecules such as antibodies and receptors. When prepared by traditional synthetic methods (i.e., with free template in solution), their usefulness has been limited by high binding site heterogeneity, the presence of residual template and the fact that the production methods are complex and difficult to standardize. To overcome some of these limitations, we developed a method for the synthesis of MIP nanoparticles (nanoMIPs) using an innovative solid-phase approach, which relies on the covalent immobilization of the template molecules onto the surface of a solid support (glass beads). The obtained nanoMIPs are virtually free of template and demonstrate high affinity for the target molecule (e.g., melamine and trypsin in our published work). Because of an affinity separation step performed on the solid phase after polymerization, poor binders and unproductive polymer are removed, so the final product has more uniform binding characteristics. The overall protocol, starting from the immobilization of the template onto the solid phase and including the purification and characterization of the nanoparticles, takes up to 1 week. PMID:26866789

  3. Formulation and characterization of hydrochlorothiazide solid lipid microparticles based on lipid matrices of Irvingia fat

    PubMed Central

    Agubata, Chukwuma O.; Chime, Salome A.; Kenechukwu, Franklin C.; Nzekwe, Ifeanyi T.; Onunkwo, Godswill C.

    2014-01-01

    Introduction: The purpose of this study was to improve the solubilization, bioavailability, and permeability of hydrochlorothiazide (HCTZ) by the formulation and characterization of HCTZ solid lipid microparticles (SLMs) based on fat derived from Irvingia gabonensis var. excelsa (Irvingia wombolu) and Phospholipon®90G (P90G). Materials and Methods: Irvingia fat was extracted from the nut of I. gabonensis var. excelsa using petroleum ether (40-60°C). HCTZ loaded SLM were formulated using hot homogenization method with 5% w/w Irvingia fat/P90G at each of 1:0, 9:1, 4:1, and 3:1 ratios, 1% w/w HCTZ, 1.5% w/w Labrasol® surfactant and distilled water. Subsequently, particle size analysis, pH, syringeability, drug encapsulation efficiency (EE%), yield, freeze-thaw cycle test, drug release, diffusion, and kinetics were evaluated. Results: The SLM dispersions showed a particle size range of 10.15 ± 2.36 to 13.50 ± 6.88 μm and pH of 5.6-6.4 while dispersions containing 3:1 Irvingia fat/P90G passed through most of the needles (18G, 21G, and 22G) after syringeability studies. A single freeze-thaw cycle caused loss of physical integrity. The EE% of the SLMs were ≥80%, with high yield. The highest drug release and diffusion was observed with SLMs prepared with 3:1 Irvingia fat-P90G mixture (HDP3) and Higuchi model best described the kinetics of the HCTZ release by Fickian diffusion. Conclusion: The release and permeability of HCTZ was improved by its incorporation into Irvingia fat and P90G (3:1) as SLMs. PMID:25426440

  4. Ultra-small lipid-polymer hybrid nanoparticles for tumor-penetrating drug delivery

    NASA Astrophysics Data System (ADS)

    Dehaini, Diana; Fang, Ronnie H.; Luk, Brian T.; Pang, Zhiqing; Hu, Che-Ming J.; Kroll, Ashley V.; Yu, Chun Lai; Gao, Weiwei; Zhang, Liangfang

    2016-07-01

    Lipid-polymer hybrid nanoparticles, consisting of a polymeric core coated by a layer of lipids, are a class of highly scalable, biodegradable nanocarriers that have shown great promise in drug delivery applications. Here, we demonstrate the facile synthesis of ultra-small, sub-25 nm lipid-polymer hybrid nanoparticles using an adapted nanoprecipitation approach and explore their utility for targeted delivery of a model chemotherapeutic. The fabrication process is first optimized to produce a monodisperse population of particles that are stable under physiological conditions. It is shown that these ultra-small hybrid nanoparticles can be functionalized with a targeting ligand on the surface and loaded with drug inside the polymeric matrix. Further, the in vivo fate of the nanoparticles after intravenous injection is characterized by examining the blood circulation and biodistribution. In a final proof-of-concept study, targeted ultra-small hybrid nanoparticles loaded with the cancer drug docetaxel are used to treat a mouse tumor model and demonstrate improved efficacy compared to a clinically available formulation of the drug. The ability to synthesize a significantly smaller version of the established lipid-polymer hybrid platform can ultimately enhance its applicability across a wider range of applications.

  5. Solid-state NMR spectra of lipid-anchored proteins under magic angle spinning.

    PubMed

    Nomura, Kaoru; Harada, Erisa; Sugase, Kenji; Shimamoto, Keiko

    2014-03-01

    Solid-state NMR is a promising tool for elucidating membrane-related biological phenomena. We achieved the measurement of high-resolution solid-state NMR spectra for a lipid-anchored protein embedded in lipid bilayers under magic angle spinning (MAS). To date, solid-state NMR measurements of lipid-anchored proteins have not been accomplished due to the difficulty in supplying sufficient amount of stable isotope labeled samples in the overexpression of lipid-anchored proteins requiring complex posttranslational modification. We designed a pseudo lipid-anchored protein in which the protein component was expressed in E. coli and attached to a chemically synthesized lipid-anchor mimic. Using two types of membranes, liposomes and bicelles, we demonstrated different types of insertion procedures for lipid-anchored protein into membranes. In the liposome sample, we were able to observe the cross-polarization and the (13)C-(13)C chemical shift correlation spectra under MAS, indicating that the liposome sample can be used to analyze molecular interactions using dipolar-based NMR experiments. In contrast, the bicelle sample showed sufficient quality of spectra through scalar-based experiments. The relaxation times and protein-membrane interaction were capable of being analyzed in the bicelle sample. These results demonstrated the applicability of two types of sample system to elucidate the roles of lipid-anchors in regulating diverse biological phenomena.

  6. Pharmacokinetics of ketoprofen in rabbit skin following topical application of lipid nanoparticles

    NASA Astrophysics Data System (ADS)

    Patel, Umesh

    The purpose of the thesis was to quantify ketoprofen (KTP) in rabbit skin following the topical application of lipid nanoparticles (Nanostructured lipid carriers, NLC). We tested two different types of formulations: one is (G') in which KTP is incorporated within the nanostructured lipid carriers (NLC) and the other is (H') which is a mixture of the nanostructured lipid carriers (NLC) and KTP dissolved in a vehicle (10% glycerol + 1% xanthan gum). Ketoprofen (KTP) is a non-steroidal anti-inflammatory drug administered systemically to treat arthritis. By conventional route severe side effects at the gastrointestinal level have been observed. Topical-application of lipid nanoparticles would be convenient alternative. The project is based on the (1) To study the calibration of microdialysis probes in both environment, in vivo as well as in vitro; (2) To compare two different type of formulation one is (G') with KTP incorporated within the nanostructured lipid carriers (NLC) and the other is (H') a mixture of the nanostructured lipid carriers (NLC) and KTP dissolved in a the vehicle (10% glycerol + 1% xanthan gum). The results of this study show a clear difference between the skin concentration profiles of the two formulations. Time to reach the maximum concentration is similar for both formulations. The formulation H', containing KTP is in external phase had higher Cmax (334ng/ml) than formulation G' containing KTP inside lipid particles (Cmax 32ng/ml).

  7. Curcumin-Loaded Lipid Cubic Liquid Crystalline Nanoparticles: Preparation, Optimization, Physicochemical Properties and Oral Absorption.

    PubMed

    He, Xiuli; Li, Qinghua; Liu, Xiuju; Wu, Guangsheng; Zhai, Guangxi

    2015-08-01

    In order to improve the oral absorption of curcumin, curcumin-loaded lipid cubic liquid crystalline nanoparticles were prepared and evaluated in vitro and in vivo. The hot and high-pressure homogenization method was used to prepare the nanoparticles. The formulation and process were optimized by uniform design with drug loading and entrapment efficiency as index, and physicochemical properties were also investigated. Spherical nanoparticles were observed under transmission electron microscope (TEM), with average particle size of 176.1 nm, zeta potential of -25.19 mV, average drug loading of (1.5 ± 0.2)% and entrapment efficiency of (95 ± 1.8)%. The in vitro release of curcumin from the nanoparticle formulation showed a sustained property, while the pharmacokinetics results after oral administration of curcumin loaded lipid cubic liquid crystalline nanoparticles in rat showed that the oral absorption of curcumin fitted one-compartment model and relative bioavailability was 395.56% when compared to crude curcumin. It can be concluded from these results that the lipid cubic liquid crystalline nanoparticles, as carriers, can markedly improve the oral absorption of curcumin.

  8. Bioactive Hybrid Particles from Poly(D,L-lactide-co-glycolide) Nanoparticle Stabilized Lipid Droplets.

    PubMed

    Joyce, Paul; Whitby, Catherine P; Prestidge, Clive A

    2015-08-12

    Biodegradable and bioactive hybrid particles composed of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles and medium-chain triglycerides were prepared by spray drying lipid-in-water emulsions stabilized by PLGA nanoparticles, to form PLGA-lipid hybrid (PLH) microparticles approximately 5 μm in mean diameter. The nanoparticle stabilizer was varied and mannitol was also incorporated during the preparation to investigate the effect of stabilizer charge and cryoprotectant content on the particle microstructure. An in vitro lipolysis model was used to demonstrate the particles' bioactivity by manipulating the digestion kinetics of encapsulated lipid by pancreatic lipase in simulated gastrointestinal fluid. Lipid digestion kinetics were enhanced in PLH and PLGA-lipid-mannitol hybrid (PLMH) microparticles for both stabilizers, compared to a coarse emulsion, in biorelevant media. An optimal digestion rate was observed for the negatively charged PLMH system, evidenced by a 2-fold increase in the pseudo-first-order rate constant compared to a coarse emulsion. Improved microparticle redispersion, probed by dual dye confocal fluorescence microscopy, increased the available surface area of lipid for lipase adsorption, enhancing digestion kinetics. Thereby, lipase action was controlled in hybrid microparticles by altering the surface charge and carbohydrate content. Our results demonstrate that bioactive microparticles composed of versatile and biodegradable polymeric particles and oil droplets have great potential for use in smart food and nutrient delivery, as well as safer and more efficacious oral delivery of drugs and drug combinations. PMID:26181279

  9. Folate-targeted gadolinium-lipid-based nanoparticles as a bimodal contrast agent for tumor fluorescent and magnetic resonance imaging.

    PubMed

    Nakamura, Taro; Kawano, Kumi; Shiraishi, Kouichi; Yokoyama, Masayuki; Maitani, Yoshie

    2014-01-01

    To enhance tumor magnetic resonance imaging (MRI) signals via the selective accumulation of contrast agents, we prepared folate-modified gadolinium-lipid-based nanoparticles as MRI contrast agents. Folate-modified nanoparticles were comprised of polyethylene glycol (PEG)-lipid, gadolinium diethylenetriamine pentaacetic acid lipid, cationic cholesterol derivatives, folate-conjugated PEG-lipid, and Cy7-PEG-lipid. Folate receptor-mediated cellular nanoparticle association was examined in KB cells, which overexpress the folate receptor. The biodistribution of nanoparticles after their intravenous injection into KB tumor-bearing mice was measured. Mice were imaged through in vivo fluorescence imaging and MRI 24 h after nanoparticle injection, and the intensity enhancement of the tumor MRI signal was evaluated. Increased cellular association of folate-modified nanoparticles was inhibited by excess free folic acid, indicating that nanoparticle association was folate receptor-mediated. Irrespective of folate modification, the amount of nanoparticles in blood 24 h after injection was ca. 10% of the injected dose. Compared with non-modified nanoparticles, folate-modified nanoparticles exhibited significant accumulation in tumor tissues without altering other biodistribution, as well as enhanced tumor fluorescence and MRI signal intensity. The results support the feasibility of MRI- and in vivo fluorescence imaging-based tumor visualization using folate-modified nanoparticles and provide opportunities to develop folate targeting-based imaging applications.

  10. Lipid drug conjugate nanoparticle as a novel lipid nanocarrier for the oral delivery of decitabine: ex vivo gut permeation studies

    NASA Astrophysics Data System (ADS)

    Neupane, Yub Raj; Sabir, M. D.; Ahmad, Nafees; Ali, Mushir; Kohli, Kanchan

    2013-10-01

    The purpose of this study was to develop lipid drug conjugate (LDC) nanoparticles of decitabine (DCB) using stearic acid as a lipid to increase the permeability of the drug along with its protection from chemical degradation. The LDC was prepared by salt formation of DCB with stearic acid and followed by cold homogenization technique to produce the LDC nanoparticles. The role of key independent variables influencing on dependent variables were determined by using a Box-Behnken design. The optimized batch revealed spherical morphology under TEM analysis with particle size of 202.6 ± 1.65 nm and 0.334 ± 0.987 PDI. The zeta potential and %EE were found to be -33.6 ± 0.845 mV and 68.89% ± 0.59 respectively. Lyophilized powder showed the crystalline structure under DSC analysis. In vitro release studies showed the initial burst release followed by a sustained release up to 24 h in PBS pH 7.4 and the data were further studied using release kinetic models which revealed the first-order model as a best-fitting model. Ex vivo gut permeation studies proved that the formulation containing lipid and surfactants has a higher permeability than the plain drug solution with nearly fourfold increase in the apparent permeability coefficients. Finally, LDC nanoparticles prepared by using stearic acid as a lipid and surfactants as Tween 80, Poloxamer 188, and Labrasol in equal ratio possess high potential for the oral delivery of hydrophilic drugs.

  11. Determination of solid state characteristics of spray-congealed Ibuprofen solid lipid microparticles and their impact on sustaining drug release.

    PubMed

    Wong, Priscilla Chui Hong; Heng, Paul Wan Sia; Chan, Lai Wah

    2015-05-01

    This study was used to find solid state characteristics of ibuprofen loaded spray-congealed solid lipid microparticles (SLMs) by employing simple lipids as matrices, with or without polymeric additives, and the impact of solid drug-matrix miscibility on sustaining drug release. Solid miscibility of ibuprofen with two lipids, cetyl alcohol (CA) and stearic acid (SA), were investigated using differential scanning calorimetry (DSC). SLMs containing 20% w/w ibuprofen with or without polymeric additives, PVP/VA and EC, were produced by spray congealing, and the resultant microparticles were subjected to visual examination by scanning electron microscopy (SEM), thermal analysis using DSC, and hot-stage microscopy. Intermolecular interactions between lipids and drug as well as additives were investigated by Fourier-transformed infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). X-ray diffractometry (XRD) was utilized to study polymorphic changes of drug and matrix over the course of a year. Ibuprofen was found to depress the melting points of CA and SA in a colligative manner, reaching maximum solubility at 10% w/w and 30% w/w for CA and SA, respectively. Drug encapsulation efficiencies and yields of spray-congealed SLMs containing 20% w/w ibuprofen were consistently high for both lipid matrices. CA and SA were found to adopt their stable γ- and β-polymorphs, respectively, immediately after spray congealing. The spray congealing process resulted in ibuprofen adopting an amorphous or poorly crystalline state, with no further changes over the course of a year. SEM, DSC, and hot stage microscope studies on the SLMs confirmed the formation of a solid dispersion between ibuprofen and CA and a solid solution between ibuprofen and SA. SA was found to sustain the release of ibuprofen significantly better than CA. PVP/VA and EC showed some interactions with CA, which led to an expansion of unit cell dimensions of CA upon spray congealing, whereas they

  12. Epidermal growth factor receptor-targeted lipid nanoparticles retain self-assembled nanostructures and provide high specificity.

    PubMed

    Zhai, Jiali; Scoble, Judith A; Li, Nan; Lovrecz, George; Waddington, Lynne J; Tran, Nhiem; Muir, Benjamin W; Coia, Gregory; Kirby, Nigel; Drummond, Calum J; Mulet, Xavier

    2015-02-21

    Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay.

  13. Strategic approaches for improving entrapment of hydrophilic peptide drugs by lipid nanoparticles.

    PubMed

    Yuan, Hong; Jiang, Sai-Ping; Du, Yong-Zhong; Miao, Jing; Zhang, Xing-Guo; Hu, Fu-Qiang

    2009-05-01

    In order to introduce hydrophilic peptide drugs into solid lipid nanoparticles (SLN), a technique of combining hydrophobic ion pairing (HIP) and non-aqueous oil-in-oil (O/O) emulsion-evaporation was developed. Leuprolide (LR) was selected as the model drug, while sodium stearate (SA-Na) was used as the negative charged ion pairing material. The formation of leuprolide-sodium stearate (LR-SA-Na) complex was confirmed by differential scanning calorimetry (DSC). It was observed that when the molar ratio of SA-Na/LR reached 2/1, ca 88.5% LR was incorporated into the hydrophobic ion complexes with SA-Na. Compared with the conventional method of solvent diffusion in an aqueous system, the efficiency of LR drug entrapment with SLN increased from 28.0% to 74.6% by the combined technique of HIP and O/O emulsion-evaporation. In vitro drug release tests revealed that employing technique of HIP obviously reduced the burst release and slowed down the rate of drug release. At meanwhile, applying the method of non-aqueous O/O emulsion-evaporation, the longer time of drug release but relatively higher drug burst release ratio was observed in comparison with those by the solvent diffusion method in an aqueous system. The drug entrapment and release behaviors of LR-SA-Na SLN prepared by the O/O emulsion-evaporation method suggested that it could potentially be exploited as an oral delivery system for leuprolide.

  14. Single-step assembly of homogenous lipid-polymeric and lipid-quantum dot nanoparticles enabled by microfluidic rapid mixing.

    PubMed

    Valencia, Pedro M; Basto, Pamela A; Zhang, Liangfang; Rhee, Minsoung; Langer, Robert; Farokhzad, Omid C; Karnik, Rohit

    2010-03-23

    A key challenge in the synthesis of multicomponent nanoparticles (NPs) for therapy or diagnosis is obtaining reproducible monodisperse NPs with a minimum number of preparation steps. Here we report the use of microfluidic rapid mixing using hydrodynamic flow focusing in combination with passive mixing structures to realize the self-assembly of monodisperse lipid-polymer and lipid-quantum dot (QD) NPs in a single mixing step. These NPs are composed of a polymeric core for drug encapsulation or a QD core for imaging purposes, a hydrophilic polymeric shell, and a lipid monolayer at the interface of the core and the shell. In contrast to slow mixing of lipid and polymeric solutions, rapid mixing directly results in formation of homogeneous NPs with relatively narrow size distribution that obviates the need for subsequent thermal or mechanical agitation for homogenization. We identify rapid mixing conditions that result in formation of homogeneous NPs and show that self-assembly of polymeric core occurs independent of the lipid component, which only provides stability against aggregation over time and in the presence of high salt concentrations. Physicochemical properties of the NPs including size (35-180 nm) and zeta potential (-10 to +20 mV in PBS) are controlled by simply varying the composition and concentration of precursors. This method for preparation of hybrid NPs in a single mixing step may be useful for combinatorial synthesis of NPs with different properties for imaging and drug delivery applications. PMID:20166699

  15. Biophysics of Cell Membrane Lipids in Cancer Drug Resistance: Implications for Drug Transport and Drug Delivery with Nanoparticles

    PubMed Central

    Peetla, Chiranjeevi; Vijayaraghavalu, Sivakumar; Labhasetwar, Vinod

    2013-01-01

    In this review, we focus on the biophysics of cell membrane lipids, particularly when cancers develop acquired drug resistance, and how biophysical changes in resistant cell membrane influence drug transport and nanoparticle-mediated drug delivery. Recent advances in membrane lipid research show the varied roles of lipids in regulating membrane P-glycoprotein function, membrane trafficking, apoptotic pathways, drug transport, and endocytic functions, particularly endocytosis, the primary mechanism of cellular uptake of nanoparticle-based drug delivery systems. Since acquired drug resistance alters lipid biosynthesis, understanding the role of lipids in cell membrane biophysics and its effect on drug transport is critical for developing effective therapeutic and drug delivery approaches to overcoming drug resistance. Here we discuss novel strategies for (a) modulating the biophysical properties of membrane lipids of resistant cells to facilitate drug transport and regain endocytic function and (b) developing effective nanoparticles based on their biophysical interactions with membrane lipids to enhance drug delivery and overcome drug resistance. PMID:24055719

  16. Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles.

    PubMed

    Peetla, Chiranjeevi; Vijayaraghavalu, Sivakumar; Labhasetwar, Vinod

    2013-11-01

    In this review, we focus on the biophysics of cell membrane lipids, particularly when cancers develop acquired drug resistance, and how biophysical changes in resistant cell membrane influence drug transport and nanoparticle-mediated drug delivery. Recent advances in membrane lipid research show the varied roles of lipids in regulating membrane P-glycoprotein function, membrane trafficking, apoptotic pathways, drug transport, and endocytic functions, particularly endocytosis, the primary mechanism of cellular uptake of nanoparticle-based drug delivery systems. Since acquired drug resistance alters lipid biosynthesis, understanding the role of lipids in cell membrane biophysics and its effect on drug transport is critical for developing effective therapeutic and drug delivery approaches to overcome drug resistance. Here we discuss novel strategies for (a) modulating the biophysical properties of membrane lipids of resistant cells to facilitate drug transport and regain endocytic function and (b) developing effective nanoparticles based on their biophysical interactions with membrane lipids to enhance drug delivery and overcome drug resistance.

  17. WO3/Pt nanoparticles promote light-induced lipid peroxidation and lysosomal instability within tumor cells

    NASA Astrophysics Data System (ADS)

    Clark, Andrea J.; Petty, Howard R.

    2016-02-01

    Although metal-metal oxide nanoparticles have attracted considerable interest as catalysts, they have attracted little interest in nanomedicine. This is likely due to the fact that metal oxide semiconductors generally require biologically harmful ultraviolet excitation. In contrast, this study focuses upon WO3/Pt nanoparticles, which can be excited by visible light. To optimize the nanoparticles’ catalytic performance, platinization was performed at alkaline pH. These nanoparticles destroyed organic dyes, consumed dissolved oxygen and produced hydroxyl radicals. 4T1 breast cancer cells internalized WO3/Pt nanoparticles within the membrane-bound endo-lysosomal compartment as shown by electron and fluorescence microscopy. During visible light exposure, but not in darkness, WO3/Pt nanoparticles manufacture reactive oxygen species, promote lipid peroxidation, and trigger lysosomal membrane disruption. As cells of the immune system degrade organic molecules, produce reactive oxygen species, and activate the lipid peroxidation pathway within target cells, these nanoparticles mimic the chemical attributes of immune effector cells. These biomimetic nanoparticles should become useful in managing certain cancers, especially ocular cancer.

  18. Interplay of electrostatics and lipid packing determines the binding of charged polymer coated nanoparticles to model membranes.

    PubMed

    Biswas, Nupur; Bhattacharya, Rupak; Saha, Arindam; Jana, Nikhil R; Basu, Jaydeep K

    2015-10-01

    Understanding of nanoparticle-membrane interactions is useful for various applications of nanoparticles like drug delivery and imaging. Here we report on the studies of interaction between hydrophilic charged polymer coated semiconductor quantum dot nanoparticles with model lipid membranes. Atomic force microscopy and X-ray reflectivity measurements suggest that cationic nanoparticles bind and penetrate bilayers of zwitterionic lipids. Penetration and binding depend on the extent of lipid packing and result in the disruption of the lipid bilayer accompanied by enhanced lipid diffusion. On the other hand, anionic nanoparticles show minimal membrane binding although, curiously, their interaction leads to reduction in lipid diffusivity. It is suggested that the enhanced binding of cationic QDs at higher lipid packing can be understood in terms of the effective surface potential of the bilayers which is tunable through membrane lipid packing. Our results bring forth the subtle interplay of membrane lipid packing and electrostatics which determine nanoparticle binding and penetration of model membranes with further implications for real cell membranes.

  19. Effects of Nanoparticle Morphology and Acyl Chain Length on Spontaneous Lipid Transfer Rates

    SciTech Connect

    Xia, Yan; Li, Ming; Charubin, Kamil; Liu, Ying; Heberle, Frederick A.; Katsaras, John; Jing, Benxin; Zhu, Yingxi; Nieh, Mu-Ping

    2015-11-05

    In this paper, we report on studies of lipid transfer rates between different morphology nanoparticles and lipids with different length acyl chains. The lipid transfer rate of dimyristoylphosphatidylcholine (di-C14, DMPC) in discoidal “bicelles” (0.156 h–1) is 2 orders of magnitude greater than that of DMPC vesicles (ULVs) (1.1 × 10–3 h–1). For both bicellar and ULV morphologies, increasing the acyl chain length by two carbons [going from di-C14 DMPC to di-C16, dipalmitoylphosphatidylcholine (DPPC)] causes lipid transfer rates to decrease by more than 2 orders of magnitude. Results from small angle neutron scattering (SANS), differential scanning calorimetry (DSC), and fluorescence correlation spectroscopy (FCS) are in good agreement. Finally, the present studies highlight the importance of lipid dynamic processes taking place in different morphology biomimetic membranes.

  20. Effects of Nanoparticle Morphology and Acyl Chain Length on Spontaneous Lipid Transfer Rates

    DOE PAGESBeta

    Xia, Yan; Li, Ming; Charubin, Kamil; Liu, Ying; Heberle, Frederick A.; Katsaras, John; Jing, Benxin; Zhu, Yingxi; Nieh, Mu-Ping

    2015-11-05

    In this paper, we report on studies of lipid transfer rates between different morphology nanoparticles and lipids with different length acyl chains. The lipid transfer rate of dimyristoylphosphatidylcholine (di-C14, DMPC) in discoidal “bicelles” (0.156 h–1) is 2 orders of magnitude greater than that of DMPC vesicles (ULVs) (1.1 × 10–3 h–1). For both bicellar and ULV morphologies, increasing the acyl chain length by two carbons [going from di-C14 DMPC to di-C16, dipalmitoylphosphatidylcholine (DPPC)] causes lipid transfer rates to decrease by more than 2 orders of magnitude. Results from small angle neutron scattering (SANS), differential scanning calorimetry (DSC), and fluorescence correlationmore » spectroscopy (FCS) are in good agreement. Finally, the present studies highlight the importance of lipid dynamic processes taking place in different morphology biomimetic membranes.« less

  1. Epidermal growth factor receptor-targeted lipid nanoparticles retain self-assembled nanostructures and provide high specificity

    NASA Astrophysics Data System (ADS)

    Zhai, Jiali; Scoble, Judith A.; Li, Nan; Lovrecz, George; Waddington, Lynne J.; Tran, Nhiem; Muir, Benjamin W.; Coia, Gregory; Kirby, Nigel; Drummond, Calum J.; Mulet, Xavier

    2015-02-01

    Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay.Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles

  2. Pattern formation in fatty acid-nanoparticle and lipid-nanoparticle mixed monolayers at water surface

    NASA Astrophysics Data System (ADS)

    Choudhuri, M.; Datta, A.; Iyengar, A. N. Sekar; Janaki, M. S.

    2015-06-01

    Dodecanethiol-capped gold nanoparticles (AuNPs) are self-organized in two different amphiphilic monolayers one of which is a single-tailed fatty acid Stearic acid (StA) and the other a double-tailed lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). In the StA-AuNP film the AuNPs self-organize to form an interconnected network of nanoclusters on compression while in the DMPC-AuNP film the AuNPs aggregate to form random, isolated clusters in the film. The long time evolution of the films at constant surface pressure reveals ring structures in the former and diffusion limited aggregates in the latter that with time evolve into an irregular porous maze of AuNPs in the DMPC film. The difference in structure of the AuNP patterns in the two films can be attributed to a difference in the lipophilic interactions between the NPs and the amphiphilic molecules. The mean square intensity fluctuations f(ln) calculated along a typical line for the 2D structures in both the films at initial and final stages of long time evolution reflect the structural changes in the films over time.

  3. Partial wrapping and spontaneous endocytosis of spherical nanoparticles by tensionless lipid membranes

    NASA Astrophysics Data System (ADS)

    Spangler, Eric J.; Upreti, Sudhir; Laradji, Mohamed

    2016-01-01

    Computer simulations of an implicit-solvent particle-based model are performed to investigate the interactions between small spherical nanoparticles and tensionless lipid bilayers. We found that nanoparticles are either unbound, wrapped by the bilayer, or endocytosed. The degree of wrapping increases with increasing the adhesion strength. The transition adhesion strength between the unbound and partially wrapped states decreases as the nanoparticle diameter is increased. We also observed that the transition adhesion strength between the wrapped states and endocytosis state decreases with increasing the nanoparticle diameter. The partial wrapping of the nanoparticles by the tensionless bilayer is explained by an elastic theory which accounts for the fact that the interaction between the nanoparticle and the bilayer extends beyond the contact region. The theory predicts that for small nanoparticles, the wrapping angle increases continuously with increasing the adhesion strength. However, for relatively large nanoparticles, the wrapping angle exhibits a discontinuity between weakly and strongly wrapped states. The size of the gap in the wrapping angle between the weakly wrapped and strongly wrapped states increases with decreasing the range of nanoparticle-bilayer interaction.

  4. Partial wrapping and spontaneous endocytosis of spherical nanoparticles by tensionless lipid membranes.

    PubMed

    Spangler, Eric J; Upreti, Sudhir; Laradji, Mohamed

    2016-01-28

    Computer simulations of an implicit-solvent particle-based model are performed to investigate the interactions between small spherical nanoparticles and tensionless lipid bilayers. We found that nanoparticles are either unbound, wrapped by the bilayer, or endocytosed. The degree of wrapping increases with increasing the adhesion strength. The transition adhesion strength between the unbound and partially wrapped states decreases as the nanoparticle diameter is increased. We also observed that the transition adhesion strength between the wrapped states and endocytosis state decreases with increasing the nanoparticle diameter. The partial wrapping of the nanoparticles by the tensionless bilayer is explained by an elastic theory which accounts for the fact that the interaction between the nanoparticle and the bilayer extends beyond the contact region. The theory predicts that for small nanoparticles, the wrapping angle increases continuously with increasing the adhesion strength. However, for relatively large nanoparticles, the wrapping angle exhibits a discontinuity between weakly and strongly wrapped states. The size of the gap in the wrapping angle between the weakly wrapped and strongly wrapped states increases with decreasing the range of nanoparticle-bilayer interaction.

  5. Controlled magnetosomes: Embedding of magnetic nanoparticles into membranes of monodisperse lipid vesicles.

    PubMed

    Bixner, Oliver; Reimhult, Erik

    2016-03-15

    Magnetic nanoparticle-containing capsules have been proposed for many uses, including triggered drug delivery and imaging. Combining superparamagnetic iron oxide nanoparticles (SPIONs) with existing liposome drug delivery technology is an enticing near-future prospect, but it requires efficient methods of synthesis and formulation compatible with pharmaceutical applications. We report a facile way of producing large, unilamellar, and homogeneously sized magnetoliposomes with high content of monodisperse, hydrophobic SPIONs integrated in the lipid membrane by use of a solvent inversion technique. For low lipid concentrations, unilamellar and monodisperse vesicles were obtained that became increasingly multilamellar with higher lipid fraction. Both, the co-self-assembled structure and loading content were significantly influenced by the purity of the nanoparticle shell. SPIONs with homogeneous shells of nitrodopamine-anchored hydrophobic dispersants could be quantitatively loaded up to 20%w/w, while SPIONs also containing residual physisorbed oleic acid exhibited a loading cut-off around 10%w/w SPIONs accompanied by drastic changes in size distribution. Lipid acyl chain length crucially influenced the formation and resultant stability of the loaded assemblies. The formation of nanoparticle-loaded vesicles is exemplified in different biologically important media, yielding ready-to-use magnetoliposome formulations. PMID:26707773

  6. Controlled magnetosomes: Embedding of magnetic nanoparticles into membranes of monodisperse lipid vesicles.

    PubMed

    Bixner, Oliver; Reimhult, Erik

    2016-03-15

    Magnetic nanoparticle-containing capsules have been proposed for many uses, including triggered drug delivery and imaging. Combining superparamagnetic iron oxide nanoparticles (SPIONs) with existing liposome drug delivery technology is an enticing near-future prospect, but it requires efficient methods of synthesis and formulation compatible with pharmaceutical applications. We report a facile way of producing large, unilamellar, and homogeneously sized magnetoliposomes with high content of monodisperse, hydrophobic SPIONs integrated in the lipid membrane by use of a solvent inversion technique. For low lipid concentrations, unilamellar and monodisperse vesicles were obtained that became increasingly multilamellar with higher lipid fraction. Both, the co-self-assembled structure and loading content were significantly influenced by the purity of the nanoparticle shell. SPIONs with homogeneous shells of nitrodopamine-anchored hydrophobic dispersants could be quantitatively loaded up to 20%w/w, while SPIONs also containing residual physisorbed oleic acid exhibited a loading cut-off around 10%w/w SPIONs accompanied by drastic changes in size distribution. Lipid acyl chain length crucially influenced the formation and resultant stability of the loaded assemblies. The formation of nanoparticle-loaded vesicles is exemplified in different biologically important media, yielding ready-to-use magnetoliposome formulations.

  7. Nanoparticle scaffolds for syngas-fed solid oxide fuel cells

    SciTech Connect

    Boldrin, Paul; Ruiz-Trejo, Enrique; Yu, Jingwen; Gruar, Robert I.; Tighe, Christopher J.; Chang, Kee-Chul; Ilavsky, Jan; Darr, Jawwad A.; Brandon, Nigel

    2014-12-17

    Incorporation of nanoparticles into devices such as solid oxide fuel cells (SOFCs) may provide benefits such as higher surface areas or finer control over microstructure. However, their use with traditional fabrication techniques such as screen-printing is problematic. Here, we show that mixing larger commercial particles with nanoparticles allows traditional ink formulation and screen-printing to be used while still providing benefits of nanoparticles such as increased porosity and lower sintering temperatures. SOFC anodes were produced by impregnating ceria–gadolinia (CGO) scaffolds with nickel nitrate solution. The scaffolds were produced from inks containing a mixture of hydrothermally-synthesised nanoparticle CGO, commercial CGO and polymeric pore formers. The scaffolds were heat-treated at either 1000 or 1300 °C, and were mechanically stable. In situ ultra-small X-ray scattering (USAXS) shows that the nanoparticles begin sintering around 900–1000 °C. Analysis by USAXS and scanning electron microscopy (SEM) revealed that the low temperature heat-treated scaffolds possessed higher porosity. Impregnated scaffolds were used to produce symmetrical cells, with the lower temperature heat-treated scaffolds showing improved gas diffusion, but poorer charge transfer. Using these scaffolds, lower temperature heat-treated cells of Ni–CGO/200 μm YSZ/CGO-LSCF performed better at 700 °C (and below) in hydrogen, and performed better at all temperatures using syngas, with power densities of up to 0.15 W cm-2 at 800 °C. This approach has the potential to allow the use of a wider range of materials and finer control over microstructure.

  8. Nanoparticle scaffolds for syngas-fed solid oxide fuel cells

    DOE PAGESBeta

    Boldrin, Paul; Ruiz-Trejo, Enrique; Yu, Jingwen; Gruar, Robert I.; Tighe, Christopher J.; Chang, Kee-Chul; Ilavsky, Jan; Darr, Jawwad A.; Brandon, Nigel

    2014-12-17

    Incorporation of nanoparticles into devices such as solid oxide fuel cells (SOFCs) may provide benefits such as higher surface areas or finer control over microstructure. However, their use with traditional fabrication techniques such as screen-printing is problematic. Here, we show that mixing larger commercial particles with nanoparticles allows traditional ink formulation and screen-printing to be used while still providing benefits of nanoparticles such as increased porosity and lower sintering temperatures. SOFC anodes were produced by impregnating ceria–gadolinia (CGO) scaffolds with nickel nitrate solution. The scaffolds were produced from inks containing a mixture of hydrothermally-synthesised nanoparticle CGO, commercial CGO and polymericmore » pore formers. The scaffolds were heat-treated at either 1000 or 1300 °C, and were mechanically stable. In situ ultra-small X-ray scattering (USAXS) shows that the nanoparticles begin sintering around 900–1000 °C. Analysis by USAXS and scanning electron microscopy (SEM) revealed that the low temperature heat-treated scaffolds possessed higher porosity. Impregnated scaffolds were used to produce symmetrical cells, with the lower temperature heat-treated scaffolds showing improved gas diffusion, but poorer charge transfer. Using these scaffolds, lower temperature heat-treated cells of Ni–CGO/200 μm YSZ/CGO-LSCF performed better at 700 °C (and below) in hydrogen, and performed better at all temperatures using syngas, with power densities of up to 0.15 W cm-2 at 800 °C. This approach has the potential to allow the use of a wider range of materials and finer control over microstructure.« less

  9. New Updates Pertaining to Drug Delivery of Local Anesthetics in Particular Bupivacaine Using Lipid Nanoparticles.

    PubMed

    Beiranvand, Siavash; Eatemadi, Ali; Karimi, Arash

    2016-12-01

    Lipid nanoparticles (liposomes) were first described in 1965, and several work have led to development of important technical advances like triggered release liposomes and drug-loaded liposomes. These advances have led to numerous clinical trials in such diverse areas such as the delivery of anti-cancer, antifungal, and antibiotic drugs; the delivery of gene medicines; and most importantly the delivery of anesthesia drugs. Quite a number of liposomes are on the market, and many more are still in developmental stage. Lipid nanoparticles are the first nano-medicine delivery system to be advanced from laboratory concept to clinical application with high considerable clinical acceptance. Drug delivery systems for local anesthetics (LAs) have caught the interest of many researchers because there are many biomedical advantages connected to their application. There have been several formulation techniques to systemically deliver LA that include encapsulation in liposomes and complexation in cyclodextrins, nanoparticles, and to a little extent gold nanoparticles. The proposed formulations help to decrease the LA concentration utilized, increase its permeability, and most importantly increase the localization of the LA for a long period of time thereby leading to increase in the duration of the LA effect and finally to reduce any local and systemic toxicity. In this review, we will highlight on new updates pertaining to drug delivery of local anesthetics in particular bupivacaine using lipid nanoparticles. PMID:27342601

  10. Live Cell Imaging of the Endocytosis and the Intracellular Trafficking of Multifunctional Lipid Nanoparticles

    SciTech Connect

    Zhang, Tieqiao; Danthi, S. N.; Xie, Jianwu; Hu, Dehong; Lu, H. Peter; Li, King H.

    2006-12-01

    Artificial lipid nanoparticles have drawn great attention due to their potential in medicine. Linked with targeting ligands, they can be used as probes and/or gene delivery vectors for specific types of target cells. Therefore, they are very promising agents in early detection, diagnosis and treatment of cancers and other genetic diseases. However, there are several barriers blocking the applications. Controlling the cellular uptake of the lipid nanoparticles is an important technical challenge to overcome. Understanding the mechanism of the endocytosis and the following intracellular trafficking is very important for improving the design and therefore the efficiency as a drug delivery system. By using fluorescence microscopy methods, we studied the endocytosis of lipid nanoparticles by live M21 cells. The movements of the nanoparticles inside the cell were quantitatively characterized and classified based on the diffusion behavior. The trajectories of nanoparticles movement over the cell membrane revealed hop-diffusion behavior prior to the endocytosis. Fast movement in large steps is observed in intracellular trafficking and is attributed to active movement along microtubule. These observations help to understand the mechanism of the endocytosis and the pathway of the particles in cells.

  11. New Updates Pertaining to Drug Delivery of Local Anesthetics in Particular Bupivacaine Using Lipid Nanoparticles

    NASA Astrophysics Data System (ADS)

    Beiranvand, Siavash; Eatemadi, Ali; Karimi, Arash

    2016-06-01

    Lipid nanoparticles (liposomes) were first described in 1965, and several work have led to development of important technical advances like triggered release liposomes and drug-loaded liposomes. These advances have led to numerous clinical trials in such diverse areas such as the delivery of anti-cancer, antifungal, and antibiotic drugs; the delivery of gene medicines; and most importantly the delivery of anesthesia drugs. Quite a number of liposomes are on the market, and many more are still in developmental stage. Lipid nanoparticles are the first nano-medicine delivery system to be advanced from laboratory concept to clinical application with high considerable clinical acceptance. Drug delivery systems for local anesthetics (LAs) have caught the interest of many researchers because there are many biomedical advantages connected to their application. There have been several formulation techniques to systemically deliver LA that include encapsulation in liposomes and complexation in cyclodextrins, nanoparticles, and to a little extent gold nanoparticles. The proposed formulations help to decrease the LA concentration utilized, increase its permeability, and most importantly increase the localization of the LA for a long period of time thereby leading to increase in the duration of the LA effect and finally to reduce any local and systemic toxicity. In this review, we will highlight on new updates pertaining to drug delivery of local anesthetics in particular bupivacaine using lipid nanoparticles.

  12. Solid-Supported Lipid Membranes: Formation, Stability and Applications

    NASA Astrophysics Data System (ADS)

    Goh, Haw Zan

    This thesis presents a comprehensive investigation of the formation of supported lipid membranes with vesicle hemifusion, their stability under detergents and organic solvents and their applications in molecular biology. In Chapter 3, we describe how isolated patches of DOPC bilayers supported on glass surfaces are dissolved by various detergents (decyl maltoside, dodecyl maltoside, CHAPS, CTAB, SDS, TritonX-100 and Tween20) at their CMC, as investigated by fluorescence video microscopy. In general, detergents partition into distal leaflets of bilayers and lead to the expansion of the bilayers through a rolling motion of the distal over the proximal leaflets, in agreement with the first stage of the established 3-stage model of lipid vesicle solubilization by detergents. Subsequently, we study the partitioning of organic solvents (methanol, ethanol, isopropanol, propanol, acetone and chloroform) into isolated bilayer patches on glass in Chapter 4 with fluorescence microscopy. The area expansion of bilayers due to the partitioning of organic solvents is measured. From the titration of organic solvents, we measured the rate of area expansion as a function of the volume fraction of organic solvents, which is proposed to be a measure of strength of interactions between solvents and membranes. From the same experiments, we also measure the maximum expansion of bilayers (or the maximum binding stoichiometry between organic solvents and lipids) before structural breakdown, which depends on the depth of penetration of solvents to the membranes. In Chapter 5, we investigate the formation of sparsely-tethered bilayer lipid membranes (stBLMs) with vesicle hemifusion. In vesicle hemifusion, lipid vesicles in contact with a hydrophobic alkyl-terminated self-assembled monolayer (SAM) deposit a lipid monolayer to the SAM surface, thus completing the bilayer. Electrical Impedance Spectroscopy and Neutron Reflectivity are used to probe the integrity of stBLMs in terms of their

  13. Conventional versus stealth lipid nanoparticles: formulation and in vivo fate prediction through FRET monitoring.

    PubMed

    Lainé, A-L; Gravier, J; Henry, M; Sancey, L; Béjaud, J; Pancani, E; Wiber, M; Texier, I; Coll, J-L; Benoit, J-P; Passirani, C

    2014-08-28

    The determination of the nanocarrier fate in preclinical models is required before any translation from laboratory to clinical trials. Modern fluorescent imaging techniques have gained considerable advances becoming a powerful technology for non-invasive visualization in living subjects. Among them, Forster (fluorescence) resonance energy transfer (FRET) is a particular fluorescence imaging which involves energy transfer between 2 fluorophores in a distance-dependent manner. Considering this feature, the encapsulation of an acceptor/donor pair in lipid nanoparticles (LNEs: lipid nanoemulsions, LNCs: lipid nanocapsules) allowed the carrier integrity to be tracked. Accordingly, we used this FRET technique to evaluate the behavior of LNEs, conventional LNCs and newly designed stealth LNCs. After the development through a one-step (OS) PEGylation process of these stealth LNCs (OS LNCs), in vitro guest exchange dynamics and release kinetics were evaluated for both LNC formulations. We thereafter assessed in vivo biodistribution of all types of lipid nanoparticles. Results showed enhanced stability of encapsulation in OS LNCs in comparison to conventional LNCs. Additionally, the presence of the long PEG chains on the lipid nanoparticle surface altered the biodistribution pattern. Despite different release kinetic profiles, OS LNCs and LNEs showed extended blood circulation time associated with a good structure stability over several hours after intravenous injection.

  14. Clathrin to Lipid Raft-Endocytosis via Controlled Surface Chemistry and Efficient Perinuclear Targeting of Nanoparticle.

    PubMed

    Chakraborty, Atanu; Jana, Nikhil R

    2015-09-17

    Nanoparticle interacts with live cells depending on their surface chemistry, enters into cell via endocytosis, and is commonly trafficked to an endosome/lysozome that restricts subcellular targeting options. Here we show that nanoparticle surface chemistry can be tuned to alter their cell uptake mechanism and subcellular trafficking. Quantum dot based nanoprobes of 20-30 nm hydrodynamic diameters have been synthesized with tunable surface charge (between +15 mV to -25 mV) and lipophilicity to influence their cellular uptake processes and subcellular trafficking. It is observed that cationic nanoprobe electrostatically interacts with cell membrane and enters into cell via clathrin-mediated endocytosis. At lower surface charge (between +10 mV to -10 mV), the electrostatic interaction with cell membrane becomes weaker, and additional lipid raft endocytosis is initiated. If a lipophilic functional group is introduced on a weakly anionic nanoparticle surface, the uptake mechanism shifts to predominant lipid raft-mediated endocytosis. In particular, the zwitterionic-lipophilic nanoprobe has the unique advantage as it weakly interacts with anionic cell membrane, migrates toward lipid rafts for interaction through lipophilic functional group, and induces lipid raft-mediated endocytosis. While predominate or partial clathrin-mediated entry traffics most of the nanoprobes to lysozome, predominate lipid raft-mediated entry traffics them to perinuclear region, particularly to the Golgi apparatus. This finding would guide in designing appropriate nanoprobe for subcellular targeting and delivery.

  15. Conventional versus stealth lipid nanoparticles: formulation and in vivo fate prediction through FRET monitoring.

    PubMed

    Lainé, A-L; Gravier, J; Henry, M; Sancey, L; Béjaud, J; Pancani, E; Wiber, M; Texier, I; Coll, J-L; Benoit, J-P; Passirani, C

    2014-08-28

    The determination of the nanocarrier fate in preclinical models is required before any translation from laboratory to clinical trials. Modern fluorescent imaging techniques have gained considerable advances becoming a powerful technology for non-invasive visualization in living subjects. Among them, Forster (fluorescence) resonance energy transfer (FRET) is a particular fluorescence imaging which involves energy transfer between 2 fluorophores in a distance-dependent manner. Considering this feature, the encapsulation of an acceptor/donor pair in lipid nanoparticles (LNEs: lipid nanoemulsions, LNCs: lipid nanocapsules) allowed the carrier integrity to be tracked. Accordingly, we used this FRET technique to evaluate the behavior of LNEs, conventional LNCs and newly designed stealth LNCs. After the development through a one-step (OS) PEGylation process of these stealth LNCs (OS LNCs), in vitro guest exchange dynamics and release kinetics were evaluated for both LNC formulations. We thereafter assessed in vivo biodistribution of all types of lipid nanoparticles. Results showed enhanced stability of encapsulation in OS LNCs in comparison to conventional LNCs. Additionally, the presence of the long PEG chains on the lipid nanoparticle surface altered the biodistribution pattern. Despite different release kinetic profiles, OS LNCs and LNEs showed extended blood circulation time associated with a good structure stability over several hours after intravenous injection. PMID:24878182

  16. Multicompartment lipid cubic nanoparticles with high protein upload: millisecond dynamics of formation.

    PubMed

    Angelov, Borislav; Angelova, Angelina; Filippov, Sergey K; Drechsler, Markus; Štěpánek, Petr; Lesieur, Sylviane

    2014-05-27

    Membrane shapes, produced by dynamically assembled lipid/protein architectures, are crucial for both physiological functions and the design of therapeutic nanotechnologies. Here we investigate the dynamics of lipid membrane-neurotrophic BDNF protein complexes formation and ordering in nanoparticles, with the purpose of innovation in nanostructure-based neuroprotection and biomimetic nanoarchitectonics. The kinetic pathway of membrane states associated with rapidly occurring nonequilibrium self-assembled lipid/protein nanoarchitectures was determined by millisecond time-resolved small-angle X-ray scattering (SAXS) at high resolution. The neurotrophin binding and millisecond trafficking along the flexible membranes induced an unusual overlay of channel-network architectures including two coexisting cubic lattices epitaxially connected to lamellar membrane stacks. These time-resolved membrane processes, involving intercalation of discrete stiff proteins in continuous soft membranes, evidence stepwise curvature control mechanisms. The obtained three-phase liquid-crystalline nanoparticles of neurotrophic composition put forward important advancements in multicompartment soft-matter nanostructure design.

  17. Interactions of lipid-based liquid crystalline nanoparticles with model and cell membranes.

    PubMed

    Barauskas, Justas; Cervin, Camilla; Jankunec, Marija; Spandyreva, Marija; Ribokaite, Kristina; Tiberg, Fredrik; Johnsson, Markus

    2010-05-31

    Lipid-based liquid crystalline nanoparticles (LCNPs) are interesting candidates for drug delivery applications, for instance as solubilizing or encapsulating carriers for intravenous (i.v.) drugs. Here it is important that the carriers are safe and tolerable and do not have, e.g. hemolytic activity. In the present study we have studied LCNP particles of different compositions with respect to their mixing behavior and membrane destabilizing effects in model and cell membrane systems. Different types of non-lamellar LCNPs were studied including cubic phase nanoparticles (Cubosome) based on glycerol monooleate (GMO), hexagonal phase nanoparticles (Hexosome) based on diglycerol monooleate (DGMO) and glycerol dioleate (GDO), sponge phase nanoparticles based on DGMO/GDO/polysorbate 80 (P80) and non-lamellar nanoparticles based on soy phosphatidylcholine (SPC)/GDO. Importantly, the LCNPs based on the long-chain monoacyl lipid, GMO, were shown to display a very fast and complete lipid mixing with model membranes composed of multilamellar SPC liposomes as assessed by a fluorescence energy transfer (FRET) assay. The result correlated well with pronounced hemolytic properties observed when the GMO-based LCNPs were mixed with rat whole blood. In sharp contrast, LCNPs based on mixtures of the long-chain diacyl lipids, SPC and GDO, were found to be practically inert towards both hemolysis in rat whole blood as well as lipid mixing with SPC model membranes. The LCNP dispersions based on a mixture of long-chain monoacyl and diacyl lipids, DGMO/GDO, displayed an intermediate behavior compared to the GMO and SPC/GDO-based systems with respect to both hemolysis and lipid mixing. It is concluded that GMO-based LCNPs are unsuitable for parenteral drug delivery applications (e.g. i.v. administration) while the SPC/GDO-based LCNPs exhibit good properties with limited lipid mixing and hemolytic activity. The correlation between results from lipid mixing or FRET experiments and the in

  18. Physical properties of griseofulvin-lipid nanoparticles in suspension and their novel interaction mechanism with saccharide during freeze-drying.

    PubMed

    Kamiya, Seitaro; Kurita, Takurou; Miyagishima, Atsuo; Itai, Shigeru; Arakawa, Masayuki

    2010-03-01

    Size reduction of drug particles to the nanoscale is important in improving the dissolution rate of poorly water-soluble drugs. The aim of this study was to investigate the physicochemical properties of griseofulvin (GF)-lipid nanoparticles and the interactions between GF-lipid nanoparticles and various saccharides during freeze-drying. The phase transition temperature of the GF-lipid nanoparticle suspension was 56.8 degrees C, whereas that of the lipid nanoparticle suspension alone was 57.9 degrees C, indicating that the GF crystals were incorporated into the lipid phase. The mean particle size of a rehydrated suspension of xylose-containing freeze-dried GF-lipid nanoparticles was about 220 nm. However, the mean particle size on the rehydration of nanoparticles containing mannose (monosaccharide), fructose (disaccharide), lactose (disaccharide), or raffinose (trisaccharide) was about 60 nm, suggesting that these saccharides prevented aggregation during the freeze-drying process. Powder X-ray diffraction revealed that xylose existed in the crystalline state in the freeze-dried nanoparticles, whereas the other saccharides existed in amorphous states. Thus, the crystallization of the saccharide was found to be strongly correlated with the aggregation property of the nanoparticles. In the case of freeze-dried xylose, the nanoparticles were squeezed out as the saccharine crystal lattice arranged itself regularly. Then, the ejected nanoparticles were aggregated. In contrast, in the case of the other freeze-dried saccharide, the saccharide remained incorporated with the GF-lipid nanoparticles because its crystal lattice was arranged irregularly. Thus, the particle size was maintained. PMID:20018239

  19. Nanoparticle size and shape characterization with Solid State Nanopores

    NASA Astrophysics Data System (ADS)

    Nandivada, Santoshi; Benamara, Mourad; Li, Jiali

    2015-03-01

    Solid State Nanopores are widely used in a variety of single molecule studies including DNA and biomolecule detection based on the principle of Resistive Pulse technique. This technique is based on electrophoretically driving charged particles through 35-60 nm solid state nanopores. The translocation of these particles produces current blockage events that provide an insight to the properties of the translocation particles and the nanopore. In this work we study the current blockage events produced by ~ 30nm negatively charged PS nanoparticles through Silicon Nitride solid state nanopores. We show how the current blockage amplitudes and durations are related to the ratio of the volume of the particle to the volume of the pore, the shape of the particle, charge of the particle and the nanopore surface, salt concentration, solution pH, and applied voltage. The solid-state nanopores are fabricated by a combination of Focus Ion Beam and low energy Ion beams in silicon nitride membranes. High resolution TEM is used to measure the 3D geometry of the nanopores and a finite element analysis program (COMSOL) is used to simulate the experimental results.

  20. Stability and magnetically induced heating behavior of lipid-coated Fe3O4 nanoparticles.

    PubMed

    Allam, Ayat A; Sadat, Md Ehsan; Potter, Sarah J; Mast, David B; Mohamed, Dina F; Habib, Fawzia S; Pauletti, Giovanni M

    2013-10-17

    Magnetic nanoparticles that are currently explored for various biomedical applications exhibit a high propensity to minimize total surface energy through aggregation. This study introduces a unique, thermoresponsive nanocomposite design demonstrating substantial colloidal stability of superparamagnetic Fe3O4 nanoparticles (SPIONs) due to a surface-immobilized lipid layer. Lipid coating was accomplished in different buffer systems, pH 7.4, using an equimolar mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and l-α-dipalmitoylphosphatidyl glycerol (DPPG). Particle size and zeta potential were measured by dynamic laser light scattering. Heating behavior within an alternating magnetic field was compared between the commercial MFG-1000 magnetic field generator at 7 mT (1 MHz) and an experimental, laboratory-made magnetic hyperthermia system at 16.6 mT (13.7 MHz). The results revealed that product quality of lipid-coated SPIONs was significantly dependent on the colloidal stability of uncoated SPIONs during the coating process. Greatest stability was achieved at 0.02 mg/mL in citrate buffer (mean diameter = 80.0 ± 1.7 nm; zeta potential = -47.1 ± 2.6 mV). Surface immobilization of an equimolar DPPC/DPPG layer effectively reduced the impact of buffer components on particle aggregation. Most stable suspensions of lipid-coated nanoparticles were obtained at 0.02 mg/mL in citrate buffer (mean diameter = 179.3 ± 13.9 nm; zeta potential = -19.1 ± 2.3 mV). The configuration of the magnetic field generator significantly affected the heating properties of fabricated SPIONs. Heating rates of uncoated nanoparticles were substantially dependent on buffer composition but less influenced by particle concentration. In contrast, thermal behavior of lipid-coated nanoparticles within an alternating magnetic field was less influenced by suspension vehicle but dramatically more sensitive to particle concentration. These results underline the advantages of lipid

  1. Characteristics of lipid micro- and nanoparticles based on supercritical formation for potential pharmaceutical application

    NASA Astrophysics Data System (ADS)

    Santo, Islane Espírito; Pedro, André São; Fialho, Rosana; Cabral-Albuquerque, Elaine

    2013-09-01

    The interest of the pharmaceutical industry in lipid drug delivery systems due to their prolonged release profile, biocompatibility, reduction of side effects, and so on is already known. However, conventional methods of preparation of these structures for their use and production in the pharmaceutical industry are difficult since these methods are usually multi-step and involve high amount of organic solvent. Furthermore, some processes need extreme conditions, which can lead to an increase of heterogeneity of particle size and degradation of the drug. An alternative for drug delivery system production is the utilization of supercritical fluid technique. Lipid particles produced by supercritical fluid have shown different physicochemical properties in comparison to lipid particles produced by classical methods. Such particles have shown more physical stability and narrower size distribution. So, in this paper, a critical overview of supercritical fluid-based processes for the production of lipid micro- and nanoparticles is given and the most important characteristics of each process are highlighted.

  2. A targeting drug delivery system for ovarian carcinoma: transferrin modified lipid coated paclitaxel-loaded nanoparticles.

    PubMed

    Li, R; Zhang, Q; Wang, X-y; Chen, X-g; He, Y-x; Yang, W-y; Yang, X

    2014-10-01

    The transferring modified lipid coated PLGA nanoparticles, as a targetable vector, were developed for the targeting delivery of anticancer drugs with paclitaxel (PTX) as a model drug to the ovarian carcinoma, which combines the advantages and avoids disadvantages of polymeric nanoparticles and liposomes in drug delivery. A transmission electron microscopy (TEM) confirmed the lipid coating on the polymeric core. Physicochemical characterizations of TFLPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. In the cellular uptake study, the TFLPs were more efficiently endocytosed by the A2780 cells with high expression of transferrin receptors than HUVEC cells without the transferrin receptors. Furthermore, the anticancer efficacy of TFLPs on the tumor spheroids was stronger than that of lipid coated PLGA nanoparticles (LPs) and PLGA nanoparticles. In the in vivo study, the TFLPs showed the best inhibition effect of the tumor growth for the ovarian carcinoma-bearing mice. In brief, the TFLPs were proved to be an efficient targeting drug delivery system for ovarian carcinoma.

  3. A general strategy to achieve ultra-high gene transfection efficiency using lipid-nanoparticle composites.

    PubMed

    Vankayala, Raviraj; Chiang, Chi-Shiun; Chao, Jui-I; Yuan, Chiun-Jye; Lin, Shyr-Yeu; Hwang, Kuo Chu

    2014-09-01

    Gene therapy provides a new hope for previously "incurable" diseases. Low gene transfection efficiency, however, is the bottle-neck to the success of gene therapy. It is very challenging to develop non-viral nanocarriers to achieve ultra-high gene transfection efficiencies. Herein, we report a novel design of "tight binding-but-detachable" lipid-nanoparticle composite to achieve ultrahigh gene transfection efficiencies of 60∼82%, approaching the best value (∼90%) obtained using viral vectors. We show that Fe@CNPs nanoparticles coated with LP-2000 lipid molecules can be used as gene carriers to achieve ultra-high (60-80%) gene transfection efficiencies in HeLa, U-87MG, and TRAMP-C1 cells. In contrast, Fe@CNPs having surface-covalently bound N,N,N-trimethyl-N-2-methacryloxyethyl ammonium chloride (TMAEA) oligomers can only achieve low (23-28%) gene transfection efficiencies. Similarly ultrahigh gene transfection/expression was also observed in zebrafish model using lipid-coated Fe@CNPs as gene carriers. Evidences for tight binding and detachability of DNA from lipid-nanoparticle nanocarriers will be presented. PMID:24973297

  4. Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea

    PubMed Central

    Bu, Meng; Tang, Jingling; Wei, Yinghui; Sun, Yanhui; Wang, Xinyu; Wu, Linhua; Liu, Hongzhuo

    2015-01-01

    Purpose Supplementation of exogenous nerve growth factor (NGF) into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route. Methods A novel nanocarrier-entrapped NGF was developed based on phytantriol by a liquid precursor dilution, with Pluronic® F127 and propylene glycol as the surfactant and solubilizer, respectively. Upon dilution of the liquid lipid precursors, monodispersed submicron-sized particles with a slight negative charge formed spontaneously. Results Biological activity of entrapped NGF was assessed using pheochromocytoma cells with NGF-loaded reservoirs to induce significant neuronal outgrowth, similar to that seen in free NGF-treated controls. Finally, a 3.28-fold increase in inner ear bioavailability was observed after administration of phytantriol lipid-based crystalline nanoparticles as compared to free drug, contributing to an enhanced drug permeability of the round window membrane. Conclusion Data presented here demonstrate the potential of lipid-based crystalline nanoparticles to improve the outcomes of patients bearing cochlear implants. PMID:26604754

  5. A general strategy to achieve ultra-high gene transfection efficiency using lipid-nanoparticle composites.

    PubMed

    Vankayala, Raviraj; Chiang, Chi-Shiun; Chao, Jui-I; Yuan, Chiun-Jye; Lin, Shyr-Yeu; Hwang, Kuo Chu

    2014-09-01

    Gene therapy provides a new hope for previously "incurable" diseases. Low gene transfection efficiency, however, is the bottle-neck to the success of gene therapy. It is very challenging to develop non-viral nanocarriers to achieve ultra-high gene transfection efficiencies. Herein, we report a novel design of "tight binding-but-detachable" lipid-nanoparticle composite to achieve ultrahigh gene transfection efficiencies of 60∼82%, approaching the best value (∼90%) obtained using viral vectors. We show that Fe@CNPs nanoparticles coated with LP-2000 lipid molecules can be used as gene carriers to achieve ultra-high (60-80%) gene transfection efficiencies in HeLa, U-87MG, and TRAMP-C1 cells. In contrast, Fe@CNPs having surface-covalently bound N,N,N-trimethyl-N-2-methacryloxyethyl ammonium chloride (TMAEA) oligomers can only achieve low (23-28%) gene transfection efficiencies. Similarly ultrahigh gene transfection/expression was also observed in zebrafish model using lipid-coated Fe@CNPs as gene carriers. Evidences for tight binding and detachability of DNA from lipid-nanoparticle nanocarriers will be presented.

  6. Analysis of lipid nanoparticles by Cryo-EM for characterizing siRNA delivery vehicles.

    PubMed

    Crawford, Randy; Dogdas, Belma; Keough, Edward; Haas, R Matthew; Wepukhulu, Wickliffe; Krotzer, Steven; Burke, Paul A; Sepp-Lorenzino, Laura; Bagchi, Ansuman; Howell, Bonnie J

    2011-01-17

    Lipid nanoparticles are self-assembling, dynamic structures commonly used as carriers of siRNA, DNA, and small molecular therapeutics. Quantitative analysis of particle characteristics such as morphological features can be very informative as biophysical properties are known to influence biological activity, biodistribution, and toxicity. However, accurate characterization of particle attributes and population distributions is difficult. Cryo-Electron Microscopy (Cryo-EM) is a leading characterization method and can reveal diversity in particle size, shape and lamellarity, however, this approach is traditionally used for qualitative review or low throughput image analysis due to inherent EM micrograph contrast characteristics and artifacts in the images which limit extraction of quantitative feature values. In this paper we describe the development of a semiautomatic image analysis framework to facilitate reliable image enhancement, object segmentation, and quantification of nanoparticle attributes in Cryo-EM micrographs. We apply this approach to characterize two formulations of siRNA-loaded lipid nanoparticles composed of cationic lipid, cholesterol, and poly(ethylene glycol)-lipid, where the formulations differ only by input component ratios. We found Cryo-EM image analysis provided reliable size and morphology information as well as the detection of smaller particle populations that were not detected by standard dynamic light scattering (DLS) analysis.

  7. Self-assembly of core-polyethylene glycol-lipid shell (CPLS) nanoparticles and their potential as drug delivery vehicles

    NASA Astrophysics Data System (ADS)

    Shen, Zhiqiang; Loe, David T.; Awino, Joseph K.; Kröger, Martin; Rouge, Jessica L.; Li, Ying

    2016-08-01

    Herein a new multifunctional formulation, referred to as a core-polyethylene glycol-lipid shell (CPLS) nanoparticle, has been proposed and studied in silico via large scale coarse-grained molecular dynamics simulations. A PEGylated core with surface tethered polyethylene glycol (PEG) chains is used as the starting configuration, where the free ends of the PEG chains are covalently bonded with lipid molecules (lipid heads). A complete lipid bilayer is formed at the surface of the PEGylated particle core upon addition of free lipids, driven by the hydrophobic properties of the lipid tails, leading to the formation of a CPLS nanoparticle. The self-assembly process is found to be sensitive to the grafting density and molecular weight of the tethered PEG chains, as well as the amount of free lipids added. At low grafting densities the assembly of CPLS nanoparticles cannot be accomplished. As demonstrated by simulations, a lipid bud/vesicle can be formed on the surface when an excess amount of free lipids is added at high grafting density. Therefore, the CPLS nanoparticles can only be formed under appropriate conditions of both PEG and free lipids. The CPLS nanoparticle has been recognized to be able to store a large quantity of water molecules, particularly with high molecular weight of PEG chains, indicating its capacity for carrying hydrophilic molecules such as therapeutic biomolecules or imaging agents. Under identical size and surface chemistry conditions of a liposome, it has been observed that the CPLS particle can be more efficiently wrapped by the lipid membrane, indicating its potential for a greater efficiency in delivering its hydrophilic cargo. As a proof-of-concept, the experimental realization of CPLS nanoparticles is explicitly demonstrated in this study. To test the capacity of the CPLS to store small molecule cargo a hydrophilic dye was successfully encapsulated in the particles' water soluble layer. The results of this study show the power and

  8. Influence of Polyethylene Glycol Density and Surface Lipid on Pharmacokinetics and Biodistribution of Lipid-Calcium-Phosphate Nanoparticles

    PubMed Central

    Liu, Yang; Hu, Yunxia; Huang, Leaf

    2014-01-01

    The pharmacokinetics (PK) and biodistribution of nanoparticles (NPs) are controlled by a complex array of interrelated, physicochemical and biological factors of NPs. The lipid-bilayer core structure of the Lipid-Calcium-Phosphate (LCP) NPs allows us to examine the effects of the density of polyethylene glycol (PEG) and the incorporation of various lipids onto the surface on their fate in vivo. Fluorescence quantification estimated that up to 20% (molar percent of outer leaflet lipids) could be grafted on the surface of LCP NPs. Contrary to the common belief that high level of PEGylation could prevent the uptake of NPs by the reticuloendothelial system (RES) organs such as liver and spleen, a significant amount of the injected dose was observed in the liver. Confocal microscopy revealed that LCP NPs were largely localized in hepatocytes not Kupffer cells. It was further demonstrated that the delivery to hepatocytes was dependent on both the concentration of PEG and the surface lipids. LCP NPs could be directed from hepatocytes to Kupffer cells by decreasing PEG concentration on the particle surface. In addition, LCP NPs with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) exhibited higher accumulation in the hepatocytes than LCP NPs with dioleoylphosphatidylcholine (DOPC). Analysis of the proteins bound to NPs suggested that apolipoprotein E (apoE) might serve as an endogenous targeting ligand for LCP-DOTAP NPs, but not LCP-DOPC NPs. The significant uptake of NPs by the hepatocytes is of great interest to formulation design for oncologic and hepatic drug deliveries. PMID:24388798

  9. Pectin-Lipid Self-Assembly: Influence on the Formation of Polyhydroxy Fatty Acids Nanoparticles

    PubMed Central

    Guzman-Puyol, Susana; Benítez, José Jesús; Domínguez, Eva; Bayer, Ilker Sefik; Cingolani, Roberto; Athanassiou, Athanassia; Heredia, Antonio; Heredia-Guerrero, José Alejandro

    2015-01-01

    Nanoparticles, named cutinsomes, have been prepared from aleuritic (9,10,16-trihidroxipalmitic) acid and tomato fruit cutin monomers (a mixture of mainly 9(10),16-dihydroxypalmitic acid (85%, w/w) and 16-hydroxyhexadecanoic acid (7.5%, w/w)) with pectin in aqueous solution. The process of formation of the nanoparticles of aleuritic acid plus pectin has been monitored by UV-Vis spectrophotometry, while their chemical and morphological characterization was analyzed by ATR-FTIR, TEM, and non-contact AFM. The structure of these nanoparticles can be described as a lipid core with a pectin shell. Pectin facilitated the formation of nanoparticles, by inducing their aggregation in branched chains and favoring the condensation between lipid monomers. Also, pectin determined the self-assembly of cutinsomes on highly ordered pyrolytic graphite (HOPG) surfaces, causing their opening and forming interconnected structures. In the case of cutin monomers, the nanoparticles are fused, and the condensation of the hydroxy fatty acids is strongly affected by the presence of the polysaccharide. The interaction of pectin with polyhydroxylated fatty acids could be related to an initial step in the formation of the plant biopolyester cutin. PMID:25915490

  10. Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles

    PubMed Central

    Wang, Ming; Zuris, John A.; Meng, Fantao; Rees, Holly; Sun, Shuo; Deng, Pu; Han, Yong; Gao, Xue; Pouli, Dimitra; Wu, Qi; Georgakoudi, Irene; Liu, David R.; Xu, Qiaobing

    2016-01-01

    A central challenge to the development of protein-based therapeutics is the inefficiency of delivery of protein cargo across the mammalian cell membrane, including escape from endosomes. Here we report that combining bioreducible lipid nanoparticles with negatively supercharged Cre recombinase or anionic Cas9:single-guide (sg)RNA complexes drives the electrostatic assembly of nanoparticles that mediate potent protein delivery and genome editing. These bioreducible lipids efficiently deliver protein cargo into cells, facilitate the escape of protein from endosomes in response to the reductive intracellular environment, and direct protein to its intracellular target sites. The delivery of supercharged Cre protein and Cas9:sgRNA complexed with bioreducible lipids into cultured human cells enables gene recombination and genome editing with efficiencies greater than 70%. In addition, we demonstrate that these lipids are effective for functional protein delivery into mouse brain for gene recombination in vivo. Therefore, the integration of this bioreducible lipid platform with protein engineering has the potential to advance the therapeutic relevance of protein-based genome editing. PMID:26929348

  11. Emerging Research and Clinical Development Trends of Liposome and Lipid Nanoparticle Drug Delivery Systems

    PubMed Central

    KRAFT, JOHN C.; FREELING, JENNIFER P.; WANG, ZIYAO; HO, RODNEY J. Y.

    2014-01-01

    Liposomes are spherical-enclosed membrane vesicles mainly constructed with lipids. Lipid nanoparticles are loaded with therapeutics and may not contain an enclosed bilayer. The majority of those clinically approved have diameters of 50–300 nm. The growing interest in nanomedicine has fueled lipid–drug and lipid–protein studies, which provide a foundation for developing lipid particles that improve drug potency and reduce off-target effects. Integrating advances in lipid membrane research has enabled therapeutic development. At present, about 600 clinical trials involve lipid particle drug delivery systems. Greater understanding of pharmacokinetics, biodistribution, and disposition of lipid–drug particles facilitated particle surface hydration technology (with polyethylene glycol) to reduce rapid clearance and provide sufficient blood circulation time for drug to reach target tissues and cells. Surface hydration enabled the liposome-encapsulated cancer drug doxorubicin (Doxil) to gain clinical approval in 1995. Fifteen lipidic therapeutics are now clinically approved. Although much research involves attaching lipid particles to ligands selective for occult cells and tissues, preparation procedures are often complex and pose scale-up challenges. With emerging knowledge in drug target and lipid–drug distribution in the body, a systems approach that integrates knowledge to design and scale lipid–drug particles may further advance translation of these systems to improve therapeutic safety and efficacy. PMID:24338748

  12. Dark-field-based observation of single-nanoparticle dynamics on a supported lipid bilayer for in situ analysis of interacting molecules and nanoparticles.

    PubMed

    Lee, Young Kwang; Kim, Sungi; Nam, Jwa-Min

    2015-01-12

    Observation of single plasmonic nanoparticles in reconstituted biological systems allows us to obtain snapshots of dynamic processes between molecules and nanoparticles with unprecedented spatiotemporal resolution and single-molecule/single-particle-level data acquisition. This Concept is intended to introduce nanoparticle-tethered supported lipid bilayer platforms that allow for the dynamic confinement of nanoparticles on a two-dimensional fluidic surface. The dark-field-based long-term, stable, real-time observation of freely diffusing plasmonic nanoparticles on a lipid bilayer enables one to extract a broad range of information about interparticle and molecular interactions throughout the entire reaction period. Herein, we highlight important developments in this context to provide ideas on how molecular interactions can be interpreted by monitoring dynamic behaviors and optical signals of laterally mobile nanoparticles.

  13. Spontaneous, Solvent-Free, Polymer-Templated, Solid-Solid Transformation of Thin Metal Films into Nanoparticles.

    PubMed

    Hernández-Cruz, Olivia; Avila-Gutierrez, Lizeth; Zolotukhin, Mikhail G; Gonzalez, Gonzalo; Monroy, B Marel; Montiel, Raúl; Vera-Graziano, Ricardo; Romero-Ibarra, Josue E; Novelo-Peralta, Omar; Massó Rojas, Felipe Alonso

    2016-09-14

    Metal nanoparticles have unusual optical, electronic, sensing, recognition, catalytic, and therapeutic properties. They are expected to form the basis of many of the technological and biological innovations of this century. A prerequisite for future applications using nanoparticles as functional entities is control of the shape, size, and homogeneity of these nanoparticles and of their interparticle spacing and arrangement on surfaces, between electrodes, or in devices. Here, we demonstrate that thin films of gold, silver, and copper sputter-deposited onto the surface of an organic polymer poly[[1,1':4',1″-terphenyl]-4,4″-diyl(2-bromo-1-carboxyethylidene)] (PTBC) undergo spontaneous solid-solid transformation into nanoparticles. Furthermore, we show that, by varying the thickness of the films, the volume-to-surface ratio of the polymer substrate, and the amount of plasticizer, it is possible to control the rate of transformation and the morphology of the nanoparticles formed. PTBC containing Au nanoparticles was found to enhance the cell adhesion and proliferation. To the best of our knowledge, our findings constitute the first experimental evidence of spontaneous, room-temperature, solid-solid transformation of metal films sputtered onto the surface of an organic polymeric substrate into nanoparticles (crystals).

  14. Regulation of egg quality and lipids metabolism by Zinc Oxide Nanoparticles.

    PubMed

    Zhao, Yong; Li, Lan; Zhang, Peng-Fei; Liu, Xin-Qi; Zhang, Wei-Dong; Ding, Zhao-Peng; Wang, Shi-Wen; Shen, Wei; Min, Ling-Jiang; Hao, Zhi-Hui

    2016-04-01

    This investigation was designed to explore the effects of Zinc Oxide Nanoparticles (ZnO NP) on egg quality and the mechanism of decreasing of yolk lipids. Different concentration of ZnO NP and ZnSO4 were used to treat hens for 24 weeks. The body weight and egg laying frequency were recorded and analyzed. Albumen height, Haugh unit, and yolk color score were analyzed by an Egg Multi Tester. Breaking strength was determined by an Egg Force Reader. Egg shell thickness was measured using an Egg Shell Thickness Gouge. Shell color was detected by a spectrophotometer. Egg shape index was measured by Egg Form Coefficient Measuring Instrument. Albumen and yolk protein was determined by the Kjeldahl method. Amino acids were determined by an amino acids analyzer. Trace elements Zn, Fe, Cu, and P (mg/kg wet mass) were determined in digested solutions using Inductively Coupled Plasma-Optical Emission Spectrometry. TC and TG were measured using commercial analytical kits. Yolk triglyceride, total cholesterol, pancreatic lipase, and phospholipids were determined by appropriate kits. β-carotene was determined by spectrophotometry. Lipid metabolism was also investigated with liver, plasma, and ovary samples. ZnO NP did not change the body weight of hens during the treatment period. ZnO NP slowed down egg laying frequency at the beginning of egg laying period but not at later time. ZnO NP did not affect egg protein or water contents, slightly decreased egg physical parameters (12 to 30%) and trace elements (20 to 35%) after 24 weeks treatment. However, yolk lipids content were significantly decreased by ZnO NP (20 to 35%). The mechanism of Zinc oxide nanoparticles decreasing yolk lipids was that they decreased the synthesis of lipids and increased lipid digestion. These data suggested ZnO NP affected egg quality and specifically regulated lipids metabolism in hens through altering the function of hen's ovary and liver. PMID:26908885

  15. Regulation of egg quality and lipids metabolism by Zinc Oxide Nanoparticles.

    PubMed

    Zhao, Yong; Li, Lan; Zhang, Peng-Fei; Liu, Xin-Qi; Zhang, Wei-Dong; Ding, Zhao-Peng; Wang, Shi-Wen; Shen, Wei; Min, Ling-Jiang; Hao, Zhi-Hui

    2016-04-01

    This investigation was designed to explore the effects of Zinc Oxide Nanoparticles (ZnO NP) on egg quality and the mechanism of decreasing of yolk lipids. Different concentration of ZnO NP and ZnSO4 were used to treat hens for 24 weeks. The body weight and egg laying frequency were recorded and analyzed. Albumen height, Haugh unit, and yolk color score were analyzed by an Egg Multi Tester. Breaking strength was determined by an Egg Force Reader. Egg shell thickness was measured using an Egg Shell Thickness Gouge. Shell color was detected by a spectrophotometer. Egg shape index was measured by Egg Form Coefficient Measuring Instrument. Albumen and yolk protein was determined by the Kjeldahl method. Amino acids were determined by an amino acids analyzer. Trace elements Zn, Fe, Cu, and P (mg/kg wet mass) were determined in digested solutions using Inductively Coupled Plasma-Optical Emission Spectrometry. TC and TG were measured using commercial analytical kits. Yolk triglyceride, total cholesterol, pancreatic lipase, and phospholipids were determined by appropriate kits. β-carotene was determined by spectrophotometry. Lipid metabolism was also investigated with liver, plasma, and ovary samples. ZnO NP did not change the body weight of hens during the treatment period. ZnO NP slowed down egg laying frequency at the beginning of egg laying period but not at later time. ZnO NP did not affect egg protein or water contents, slightly decreased egg physical parameters (12 to 30%) and trace elements (20 to 35%) after 24 weeks treatment. However, yolk lipids content were significantly decreased by ZnO NP (20 to 35%). The mechanism of Zinc oxide nanoparticles decreasing yolk lipids was that they decreased the synthesis of lipids and increased lipid digestion. These data suggested ZnO NP affected egg quality and specifically regulated lipids metabolism in hens through altering the function of hen's ovary and liver.

  16. Lipid nanoparticle vectorization of indocyanine green improves fluorescence imaging for tumor diagnosis and lymph node resection.

    PubMed

    Navarro, Fabrice P; Berger, Michel; Guillermet, Stéphanie; Josserand, Véronique; Guyon, Laurent; Neumann, Emmanuelle; Vinet, Françoise; Texier, Isabelle

    2012-10-01

    Fluorescence imaging is opening a new era in image-guided surgery and other medical applications. The only FDA approved contrast agent in the near infrared is IndoCyanine Green (ICG), which despites its low toxicity, displays poor chemical and optical properties for long-term and sensitive imaging applications in human. Lipid nanoparticles are investigated for improving ICG optical properties and in vivo fluorescence imaging sensitivity. 30 nm diameter lipid nanoparticles (LNP) are loaded with ICG. Their characterization and use for tumor and lymph node imaging are described. Nano-formulation benefits dye optical properties (6 times improved brightness) and chemical stability (>6 months at 4 degrees C in aqueous buffer). More importantly, LNP vectorization allows never reported sensitive and prolonged (>1 day) labeling of tumors and lymph nodes. Composed of human-use approved ingredients, this novel ICG nanometric formulation is foreseen to expand rapidly the field of clinical fluorescence imaging applications.

  17. Ferromagnetic filled carbon nanotubes and nanoparticles: synthesis and lipid-mediated delivery into human tumor cells

    NASA Astrophysics Data System (ADS)

    Mönch, I.; Meye, A.; Leonhardt, A.; Krämer, K.; Kozhuharova, R.; Gemming, T.; Wirth, M. P.; Büchner, B.

    2005-04-01

    We describe the synthesis and the properties of Fe-filled multi-walled carbon nanotubes (MWNTs) and nanoparticles (NP) produced by chemical vapor deposition (CVD). We have employed ferrocene as a starting substance and oxidized Si-wafers as substrates. The magnetic properties and the interaction of the material with bladder cancer cells were determined. After the addition of NP suspensions to cultured cells, no adhesion of the nanoparticles/nanotubes (NT/NP) to the cell membrane and also no cellular uptake were observed. However, the preincubation of the (NT/NP) suspension with cationic lipid caused an efficient delivery of the lipid-nanostructure complexes into the cytoplasm within 2 h after adding to the culture medium.

  18. In situ transmission electron microscopy of solid-liquid phase transition of silica encapsulated bismuth nanoparticles

    NASA Astrophysics Data System (ADS)

    Hu, Jianjun; Hong, Yan; Muratore, Chris; Su, Ming; Voevodin, Andrey A.

    2011-09-01

    The solid-liquid phase transition of silica encapsulated bismuth nanoparticles was studied by in situ transmission electron microscopy (TEM). The nanoparticles were prepared by a two-step chemical synthesis process involving thermal decomposition of organometallic precursors for nucleating bismuth and a sol-gel process for growing silica. The microstructural and chemical analyses of the nanoparticles were performed using high-resolution TEM, Z-contrast imaging, focused ion beam milling, and X-ray energy dispersive spectroscopy. Solid-liquid-solid phase transitions of the nanoparticles were directly recorded by electron diffractions and TEM images. The silica encapsulation of the nanoparticles prevented agglomeration and allowed particles to preserve their original volume upon melting, which is desirable for applications of phase change nanoparticles with consistently repeatable thermal properties.

  19. In situ transmission electron microscopy of solid-liquid phase transition of silica encapsulated bismuth nanoparticles.

    PubMed

    Hu, Jianjun; Hong, Yan; Muratore, Chris; Su, Ming; Voevodin, Andrey A

    2011-09-01

    The solid-liquid phase transition of silica encapsulated bismuth nanoparticles was studied by in situ transmission electron microscopy (TEM). The nanoparticles were prepared by a two-step chemical synthesis process involving thermal decomposition of organometallic precursors for nucleating bismuth and a sol-gel process for growing silica. The microstructural and chemical analyses of the nanoparticles were performed using high-resolution TEM, Z-contrast imaging, focused ion beam milling, and X-ray energy dispersive spectroscopy. Solid-liquid-solid phase transitions of the nanoparticles were directly recorded by electron diffractions and TEM images. The silica encapsulation of the nanoparticles prevented agglomeration and allowed particles to preserve their original volume upon melting, which is desirable for applications of phase change nanoparticles with consistently repeatable thermal properties.

  20. Lipid-peptide-polymer conjugates and nanoparticles thereof

    SciTech Connect

    Xu, Ting; Dong, He; Shu, Jessica

    2015-06-02

    The present invention provides a conjugate having a peptide with from about 10 to about 100 amino acids, wherein the peptide adopts a helical structure. The conjugate also includes a first polymer covalently linked to the peptide, and a hydrophobic moiety covalently linked to the N-terminus of the peptide, wherein the hydrophobic moiety comprises a second polymer or a lipid moiety. The present invention also provides helix bundles form by self-assembling the conjugates, and particles formed by self-assembling the helix bundles. Methods of preparing the helix bundles and particles are also provided.

  1. Optimizing Oriented Planar-Supported Lipid Samples for Solid-State Protein NMR

    PubMed Central

    Rainey, Jan K.; Sykes, Brian D.

    2005-01-01

    Sample orientation relative to the static magnetic field of an NMR spectrometer allows study of membrane proteins in the lipid bilayer setting. The straightforward preparation and handling of extremely thin mica substrates with consistent surface properties has prompted us to examine oriented phospholipid bilayer and hexagonal phases on mica. The spectral characteristics of oriented lipid samples formed on mica are as good as or better than those on glass. Nine solvents with varying dielectric constants were used to cast lipid films or for vesicle spreading; film characteristics were then compared, and static solid-state 31P-NMR was used to characterize the degree of orientation of the hydrated lipid species. Lipids with four headgroup chemistries were tested: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Solvent affected orientation of POPG, DOPA, and DOPE, but not POPC. Film characteristics varied with solvent, with ramifications for producing homogeneous oriented lipid samples. POPC was used to optimize the amount of lipid per substrate and compare hydration methods. POPG did not orient reproducibly, whereas POPG-POPC mixtures did. DOPA showed 1–2 oriented states depending upon hydration level and deposition method. DOPE formed an oriented hexagonal phase that underwent a reversible temperature-induced phase transition to the oriented bilayer phase. PMID:16085766

  2. Optimization of Nanoparticle Separation through Solid State Nanopore

    NASA Astrophysics Data System (ADS)

    Dutta, Prashanta; Jubery, Talukder; Prabhu, Anmiv; Kim, Minjun

    2010-11-01

    Recently there has been a growing interest on solid state nanopores to separate biological molecules such as proteins, DNA, and RNA. However, efficient separation of biomolecules through nanopores is a challenging task as a number of factors such as size and charge density of particle, size and charge density of membrane pore, and the concentration of bulk electrolyte influence the translocation behavior of nanoparticles through pores. To address this issue, a mathematical model is developed based on mass, momentum, and charge conservation equations to study the behavior of particles through pores. The surface charge density of the membrane pore was identified as the most critical parameter that determines the selectivity of the membrane and the throughput of the separation process. Based on this model, a single 150 nm pore was fabricated in a 50 nm thick free standing silicon nitride substrate by focused ion beam milling. This pore was subsequently chemically modified with (3-Aminopropyl) triethoxysilane to change its surface charge density. This chemically modified nanofluidic architecture was then used to separate 22 nm and 58 nm polystyrene nanoparticles.

  3. Chemically modified solid state nanopores for high throughput nanoparticle separation

    NASA Astrophysics Data System (ADS)

    Prabhu, Anmiv S.; Jubery, Talukder Zaki N.; Freedman, Kevin J.; Mulero, Rafael; Dutta, Prashanta; Kim, Min Jun

    2010-11-01

    The separation of biomolecules and other nanoparticles is a vital step in several analytical and diagnostic techniques. Towards this end we present a solid state nanopore-based set-up as an efficient separation platform. The translocation of charged particles through a nanopore was first modeled mathematically using the multi-ion model and the surface charge density of the nanopore membrane was identified as a critical parameter that determines the selectivity of the membrane and the throughput of the separation process. Drawing from these simulations a single 150 nm pore was fabricated in a 50 nm thick free-standing silicon nitride membrane by focused-ion-beam milling and was chemically modified with (3-aminopropyl)triethoxysilane to change its surface charge density. This chemically modified membrane was then used to separate 22 and 58 nm polystyrene nanoparticles in solution. Once optimized, this approach can readily be scaled up to nanopore arrays which would function as a key component of next-generation nanosieving systems.

  4. Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

    PubMed

    García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

    2015-03-30

    Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes.

  5. Lipid nanoparticles with no surfactant improve oral absorption rate of poorly water-soluble drug.

    PubMed

    Funakoshi, Yuka; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2013-07-15

    A pharmacokinetic study was performed in rats to evaluate the oral absorption ratios of nanoparticle suspensions containing the poorly water-soluble compound nifedipine (NI) and two different types of lipids, including hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol. NI-lipid nanoparticle (LN) suspensions with a mean particle size of 48.0 nm and a zeta potential of -57.2 mV were prepared by co-grinding combined with a high-pressure homogenization process. The oral administration of NI-LN suspensions to rats led to a significant increase in the NI plasma concentration, and the area under the curve (AUC) value was found to be 108 min μg mL⁻¹, indicating a 4-fold increase relative to the NI suspensions. A comparison of the pharmacokinetic parameters of the NI-LN suspensions with those of the NI solution prepared using only the surfactant polysorbate 80 revealed that although the AUC and bioavailability (59%) values were almost identical, a rapid absorption rate was still observed in the NI-LN suspensions. These results therefore indicated that lipid nanoparticles prepared using only two types of phospholipid with a mean particle size of less than 50 nm could improve the absorption of the poorly water-soluble drug.

  6. Magnetic field activated lipid-polymer hybrid nanoparticles for stimuli-responsive drug release.

    PubMed

    Kong, Seong Deok; Sartor, Marta; Hu, Che-Ming Jack; Zhang, Weizhou; Zhang, Liangfang; Jin, Sungho

    2013-03-01

    Stimuli-responsive nanoparticles (SRNPs) offer the potential of enhancing the therapeutic efficacy and minimizing the side-effects of chemotherapeutics by controllably releasing the encapsulated drug at the target site. Currently controlled drug release through external activation remains a major challenge during the delivery of therapeutic agents. Here we report a lipid-polymer hybrid nanoparticle system containing magnetic beads for stimuli-responsive drug release using a remote radio frequency (RF) magnetic field. These hybrid nanoparticles show long-term stability in terms of particle size and polydispersity index in phosphate-buffered saline (PBS). Controllable loading of camptothecin (CPT) and Fe(3)O(4) in the hybrid nanoparticles was demonstrated. RF-controlled drug release from these nanoparticles was observed. In addition, cellular uptake of the SRNPs into MT2 mouse breast cancer cells was examined. Using CPT as a model anticancer drug the nanoparticles showed a significant reduction in MT2 mouse breast cancer cell growth in vitro in the presence of a remote RF field. The ease of preparation, stability, and controllable drug release are the strengths of the platform and provide the opportunity to improve cancer chemotherapy.

  7. Quantitative Intracellular Localization of Cationic Lipid-Nucleic Acid Nanoparticles with Fluorescence Microscopy.

    PubMed

    Majzoub, Ramsey N; Ewert, Kai K; Safinya, Cyrus R

    2016-01-01

    Current activity in developing synthetic carriers of nucleic acids (NA) and small molecule drugs for therapeutic applications is unprecedented. One promising class of synthetic vectors for the delivery of therapeutic NA is PEGylated cationic liposome (CL)-NA nanoparticles (NPs). Chemically modified PEG-lipids can be used to surface-functionalize lipid-NA nanoparticles, allowing researchers to design active nanoparticles that can overcome the various intracellular and extracellular barriers to efficient delivery. Optimization of these functionalized vectors requires a comprehensive understanding of their intracellular pathways. In this chapter we present two distinct methods for investigating the intracellular activity of PEGylated CL-NA NPs using quantitative analysis with fluorescence microscopy.The first method, spatial localization, describes how to prepare fluorescently labeled CL-NA NPs, perform fluorescence microscopy and properly analyze the data to measure the intracellular distribution of nanoparticles and fluorescent signal. We provide software which allows data from multiple cells to be averaged together and yield statistically significant results. The second method, fluorescence colocalization, describes how to label endocytic organelles via Rab-GFPs and generate micrographs for software-assisted NP-endocytic marker colocalization measurements. These tools will allow researchers to study the endosomal trafficking of CL-NA NPs which can guide their design and improve their efficiency. PMID:27436314

  8. Silica nanoparticle stabilization of liquid crystalline lipid dispersions: impact on enzymatic digestion and drug solubilization.

    PubMed

    Bhatt, Achal B; Barnes, Timothy J; Prestidge, Clive A

    2015-01-01

    The high internal surface area and drug solubilizing capacity of liquid crystal lipids makes them promising oral drug delivery systems. Pluronic F127 is typically used to disperse highly viscous cubic liquid crystal lipids into cubosomes; however, such copolymers alter the internal structure and prov