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Sample records for mucoadhesive drug delivery

  1. Mucoadhesive drug delivery systems

    PubMed Central

    Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

    2011-01-01

    Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

  2. A clinical perspective on mucoadhesive buccal drug delivery systems

    PubMed Central

    Gilhotra, Ritu M; Ikram, Mohd; Srivastava, Sunny; Gilhotra, Neeraj

    2014-01-01

    Mucoadhesion can be defined as a state in which two components, of which one is of biological origin, are held together for extended periods of time by the help of interfacial forces. Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhesive buccal drug delivery systems (MBDDS), with a clinical perspective. Starting with a brief introduction of the mucoadhesive drug delivery systems, oral mucosa, and the theories of mucoadhesion, this article then proceeds to cover the works done so far in the field of MBDDS, categorizing them on the basis of ailments they are meant to cure. Additionally, we focus on the various patents, recent advancements, and challenges as well as the future prospects for mucoadhesive buccal drug delivery systems. PMID:24683406

  3. Mucoadhesive and thermogelling systems for vaginal drug delivery.

    PubMed

    Caramella, Carla M; Rossi, Silvia; Ferrari, Franca; Bonferoni, Maria Cristina; Sandri, Giuseppina

    2015-09-15

    This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described.

  4. Thiopyrazole preactivated chitosan: combining mucoadhesion and drug delivery.

    PubMed

    Müller, Christiane; Ma, Benjamin N; Gust, Ronald; Bernkop-Schnürch, Andreas

    2013-05-01

    The objective of this study was to develop a preactivated chitosan derivative by the introduction of thioglycolic acid followed by 3-methyl-1-phenylpyrazole-5-thiol (MPPT) coupling via disulfide bond formation. The newly synthesized conjugate was characterized in terms of water-absorbing capacity, cohesive properties, mucoadhesion and drug release kinetics. Further in vitro characterization was conducted regarding permeation enhancement of the model compound fluorescein isothiocyanate dextran (FD4) and cytotoxic effects on Caco-2 cells. Based on the attachment of the hydrophobic residue, chitosan-S-S-MPPT test discs showed increased stability of the polymer matrix as well as improved water uptake and liberation of fluorescein isothiocyanate dextran (FD4) compared to chitosan only. The mucoadhesive qualities on porcine intestinal mucosa could be improved 38-fold based on the enhanced bonding between chitosan-S-S-MPPT and mucus through the thiol/disulfide exchange reaction of polymer and mucosal cysteine-rich domains supported by MPPT as the leaving group. This novel biomaterial presents a disulfide conjugation-based delivery system that releases the antibacterial thiopyrazole when the polymer comes into contact with the intestinal mucosa. These properties, together with the safe toxicological profile, make chitosan-S-S-MPPT a valuable carrier for mucoadhesive drug delivery systems and a promising matrix for the development of antimicrobial excipients. PMID:23321304

  5. Preactivated thiomers as mucoadhesive polymers for drug delivery

    PubMed Central

    Iqbal, Javed; Shahnaz, Gul; Dünnhaupt, Sarah; Müller, Christiane; Hintzen, Fabian; Bernkop-Schnürch, Andreas

    2012-01-01

    found non-toxic over Caco-2 cells. Thus, on the basis of achieved results the pre-activated thiomers seem to represent a promising generation of mucoadhesive polymers which are safe to use for prolonged residence time of drug delivery systems to target various mucosa. PMID:22118819

  6. Formulation of mucoadhesive gastric retentive drug delivery using thiolated xyloglucan.

    PubMed

    Bhalekar, Mangesh R; Bargaje, Rajesh V; Upadhaya, Prashant G; Madgulkar, Ashwini R; Kshirsagar, Sanjay J

    2016-01-20

    Tamarind seed xyloglucan is a polymer reported to possess mucoadhesive property. In the present work, role of cysteine derivative of tamarind seed polysaccharide (thiomer) to enhance the mucoadhesion and its influence on drug permeation has been studied. The xyloglucan was first chemically modified to carboxymethyl derivative which was further converted to thiomer by conjugation with cysteine in presence of a coupling agent, EDAC. The matrix tablets of simvastatin prepared using thiomer demonstrated drug release retardation, increased mucoadhesion force and increased ex vivo permeation, the same were proportional to the increase in the amount of thiomer. The in vivo residence of thiomer placebo was more than 7h in rabbit. Pharmacokinetic evaluation in rabbits indicated higher AUC for the formulation with highest content of thiomer and level 'A' correlation could be established from the generated dissolution and bioavailability data. PMID:26572385

  7. Modified alginate beads for mucoadhesive drug delivery system: an updated review of patents.

    PubMed

    Swain, Suryakanta; Behera, Aurobinda; Beg, Sarwar; Patra, Chinam N; Dinda, Subash C; Sruti, Jammula; Rao, Muddana E B

    2012-12-01

    Pharmaceutical research and inventions are increasingly developed for the design of an ideal dosage regimen in drug therapy of many diseases, which attains therapeutic concentration of drug in plasma and maintains it constant for the entire duration of treatment and also minimizes the side effects. Recent trends in pharmaceutical technology indicated that mucoadhesive micro particle and modified alginate beads as drug delivery system especially suitable for achieving delivery of drug in a predetermined rate locally or systemically for a prolonged period of time. The release of drug from microparticle depends on a variety of factors including carrier used to form the micro particle and amount of drug contained in them. The main aim of the present review is to explain the various theories, mechanisms, advanced mucoadhesive polymers, various delivery approaches, methodologies for developing a mucoadhesive micro-particle and modified alginate beads formulation, in vitro, ex vivo and in vivo characterization. Apart from this, an innovative test method that is biacore is highlighted in this review to measure the mucoadhesive strength. This review is also briefly explained about the updated patenting system for the development of micro-particle and modified alginate beads as drug delivery system.

  8. Natural mucoadhesive microspheres of Abelmoschus esculentus polysaccharide as a new carrier for nasal drug delivery.

    PubMed

    Sharma, Nitin; Kulkarni, Giriraj T; Sharma, Anjana; Bhatnagar, Aseem; Kumar, Neeraj

    2013-01-01

    This work describes the preparation and evaluation of mucoadhesive microspheres, using Abelmoschus esculentus polysaccharide as a novel carrier for safe and effective delivery of rizatriptan benzoate into nasal cavity. The polysaccharide was extracted from the fruit of A. esculentus and mucoadhesive microspheres were prepared by emulsification, followed by crosslinking using epichlorohydrin. Prepared microspheres were evaluated for size, morphology, swelling properties, mucoadhesive strength, encapsulation efficiency and drug release. Microspheres were found to release 50% of drug within 15 min and rest of the drug was released within 60 min. The drug release was found to decrease with increasing concentration of polysaccharide. To determine the retention time of the microspheres in the nasal cavity of rabbits, the microspheres were radiolabelled with (99m)Tc and subjected to gamma scintigraphy. The results showed a significant improvement in the nasal retention of the microspheres as compared to the aqueous solution of radiolabelled free-drug. PMID:23379506

  9. The mucoadhesive and gastroretentive properties of hydrophobin-coated porous silicon nanoparticle oral drug delivery systems.

    PubMed

    Sarparanta, Mirkka P; Bimbo, Luis M; Mäkilä, Ermei M; Salonen, Jarno J; Laaksonen, Päivi H; Helariutta, A M Kerttuli; Linder, Markus B; Hirvonen, Jouni T; Laaksonen, Timo J; Santos, Hélder A; Airaksinen, Anu J

    2012-04-01

    Impediments to intestinal absorption, such as poor solubility and instability in the variable conditions of the gastrointestinal (GI) tract plague many of the current drugs restricting their oral bioavailability. Particulate drug delivery systems hold great promise in solving these problems, but their effectiveness might be limited by their often rapid transit through the GI tract. Here we describe a bioadhesive oral drug delivery system based on thermally-hydrocarbonized porous silicon (THCPSi) functionalized with a self-assembled amphiphilic protein coating consisting of a class II hydrophobin (HFBII) from Trichoderma reesei. The HFBII-THCPSi nanoparticles were found to be non-cytotoxic and mucoadhesive in AGS cells, prompting their use in a biodistribution study in rats after oral administration. The passage of HFBII-THCPSi nanoparticles in the rat GI tract was significantly slower than that of uncoated THCPSi, and the nanoparticles were retained in stomach by gastric mucoadhesion up to 3 h after administration. Upon entry to the small intestine, the mucoadhesive properties were lost, resulting in the rapid transit of the nanoparticles through the remainder of the GI tract. The gastroretentive drug delivery system with a dual function presented here is a viable alternative for improving drug bioavailability in the oral route.

  10. Mucoadhesive acrylated block copolymers micelles for the delivery of hydrophobic drugs.

    PubMed

    Eshel-Green, Tal; Bianco-Peled, Havazelet

    2016-03-01

    Blockpolymer micelles having acrylated end groups were fabricated for the development of mucoadhesive drug loaded vehicle. The critical micelle concentration (CMC) of Pluronic(®) F127 modified with acrylate end groups (F127DA) was found to be similar to that of the unmodified Pluronic(®) F127 (F127). Small angle X-ray scattering verified existence of micelles with an inner core of 4.9±0.2 and 5.5±0.3 for F127 and F127DA respectively. Indomethacin, a hydrophobic drug, was incorporated into the micelles using the thin-film hydration method. In vitro drug release assay demonstrated that the micelles sustained the release of the drug in comparison with free drug in solution. Several methods were used for mucoadhesion evaluation. Viscosity profiling was performed by shear rate sweep experiment of hydrated commercial mucin, F127 or F127DA, and combination of both mucin and a copolymer. Elevated viscosity was achieved for acrylated micelles with mucin compared to mixtures of non-acrylated micelles with mucin. The mucoadhesivity of the acrylated micelles was further characterized using nuclear magnetic resonance (NMR); data affirmed the Michael type addition reaction occurred between acrylates on the micelles corona and thiols present in the mucin. SAXS scattering data further showed a modification in the scattering of F127DA micelles with the addition of pig gastric mucin. Cryo-transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) data detected increase in the aggregates size while using acrylated micelles enhance mucoadhesion. Thus acrylated F127DA micelles were found to be mucoadhesive, and a suitable and preferred candidate for micellar drug delivery to mucosal surfaces. PMID:26700232

  11. Molecular Aspects of Mucoadhesive Carrier Development for Drug Delivery and Improved Absorption

    PubMed Central

    Peppas, Nicholas A; Thomas, J. Brock; McGinity, James

    2011-01-01

    Although the oral route remains the most favored route of drug administration, major scientific obstacles prevent the effective and efficient delivery of low-molecular-mass drugs, peptides and proteins that exhibit poor solubility and permeability. Mucoadhesive dosage forms and the associated drug carriers have the ability to interact at a molecular level with the mucus gel layer that lines the epithelial surfaces of the major absorptive regions of the body. This interaction provides an increased residence time of the therapeutic formulation while localizing the drug at the site of administration. Such local, non-specific targeting leads to an increase in both oral absorption and bioavailability. Fundamental understanding of the biological processes encountered along the gastrointestinal tract can provide a sufficient engineer of carriers that are capable to provide this increase in residence time. Here we discuss the theoretical framework for achieving mucoadhesive systems as related to biomaterials science and the structure of the biomaterials used. PMID:19105897

  12. Whey protein mucoadhesive properties for oral drug delivery: Mucin-whey protein interaction and mucoadhesive bond strength.

    PubMed

    Hsein, Hassana; Garrait, Ghislain; Beyssac, Eric; Hoffart, Valérie

    2015-12-01

    Whey protein is a natural polymer recently used as an excipient in buccoadhesive tablets but its mucoadhesive properties were barely studied. In this work, we characterize mucoadhesion of whey protein in order to determine the mechanisms and optimal conditions for use as excipient in oral drug delivery. Thus, native and denatured whey protein (NWP and DWP) were investigated and the effect of concentration and pH were also studied. Many methods of characterization were selected to allow the study of chemical and physical interactions with mucin and then the results were bound with an ex vivo experiments. Turbidity of WP-mucin mixture increased at acidic pH 1.2 till 4.5 indicating interaction with mucin but not at pH 6.8. No interaction with mucin was also found by ITC method at pH 6.8 for native and denatured whey protein used at 1% (w/w). Forces of bioadhesion evaluated by viscosity measurements were the best for high concentrated (10.8%) DWP solutions at pH 6.8 and were low at pH 1.2 for NWP and DWP solutions. Addition of chemical blockers indicated that hydrogen bondings and disulfide bridges were the main mechanisms of interactions with mucin. Reticulation of DWP with calcium ions to obtain microparticles (MP) did not influence the ability of interaction with mucin as shown by FTIR analysis. These results correlated with ex vivo study on rat tissue demonstrating important adhesion (75%) of WP MP on the intestine and null on the stomach after 2h of deposit.

  13. The Potential of Silk and Silk-Like Proteins as Natural Mucoadhesive Biopolymers for Controlled Drug Delivery.

    PubMed

    Brooks, Amanda E

    2015-01-01

    Drug delivery across mucus membranes is a particularly effective route of administration due to the large surface area. However, the unique environment present at the mucosa necessitates altered drug formulations designed to (1) deliver sensitive biologic molecules, (2) promote intimate contact between the mucosa and the drug, and (3) prolong the drug's local residence time. Thus, the pharmaceutical industry has an interest in drug delivery systems formulated around the use of mucoadhesive polymers. Mucoadhesive polymers, both synthetic and biological, have a history of use in local drug delivery. Prominently featured in the literature are chitosan, alginate, and cellulose derivatives. More recently, silk and silk-like derivatives have been explored for their potential as mucoadhesive polymers. Both silkworms and spiders produce sticky silk-like glue substances, sericin and aggregate silk respectively, that may prove an effective, natural matrix for drug delivery to the mucosa. This mini review will explore the potential of silk and silk-like derivatives as a biocompatible mucoadhesive polymer matrix for local controlled drug delivery. PMID:26636069

  14. The Potential of Silk and Silk-Like Proteins as Natural Mucoadhesive Biopolymers for Controlled Drug Delivery

    PubMed Central

    Brooks, Amanda E.

    2015-01-01

    Drug delivery across mucus membranes is a particularly effective route of administration due to the large surface area. However, the unique environment present at the mucosa necessitates altered drug formulations designed to (1) deliver sensitive biologic molecules, (2) promote intimate contact between the mucosa and the drug, and (3) prolong the drug's local residence time. Thus, the pharmaceutical industry has an interest in drug delivery systems formulated around the use of mucoadhesive polymers. Mucoadhesive polymers, both synthetic and biological, have a history of use in local drug delivery. Prominently featured in the literature are chitosan, alginate, and cellulose derivatives. More recently, silk and silk-like derivatives have been explored for their potential as mucoadhesive polymers. Both silkworms and spiders produce sticky silk-like glue substances, sericin and aggregate silk respectively, that may prove an effective, natural matrix for drug delivery to the mucosa. This mini review will explore the potential of silk and silk-like derivatives as a biocompatible mucoadhesive polymer matrix for local controlled drug delivery. PMID:26636069

  15. The potential of silk and silk-like proteins as natural mucoadhesive biopolymers for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Brooks, Amanda

    2015-11-01

    Drug delivery across mucus membranes is a particularly effective route of administration due to the large surface area. However, the unique environment present at the mucosa necessitates altered drug formulations designed to (1) deliver sensitive biologic molecules, (2) promote intimate contact between the mucosa and the drug, and (3) prolong the drug’s local residence time. Thus, the pharmaceutical industry has an interest in drug delivery systems formulated around the use of mucoadhesive polymers. Mucoadhesive polymers, both synthetic and biological, have a history of use in local drug delivery. Prominently featured in the literature are chitosan, alginate, and cellulose derivatives. More recently, silk and silk-like derivatives have been explored for their potential as mucoadhesive polymers. Both silkworms and spiders produce sticky silk-like glue substances, sericin and aggregate silk respectively, that may prove an effective, natural matrix for drug delivery to the mucosa. This mini review will explore the potential of silk and silk-like derivatives as a biocompatible mucoadhesive polymer matrix for local controlled drug delivery.

  16. Bioadhesive drug delivery systems. I. Characterisation of mucoadhesive properties of systems based on glyceryl mono-oleate and glyceryl monolinoleate.

    PubMed

    Nielsen, L S; Schubert, L; Hansen, J

    1998-07-01

    A group of fatty acid esters capable of forming liquid crystals has been identified as a new class of potential bioadhesive substances. The liquid crystals may act as a controlled release system. The experimental work was focused on the monoglycerides, glyceryl mono-oleate (GMO) and glyceryl monolinoleate (GML). The mucoadhesive properties of GMO and GML were demonstrated in vitro by a 'flushing' bioadhesion test system and a tensiometric method. The flushing system was validated with GMO. Mucoadhesion is influenced by the drug and excipient added, their concentrations, and the ability to form especially the cubic phase. It has been shown that the cubic phase is mucoadhesive when formed on wet mucosa, such as rabbit jejunum, and that drug added to the precursor formulation is incorporated in the cubic phase formed. Tensiometric measurements have shown that the unswollen monoglycerides have the greatest mucoadhesion, followed by the partly swollen lamellar phase and the fully swollen cubic phase. The values found for the work of adhesion were in the range 0.007-0.048 mJcm-2. The mechanism of mucoadhesion is unspecific and probably involves dehydration of the mucosa. The cubic phase of GMO and GML may be an interesting candidate for a bioadhesive drug delivery system.

  17. Mucoadhesive microparticulate drug delivery system of curcumin against Helicobacter pylori infection: Design, development and optimization

    PubMed Central

    Ali, Mohd Sajid; Pandit, Vinay; Jain, Mahendra; Dhar, Kanhiya Lal

    2014-01-01

    The purpose of the present research was to develop and characterize mucoadhesive microspheres of curcumin for the potential use of treating gastric adenocarcinoma, gastric and duodenal ulcer associated with Helicobacter pylori. Curcumin mucoadhesive microspheres were prepared using ethyl cellulose as a matrix and carbopol 934P as a mucoadhesive polymer by an emulsion-solvent evaporation technique. Response surface methodology was used for optimization of formulation using central composite design (CCD) for two factors at three levels each was employed to study the effect of independent variables, drug:polymer:polymer ratio (curcumin:ethylcellulose:carbopol 934P)(X1) and surfactant concentration (X2) on dependent variables, namely drug entrapment efficiency (DEE), percentage mucoadhesion (PM), in vitro drug release and particle size (PS). Optimized formulation was obtained using desirability approach of numerical optimization. The experimental values of DEE, PM, % release and PS after 8 h for the optimized formulation were found to be 50.256 ± 1.38%, 66.23%±0.06, 73.564 ± 1.32%, and 139.881 ± 2.56 μm, respectively, which were in close agreement with those predicted by the mathematical models. The drug release was also found to be slow and extended more than 8 h and release rates were fitted to the Power law equation and Higuchi model to compute the diffusional parameters. The prolonged stomach residence time of curcumin mucoadhesive microspheres might make a contribution to H. pylori complete eradication in combination with other antimicrobial agents. PMID:24696817

  18. Preparation and Evaluation of Mucoadhesive Beads/Discs of Alginate and Algino-Pectinate of Piroxicam for Colon-Specific Drug Delivery Via Oral Route

    PubMed Central

    Jelvehgari, Mitra; Mobaraki, Vajihe; Montazam, Seyed Hassan

    2014-01-01

    Background: Targeted drug delivery to colon would ensure direct treatment at the disease site, decrease in dose administration and reduction side effects improved drug utilization. Objective: The purpose of this research was to decrease gastric side effects of piroxicam by formulating microspheres of alginate and algino-pectinate beads of the drug. Materials and Methods: Ionotropic gelation was used to entrap piroxicam into alginate and algino-pectinate mucoadhesive microspheres as a potential drug carrier for oral delivery of piroxicam. Microparticles with different drug to polymers ratio were prepared and characterized by encapsulation efficiency, particle size, DSC (differential scanning calorimetric), mucoadhesive property, gastroretentive time and drug release studies. Results: The best drug to polymer ratio of microparticles was 1:2.5 (F1) with Na-Alg and 1:7.5 (F4) with Alg-Na with pectin, respectively. The microparticles F1 and F4 showed 28.80%, 50.01% loading efficiency, 82.57%, 82.31% production yield and 945.4, 899.91 µm mean particle size. DSC showed stable character of piroxicam in drug-loaded microparticles and revealed amorphous form. It was found that microparticles (Na-Alg) prepared had faster release and microparticles (Alg-Na and pectin mixture) prepared had slower release than untreated piroxicam (P < 0.05). Microparticles (mixture of Na-Alg and pectin) exhibited very good percentage of mucoadhesion and flowability properties. Mucoadhesion strength and retention time study showed better retention of piroxicam microparticles in intestine. Besides, there was a significant higher retention of mucoadhesive microparticles in upper GI tract. Conclusions: Algino-pectinate mucoadhesive formulations exhibited promising properties of a sustained release form for piroxicam and provided distinct tissue protection in stomach. PMID:25625047

  19. Mucoadhesive elementary osmotic pump tablets of trimetazidine for controlled drug delivery and reduced variability in oral bioavailability.

    PubMed

    Alam, Naushad; Beg, Sarwar; Rizwan, Mohammad; Ahmad, Akifa; Ahmad, Farhan Jalees; Ali, Asgar; Aqil, Mohammad

    2015-04-01

    The objectives of this work was preparation and evaluation of the mucoadhesive elementary osmotic pump tablets of trimetazidine hydrochloride to achieve desired controlled release action and augmentation of oral drug absorption. The drug-loaded core tablets were prepared employing the suitable tableting excipients and coated with polymeric blend of ethyl cellulose and hydroxypropyl methylethylcellulose E5 (4:1). The prepared tablets were characterized for various quality control tests and in vitro drug release. Evaluation of drug release kinetics through model fitting suggested the Fickian mechanism of drug release, which was regulated by osmosis and diffusion as the predominant mechanism. Evaluation of mucoadhesion property using texture analyzer suggested good mucoadhesion potential of the developed osmotic systems. Solid state characterization using Fourier-transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction spectroscopy confirmed the absence of any physiochemical incompatibilities between drug and excipients. Scanning electron microscopy analysis showed the smooth surface appearance of the coated tablets with intact polymeric membrane without any fracture. In vivo pharmacokinetic studies in rabbits revealed 3.01-fold enhancement in the oral bioavailability vis-à-vis the marketed formulation (Vastarel MR®). These studies successfully demonstrate the bioavailability enhancement potential of the mucoadhesive elementary osmotic pumps as novel therapeutic systems for other drugs too. PMID:24669975

  20. Multistage pH-responsive mucoadhesive nanocarriers prepared by aerosol flow reactor technology: A controlled dual protein-drug delivery system.

    PubMed

    Shrestha, Neha; Shahbazi, Mohammad-Ali; Araújo, Francisca; Mäkilä, Ermei; Raula, Janne; Kauppinen, Esko I; Salonen, Jarno; Sarmento, Bruno; Hirvonen, Jouni; Santos, Hélder A

    2015-11-01

    Nanotechnology based drug delivery systems are anticipated to overcome the persistent challenges in oral protein and peptide administration, and lead to the development of long awaited non-invasive therapies. Herein, an advanced single-step aerosol flow reactor based technology was used to develop a multifunctional site specific dual protein-drug delivery nanosystem. For this purpose, mucoadhesive porous silicon (PSi) nanoparticles encapsulated into a pH-responsive polymeric nanomatrix was developed for advanced oral type 2 diabetes mellitus therapy with an antidiabetic peptide, glucagon like peptide-1 (GLP-1), and the enzyme inhibitor, dipeptidyl peptidase-4 (DPP4). Chitosan surface modification inherited the mucoadhesiveness to the nanosystem which led to enhanced cellular interactions and increased cellular compatibility. An advanced aerosol flow reactor technology was used to encapsulate the chitosan modified nanoparticles into an enteric polymeric nanomatrix. The pH-sensitive polymeric matrix simultaneously prevented the gastric degradation of the encapsulated peptide and also preserved the mucoadhesive functionality of the chitosan-modified PSi nanoparticles in the harsh stomach environment. The multidrug loaded nanosystem showed augmented intestinal permeability of GLP-1, evaluated in an in vitro cell-based intestinal epithelium model, attributed to the permeation enhancer effect of chitosan and inhibition of GLP-1 degradation by the DPP4 inhibitor. The applied technology resulted in the development of a dual-drug delivery nanosystem that synergizes the antidiabetic effect of the loaded peptide and the enzyme inhibitor, thereby indicating high clinical potential of the system and preparation technique.

  1. Development of starch based mucoadhesive vaginal drug delivery systems for application in veterinary medicine.

    PubMed

    Gök, Mehmet Koray; Özgümüş, Saadet; Demir, Kamber; Cirit, Ümüt; Pabuccuoğlu, Serhat; Cevher, Erdal; Özsoy, Yıldız; Bacınoğlu, Süleyman

    2016-01-20

    The aim of this study was to prepare and evaluate the mucoadhesive, biocompatible and biodegradable progesterone containing vaginal tablets based on modified starch copolymers for the estrus synchronization of ewes. Starch-graft-poly(acrylic acid) copolymers (S-g-PAA) were synthesized and characterized. The vaginal tablets were fabricated with S-g-PAA and their equilibrium swelling degree (Qe) and matrix erosion (ME%) were determined in lactate buffer solution. In vitro, mucoadhesive properties of the tablets were investigated by using ewe vaginal mucosa and in vivo residence time were also investigated. In vitro and in vivo progesterone release profiles from the tablets were compared with two commercial products. Tablet formulation containing wheat starch based grafted copolymer (WS-g-PAA)gc indicated promising results and might be convenient as an alternative product to the commercial products in veterinary medicine.

  2. Feasibility Investigation of Cellulose Polymers for Mucoadhesive Nasal Drug Delivery Applications.

    PubMed

    Hansen, Kellisa; Kim, Gwangseong; Desai, Kashappa-Goud H; Patel, Hiren; Olsen, Karl F; Curtis-Fisk, Jaime; Tocce, Elizabeth; Jordan, Susan; Schwendeman, Steven P

    2015-08-01

    The feasibility of various cellulose polymer derivatives, including methylcellulose (MC), hydroxypropyl methylcellulose (HPMC), sodium-carboxymethylcellulose (sodium-CMC), and cationic-hydroxyethylcellulose (cationic-HEC), for use as an excipient to enhance drug delivery in nasal spray formulations was investigated. Three main parameters for evaluating the polymers in nasal drug delivery applications include rheology, ciliary beat frequency (CBF), and permeation across nasal tissue. Reversible thermally induced viscosity enhancement was observed at near nasal physiological temperature when cellulose derivatives were combined with an additional excipient, poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) graft copolymer (PVCL-PVA-PEG). Cationic-HEC was shown to enhance acyclovir permeation across the nasal mucosa. None of the tested cellulosic polymers caused any adverse effects on porcine nasal tissues and cells, as assessed by alterations in CBF. Upon an increase in polymer concentration, a reduction in CBF was observed when ciliated cells were immersed in the polymer solution, and this decrease returned to baseline when the polymer was removed. While each cellulose derivative exhibited unique advantages for nasal drug delivery applications, none stood out on their own to improve more than one of the performance characteristics examined. Hence, these data may be useful for the development of new cellulose derivatives in nasal drug formulations.

  3. Synthesis and characterization of thiolated β-cyclodextrin as a novel mucoadhesive excipient for intra-oral drug delivery.

    PubMed

    Ijaz, Muhammad; Matuszczak, Barbara; Rahmat, Deni; Mahmood, Arshad; Bonengel, Sonja; Hussain, Shah; Huck, Christian W; Bernkop-Schnürch, Andreas

    2015-11-01

    The objective of the present study was to synthesize and characterize cysteamine conjugated β-cyclodextrin (β-CD-Cys) as a novel mucoadhesive oligomeric excipient for intra-oral drug delivery. β-CD-Cys conjugates were obtained in a two-step synthetic pathway, whereby, vicinal diol groups of the oligomer were oxidized using increasing concentrations of sodium-per-iodate (NaIO4), prior to the covalent coupling of cysteamine via reductive amination. Quantification of immobilized thiol groups through Ellman's test revealed 561.56 ± 81 μmol/g, 1054.26 ± 131 μmol/g and 1783.92 ± 201 μmol/g of free thiol groups attached to the oligomer backbone depending on the extent of oxidation. β-CD-Cys conjugates at concentrations of 0.5% (m/v) showed no toxic effects on Caco-2 cells within 72 h. Furthermore, β-CD-Cys conjugates displayed a 4-fold improved water solubility compared to the parent oligomer. β-CD-Cys conjugates (β-CD-Cys561, β-CD-Cys1054 and β-CD-Cys1783) showed 2.86-, 15.09- and 49.08-fold improved retention time on porcine intestinal mucosa and 9.66-, 16.43- and 34.51-fold improved on the porcine buccal mucosa, respectively. Formation of inclusion complexes of miconazole nitrate and β-CD-Cys1054 resulted in 150-fold increased solubility of miconazole nitrate. According to these results, it seems that β-CD-Cys conjugates might provide a new promising tool for delivery of poorly water soluble therapeutic agents, such as miconazole nitrate for intra-oral delivery. PMID:26256340

  4. Cellulose triacetate films obtained from sugarcane bagasse: Evaluation as coating and mucoadhesive material for drug delivery systems.

    PubMed

    Ribeiro, Sabrina Dias; Guimes, Rodrigues Filho; Meneguin, Andréia Bagliotti; Prezotti, Fabíola Garavello; Boni, Fernanda Isadora; Cury, Beatriz Stringhetti Ferreira; Gremião, Maria Palmira Daflon

    2016-11-01

    Cellulose triacetate (CTA) films were produced from cellulose extracted from sugarcane bagasse. The films were characterized using scanning electron microscopy (SEM), water vapor permeability (WVP), mechanical properties (MP), enzymatic digestion (ED), and mucoadhesive properties evaluation (MPE). WVP showed that more concentrated films have higher values; asymmetric films had higher values than symmetric films. MP showed that symmetric membranes are more resistant than asymmetric ones. All films presented high mucoadhesiveness. From the WVP and MP results, a symmetric membrane with 6.5% CTA was selected for the coating of gellan gum (GG) particles incorporating ketoprofen (KET). Thermogravimetric analysis (TGA) showed that the CTA coating does not influence the thermal stability of the particles. Coated particles released 100% of the KET in 24h, while uncoated particles released the same amount in 4h. The results highlight the CTA potential in the development of new controlled oral delivery systems. PMID:27516328

  5. Chitosan-based mucoadhesive tablets for oral delivery of ibuprofen.

    PubMed

    Sogias, Ioannis A; Williams, Adrian C; Khutoryanskiy, Vitaliy V

    2012-10-15

    Chitosan and its half-acetylated derivative have been compared as excipients in mucoadhesive tablets containing ibuprofen. Initially the powder formulations containing the polymers and the drug were prepared by either co-spray drying or physical co-grinding. Polymer-drug interactions and the degree of drug crystallinity in these formulations were assessed by infrared spectroscopy and differential scanning calorimetry. Tablets were prepared and their swelling and dissolution properties were studied in media of various pHs. Mucoadhesive properties of ibuprofen-loaded and drug-free tablets were evaluated by analysing their detachment from pig gastric mucosa over a range of pHs. Greater polymer-drug interactions were seen for spray-dried particles compared to co-ground samples and drug loading into chitosan-based microparticles (41%) was greater than the corresponding half-acetylated samples (32%). Swelling and drug release was greater with the half-acetylated chitosan tablets than tablets containing the parent polymer and both tablets were mucoadhesive, the extent of which was dependent on substrate pH. The results illustrate the potential sustained drug delivery benefits of both chitosan and its half-acetylated derivative as mucoadhesive tablet excipients. PMID:22842627

  6. Mucoadhesive platforms for targeted delivery to the colon.

    PubMed

    Varum, Felipe J O; Veiga, Francisco; Sousa, João S; Basit, Abdul W

    2011-11-25

    A novel platform system, comprising a mucoadhesive core and a rapid release carrier, was designed for targeted drug delivery to the colon. Prednisolone pellets containing different carbomers, including Carbopol 971P, Carbopol 974P and Polycarbophil AA-1, with or without organic acids, were produced by extrusion-spheronization. Mucoadhesive pellets were coated with a new enteric double-coating system, which dissolves at pH 7. This system comprises an inner layer of partially neutralized Eudragit S and buffer salt and an outer coating of standard Eudragit S. A single layer of standard Eudragit S was also applied for comparison purposes. Dissolution of the coated pellets was assessed in USP II apparatus in 0.1N HCl followed by Krebs bicarbonate buffer pH 7.4. Visualization of the coating dissolution process was performed by confocal laser scanning microscopy using fluorescent markers in both layers. The mucoadhesive properties of uncoated, single-coated and-double coated pellets were evaluated ex vivo on porcine colonic mucosa. Mucoadhesive pellets coated with a single layer of Eudragit S release its cargo after a lag time of 120 min in Krebs buffer. In contrast, drug release from the double-coated mucoadhesive pellets was significantly accelerated, starting at 75 min. In addition, the mucoadhesive properties of the core of the double coated pellets were higher than those from single-coated pellets after the core had been exposed to the buffer medium. This novel platform technology has the potential to target the colon and overcome the variability in transit and harmonize drug release and bioavailability.

  7. Transbuccal delivery of chlorpheniramine maleate from mucoadhesive buccal patches.

    PubMed

    Sekhar, K Chandra; Naidu, K V S; Vishnu, Y Vamshi; Gannu, Ramesh; Kishan, V; Rao, Y Madhusudan

    2008-01-01

    This article describes buccal permeation of chlorpheniramine maleate (CPM) and its transbuccal delivery using mucoadhesive buccal patches. Permeation of CPM was calculated in vitro using porcine buccal membrane and in vivo in healthy humans. Buccal formulations were developed with hydroxyethylcellulose (HEC) and evaluated for in vitro release, moisture absorption, mechanical properties, and bioadhesion, and optimized formulation was subjected for bioavailability studies in healthy human volunteers. In vitro flux of CPM was calculated to be 0.14 +/- 0.03 mg.h(-1).cm(-2) and buccal absorption also was demonstrated in vivo in human volunteers. In vitro drug release and moisture absorbed were governed by HEC content and formulations exhibited good tensile and mucoadhesive properties. Bioavailability from optimized buccal patch was 1.46 times higher than the oral dosage form and the results showed statistically significant difference.

  8. Development and in vitro evaluation of diclofenac sodium loaded mucoadhesive microsphere with natural gum for sustained delivery.

    PubMed

    Amin, Md Lutful; Jesmeen, Tasbira; Sutradhar, Kumar Bishwajit; Mannan, Md Abdul

    2013-12-01

    The objective of this study was to develop and evaluate mucoadhesive microsphere of diclofenac sodium with natural gums for sustained delivery. Guar gum and tragacanth were used along with sodium alginate as mucoadhesive polymers. Microspheres were formulated using orifice-ionic gelation method. Particle size, surface morphology, swelling study and drug entrapment efficiency of the prepared microspheres were determined. In vitro evaluation was carried out comprising of mucoadhesion and drug release study. The prepared microspheres were discrete and free flowing. Sodium alginate and natural gum, at a ratio of 1:0.25, showed good mucoadhesive property and they had high drug entrapment efficiencies. They also exhibited the best rate retarding effect among all the formulations. Drug entrapment efficiency of all the microspheres ranged from 80.42% to 91.67%. An inverse relationship was found between extent of crosslinking and drug release rate. Release rate was slow and extended in case of the formulations of 1:0.25 ratio (F1 and F3), releasing 68.36% and 70.56% drug respectively after 8 hours. Tragacanth-containing microspheres of F1 showed superiority over other formulations, with best mucoadhesive and rate retarding profile. The correlation value (r(2)) indicated that the drug release of all the formulations followed Higuchi's model. Overall, the results indicated that mucoadhesive microspheres containing natural gum can be promising in terms of prolonged delivery with good mucoadhesive action, targeting the absorption site to thrive oral drug delivery.

  9. Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets.

    PubMed

    Agarwal, Shweta; Murthy, R S R

    2015-01-01

    Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches. PMID:26997698

  10. Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets

    PubMed Central

    Agarwal, Shweta; Murthy, R. S. R.

    2015-01-01

    Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches. PMID:26997698

  11. A mucoadhesive in situ gel delivery system for paclitaxel.

    PubMed

    Jauhari, Saurabh; Dash, Alekha K

    2006-01-01

    MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37 degrees C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61% +/- 0.19%, 12.0% +/- 0.98%, 31.7% +/- 0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1% +/- 4.35%, 44.2% +/- 6.35%, and 97.1% +/- 1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell.

  12. Mucoadhesive Buccal Tablets Based on Chitosan/Gelatin Microparticles for Delivery of Propranolol Hydrochloride.

    PubMed

    Abruzzo, Angela; Cerchiara, Teresa; Bigucci, Federica; Gallucci, Maria Caterina; Luppi, Barbara

    2015-12-01

    Propranolol administration through buccal route offers some distinct advantages thanks to the easy access to the oral mucosa, fast onset of action, and avoidance of hepatic and intestinal degradation mechanisms. To overcome the effective removal existing in the buccal cavity, mucoadhesive delivery systems are considered a promising approach as they facilitate a close contact with the buccal mucosa. The aim of this study was to prepare mucoadhesive tablets based on chitosan/gelatin microparticles for buccal delivery of propranolol hydrochloride. Spray-dried microparticles were prepared with different chitosan-gelatin weight ratios and characterized in terms of yield and morphology. Microparticles were subsequently compressed with the drug to obtain loaded buccal tablets. In vitro water uptake, mucoadhesion, release, and permeation tests were performed to investigate tablet ability to hydrate, to adhere to the mucosa, and to deliver drug through buccal mucosa. Microparticles showed a different morphology based on the different chitosan-gelatin weight ratios. Moreover, buccal tablets based on the prepared microparticles showed different technological and functional characteristics in virtue of their composition. In particular, tablets with an excess of chitosan showed the best mucoadhesive properties, allowed the permeation of the greatest drug amount among all formulations, and could be promising for buccal administration of propranolol hydrochloride.

  13. Mucoadhesive Microparticles for Gastroretentive Delivery: Preparation, Biodistribution and Targeting Evaluation

    PubMed Central

    Hou, Jing-Yi; Gao, Li-Na; Meng, Fan-Yun; Cui, Yuan-Lu

    2014-01-01

    The aim of this research was to prepare and characterize alginate-chitosan mucoadhesive microparticles containing puerarin. The microparticles were prepared by an emulsification-internal gelatin method using a combination of chitosan and Ca2+ as cationic components and alginate as anions. Surface morphology, particle size, drug loading, encapsulation efficiency and swelling ratio, in vitro drug released, in vitro evaluation of mucoadhesiveness and Fluorescence imaging of the gastrointestinal tract were determined. After optimization of the formulation, the encapsulation efficiency was dramatically increased from 70.3% to 99.2%, and a highly swelling ratio was achieved with a change in particle size from 50.3 ± 11.2 μm to 124.7 ± 25.6 μm. In ethanol induced gastric ulcers, administration of puerarin mucoadhesive microparticles at doses of 150 mg/kg, 300 mg/kg, 450 mg/kg and 600 mg/kg body weight prior to ethanol ingestion significantly protected the stomach ulceration. Consequently, significant changes were observed in inflammatory cytokines, such as prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and interleukin1β (IL-1β), in stomach tissues compared with the ethanol control group. In conclusion, core-shell type pH-sensitive mucoadhesive microparticles loaded with puerarin could enhance puerarin bioavailability and have the potential to alleviate ethanol-mediated gastric ulcers. PMID:25470180

  14. Mucoadhesive buccal patches based on interpolymer complexes of chitosan–pectin for delivery of carvedilol

    PubMed Central

    Kaur, Amanpreet; Kaur, Gurpreet

    2011-01-01

    The study was designed to develop bioadhesive patches of carvedilol hydrochloride using chitosan (CH) and pectin (PE) interpolymer complexes and to systematically evaluate their in vitro and in vivo performances. Mucoadhesive buccal patches of carvedilol were prepared using solvent casting method. The physicochemical interaction between CH and PE was investigated by FTIR and DSC studies. The patches were evaluated for their physical characteristics like mass variation, content uniformity, folding endurance, ex vivo mucoadhesion strength, ex vivo mucoadhesion time, surface pH, in vitro drug release, in situ release study, and in vivo bioavailability study. The swelling index of the patches was found to be proportional to the PE concentration. The surface pH of all the formulated bioadhesive patches was found to lie between 6.2 and 7.2. The optimized bioadhesive patch (C1, CH:PE 20:80) showed bioadhesive strength of 22.10 ± 0.20 g, in vitro release of 98.73% and ex vivo mucoadhesion time of 451 min with in a period of 8 h. The optimized patch demonstrated good in vitro and in vivo results. The buccal delivery of carvedilol in rabbits showed a significant improvement in bioavailability of carvedilol from patches when compared to oral route. PMID:23960773

  15. COMPETING PROPERTIES OF MUCOADHESIVE FILMS DESIGNED FOR LOCALIZED DELIVERY OF IMIQUIMOD

    PubMed Central

    Ramineni, Sandeep K; Cunningham, Larry L; Dziubla, Thomas D; Puleo, David A

    2013-01-01

    Oral mucosal delivery has gained prominence in the last two decades because the rich vasculature of the tissue enables rapid delivery and avoidance of first pass metabolism. Although commercial mucoadhesives are used for systemic delivery, systems are not currently available for treatment of local conditions. In the present work, mucoadhesive films are being developed for locally controlled release of an immune response modifier for preventing precancerous lesions from progressing to oral squamous cell carcinoma. Previous research showed that films composed of polyvinylpyrrolidone (PVP) and carboxymethylcellulose (CMC) released imiquimod in a sustained manner for 3 hr. In continuing development of the system, additional key properties were investigated with changes in composition. While adhesive properties in pull-off (0.42±0.03 to 1.1±0.1 N/cm2) and shear adhesion (1.7±0.25 to 5.6±1.4 N/cm2) increased with increasing PVP content of films, tensile properties, such as modulus (6.9±1.5 to 1.8±0.2 MPa) and ultimate strength (4.2±0.7 to 2.1±0.02 MPa), decreased as PVP content increased. Release profiles of the films showed that an increased PVP content resulted in burst release and faster erosion compared to sustained release and slower erosion with more CMC. Studies of transport kinetics showed that the films doubled the amount of imiquimod localized within epithelium compared to drug in solution, increasing their potential for local treatment of oral dysplasia. The mucoadhesive drug delivery system based on CMC and PVP offers a wide range of these properties without addition of new constituents. PMID:23750320

  16. Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics.

    PubMed

    Gavin, Amy; Pham, Jimmy Th; Wang, Dawei; Brownlow, Bill; Elbayoumi, Tamer A

    2015-01-01

    Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis). The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety-enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen), were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively charged chitosan-free/primary aqueous NE (-28 mV) exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05). Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE formulations, against two oropahryngeal carcinomas, was observed. The data strongly indicate the potential of such nanomucoadhesive systems as maintenance therapy for oral cancer patients awaiting surgical removal, or postresection of identified cancerous lesions. PMID:25759580

  17. Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics.

    PubMed

    Gavin, Amy; Pham, Jimmy Th; Wang, Dawei; Brownlow, Bill; Elbayoumi, Tamer A

    2015-01-01

    Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis). The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety-enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen), were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively charged chitosan-free/primary aqueous NE (-28 mV) exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05). Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE formulations, against two oropahryngeal carcinomas, was observed. The data strongly indicate the potential of such nanomucoadhesive systems as maintenance therapy for oral cancer patients awaiting surgical removal, or postresection of identified cancerous lesions.

  18. Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics

    PubMed Central

    Gavin, Amy; Pham, Jimmy TH; Wang, Dawei; Brownlow, Bill; Elbayoumi, Tamer A

    2015-01-01

    Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis). The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety–enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen), were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively charged chitosan-free/primary aqueous NE (−28 mV) exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05). Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE formulations, against two oropahryngeal carcinomas, was observed. The data strongly indicate the potential of such nanomucoadhesive systems as maintenance therapy for oral cancer patients awaiting surgical removal, or postresection of identified cancerous lesions. PMID:25759580

  19. Nasal mucoadhesive delivery systems of the anti-parkinsonian drug, apomorphine: influence of drug-loading on in vitro and in vivo release in rabbits.

    PubMed

    Ikechukwu Ugwoke, M; Sam, E; Van Den Mooter, G; Verbeke, N; Kinget, R

    1999-04-20

    Lyophilized polyacrylic acid powder formulations loaded with apomorphine HCl were prepared and the influence of drug loading on in vitro release and in vivo absorption studied after intranasal administration in rabbits. These formulations prepared with Carbopol 971P, Carbopol 974P and polycarbophil sustained apomorphine release both in vitro and in vivo. The in vitro release rate and mechanism were both influenced by the drug loading. There was no large influence of drug loading on the time to achieve the peak (Tmax) for a particular polymer, but Tmax differed between different polymers. For a particular drug loading, the Tmax from Carbopol 971P was the slowest compared with that for Carbopol 974P and polycarbophil; however, only the Tmax from Carbopol 971P loaded with 15% w/w of apomorphine was significantly longer than polycarbophil of similar drug loading (P=0.0386). The trend further observed was that increasing drug loading led to increased peak plasma concentration and area under the curve (AUC). In the second part of this study, a mixture containing an immediate release component and sustained release formulation was administered in an attempt to increase the initial plasma level, as this could be therapeutically beneficial. Only one peak plasma concentration was observed and the initial plasma concentrations were no higher than those obtained with solely sustained release formulation. The Tmax, the peak plasma drug concentration (Cmax) and AUC from the lactose-containing formulation were lower than the formulation without lactose but the differences were only marginally statistically significant for Cmax (P=0.0911) and AUC (P=0.0668), but not Tmax (P=0.2788).

  20. Bioactivation antioxidant and transglycating properties of N-acetylcarnosine autoinduction prodrug of a dipeptide L-carnosine in mucoadhesive drug delivery eye-drop formulation: powerful eye health application technique and therapeutic platform.

    PubMed

    Babizhayev, Mark A

    2012-06-01

    A considerable interest in N-acetylcarnosine ocular drug design for eye health is based on clinical strategies to improve ocular drug delivery through metabolic enzymatic activation. Human biology aspects of ocular N-acetylcarnosine deacetylation during its pass through the cornea to the aqueous humor and dipeptide hydrolyzing enzymes are characterized. Novel approaches to ocular drug delivery increasing intraocular bioavailability of N-acetylcarnosine biologically activated metabolite carnosine become an integral development ensuring prolonged retention of the medication in the mucoadhesive precorneal area and facilitating transcorneal penetration of the natural dipeptide with the corneal promoters. A comprehensive list of techniques for peptide drug design, synthesis, purification, and biological analyses was considered: liquid chromatography (LC), high performance liquid chromatography (HPLC), (1) H and (13) C nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectroscopy, and spectrophotometry. The antioxidant activity of therapeutics-targeted molecules was studied in aqueous solution and in a lipid membrane environment. A deglycation therapeutic system was developed involving removal, by transglycation of sugar or aldehyde moieties from Schiff bases by histidyl-hydrazide compounds or aldehyde scavenger L-carnosine. Clinical studies included ophthalmoscopy, visual acuity (VA), halometer disability glare tests, slit-image, and retro-illumination photography. N-acetylcarnosine 1% lubricant eye drops are considered as an auto-induction prodrug and natural ocular redox state balance therapies with implications in prevention and treatment of serious eye diseases that involve pathways of continuous oxidative damage to ocular tissues(cataracts, primary open-angle glaucoma, age-related macular degeneration) and sight-threatening glycosylation processes (diabetic retinopathy and consequent visual impairment) important for public health. The results of

  1. Topical delivery of a Rho-kinase inhibitor to the cornea via mucoadhesive film.

    PubMed

    Chan, Wendy; Akhbanbetova, Alina; Quantock, Andrew J; Heard, Charles M

    2016-08-25

    The application of inhibitors of the Rho kinase pathway (ROCK inhibitors) to the surface of the eye in the form of eyedrops has beneficial effects which aid the recovery of diseased or injured endothelial cells that line the inner surface of the cornea. The aim of this study was to test the plausibility of delivering a selective ROCK inhibitor, Y-27632, to the cornea using a thin polymeric film. Mucoadhesive polymeric thin films were prepared incorporating Y-27632 and diffusional release into PBS was determined. Topical ocular delivery from the applied film was investigated using freshly excised porcine eyes and eyedrops of equivalent concentration acted as comparators; after 24h the formulations were removed and the corneas extracted. Drug-loaded thin polymeric films, with high clarity and pliability were produced. ROCK inhibitor Y-27632 was weakly retained within the film, with release attaining equilibrium after 1h. This in turn facilitated its rapid ocular delivery, and an approximately three-fold greater penetration of Y-27632 into cryoprobe-treated corneas was observed from the thin film (p<0.01) compared to eyedrops. These findings support the further development of ROCK inhibitor delivery to the cornea via release from thin mucoadhesive films to treat vision loss cause by corneal endothelial dysfunction. PMID:27196964

  2. Mucoadhesive controlled release ciprofloxacin nanoparticles for pulmonary delivery

    NASA Astrophysics Data System (ADS)

    Mudumba, Sujata S.

    Controlled release of drugs to the lungs is an interesting and evolving field of research. The influence of physicochemical properties of nanoparticles on the controlled release of ciprofloxacin and in-vivo pharmacokinetics following pulmonary administration was evaluated. The physicochemical properties had an effect on encapsulation efficiency and surface charge, but no significant effect on particle size. The in-vitro release profiles of ciprofloxacin in phosphate buffered saline showed small differences over the range of physicochemical properties evaluated. The physicochemical properties of ciprofloxacin nanoparticles resulted in variable and unreliable nebulizer output using a vibrating mesh nebulizer whereas the impact on the aerosol properties of a jet nebulizer was negligible. Addition of mucoadhesive polymers in the nanoparticles had a three-fold increase in apparent half-life in rats by releasing ciprofloxacin over an extended release period on the surfaces of the lungs.

  3. Thiolated Cyclodextrin: Development of a Mucoadhesive Vaginal Delivery System for Acyclovir.

    PubMed

    Ijaz, Muhammad; Griessinger, Julia Anita; Mahmood, Arshad; Laffleur, Flavia; Bernkop-Schnürch, Andreas

    2016-05-01

    The objective of this study was the development of a mucoadhesive vaginal delivery system for acyclovir (Acv). Sodium-per-iodate (NaIO4) was used to introduce aldehyde substructures into beta-cyclodextrin (β-CD) by oxidative cleavage of vicinal diol bonds. Cysteamine was covalently attached to β-CD-CHO via reductive amination. Ellman's reagent was utilized for quantification of free thiol groups attached and resazurin assay was used for cytotoxicity studies. Mucoadhesive properties were evaluated on porcine vaginal mucosa in comparison to intestinal mucosa. Quantification of thiol groups revealed 851.84 ± 107, 1040.44 ± 132, and 1563.72 ± 171 μmol/g of free thiol groups attached to the β-CD-SH851, β-CD-SH1040, and β-CD-SH1563, respectively. β-CD-SH derivatives at concentrations of 0.5% (m/v) did not show significant reduction of viability of Caco-2 cells within 24 h. Furthermore, water solubility of β-CD-SH1563 was improved 7.6-fold in comparison to unmodified β-CD. β-CD-SH851, β-CD-SH1040, and β-CD-SH1563 showed 5.84-, 15.95-, and 17.14-fold improved mucoadhesive properties on porcine vaginal mucosa and 3-, 12.47-, and 32.13-fold on porcine intestinal mucosa, respectively. Inclusion complex of Acv with β-CD-SH1563 resulted in significantly improved drug dissolution. According to the results, β-CD-SH derivatives might be promising new tools for local vaginal delivery of Acv. PMID:27112405

  4. Advances in ophthalmic drug delivery.

    PubMed

    Morrison, Peter W J; Khutoryanskiy, Vitaliy V

    2014-12-01

    Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug-loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long-term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient's lifetime.

  5. Changes in the mucoadhesion of powder formulations after drug application investigated with a simplified method.

    PubMed

    Fransén, Nelly; Björk, Erik; Edsman, Katarina

    2008-09-01

    The residence time in the nasal cavity can be prolonged by dry particles that absorb water and subsequently increase the viscosity of the mucus layer. A novel nasal drug delivery system based on interactive mixtures has previously been developed, where fine particles of the active component are adhered to the surface of mucoadhesive carrier particles by dry mixing. The surface coverage may alter the original mucoadhesiveness of the carrier particles and to investigate this, a simplified tensile strength method was developed and evaluated. Reliable results were obtained with a plastic coated absorbent paper covered by a mucin solution as a substitution for porcine nasal mucosa and should also be applicable to other dry particle systems. The method showed that the swelling of sodium starch glycolate particles was slightly delayed, corresponding to the degree of hydrophobic surface coverage. Carrier particles of partly pregelatinized maize starch were not influenced by the addition of a hydrophobic substance, probably because of the rough particle shape that inhibited a complete surface coverage. It was concluded that the surface coverage of carrier particles in interactive mixtures only could cause a short delay in water absorption that should not affect their mucoadhesive characteristics in vivo.

  6. Polymeric mucoadhesive tablets for topical or systemic buccal delivery of clonazepam: Effect of cyclodextrin complexation.

    PubMed

    Mura, P; Cirri, M; Mennini, N; Casella, G; Maestrelli, F

    2016-11-01

    Two kinds of mucoadhesive buccal tablets of clonazepam (CLZ) were developed to provide, a prolonged local or systemic delivery respectively. Tablets prepared by direct compression of combinations of different polymers were tested for swelling, erosion and residence time properties. Carbopol 971P/hydroxypropylmethylcellulose and Poloxamer/chitosan mixtures were the best and were selected for drug loading. The effect of CLZ complexation with different cyclodextrins was investigated. Randomly-methylated-βCD (RAMEßCD) was the most effective, allowing 100% drug released increase from local-delivery buccal tablets. Kollicoat was the best among the tested backing-layers, assuring a unidirectional release from systemic-delivery buccal tablets (<0.8% drug released in simulated saliva after 24h). In vitro permeation studies from coated-tablets showed that CLZ loading as RAMEßCD-coground enabled a 5-times increase in drug flux and permeability. Therefore, complexation with RAMEßCD was a successful strategy to improve the CLZ performance from buccal tablets for both local or systemic action. PMID:27516327

  7. Chitosan-based intragastric delivery of cefuroxime axetil: development and in-vitro evaluation of mucoadhesive approach.

    PubMed

    Nagar, Mitesh; Yadav, Adhikrao V

    2012-12-01

    To have advantages of reduced dosing frequency, improved bioavailability and effective delivery system of Cefuroxime Axetil, a Chitosan based intragastric sustained release microbead formulation of Cefuroxime Axetil was developed. The drug delivery system was prepared by ionotropic gelation of Chitosan in presence of sodium tripolyphosphate as polyanion and optimized by box-behnken experimental design. Response surface methodology was applied to evaluate various vitro characteristics of prepared mucoadhesive microbeads. Multiple independent variables were optimized to achieve responses of interest, thereby to get the desired sustained release profile of Cefuroxime Axetil in gastric environment.

  8. Transmucosal sustained-delivery of chlorpheniramine maleate in rabbits using a novel, natural mucoadhesive gum as an excipient in buccal tablets.

    PubMed

    Alur, H H; Pather, S I; Mitra, A K; Johnston, T P

    1999-10-15

    The objective of this study was to evaluate the gum from Hakea gibbosa (Hakea) as a sustained-release and mucoadhesive component in buccal tablets following their application to the buccal mucosa of rabbits. Flat-faced core tablets containing either 22 or 32 mg of Hakea and 40 or 25 mg of chlorpheniramine maleate (CPM) per tablet with either sodium bicarbonate or tartaric acid in a 1:1.5 molar ratio were formulated using a direct compression technique and were coated with Cutina(R) on all but one face. The resulting plasma CPM concentration versus time profiles were determined following buccal application of the tablets in rabbits. The strength of mucoadhesion of the tablets was also quantitated in terms of the force of detachment as a function of time. Following the application of the mucoadhesive buccal tablets, the following values for several pharmacokinetic parameters were obtained. The force of detachment for the mucoadhesive buccal tablets containing 22 mg of Hakea and either 25 and 40 mg CPM, and 32 mg Hakea and 40 mg CPM increased from 1.64+/-0.47 to 7.32+/-0.34 N, 1.67+/-0.30 to 7.21+/-0.36 N, and 2.93+/-0.73 to 7.92+/-0.60 N, respectively from 5 to 90 min following application to excised intestinal mucosa. Addition of either sodium bicarbonate or tartaric acid, as well as higher amounts of CPM, did not affect the mucoadhesive bond strength. These results demonstrate that the novel, natural gum, H. gibbosa, may not only be used to sustain the release of CPM from a unidirectional-release buccal tablet, but also demonstrate that the tablets are sufficiently mucoadhesive for clinical application. The mucoadhesive strength as measured by the force of detachment, can be modulated by altering the amount of Hakea in the tablet. The mucoadhesive buccal tablets evaluated represent an improved transbuccal delivery system for conventional drug substances.

  9. Transmucosal sustained-delivery of chlorpheniramine maleate in rabbits using a novel, natural mucoadhesive gum as an excipient in buccal tablets.

    PubMed

    Alur, H H; Pather, S I; Mitra, A K; Johnston, T P

    1999-10-15

    The objective of this study was to evaluate the gum from Hakea gibbosa (Hakea) as a sustained-release and mucoadhesive component in buccal tablets following their application to the buccal mucosa of rabbits. Flat-faced core tablets containing either 22 or 32 mg of Hakea and 40 or 25 mg of chlorpheniramine maleate (CPM) per tablet with either sodium bicarbonate or tartaric acid in a 1:1.5 molar ratio were formulated using a direct compression technique and were coated with Cutina(R) on all but one face. The resulting plasma CPM concentration versus time profiles were determined following buccal application of the tablets in rabbits. The strength of mucoadhesion of the tablets was also quantitated in terms of the force of detachment as a function of time. Following the application of the mucoadhesive buccal tablets, the following values for several pharmacokinetic parameters were obtained. The force of detachment for the mucoadhesive buccal tablets containing 22 mg of Hakea and either 25 and 40 mg CPM, and 32 mg Hakea and 40 mg CPM increased from 1.64+/-0.47 to 7.32+/-0.34 N, 1.67+/-0.30 to 7.21+/-0.36 N, and 2.93+/-0.73 to 7.92+/-0.60 N, respectively from 5 to 90 min following application to excised intestinal mucosa. Addition of either sodium bicarbonate or tartaric acid, as well as higher amounts of CPM, did not affect the mucoadhesive bond strength. These results demonstrate that the novel, natural gum, H. gibbosa, may not only be used to sustain the release of CPM from a unidirectional-release buccal tablet, but also demonstrate that the tablets are sufficiently mucoadhesive for clinical application. The mucoadhesive strength as measured by the force of detachment, can be modulated by altering the amount of Hakea in the tablet. The mucoadhesive buccal tablets evaluated represent an improved transbuccal delivery system for conventional drug substances. PMID:10528077

  10. Improved mucoadhesion and cell uptake of chitosan and chitosan oligosaccharide surface-modified polymer nanoparticles for mucosal delivery of proteins.

    PubMed

    Dyawanapelly, Sathish; Koli, Uday; Dharamdasani, Vimisha; Jain, Ratnesh; Dandekar, Prajakta

    2016-08-01

    The main aim of the present study was to compare mucoadhesion and cellular uptake efficiency of chitosan (CS) and chitosan oligosaccharide (COS) surface-modified polymer nanoparticles (NPs) for mucosal delivery of proteins. We have developed poly (D, L-lactide-co-glycolide) (PLGA) NPs, surface-modified COS-PLGA NPs and CS-PLGA NPs, by using double emulsion solvent evaporation method, for encapsulating bovine serum albumin (BSA) as a model protein. Surface modification of NPs was confirmed using physicochemical characterization methods such as particle size and zeta potential, SEM, TEM and FTIR analysis. Both surface-modified PLGA NPs displayed a slow release of protein compared to PLGA NPs. Furthermore, we have explored the mucoadhesive property of COS as a material for modifying the surface of polymeric NPs. During in vitro mucoadhesion test, positively charged COS-PLGA NPs and CS-PLGA NPs exhibited enhanced mucoadhesion, compared to negatively charged PLGA NPs. This interaction was anticipated to improve the cell interaction and uptake of NPs, which is an important requirement for mucosal delivery of proteins. All nanoformulations were found to be safe for cellular delivery when evaluated in A549 cells. Moreover, intracellular uptake behaviour of FITC-BSA loaded NPs was extensively investigated by confocal laser scanning microscopy and flow cytometry. As we hypothesized, positively charged COS-PLGA NPs and CS-PLGA NPs displayed enhanced intracellular uptake compared to negatively charged PLGA NPs. Our results demonstrated that CS- and COS-modified polymer NPs could be promising carriers for proteins, drugs and nucleic acids via nasal, oral, buccal, ocular and vaginal mucosal routes. PMID:27106502

  11. Mucoadhesive buccal films containing phospholipid-bile salts-mixed micelles as an effective carrier for Cucurbitacin B delivery.

    PubMed

    Lv, Qingyuan; Shen, Chengying; Li, Xianyi; Shen, Baode; Yu, Chao; Xu, Pinghua; Xu, He; Han, Jin; Yuan, Hailong

    2015-05-01

    Cucurbitacin B (Cu B), a potent anti-cancer agent, suffers with the problems of water-insoluble, gastrointestinal side effects and non-specific toxicity via oral administration and drawbacks in patient's compliance and acceptance through injections. An integration of nanoscale carriers with mucoadhesive buccal films drug delivery system would resolve these issues effectively with greater therapeutic benefits and clinical significance. Thus, the drug loaded mucoadhesive buccal film was developed and characterized in this study and the carboxymethyl chitosan (CCS) was chosen as a bioadhesive polymer, glycerol was chosen as a plasticizer and phospholipid-bile salts-mixed micelles (PL-BS-MMs) was selected as the nanoscale carriers. The CCS-films containing Cu B loaded PL-SDC-MMs was evaluated for the mechanical properties, mucoadhesion properties, in vitro water-uptake, in vitro release and morphological properties, respectively. The optimal CCS-films containing Cu B loaded PL-SDC-MMs was easily reconstituted in a transparent and clear solution with spherical micelles in the submicron range. The in vivo study revealed a greater and more extended release of Cu B from nanoscale CCS-films compared to that from a conventional CCS films (C-CCS-films) and oral marketed tablet (Hulusupian). The absorption of Cu B from CCS-films containing Cu B loaded PL-SDC-MMs resulted in 2.69-fold increased in bioavailability as compared to conventional tablet formulation and 10.46 times with reference to the C-CCS-films formulation. Thus, this kind of mucoadhesive buccal film might be an alternative safe route for delivery of Cu B with better patient compliance and higher bioavailability for the treatments.

  12. Liposomal buccal mucoadhesive film for improved delivery and permeation of water-soluble vitamins.

    PubMed

    Abd El Azim, Heba; Nafee, Noha; Ramadan, Alyaa; Khalafallah, Nawal

    2015-07-01

    This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-soluble, low permeable vitamin. Two main strategies were combined; first VB6 was entrapped in liposomes, which were then formulated as mucoadhesive film. Both plain and VB6-loaded liposomes (LPs) containing Lipoid S100 and propylene glycol (∼ 200 nm) were then incorporated into mucoadhesive film composed of SCMC and HPMC. Results showed prolonged release of VB6 (72.65%, T50% diss 105 min) after 6h from LP-film compared to control film containing free VB6 (96.37%, T50% diss 30 min). Mucoadhesion was assessed both ex vivo on chicken pouch and in vivo in human. Mucoadhesive force of 0.2N and residence time of 4.4h were recorded. Ex vivo permeation of VB6, across chicken pouch mucosa indicated increased permeation from LP-systems compared to corresponding controls. Interestingly, incorporation of the vesicles in mucoadhesive film reduced the flux by 36.89% relative to LP-dispersion. Meanwhile, both films provided faster initial permeation than the liquid forms. Correlating the cumulative percent permeated ex vivo with the cumulative percent released in vitro indicated that LPs retarded VB6 release but improved permeation. These promising results represent a step forward in the field of buccal delivery of water-soluble vitamins.

  13. Liposomal buccal mucoadhesive film for improved delivery and permeation of water-soluble vitamins.

    PubMed

    Abd El Azim, Heba; Nafee, Noha; Ramadan, Alyaa; Khalafallah, Nawal

    2015-07-01

    This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-soluble, low permeable vitamin. Two main strategies were combined; first VB6 was entrapped in liposomes, which were then formulated as mucoadhesive film. Both plain and VB6-loaded liposomes (LPs) containing Lipoid S100 and propylene glycol (∼ 200 nm) were then incorporated into mucoadhesive film composed of SCMC and HPMC. Results showed prolonged release of VB6 (72.65%, T50% diss 105 min) after 6h from LP-film compared to control film containing free VB6 (96.37%, T50% diss 30 min). Mucoadhesion was assessed both ex vivo on chicken pouch and in vivo in human. Mucoadhesive force of 0.2N and residence time of 4.4h were recorded. Ex vivo permeation of VB6, across chicken pouch mucosa indicated increased permeation from LP-systems compared to corresponding controls. Interestingly, incorporation of the vesicles in mucoadhesive film reduced the flux by 36.89% relative to LP-dispersion. Meanwhile, both films provided faster initial permeation than the liquid forms. Correlating the cumulative percent permeated ex vivo with the cumulative percent released in vitro indicated that LPs retarded VB6 release but improved permeation. These promising results represent a step forward in the field of buccal delivery of water-soluble vitamins. PMID:25899288

  14. Lyophilized sustained release mucoadhesive chitosan sponges for buccal buspirone hydrochloride delivery: formulation and in vitro evaluation.

    PubMed

    Kassem, Mohamed A A; ElMeshad, Aliaa N; Fares, Ahmed R

    2015-06-01

    This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/freeze-drying technique according to 3(2) factorial design where chitosan grade was set at three levels (low, medium, and high molecular weight), and concentration of chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of 50% BH (T50%) were chosen as dependent variables. Additional BH cup and core buccal chitosan sponge were prepared to achieve uni-directional BH release toward the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH, scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and exhibited a uni-directional drug release profile following Higuchi diffusion model.

  15. Hyaluronic acid-coated niosomes facilitate tacrolimus ocular delivery: Mucoadhesion, precorneal retention, aqueous humor pharmacokinetics, and transcorneal permeability.

    PubMed

    Zeng, Weidong; Li, Qi; Wan, Tao; Liu, Cui; Pan, Wenhui; Wu, Zushuai; Zhang, Guoguang; Pan, Jingtong; Qin, Mengyao; Lin, Yuanyuan; Wu, Chuanbin; Xu, Yuehong

    2016-05-01

    Tacrolimus (FK506) was used to prevent corneal allograft rejection in patients who were resistant to steroids and cyclosporine. However, the formulation for FK506 ocular delivery remained a challenge due to the drug's high hydrophobicity, high molecular weight, and eye's physiological and anatomical constraints. The aim of this project is to develop an ocular delivery system for FK506 based on a combined strategy of niosomes and mucoadhesive hyaluronic acid (HA), i.e., FK506HA-coated niosomes, which exploits virtues of both niosomes and HA to synergistically improve ophthalmic bioavailability. The FK506HA-coated niosomes were characterized with particle size, zeta potential, and rheology behavior. Mucoadhesion of FK506HA-coated niosomes to mucin was investigated through surface plasmon resonance in comparison with non-coated niosomes and HA solution. The results showed that niosomes possessed adhesion to mucin, and HA coating enhanced the adhesion. The in vivo precorneal retention was evaluated in rabbit, and the results showed that HA-coated niosomes prolonged the residence of FK506 significantly in comparison with non-coated niosomes or suspension. Aqueous humor pharmacokinetics test showed that area under curve of HA-coated niosomes was 2.3-fold and 1.2-fold as that of suspension and non-coated niosomes, respectively. Moreover, the synergetic corneal permeability enhancement of the hybrid delivery system on FK506 was visualized and confirmed by confocal laser scanning microscope. Overall, the results indicated that the hybrid system facilitated FK506 ocular delivery on mucoadhesion, precorneal retention, aqueous humor pharmacokinetics and transcorneal permeability. Therefore, HA-coated niosomes may be a promising approach for ocular targeting delivery of FK506. PMID:26820107

  16. Lyophilized Chitosan/xanthan Polyelectrolyte Complex Based Mucoadhesive Inserts for Nasal Delivery of Promethazine Hydrochloride

    PubMed Central

    G Dehghan, Mohamed Hassan; Marzuka, Marzuka

    2014-01-01

    The objective of this investigation was the development of chitosan/xanthan polyelectrolyte complex based mucoadhesive nasal insert of promethazine hydrochloride a drug used in the treatment of motion sickness. A 32 factorial design was applied for preparing chitosan/xanthan polyelectrolyte complex and to study the effect of independent variables i.e. concentration of xanthan [X1] and concentration of chitosan [X2] on various responses i.e. viscosity of polyelectrolyte complex solution, water uptake of nasal inserts (at pH 2, 5.5, 7.4), bioadhesion potential of nasal inserts and in-vitro drug release at Q6h through nasal inserts. FTIR and DSC analysis were carried out to confirm complex formation and on loaded and unloaded nasal insert to investigate any drug excipient interaction. The nasal inserts were also characterized by powder X-ray diffractometry (PXRD) and Scanning electron microscopy (SEM) and for ex-vivo permeation studies. The results show that higher amount of xanthan in polyelectrolyte complexes with respect to higher amount of chitosan retarded in-vitro drug release. The water uptake behaviour of nasal insert was strongly influenced by pH of the medium and by polycation/ polyanion concentration. The investigation verifies the formation of polyelectrolyte complexes formation between chitosan and xanthan at pH values in the vicinity of pKa intervals of the two polymers and confirms their potential for the nasal delivery of promethazine hydrochloride. PMID:25276178

  17. Vaginal delivery of paclitaxel via nanoparticles with non-mucoadhesive surfaces suppresses cervical tumor growth

    PubMed Central

    Yang, Ming; Yu, Tao; Wang, Ying-Ying; Lai, Samuel K.; Zeng, Qi; Miao, Bolong; Tang, Benjamin C.; Simons, Brian W.; Ensign, Laura; Liu, Guanshu; Chan, Kannie W. Y.; Juang, Chih-Yin; Mert, Olcay; Wood, Joseph; Fu, Jie; McMahon, Michael T.; Wu, T.-C.; Hung, Chien-Fu; Hanes, Justin

    2014-01-01

    Local delivery of chemotherapeutics in the cervicovaginal tract using nanoparticles may reduce adverse side effects associated with systemic chemotherapy, while improving outcomes for early stage cervical cancer. We hypothesize drug-loaded nanoparticles must rapidly penetrate cervicovaginal mucus (CVM) lining the female reproductive tract to effectively deliver their payload to underlying diseased tissues in a uniform and sustained manner. We develop paclitaxel-loaded nanoparticles, composed entirely of polymers used in FDA-approved products, which rapidly penetrate human CVM and provide sustained drug release with minimal burst effect. We further employ a mouse model with aggressive cervical tumors established in the cervicovaginal tract to compare paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (conventional particles , or CP) and similar particles coated with Pluronic® F127 (mucus-penetrating particles , or MPP). CP are mucoadhesive and, thus, aggregated in mucus, while MPP achieve more uniform distribution and close proximity to cervical tumors. Paclitaxel-MPP suppress tumor growth more effectively and prolong median survival of mice compared to free paclitaxel or paclitaxel-CP. Histopathological studies demonstrate minimal toxicity to the cervicovaginal epithelia, suggesting paclitaxel-MPP may be safe for intravaginal use. These results demonstrate for the first time the in vivo advantages of polymer-based MPP for treatment of tumors localized to a mucosal surface. PMID:24339398

  18. Preparation and characterization of gelatin-based mucoadhesive nanocomposites as intravesical gene delivery scaffolds.

    PubMed

    Liu, Ching-Wen; Chang, Li-Ching; Lin, Kai-Jen; Yu, Tsan-Jung; Tsai, Ching-Chung; Wang, Hao-Kuang; Tsai, Tong-Rong

    2014-01-01

    This study aimed to develop optimal gelatin-based mucoadhesive nanocomposites as scaffolds for intravesical gene delivery to the urothelium. Hydrogels were prepared by chemically crosslinking gelatin A or B with glutaraldehyde. Physicochemical and delivery properties including hydration ratio, viscosity, size, yield, thermosensitivity, and enzymatic degradation were studied, and scanning electron microscopy (SEM) was carried out. The optimal hydrogels (H), composed of 15% gelatin A175, displayed an 81.5% yield rate, 87.1% hydration ratio, 42.9 Pa·s viscosity, and 125.8 nm particle size. The crosslinking density of the hydrogels was determined by performing pronase degradation and ninhydrin assays. In vitro lentivirus (LV) release studies involving p24 capsid protein analysis in 293T cells revealed that hydrogels containing lentivirus (H-LV) had a higher cumulative release than that observed for LV alone (3.7-, 2.3-, and 2.3-fold at days 1, 3, and 5, resp.). Lentivirus from lentivector constructed green fluorescent protein (GFP) was then entrapped in hydrogels (H-LV-GFP). H-LV-GFP showed enhanced gene delivery in AY-27 cells in vitro and to rat urothelium by intravesical instillation in vivo. Cystometrogram showed mucoadhesive H-LV reduced peak micturition and threshold pressure and increased bladder compliance. In this study, we successfully developed first optimal gelatin-based mucoadhesive nanocomposites as intravesical gene delivery scaffolds. PMID:25580433

  19. Synthesis and characterisation of mucoadhesive thiolated polyallylamine.

    PubMed

    Duggan, Sarah; Hughes, Helen; Owens, Eleanor; Duggan, Elaine; Cummins, Wayne; O' Donovan, Orla

    2016-02-29

    The thiolation of polyallylamine (PAAm) for use in mucoadhesive drug delivery has been achieved. PAAm was reacted with different ratios of Traut's reagent, yielding products with thiol contents ranging from 134-487μmol/g. Full mucoadhesive characterisation of the thiolated PAAm samples was conducted using swelling studies, mucoadhesive testing on porcine intestinal tissue and rheology. Both swelling and cohesive properties of the thiolated PAAm products were vastly improved in comparison to an unmodified PAAm control. The swelling abilities of the thiolated samples were high and the degree of thiolation of the products affected the initial rate of swelling. High levels of mucoadhesion were demonstrated by the thiolated PAAm samples, with adhesion times of greater than 24h measured for all three samples and, thus, thiol content did not appear to influence mucoadhesion. Rheological studies of the thiolated PAAm samples showed an increase in G' and G″ values upon the addition of a mucin solution which was not observed in the unmodified control, again highlighting the mucoadhesive interactions between these thiolated polymers and mucin. The synthesis of thiolated PAAm by reaction with Traut's reagent and resulting mucoadhesive properties demonstrates its potential for use a mucoadhesive drug delivery device.

  20. Preparation and in vitro characterization of thermosensitive and mucoadhesive hydrogels for nasal delivery of phenylephrine hydrochloride.

    PubMed

    Xu, Xiaofeng; Shen, Yan; Wang, Wei; Sun, Chunmeng; Li, Chang; Xiong, Yerong; Tu, Jiasheng

    2014-11-01

    The aim of the present work was to develop a nasal delivery system of phenylephrine hydrochloride (PE) in spray form to make prolonged remedy of nasal congestion. The formulations contain the thermosensitive hydrogel, i.e., Poloxamer 407 (P407) and Poloxamer 188 (P188) mixtures, and mucoadhesives, i.e., ε-polylysine (ε-PL) and low molecular weight sodium hyaluronate (MW 11,000Da). The in vitro characterizations of formulations including rheology studies, texture profiles and in vitro mucoadhesion potential were investigated after gelation temperatures measurements. The results showed that the concentration of P407 or P188 had significant influence on gelation temperature and texture profiles. The addition of mucoadhesives, though lowered the gel strength of formulations, increased interaction with mucin. After screening, two formulations (i.e., 1.0% PE/0.5% ε-PL/17% P407/0.5% P188 or Formulation A; and 1.0% PE/0.5% HA/17% P407/0.8% P188 or Formulation B) presenting suitable gelation temperatures (∼32°C) were used for further studies on in vitro release behaviors and mucosa ciliotoxicity. Both formulations showed sustained release of PE for up to 8h and similar toxicity to saline, the negative control. Thus, the thermosensitive and mucoadhesive PE-containing hydrogels are promising to achieve prolonged decongestion in nasal cavity.

  1. Assam Bora rice starch based biocompatible mucoadhesive microsphere for targeted delivery of 5-fluorouracil in colorectal cancer.

    PubMed

    Ahmad, Mohammad Zaki; Akhter, Sohail; Anwar, Mohammed; Ahmad, Farhan Jalees

    2012-11-01

    The aim of this study was to develop novel colon targeted mucoadhesive microspheres (MAMs) for site specific delivery of 5-fluorouracil (5-FU) to colon without the drug being released in the stomach or small intestine. MAMs were prepared using Assam Bora rice starch, a natural mucoadhesive polymer, by a double emulsion solvent evaporation method. The microspheres were characterized for their shape, size, surface morphology, size distribution, incorporation efficiency, and in vitro and in vivo drug release studies. The release study confirmed the insignificant release of 5-FU in physiological condition of stomach and small intestine and major drug release in the cecal content. In vivo release study of the optimized MAMs was compared with immediate release (IR) 5-FU. 5-FU was distributed predominantly in the upper GI tract from the IR, whereas 5-FU was distributed primarily to the lower part of the GI tract from the MAM formulation. Enhanced levels of liver enzymes were found in animals given IR 5-FU as well as augmented levels of serum albumin, creatinine, leucocytopenia and thrombocytopenia was also observed. Thus to sum up, it can be appropriately established that the 5-FU release pattern from MAMs exhibits slow and extended release over longer periods of time with reduced systemic side effects. PMID:22994847

  2. Evaluation of a mucoadhesive fenretinide patch for local intraoral delivery: a strategy to reintroduce fenretinide for oral cancer chemoprevention.

    PubMed

    Holpuch, Andrew S; Phelps, Maynard P; Desai, Kashappa-Goud H; Chen, Wei; Koutras, George M; Han, Byungdo B; Warner, Blake M; Pei, Ping; Seghi, Garrett A; Tong, Meng; Border, Michael B; Fields, Henry W; Stoner, Gary D; Larsen, Peter E; Liu, Zhongfa; Schwendeman, Steven P; Mallery, Susan R

    2012-05-01

    Systemic delivery of fenretinide in oral cancer chemoprevention trials has been largely unsuccessful due to dose-limiting toxicities and subtherapeutic intraoral drug levels. Local drug delivery, however, provides site-specific therapeutically relevant levels while minimizing systemic exposure. These studies evaluated the pharmacokinetic and growth-modulatory parameters of fenretinide mucoadhesive patch application on rabbit buccal mucosa. Fenretinide and blank-control patches were placed on right/left buccal mucosa, respectively, in eight rabbits (30 min, q.d., 10 days). No clinical or histological deleterious effects occurred. LC-MS/MS analyses of post-treatment samples revealed a delivery gradient with highest fenretinide levels achieved at the patch-mucosal interface (no metabolites), pharmacologically active levels in fenretinide-treated oral mucosa (mean: 5.65 μM; trace amounts of 4-oxo-4-HPR) and undetectable sera levels. Epithelial markers for cell proliferation (Ki-67), terminal differentiation (transglutaminase 1-TGase1) and glucuronidation (UDP-glucuronosyltransferase1A1-UGT1A1) exhibited fenretinide concentration-specific relationships (elevated TGase1 and UGT1A1 levels <5 μM, reduced Ki-67 indices >5 μM) relative to blank-treated epithelium. All fenretinide-treated tissues showed significantly increased intraepithelial apoptosis (TUNEL) positivity, implying activation of intersecting apoptotic and differentiation pathways. Human oral mucosal correlative studies showed substantial interdonor variations in levels of the enzyme (cytochrome P450 3A4-CYP3A4) responsible for conversion of fenretinide to its highly active metabolite, 4-oxo-4-HPR. Complementary in vitro assays in human oral keratinocytes revealed fenretinide and 4-oxo-4-HPR's preferential suppression of DNA synthesis in dysplastic as opposed to normal oral keratinocytes. Collectively, these data showed that mucoadhesive patch-mediated fenretinide delivery is a viable strategy to reintroduce

  3. Evaluation of a mucoadhesive fenretinide patch for local intraoral delivery: a strategy to reintroduce fenretinide for oral cancer chemoprevention.

    PubMed

    Holpuch, Andrew S; Phelps, Maynard P; Desai, Kashappa-Goud H; Chen, Wei; Koutras, George M; Han, Byungdo B; Warner, Blake M; Pei, Ping; Seghi, Garrett A; Tong, Meng; Border, Michael B; Fields, Henry W; Stoner, Gary D; Larsen, Peter E; Liu, Zhongfa; Schwendeman, Steven P; Mallery, Susan R

    2012-05-01

    Systemic delivery of fenretinide in oral cancer chemoprevention trials has been largely unsuccessful due to dose-limiting toxicities and subtherapeutic intraoral drug levels. Local drug delivery, however, provides site-specific therapeutically relevant levels while minimizing systemic exposure. These studies evaluated the pharmacokinetic and growth-modulatory parameters of fenretinide mucoadhesive patch application on rabbit buccal mucosa. Fenretinide and blank-control patches were placed on right/left buccal mucosa, respectively, in eight rabbits (30 min, q.d., 10 days). No clinical or histological deleterious effects occurred. LC-MS/MS analyses of post-treatment samples revealed a delivery gradient with highest fenretinide levels achieved at the patch-mucosal interface (no metabolites), pharmacologically active levels in fenretinide-treated oral mucosa (mean: 5.65 μM; trace amounts of 4-oxo-4-HPR) and undetectable sera levels. Epithelial markers for cell proliferation (Ki-67), terminal differentiation (transglutaminase 1-TGase1) and glucuronidation (UDP-glucuronosyltransferase1A1-UGT1A1) exhibited fenretinide concentration-specific relationships (elevated TGase1 and UGT1A1 levels <5 μM, reduced Ki-67 indices >5 μM) relative to blank-treated epithelium. All fenretinide-treated tissues showed significantly increased intraepithelial apoptosis (TUNEL) positivity, implying activation of intersecting apoptotic and differentiation pathways. Human oral mucosal correlative studies showed substantial interdonor variations in levels of the enzyme (cytochrome P450 3A4-CYP3A4) responsible for conversion of fenretinide to its highly active metabolite, 4-oxo-4-HPR. Complementary in vitro assays in human oral keratinocytes revealed fenretinide and 4-oxo-4-HPR's preferential suppression of DNA synthesis in dysplastic as opposed to normal oral keratinocytes. Collectively, these data showed that mucoadhesive patch-mediated fenretinide delivery is a viable strategy to reintroduce

  4. External Cross-linked Mucoadhesive Microbeads for Prolonged Drug Release: Development and In vitro Characterization

    PubMed Central

    Patel, Harshil; Srinatha, A.; Sridhar, B. K.

    2014-01-01

    Mucoadhesive microbeads of low methoxyl pectin were prepared, either alone or in combinations with hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, methyl cellulose and carbopol 934P, by ionotropic gelation. The influence of copolymers on mucoadhesivity, microbeads characteristics and in vitro drug release was investigated. Spherical microbeads with 78.69±0.59 to 85.84±0.78% drug entrapment and of a size of 791.90±4.58 to 960.88±4.61 μm were prepared. The concentration of cross linking agent affects the encapsulation efficiency of microbeads. Mucoadhesiveness of microbeads was dependent on the concentration of copolymers. The formulations exhibiteda pH-dependent release and followed diffusion-controlled first-order kinetics. PMID:25425758

  5. Effective mucoadhesive liposomal delivery system for risedronate: preparation and in vitro/in vivo characterization

    PubMed Central

    Jung, Il-Woo; Han, Hyo-Kyung

    2014-01-01

    In this work, we aimed to develop chitosan-coated mucoadhesive liposomes containing risedronate to improve intestinal drug absorption. Liposomes containing risedronate were prepared with 1,2-distearoryl-sn-glycero-3-phosphocholine and distearoryl-sn-glycero-3-[phospho-rac-(1-glycerol)] using the freeze-drying method, with subsequent coating of the anionic surfaces of the liposomes with chitosan. The in vitro characteristics of the chitosan-coated liposomes were investigated, including their stability, mucoadhesiveness, and Caco-2 cell permeability. This formulation was stable in simulated gastric and intestinal fluids, with the percentage of drug remaining in the liposomes being more than 90% after 24 hours of incubation. Chitosan-coated liposomes also showed strong mucoadhesive properties, implying potential electrostatic interaction with the mucous layer in the gastrointestinal tract. Compared with the untreated drug, chitosan-coated liposomes significantly enhanced the cellular uptake of risedronate, resulting in an approximately 2.1–2.6-fold increase in Caco-2 cells. Further, the chitosan-coated liposomes increased the oral exposure of risedronate by three-fold in rats. Taken together, the results of this study suggest that chitosan-coated liposomes containing risedronate should be effective for improving the bioavailability of risedronate. PMID:24872692

  6. Effective mucoadhesive liposomal delivery system for risedronate: preparation and in vitro/in vivo characterization.

    PubMed

    Jung, Il-Woo; Han, Hyo-Kyung

    2014-01-01

    In this work, we aimed to develop chitosan-coated mucoadhesive liposomes containing risedronate to improve intestinal drug absorption. Liposomes containing risedronate were prepared with 1,2-distearoryl-sn-glycero-3-phosphocholine and distearoryl-sn-glycero-3-[phospho-rac-(1-glycerol)] using the freeze-drying method, with subsequent coating of the anionic surfaces of the liposomes with chitosan. The in vitro characteristics of the chitosan-coated liposomes were investigated, including their stability, mucoadhesiveness, and Caco-2 cell permeability. This formulation was stable in simulated gastric and intestinal fluids, with the percentage of drug remaining in the liposomes being more than 90% after 24 hours of incubation. Chitosan-coated liposomes also showed strong mucoadhesive properties, implying potential electrostatic interaction with the mucous layer in the gastrointestinal tract. Compared with the untreated drug, chitosan-coated liposomes significantly enhanced the cellular uptake of risedronate, resulting in an approximately 2.1-2.6-fold increase in Caco-2 cells. Further, the chitosan-coated liposomes increased the oral exposure of risedronate by three-fold in rats. Taken together, the results of this study suggest that chitosan-coated liposomes containing risedronate should be effective for improving the bioavailability of risedronate. PMID:24872692

  7. Con-A conjugated mucoadhesive microspheres for the colonic delivery of diloxanide furoate.

    PubMed

    Anande, Nalini M; Jain, Sunil K; Jain, Narendra K

    2008-07-01

    The aim of the research work was to develop cyst-targeted novel concanavalin-A (Con-A) conjugated mucoadhesive microspheres of diloxanide furoate (DF) for the effective treatment of amoebiasis. Eudragit microspheres of DF were prepared using emulsification-solvent evaporation method. Formulations were characterized for particle size and size distribution, % drug entrapment, surface morphology and in vitro drug release in simulated gastrointestinal (GI) fluids. Eudragit microspheres of DF were conjugated with Con-A. IR spectroscopy and DSC were used to confirm successful conjugation of Con-A to Eudragit microspheres while Con-A conjugated microspheres were further characterized using the parameters of zeta potential, mucoadhesiveness to colonic mucosa and Con-A conjugation efficiency with microspheres. IR studies confirmed the attachment of Con-A with Eudragit microspheres. All the microsphere formulations showed good % drug entrapment (78+/-5%). Zeta potential of Eudragit microspheres and Con-A conjugated Eudragit microspheres were found to be 3.12+/-0.7mV and 16.12+/-0.5mV, respectively. Attachment of lectin to the Eudragit microspheres significantly increases the mucoadhesiveness and also controls the release of DF in simulated GI fluids. Gamma scintigraphy study suggested that Eudragit S100 coated gelatin capsule retarded the release of Con-A conjugated microspheres at low pH and released microspheres slowly at pH 7.4 in the colon.

  8. Effects of the mucoadhesive polymer polycarbophil on the intestinal absorption of a peptide drug in the rat.

    PubMed

    Lehr, C M; Bouwstra, J A; Kok, W; De Boer, A G; Tukker, J J; Verhoef, J C; Breimer, D D; Junginger, H E

    1992-05-01

    The absorption across rat intestinal tissue of the model peptide drug 9-desglycinamide, 8-arginine vasopressin from bioadhesive formulations was studied in-vitro, in a chronically isolated internal loop in-situ and after intraduodenal administration in-vivo. A controlled-release bioadhesive drug delivery system was tested, consisting of microspheres of poly(2-hydroxyethyl methacrylate) with a mucoadhesive Polycarbophil-coating, as well as fast-release formulation consisting of an aqueous solution of the peptide in a suspension of Polycarbophil particles. Using the controlled-release system, a slight improvement of peptide absorption was found in-vitro in comparison with a non-adhesive control system, but not in-situ or in-vivo. In contrast, bioavailability was significantly increased in all three models from the Polycarbophil suspension in comparison with a solution of the drug in saline. The effect appeared to be dose-dependent, indicative of intrinsic penetration-enhancing properties of the mucoadhesive polymer. A prolongation of the absorption phase in-vitro and in the chronically isolated loop in-situ suggested that the polymer was able to protect the peptide from proteolytic degradation. This could be confirmed by degradation studies in-vitro. The duration of the penetration enhancing/enzyme inhibiting effect was diminished with increasing complexity of the test model, in the same way as was previously found for the bioadhesive effect. This interrelationship suggests that the observed improvement in peptide absorption and the mucoadhesive properties of this polymer are associated. The development of a fast-release oral dosage form for peptide drugs on the basis of Polycarbophil appears to be possible.

  9. Smart Polymers in Nasal Drug Delivery

    PubMed Central

    Chonkar, Ankita; Nayak, Usha; Udupa, N.

    2015-01-01

    Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones. PMID:26664051

  10. Recent advances in ophthalmic drug delivery

    PubMed Central

    Kompella, Uday B; Kadam, Rajendra S; Lee, Vincent HL

    2011-01-01

    Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert™ (~6 months), Retisert™ (~3 years) and Iluvien™ (~3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems. PMID:21399724

  11. Tragacanth as an oral peptide and protein delivery carrier: Characterization and mucoadhesion.

    PubMed

    Nur, M; Ramchandran, L; Vasiljevic, T

    2016-06-01

    Biopolymers such as tragacanth, an anionic polysaccharide gum, can be alternative polymeric carrier for physiologically important peptides and proteins. Characterization of tragacanth is thus essential for providing a foundation for possible applications. Rheological studies colloidal solution of tragacanth at pH 3, 5 or 7 were carried out by means of steady shear and small amplitude oscillatory measurements. Tragacanth mucoadhesivity was also analyzed using an applicable rheological method and compared to chitosan, alginate and PVP. The particle size and zeta potential were measured by a zetasizer. Thermal properties of solutions were obtained using a differential scanning calorimetry. The solution exhibited shear-thinning characteristics. The value of the storage modulus (G') and the loss modulus (G″) increased with an increase in angular frequency (Ω). In all cases, loss modulus values were higher than storage values (G″>G') and viscous character was, therefore, dominant. Tragacanth and alginate showed a good mucoadhesion. Tragacanth upon dispersion created particles of a submicron size with a negative zeta potential (-7.98 to -11.92 mV). These properties were pH dependant resulting in acid gel formation at pH 3.5. Tragacanth has thus a potential to be used as an excipient for peptide/protein delivery.

  12. Tapioca starch blended alginate mucoadhesive-floating beads for intragastric delivery of Metoprolol Tartrate.

    PubMed

    Biswas, Nikhil; Sahoo, Ranjan Kumar

    2016-02-01

    The objective of the study was to develop tapioca starch blended alginate mucoadhesive-floating beads for the intragastric delivery of Metoprolol Tartrate (MT). The beads were prepared by ionotropic gelation method using calcium chloride as crosslinker and gas forming calcium carbonate (CaCO3) as floating inducer. The alginate gel beads having 51-58% entrapped MT showed 90% release within 45 min in gastric medium (pH 1.2). Tapioca starch blending markedly improved the entrapment efficiency (88%) and sustained the release for 3-4 h. A 12% w/w HPMC coating on these beads extended the release upto 9-11 h. In vitro wash off and buoyancy test in gastric media revealed that the beads containing CaCO3 has gastric residence of more than 12 h. In vitro optimized multi-unit formulation consisting of immediate and sustained release mucoadhesive-floating beads (40:60) showed good initial release of 42% MT within 1h followed by a sustained release of over 90% for 11 h. Pharmacokinetic study performed in rabbit model showed that the relative oral bioavailability of MT after administration of oral solution, sustain release and optimized formulation was 51%, 67% and 87%, respectively. Optimized formulation showed a higher percent inhibition of isoprenaline induced heart rate in rabbits for almost 12 h.

  13. Transmucosal macromolecular drug delivery.

    PubMed

    Prego, C; García, M; Torres, D; Alonso, M J

    2005-01-01

    Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, the use of nanoparticulate carriers represents a challenging but promising strategy. The present paper aims to compare the characteristics and potential of nanostructures based on the mucoadhesive polysaccharide chitosan (CS). These are CS nanoparticles, CS-coated oil nanodroplets (nanocapsules) and CS-coated lipid nanoparticles. The characteristics and behavior of CS nanoparticles and CS-coated lipid nanoparticles already reported [A. Vila, A. Sanchez, M. Tobio, P. Calvo, M.J. Alonso, Design of biodegradable particles for protein delivery, J. Control. Rel. 78 (2002) 15-24; R. Fernandez-Urrusuno, P. Calvo, C. Remunan-Lopez, J.L. Vila-Jato, M.J. Alonso, Enhancement of nasal absorption of insulin using chitosan nanoparticles, Pharm. Res. 16 (1999) 1576-1581; M. Garcia-Fuentes, D. Torres, M.J. Alonso, New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin (submitted for publication).] are compared with those of CS nanocapsules originally reported here. The three types of systems have a size in the nanometer range and a positive zeta potential that was attributed to the presence of CS on their surface. They showed an important capacity for the association of peptides such as insulin, salmon calcitonin and proteins, such as tetanus toxoid. Their mechanism of interaction with epithelia was investigated using the Caco-2 model cell line. The results showed that CS-coated systems caused a concentration-dependent reduction in the transepithelial resistance of the cell monolayer. Moreover, within the range of concentrations investigated, these systems were internalized in the

  14. Polysaccharide-Based Micelles for Drug Delivery

    PubMed Central

    Zhang, Nan; Wardwell, Patricia R.; Bader, Rebecca A.

    2013-01-01

    Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems. By grafting hydrophobic moieties to the polysaccharide backbone, self-assembled micelles can be readily formed in aqueous solution. Many polysaccharides also possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting of specific tissues, and a reduction in the inflammatory response. Furthermore, the hydrophilic nature of some polysaccharides can be exploited to enhance circulatory stability. This review will highlight the advantages of polysaccharide use in the development of drug delivery systems and will provide an overview of the polysaccharide-based micelles that have been developed to date. PMID:24300453

  15. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

    Soluble nanotransporters for drugs can be profiled for targeted delivery particularly to maximize the efficacy of highly potent drugs while minimizing off target effects. This article outlines on the use of biological carrier molecules with a focus on albumin, various drug linkers for site specific release of the drug payload from the nanotransporter and strategies to combine these in various ways to meet different drug delivery demands particularly the optimization of the payload per nanotransporter.

  16. Overview on gastroretentive drug delivery systems for improving drug bioavailability.

    PubMed

    Lopes, Carla M; Bettencourt, Catarina; Rossi, Alessandra; Buttini, Francesca; Barata, Pedro

    2016-08-20

    In recent decades, many efforts have been made in order to improve drug bioavailability after oral administration. Gastroretentive drug delivery systems are a good example; they emerged to enhance the bioavailability and effectiveness of drugs with a narrow absorption window in the upper gastrointestinal tract and/or to promote local activity in the stomach and duodenum. Several strategies are used to increase the gastric residence time, namely bioadhesive or mucoadhesive systems, expandable systems, high-density systems, floating systems, superporous hydrogels and magnetic systems. The present review highlights some of the drugs that can benefit from gastroretentive strategies, such as the factors that influence gastric retention time and the mechanism of action of gastroretentive systems, as well as their classification into single and multiple unit systems.

  17. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases. PMID:20437123

  18. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.

  19. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  20. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

    Nanosize materials provide hopes, speculations and chances for an unprecedented change in drug delivery in near future. Nanotechnology is an emerging field to produce nanomaterials for drug delivery that can offer a new tool, opportunities and scope to provide more focused and fine-tuned treatment of diseases at a molecular level, enhancing the therapeutic potential of drugs so that they become less toxic and more effective. Nanodimensional drug delivery systems are of great scientific interest as they project their tremendous utility because of their capability of altering biodistribution of therapeutic agents so that they can concentrate more in the target tissues. Nanosize drug delivery systems generally focus on formulating bioactive molecules in biocompatible nanosystems such as nanocrystals, solid lipid nanoparticles, nanostructure lipid carriers, lipid drug conjugates, nanoliposomes, dendrimers, nanoshells, emulsions, nanotubes, quantum dots etc. Extensively versatile molecules like synthetic chemicals to naturally occurring complex macromolecules such as nucleic acids and proteins could be dispensed in such formulations maintaining their stability and efficacy. Empty viral capsids are being tried to deliver drug as these uniformly sized bionanomaterials can be utilized to load drug to improve solubility, reduce toxicity and provide site specific targeting. Nanomedicines offer a wide scope for delivery of smart materials from tissue engineering to more recently artificial RBCs. Nanocomposites are the future hope for tailored and personalized medicines as well as for bone repairing and rectification of cartilage impairment. Nanosize drug delivery systems are addressing the challenges to overcome the delivery problems of wide ranges of drugs through their narrow submicron particle size range, easily manipulatable surface characteristics in achievement of versatile tissue targeting (includes active and passive drug targeting), controlled and sustained drug

  1. Protein and Peptide drug delivery: oral approaches.

    PubMed

    Shaji, Jessy; Patole, V

    2008-01-01

    Till recent, injections remained the most common means for administering therapeutic proteins and peptides because of their poor oral bioavailability. However, oral route would be preferred to any other route because of its high levels of patient acceptance and long term compliance, which increases the therapeutic value of the drug. Designing and formulating a polypeptide drug delivery through the gastro intestinal tract has been a persistent challenge because of their unfavorable physicochemical properties, which includes enzymatic degradation, poor membrane permeability and large molecular size. The main challenge is to improve the oral bioavailability from less than 1% to at least 30-50%. Consequently, efforts have intensified over the past few decades, where every oral dosage form used for the conventional small molecule drugs has been used to explore oral protein and peptide delivery. Various strategies currently under investigation include chemical modification, formulation vehicles and use of enzyme inhibitors, absorption enhancers and mucoadhesive polymers. This review summarizes different pharmaceutical approaches which overcome various physiological barriers that help to improve oral bioavailability that ultimately achieve formulation goals for oral delivery.

  2. Novel tamarind seed polysaccharide-alginate mucoadhesive microspheres for oral gliclazide delivery: in vitro-in vivo evaluation.

    PubMed

    Pal, Dilipkumar; Nayak, Amit Kumar

    2012-04-01

    Novel tamarind seed polysaccharide (TSP)-alginate mucoadhesive microspheres were prepared using TSP and alginate as blend in different ratios with different calcium chloride (CaCl(2)) concentration as a cross linker by ionotropic gelation. The prepared microspheres were of spherical shape having rough surfaces, and average particle sizes within the range of 752.12 ± 6.42 to 948.49 ± 20.92 µm. The drug entrapment efficiency of these microspheres were within the range between 58.12 ± 2.42 to 82.78 ± 3.43% w/w. Fourier transform infrared (FTIR) studies indicated that there were no reactions between gliclazide, and polymers (TSP, and sodium alginate) used. Different formulations of gliclazide loaded TSP-alginate microspheres showed prolonged in vitro release profiles of gliclazide over 12 hours in both stomach pH (pH 1.2), and intestinal pH (pH 7.4). It was found that the gliclazide release in gastric pH was comparatively slow and sustained than intestinal pH. These TSP-alginate microspheres also exhibited good mucoadhesivity. The in vivo studies on alloxan-induced diabetic rats (Animal Ethical Committee registration number: IFTM/837ac/0160) demonstrated the significant hypoglycemic effect of selected formulation of TSP-alginate mucoadhesive microspheres containing gliclazide on oral administration. This developed gliclazide loaded new TSP-alginate mucoadhesive microspheres may be very much useful for prolonged systemic absorption of gliclazide for proper maintaining blood glucose level and advanced patient compliance.

  3. Novel tamarind seed polysaccharide-alginate mucoadhesive microspheres for oral gliclazide delivery: in vitro-in vivo evaluation.

    PubMed

    Pal, Dilipkumar; Nayak, Amit Kumar

    2012-04-01

    Novel tamarind seed polysaccharide (TSP)-alginate mucoadhesive microspheres were prepared using TSP and alginate as blend in different ratios with different calcium chloride (CaCl(2)) concentration as a cross linker by ionotropic gelation. The prepared microspheres were of spherical shape having rough surfaces, and average particle sizes within the range of 752.12 ± 6.42 to 948.49 ± 20.92 µm. The drug entrapment efficiency of these microspheres were within the range between 58.12 ± 2.42 to 82.78 ± 3.43% w/w. Fourier transform infrared (FTIR) studies indicated that there were no reactions between gliclazide, and polymers (TSP, and sodium alginate) used. Different formulations of gliclazide loaded TSP-alginate microspheres showed prolonged in vitro release profiles of gliclazide over 12 hours in both stomach pH (pH 1.2), and intestinal pH (pH 7.4). It was found that the gliclazide release in gastric pH was comparatively slow and sustained than intestinal pH. These TSP-alginate microspheres also exhibited good mucoadhesivity. The in vivo studies on alloxan-induced diabetic rats (Animal Ethical Committee registration number: IFTM/837ac/0160) demonstrated the significant hypoglycemic effect of selected formulation of TSP-alginate mucoadhesive microspheres containing gliclazide on oral administration. This developed gliclazide loaded new TSP-alginate mucoadhesive microspheres may be very much useful for prolonged systemic absorption of gliclazide for proper maintaining blood glucose level and advanced patient compliance. PMID:22352984

  4. Single compartment drug delivery

    PubMed Central

    Cima, Michael J.; Lee, Heejin; Daniel, Karen; Tanenbaum, Laura M.; Mantzavinou, Aikaterini; Spencer, Kevin C.; Ong, Qunya; Sy, Jay C.; Santini, John; Schoellhammer, Carl M.; Blankschtein, Daniel; Langer, Robert S.

    2014-01-01

    Drug design is built on the concept that key molecular targets of disease are isolated in the diseased tissue. Systemic drug administration would be sufficient for targeting in such a case. It is, however, common for enzymes or receptors that are integral to disease to be structurally similar or identical to those that play important biological roles in normal tissues of the body. Additionally, systemic administration may not lead to local drug concentrations high enough to yield disease modification because of rapid systemic metabolism or lack of sufficient partitioning into the diseased tissue compartment. This review focuses on drug delivery methods that physically target drugs to individual compartments of the body. Compartments such as the bladder, peritoneum, brain, eye and skin are often sites of disease and can sometimes be viewed as “privileged,” since they intrinsically hinder partitioning of systemically administered agents. These compartments have become the focus of a wide array of procedures and devices for direct administration of drugs. We discuss the rationale behind single compartment drug delivery for each of these compartments, and give an overview of examples at different development stages, from the lab bench to phase III clinical trials to clinical practice. We approach single compartment drug delivery from both a translational and a technological perspective. PMID:24798478

  5. New developments and opportunities in oral mucosal drug delivery for local and systemic disease.

    PubMed

    Hearnden, Vanessa; Sankar, Vidya; Hull, Katrusha; Juras, Danica Vidović; Greenberg, Martin; Kerr, A Ross; Lockhart, Peter B; Patton, Lauren L; Porter, Stephen; Thornhill, Martin H

    2012-01-01

    The oral mucosa's accessibility, excellent blood supply, by-pass of hepatic first-pass metabolism, rapid repair and permeability profile make it an attractive site for local and systemic drug delivery. Technological advances in mucoadhesives, sustained drug release, permeability enhancers and drug delivery vectors are increasing the efficient delivery of drugs to treat oral and systemic diseases. When treating oral diseases, these advances result in enhanced therapeutic efficacy, reduced drug wastage and the prospect of using biological agents such as genes, peptides and antibodies. These technologies are also increasing the repertoire of drugs that can be delivered across the oral mucosa to treat systemic diseases. Trans-mucosal delivery is now a favoured route for non-parenteral administration of emergency drugs and agents where a rapid onset of action is required. Furthermore, advances in drug delivery technology are bringing forward the likelihood of transmucosal systemic delivery of biological agents.

  6. Polymeric Micelles, a Promising Drug Delivery System to Enhance Bioavailability of Poorly Water-Soluble Drugs

    PubMed Central

    Ling, Peixue; Zhang, Tianmin

    2013-01-01

    Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs) can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1) protection of the loaded drug from the harsh environment of the GI tract, (2) release of the drug in a controlled manner at target sites, (3) prolongation of the residence time in the gut by mucoadhesion, and (4) inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained. PMID:23936656

  7. Fabrication of a multifunctional nano-in-micro drug delivery platform by microfluidic templated encapsulation of porous silicon in polymer matrix.

    PubMed

    Zhang, Hongbo; Liu, Dongfei; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Herranz-Blanco, Bárbara; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

    2014-07-01

    A multifunctional nano-in-micro drug delivery platform is developed by conjugating the porous silicon nanoparticles with mucoadhesive polymers and subsequent encapsulation into a pH-responsive polymer using microfluidics. The multistage platform shows monodisperse size distribution and pH-responsive payload release, and the released nanoparticles are mucoadhesive. Moreover, this platform is capable of simultaneously loading and releasing multidrugs with distinct properties.

  8. Photomechanical drug delivery

    NASA Astrophysics Data System (ADS)

    Doukas, Apostolos G.; Lee, Shun

    2000-05-01

    Photomechanical waves (PW) are generated by Q-switched or mode-locked lasers. Ablation is a reliable method for generating PWs with consistent characteristics. Depending on the laser wavelength and target material, PWs with different parameters can be generated which allows the investigation of PWs with cells and tissue. PWs have been shown to permeabilize the stratum corneum (SC) in vivo and facilitate the transport of drugs into the skin. Once a drug has diffused into the dermis it can enter the vasculature, thus producing a systemic effect. Fluorescence microscopy of biopsies show that 40-kDa molecules can be delivered to a depth of > 300 micrometers into the viable skin of rats. Many important drugs such as insulin, and erythropoietin are smaller or comparable in size, making the PWs attractive for transdermal drug delivery. There are three possible pathways through the SC: Transappendageal via hair follicles or other appendages, transcellular through the corneocytes, and intercellular via the extracellular matrix. The intracellular route appears to be the most likely pathway of drug delivery through the SC.

  9. Nanoparticles incorporated in bilaminated films: a smart drug delivery system for oral formulations.

    PubMed

    Cui, Fuying; He, Chunbai; Yin, Lichen; Qian, Feng; He, Miao; Tang, Cui; Yin, Chunhua

    2007-09-01

    A novel smart drug delivery system (NP-Film) consisting of carboxylation chitosan-grafted nanoparticles (CCGNs) and bilaminated films, which were composed of the mucoadhesive chitosan-ethylenediaminetetraacetic acid hydrogel layer and the hydrophobic ethylcellulose layer, was developed for oral delivery of protein drugs. NP-Film was characterized by electron microscopy and fluorescence microscopy, and the results showed that the solid, spherical nanoparticles dispersed evenly in the porous structures of films. The properties of nanoparticles and films were investigated. The mucoadhesive force, CCGNs released from the NP-Film, and the toxicity of NP-Film were also evaluated. Results showed that the nanoparticles could reversibly open the tight junction of the intestine and inhibit trypsin activity. The release behavior of the nanoparticles from the NP-Film exhibited pH sensitivity. The drug delivery system possessed high mucoadhesive force and low intestinal toxicity. Therefore, the NP-Film would be a promising delivery carrier for protein drugs via oral administration.

  10. Alginate-based hybrid aerogel microparticles for mucosal drug delivery.

    PubMed

    Gonçalves, V S S; Gurikov, P; Poejo, J; Matias, A A; Heinrich, S; Duarte, C M M; Smirnova, I

    2016-10-01

    The application of biopolymer aerogels as drug delivery systems (DDS) has gained increased interest during the last decade since these structures have large surface area and accessible pores allowing for high drug loadings. Being biocompatible, biodegradable and presenting low toxicity, polysaccharide-based aerogels are an attractive carrier to be applied in pharmaceutical industry. Moreover, some polysaccharides (e.g. alginate and chitosan) present mucoadhesive properties, an important feature for mucosal drug delivery. This feature allows to extend the contact of DDS with biological membranes, thereby increasing the absorption of drugs through the mucosa. Alginate-based hybrid aerogels in the form of microparticles (<50μm) were investigated in this work as carriers for mucosal administration of drugs. Low methoxyl pectin and κ-carrageenan were co-gelled with alginate and further dried with supercritical CO2 (sc-CO2). Spherical mesoporous aerogel microparticles were obtained for alginate, hybrid alginate/pectin and alginate/κ-carrageenan aerogels, presenting high specific surface area (370-548m(2)g(-1)) and mucoadhesive properties. The microparticles were loaded with ketoprofen via adsorption from its solution in sc-CO2, and with quercetin via supercritical anti-solvent precipitation. Loading of ketoprofen was in the range between 17 and 22wt% whereas quercetin demonstrated loadings of 3.1-5.4wt%. Both the drugs were present in amorphous state. Loading procedure allowed the preservation of antioxidant activity of quercetin. Release of both drugs from alginate/κ-carrageenan aerogel was slightly faster compared to alginate/pectin. The results indicate that alginate-based aerogel microparticles can be viewed as promising matrices for mucosal drug delivery applications.

  11. Alginate-based hybrid aerogel microparticles for mucosal drug delivery.

    PubMed

    Gonçalves, V S S; Gurikov, P; Poejo, J; Matias, A A; Heinrich, S; Duarte, C M M; Smirnova, I

    2016-10-01

    The application of biopolymer aerogels as drug delivery systems (DDS) has gained increased interest during the last decade since these structures have large surface area and accessible pores allowing for high drug loadings. Being biocompatible, biodegradable and presenting low toxicity, polysaccharide-based aerogels are an attractive carrier to be applied in pharmaceutical industry. Moreover, some polysaccharides (e.g. alginate and chitosan) present mucoadhesive properties, an important feature for mucosal drug delivery. This feature allows to extend the contact of DDS with biological membranes, thereby increasing the absorption of drugs through the mucosa. Alginate-based hybrid aerogels in the form of microparticles (<50μm) were investigated in this work as carriers for mucosal administration of drugs. Low methoxyl pectin and κ-carrageenan were co-gelled with alginate and further dried with supercritical CO2 (sc-CO2). Spherical mesoporous aerogel microparticles were obtained for alginate, hybrid alginate/pectin and alginate/κ-carrageenan aerogels, presenting high specific surface area (370-548m(2)g(-1)) and mucoadhesive properties. The microparticles were loaded with ketoprofen via adsorption from its solution in sc-CO2, and with quercetin via supercritical anti-solvent precipitation. Loading of ketoprofen was in the range between 17 and 22wt% whereas quercetin demonstrated loadings of 3.1-5.4wt%. Both the drugs were present in amorphous state. Loading procedure allowed the preservation of antioxidant activity of quercetin. Release of both drugs from alginate/κ-carrageenan aerogel was slightly faster compared to alginate/pectin. The results indicate that alginate-based aerogel microparticles can be viewed as promising matrices for mucosal drug delivery applications. PMID:27393563

  12. Bioadhesive okra polymer based buccal patches as platform for controlled drug delivery.

    PubMed

    Kaur, Gurpreet; Singh, Deepinder; Brar, Vivekjot

    2014-09-01

    In the present investigation, polysaccharide from the Okra fruits (Hibiscus esculentus) was extracted, characterized and explored for its mucoadhesive potential. Mucoadhesive films of okra polymer (OP) were prepared by solvent casting method based on 3(2) factorial design. For these studies, OP (2.0%, 2.5%, 3.0%, w/v) and glycerol (plasticizer) (0.25%, 0.50%, 0.75%, v/v) were taken as independent variables while tensile strength, mucoadhesive strength, contact angle, swelling index and residence time as dependent variables. The developed films were evaluated for their physicochemical, mechanical and electrical properties. The formulated films were found to be smooth, flexible, and displayed adequate mucoadhesive and tensile strength. Their near neutral pH and negative hemolytic studies indicated their non-irritability and biocompatible nature with biological tissues. The formulation comprising of 3% OP and 0.5% glycerol (F8) was found to exhibit optimum mechanical properties. Further, optimized film was loaded with zolmitriptan (model drug) to determine its drug release profiles. In vitro and ex vivo drug release studies demonstrated a controlled release of zolmitriptan over a period of 8h in simulated salivary fluid (SSF) pH 6.8, with the correlation coefficient values indicating its non-Fickian kinetics. Thus, OP can be used as a promising biomaterial for controlled drug delivery.

  13. Bioadhesive okra polymer based buccal patches as platform for controlled drug delivery.

    PubMed

    Kaur, Gurpreet; Singh, Deepinder; Brar, Vivekjot

    2014-09-01

    In the present investigation, polysaccharide from the Okra fruits (Hibiscus esculentus) was extracted, characterized and explored for its mucoadhesive potential. Mucoadhesive films of okra polymer (OP) were prepared by solvent casting method based on 3(2) factorial design. For these studies, OP (2.0%, 2.5%, 3.0%, w/v) and glycerol (plasticizer) (0.25%, 0.50%, 0.75%, v/v) were taken as independent variables while tensile strength, mucoadhesive strength, contact angle, swelling index and residence time as dependent variables. The developed films were evaluated for their physicochemical, mechanical and electrical properties. The formulated films were found to be smooth, flexible, and displayed adequate mucoadhesive and tensile strength. Their near neutral pH and negative hemolytic studies indicated their non-irritability and biocompatible nature with biological tissues. The formulation comprising of 3% OP and 0.5% glycerol (F8) was found to exhibit optimum mechanical properties. Further, optimized film was loaded with zolmitriptan (model drug) to determine its drug release profiles. In vitro and ex vivo drug release studies demonstrated a controlled release of zolmitriptan over a period of 8h in simulated salivary fluid (SSF) pH 6.8, with the correlation coefficient values indicating its non-Fickian kinetics. Thus, OP can be used as a promising biomaterial for controlled drug delivery. PMID:25036601

  14. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed.

  15. Transdermal delivery of propranolol hydrochloride through chitosan nanoparticles dispersed in mucoadhesive gel.

    PubMed

    Al-Kassas, Raida; Wen, Jingyuan; Cheng, Angel En-Miao; Kim, Amy Moon-Jung; Liu, Stephanie Sze Mei; Yu, Joohee

    2016-11-20

    This study aimed at improving the systemic bioavailability of propranolol-HCl by the design of transdermal drug delivery system based on chitosan nanoparticles dispersed into gels. Chitosan nanoparticles were prepared by ionic gelation technique using tripolyphosphate (TPP) as a cross-linking agent. Characterization of the nanoparticles was focused on particle size, zeta potential, surface texture and morphology, and drug encapsulation efficiency. The prepared freeze dried chitosan nanoparticles were dispersed into gels made of poloxamer and carbopol and the rheological behaviour and the adhesiveness of the gels were investigated. The results showed that smallest propranolol loaded chitosan nanoparticles were achieved with 0.2% chitosan and 0.05% TPP. Nanoparticles were stable in suspension with a zeta potential (ZP) above ±30mV to prevent aggregation of the colloid. Zeta potential was found to increase with increasing chitosan concentration due to its cationic nature. At least 70% of entrapment efficiency and drug loading were achieved for all prepared nanoparticles. When chitosan nanoparticles dispersed into gel consisting of poloxamer and carbopol, the resultant formulation exhibited thixotropic behaviour with a prolonged drug release properties as shown by the permeation studies through pig ear skin. Our study demonstrated that the designed nanoparticles-gel transdermal delivery system has a potential to improve the systemic bioavailability and the therapeutic efficacy of propranolol-HCl. PMID:27561485

  16. Design, synthesis, fabrication and in vitro evalution of mucoadhesive 5-amino-2-mercaptobenzimidazole chitosan as low water soluble drug carriers.

    PubMed

    Kongsong, Mullika; Songsurang, Kultida; Sangvanich, Polkit; Siralertmukul, Krisana; Muangsin, Nongnuj

    2014-11-01

    Mucoadhesive thiolated chitosan suitable as a carrier for low water soluble drugs was designed and synthesized by conjugating 5-amino-2-mercaptobenzimidazole (MBI) using methylacrylate (MA) as the linking agent. A 14.4% degree of substitution of MA, as determined by (1)H NMR analysis, and 11.86±0.01μmol thiol groups/g of polymer, as determined by Ellman's method, was obtained. The MBI-MA-chitosan had an 11-fold stronger mucoadhesive property compared to unmodified chitosan at pH 1.2, as determined by the periodic acid: Schiff colorimetric method. Chitosan, MA-chitosan and MBI-MA-chitosan were fabricated as well-formed microspheres using electrospray ionization, including an entrapment efficiency of simvastatin (SV) of over 80% for the MBI-MA-chitosan. The mucoadhesiveness of the SV-loaded MBI-MA-CS microspheres was still higher than that for SV-loaded chitosan at pH 1.2 and 6.4. The SV-loaded MBI-MA-CS microspheres revealed a reduced burst effect and an increased release rate (more than fivefold higher than pure SV) of SV over 12h.

  17. Polymers for Drug Delivery Systems

    PubMed Central

    Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

    2012-01-01

    Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

  18. Evaluation of Calendula mucilage as a mucoadhesive and controlled release component in buccal tablets.

    PubMed

    Sabale, V; Patel, V; Paranjape, A

    2014-01-01

    Mucoadhesive drug delivery systems were developed to sustain drug delivery via various mucus membranes for either local or systemic delivery of poorly absorbed drugs such as peptides and proteins as well as drugs that are subjected to high first-pass metabolism. The present study was undertaken to use isolated Calendula mucilage as a mucoadhesive agent and to formulate controlled release buccoadhesive tablets with an intention to avoid hepatic first-pass metabolism as well as to enhance residence time of drug in the buccal cavity. The mucilage was isolated from the Calendula petals by aqueous extraction method and characterized for various physiochemical parameters as well as for its adhesive properties. By using direct compression technique, tablets were prepared containing dried mucilage and chlorpheniramine maleate (CPM) as a model drug. Three batches of tablets were prepared and evaluated containing three mucoadhesive components namely Methocel K4M, Carbopol 974P and isolated Calendula mucilage in 16.66%, 33.33 % and 50 % (1:2:3 ratio) resulting in 9 different formulations. FTIR studies between mucilage and CPM suggested the absence of a chemical interaction between CPM and Calendula mucilage. The results of the study showed that the isolated mucilage had good physicochemical and morphological characteristics and tablets conformed to the pharmacopoeial specifications. Also in vitro release studies showed controlled action of drug with increasing the concentration of the isolated Calendula mucilage as a mucoadhesive agent in the formulations. Permeability studies indicated that permeability behavior was not statistically different (P>0.05) by changing the mucoadhesive component. The formulated mucoadhesive tablets for buccal administration containing 75 mg Calendula mucilage showed controlled drug release. Thus, mucoadhesive natural Calendula mucilage based buccal tablets for controlled release were successfully formulated. PMID:25598798

  19. Evaluation of Calendula mucilage as a mucoadhesive and controlled release component in buccal tablets

    PubMed Central

    Sabale, V.; Patel, V.; Paranjape, A.

    2014-01-01

    Mucoadhesive drug delivery systems were developed to sustain drug delivery via various mucus membranes for either local or systemic delivery of poorly absorbed drugs such as peptides and proteins as well as drugs that are subjected to high first-pass metabolism. The present study was undertaken to use isolated Calendula mucilage as a mucoadhesive agent and to formulate controlled release buccoadhesive tablets with an intention to avoid hepatic first-pass metabolism as well as to enhance residence time of drug in the buccal cavity. The mucilage was isolated from the Calendula petals by aqueous extraction method and characterized for various physiochemical parameters as well as for its adhesive properties. By using direct compression technique, tablets were prepared containing dried mucilage and chlorpheniramine maleate (CPM) as a model drug. Three batches of tablets were prepared and evaluated containing three mucoadhesive components namely Methocel K4M, Carbopol 974P and isolated Calendula mucilage in 16.66%, 33.33 % and 50 % (1:2:3 ratio) resulting in 9 different formulations. FTIR studies between mucilage and CPM suggested the absence of a chemical interaction between CPM and Calendula mucilage. The results of the study showed that the isolated mucilage had good physicochemical and morphological characteristics and tablets conformed to the pharmacopoeial specifications. Also in vitro release studies showed controlled action of drug with increasing the concentration of the isolated Calendula mucilage as a mucoadhesive agent in the formulations. Permeability studies indicated that permeability behavior was not statistically different (P>0.05) by changing the mucoadhesive component. The formulated mucoadhesive tablets for buccal administration containing 75 mg Calendula mucilage showed controlled drug release. Thus, mucoadhesive natural Calendula mucilage based buccal tablets for controlled release were successfully formulated. PMID:25598798

  20. Evaluation of Calendula mucilage as a mucoadhesive and controlled release component in buccal tablets.

    PubMed

    Sabale, V; Patel, V; Paranjape, A

    2014-01-01

    Mucoadhesive drug delivery systems were developed to sustain drug delivery via various mucus membranes for either local or systemic delivery of poorly absorbed drugs such as peptides and proteins as well as drugs that are subjected to high first-pass metabolism. The present study was undertaken to use isolated Calendula mucilage as a mucoadhesive agent and to formulate controlled release buccoadhesive tablets with an intention to avoid hepatic first-pass metabolism as well as to enhance residence time of drug in the buccal cavity. The mucilage was isolated from the Calendula petals by aqueous extraction method and characterized for various physiochemical parameters as well as for its adhesive properties. By using direct compression technique, tablets were prepared containing dried mucilage and chlorpheniramine maleate (CPM) as a model drug. Three batches of tablets were prepared and evaluated containing three mucoadhesive components namely Methocel K4M, Carbopol 974P and isolated Calendula mucilage in 16.66%, 33.33 % and 50 % (1:2:3 ratio) resulting in 9 different formulations. FTIR studies between mucilage and CPM suggested the absence of a chemical interaction between CPM and Calendula mucilage. The results of the study showed that the isolated mucilage had good physicochemical and morphological characteristics and tablets conformed to the pharmacopoeial specifications. Also in vitro release studies showed controlled action of drug with increasing the concentration of the isolated Calendula mucilage as a mucoadhesive agent in the formulations. Permeability studies indicated that permeability behavior was not statistically different (P>0.05) by changing the mucoadhesive component. The formulated mucoadhesive tablets for buccal administration containing 75 mg Calendula mucilage showed controlled drug release. Thus, mucoadhesive natural Calendula mucilage based buccal tablets for controlled release were successfully formulated.

  1. Microprocessor controlled transdermal drug delivery.

    PubMed

    Subramony, J Anand; Sharma, Ashutosh; Phipps, J B

    2006-07-01

    Transdermal drug delivery via iontophoresis is reviewed with special focus on the delivery of lidocaine for local anesthesia and fentanyl for patient controlled acute therapy such as postoperative pain. The role of the microprocessor controller in achieving dosimetry, alternating/reverse polarity, pre-programmed, and sensor-based delivery is highlighted. Unique features such as the use of tactile signaling, telemetry control, and pulsatile waveforms in iontophoretic drug delivery are described briefly.

  2. Designing mucoadhesive discs containing stem bark extract of Ziziphus jujuba based on Iranian traditional documents

    PubMed Central

    Hamedi, Shokouhsadat; Shams-Ardakani, Mohammad Reza; Sadeghpour, Omid; Amin, Gholamreza; Hajighasemali, Dawood; Orafai, Hossein

    2016-01-01

    Objective (s): Mucoadhesive disc is one of the various routes of drug delivery for curing buccal disease Materials and Methods: Every discs containing 70 mg stem bark extract of Ziziphus jujuba were formulated by using Carbopol 934, PVP k30 and gelatin as polymers. Discs were made by granulation and direct compression. Discs were standardized based on the total phenol. Properties such as in vitro and in vivo mucoadhesion, drug release, water uptake, and disintegration were carried out. Results: Discs showed excellent mucoadhesion and released high amount of the active ingredients (47%) immediately and completed after approximately the first hour. They had a good adhesion in buccal cavity. Conclusion: This study showed that the kinetics of release of the active substance from the mucoadhesive disc obeyed the zero order kinetic and didn’t follow the fick's law. The water uptake and dissolution (DS), increased with the passing of time. PMID:27114804

  3. Emerging Frontiers in Drug Delivery.

    PubMed

    Tibbitt, Mark W; Dahlman, James E; Langer, Robert

    2016-01-27

    Medicine relies on the use of pharmacologically active agents (drugs) to manage and treat disease. However, drugs are not inherently effective; the benefit of a drug is directly related to the manner by which it is administered or delivered. Drug delivery can affect drug pharmacokinetics, absorption, distribution, metabolism, duration of therapeutic effect, excretion, and toxicity. As new therapeutics (e.g., biologics) are being developed, there is an accompanying need for improved chemistries and materials to deliver them to the target site in the body, at a therapeutic concentration, and for the required period of time. In this Perspective, we provide an historical overview of drug delivery and controlled release followed by highlights of four emerging areas in the field of drug delivery: systemic RNA delivery, drug delivery for localized therapy, oral drug delivery systems, and biologic drug delivery systems. In each case, we present the barriers to effective drug delivery as well as chemical and materials advances that are enabling the field to overcome these hurdles for clinical impact.

  4. Hollow Pollen Shells to Enhance Drug Delivery

    PubMed Central

    Diego-Taboada, Alberto; Beckett, Stephen T.; Atkin, Stephen L.; Mackenzie, Grahame

    2014-01-01

    Pollen grain and spore shells are natural microcapsules designed to protect the genetic material of the plant from external damage. The shell is made up of two layers, the inner layer (intine), made largely of cellulose, and the outer layer (exine), composed mainly of sporopollenin. The relative proportion of each varies according to the plant species. The structure of sporopollenin has not been fully characterised but different studies suggest the presence of conjugated phenols, which provide antioxidant properties to the microcapsule and UV (ultraviolet) protection to the material inside it. These microcapsule shells have many advantageous properties, such as homogeneity in size, resilience to both alkalis and acids, and the ability to withstand temperatures up to 250 °C. These hollow microcapsules have the ability to encapsulate and release actives in a controlled manner. Their mucoadhesion to intestinal tissues may contribute to the extended contact of the sporopollenin with the intestinal mucosa leading to an increased efficiency of delivery of nutraceuticals and drugs. The hollow microcapsules can be filled with a solution of the active or active in a liquid form by simply mixing both together, and in some cases operating a vacuum. The active payload can be released in the human body depending on pressure on the microcapsule, solubility and/or pH factors. Active release can be controlled by adding a coating on the shell, or co-encapsulation with the active inside the shell. PMID:24638098

  5. Optimisation of polyherbal gels for vaginal drug delivery by Box-Behnken statistical design.

    PubMed

    Chopra, Shruti; Motwani, Sanjay K; Iqbal, Zeenat; Talegaonkar, Sushma; Ahmad, Farhan J; Khar, Roop K

    2007-08-01

    The present research work aimed at development and optimisation of mucoadhesive polyherbal gels (MPG) for vaginal drug delivery. As the rheological and mucoadhesive properties of the gels correlate well to each other the prepared MPGs were optimised for maximum mucoadhesion using a relationship between the storage modulus (G') and Gel Index (GI), by employing a 3-factor, 3-level Box-Behnken statistical design. Independent variables studied were the polymer concentration (X(1)), honey concentration (X(2)) and aerosil concentration (X(3)). Aerosil has been investigated for the first time to improve the consistency of gels. The dependent variables studied were the elastic modulus, G'(Y(1)), gel index (Y(2)), and maximum detachment force (Y(3)) with applied constraints of 500mucoadhesion properties by about 50-54% and 7-11%, respectively. The Box-Behnken design facilitated the optimisation of polyherbal gel formulations for enhanced vaginal drug delivery by optimum mucoadhesion and longer retention.

  6. Cell-Mediated Drugs Delivery

    PubMed Central

    Batrakova, Elena V.; Gendelman, Howard E.; Kabanov, Alexander V.

    2011-01-01

    INTRODUCTION Drug targeting to sites of tissue injury, tumor or infection with limited toxicity is the goal for successful pharmaceutics. Immunocytes (including mononuclear phagocytes (dendritic cells, monocytes and macrophages), neutrophils, and lymphocytes) are highly mobile; they can migrate across impermeable barriers and release their drug cargo at sites of infection or tissue injury. Thus immune cells can be exploited as trojan horses for drug delivery. AREAS COVERED IN THIS REVIEW This paper reviews how immunocytes laden with drugs can cross the blood brain or blood tumor barriers, to facilitate treatments for infectious diseases, injury, cancer, or inflammatory diseases. The promises and perils of cell-mediated drug delivery are reviewed, with examples of how immunocytes can be harnessed to improve therapeutic end points. EXPERT OPINION Using cells as delivery vehicles enables targeted drug transport, and prolonged circulation times, along with reductions in cell and tissue toxicities. Such systems for drug carriage and targeted release represent a novel disease combating strategy being applied to a spectrum of human disorders. The design of nanocarriers for cell-mediated drug delivery may differ from those used for conventional drug delivery systems; nevertheless, engaging different defense mechanisms into drug delivery may open new perspectives for the active delivery of drugs. PMID:21348773

  7. Development and evaluation of tamarind seed xyloglucan-based mucoadhesive buccal films of rizatriptan benzoate.

    PubMed

    Avachat, Amelia M; Gujar, Kishore N; Wagh, Kishor V

    2013-01-16

    Mucoadhesive buccal films were developed using tamarind seed xyloglucan (TSX) as novel mucoadhesive polysaccharide polymer for systemic delivery of rizatriptan benzoate through buccal route. Formulations were prepared based on 3(2) factorial design with concentrations of TSX and carbopol 934P (CP) as independent variables. Three dependent variables considered were tensile strength, bioadhesion force and drug release. DSC analysis revealed no interaction between drug and polymers. Ex vivo diffusion studies were carried out using Franz diffusion cell, while bioadhesive properties were evaluated using texture analyzer with porcine buccal mucosa as model tissue. Results revealed that bilayer film containing 4% (w/v) TSX and 0.5% (w/v) CP in the drug layer and 1% (w/v) ethyl cellulose in backing layer demonstrated diffusion of 93.45% through the porcine buccal mucosa. Thus, this study suggests that tamarind seed polysaccharide can act as a potential mucoadhesive polymer for buccal delivery of a highly soluble drug like rizatriptan benzoate.

  8. Why Chitosan? From properties to perspective of mucosal drug delivery.

    PubMed

    Kumar, Ashwini; Vimal, Archana; Kumar, Awanish

    2016-10-01

    Non-parenteral drug delivery routes primarily remove the local pain at the injection site. The drugs administered through the oral route encounter the process of hepatic first pass metabolism. Among the alternative delivery routes, mucosal route is being investigated as the most preferred route. Different mucosal routes include the gastrointestinal tract (oral), vagina, buccal cavity and nasal cavity. Novel formulations are being developed using natural and synthetic polymers that could increase the residence time of the drug at mucosal surface in order to facilitate permeation and reduce (or bypass) the first pass metabolism. For recombinant drugs, the formulations are accompanied by enzyme inhibitors and penetration enhancers. Buccal cavity (buccal and sublingual mucosa) has smaller surface area than the gastrointestinal tract but the drugs can easily escape the first pass metabolism. Chitosan is the most applied natural polymer while synthetic polymers include Carbopol and Eudragit. Chitosan has inherent properties of mucoadhesion and penetration enhancement apart from biodegradability and efflux pump inhibition. This review hoards the important research purview of chitosan as a compatible drug carrier macromolecule for mucosal delivery on single platform.

  9. Chitosan/sulfobutylether-β-cyclodextrin nanoparticles as a potential approach for ocular drug delivery.

    PubMed

    Mahmoud, Azza A; El-Feky, Gina S; Kamel, Rabab; Awad, Ghada E A

    2011-07-15

    Development of efficient ocular delivery nanosystems remains a major challenge to achieve sustained therapeutic effect. The purpose of this work was to develop chitosan nanoparticles using sulfobutylether-β-cyclodextrin (SBE-β-CD) as polyanionic crosslinker and to investigate the potential of using those nanostructures as ocular drug delivery systems. Econazole nitrate (ECO) was chosen as model drug molecule. The influence of different process variables (chitosan molecular weight and the concentration of the two ionic agents) on particle size, polydispersity index, zeta potential, drug content, in vitro release and mucoadhesive properties was investigated. The results showed that the prepared nanoparticles were predominant spherical in shape having average particle diameter from 90 to 673 nm with positive zeta potential values from 22 to 33 mV and drug content values ranging from 13 to 45%. Drug release from optimized nanoparticles was controlled with approximately 50% of the original amount released over a 8h period. The release profile of nanoparticles followed a zero-order release kinetics. The optimized nanoparticles were tested for their use as ocular drug delivery systems on albino rabbits. The in vivo studies revealed that the prepared mucoadhesive nanoparticles had better ability in sustaining the antifungal effect of ECO than the ECO solution. Therefore, chitosan/SBE-β-CD nanoparticles developed showed a promising carrier for controlled delivery of drug to the eye.

  10. Synthesis of mucoadhesive thiolated gelatin using a two-step reaction process.

    PubMed

    Duggan, Sarah; O'Donovan, Orla; Owens, Eleanor; Cummins, Wayne; Hughes, Helen

    2015-04-01

    Using a novel two-step approach, the thiolation of gelatin for mucoadhesive drug delivery has been achieved. The initial step involved the amination of native gelatin via an amine to carboxylic acid coupling reaction with ethylene diamine, followed by thiolation with Traut's reagent. The resulting thiolated product showed an increase in thiol content of up to 10-fold in comparison with control gelatin samples. Improved cohesion and mucoadhesion in comparison with unmodified and control gelatin samples was also observed. This reaction process was observed to be influenced by both the temperature and the pH of the amination reaction, affecting both amine content and product yield. Swelling ability, cohesion and mucoadhesion were all observed to be strongly dependent on the thiol content of the samples but also, importantly, the molecular weight (MW) of the gelatin used. Gelatin with a MW of 20-25 kDa proved to be optimal in creating this novel mucoadhesive gelatin material.

  11. Drug delivery to the ear.

    PubMed

    Hoskison, E; Daniel, M; Al-Zahid, S; Shakesheff, K M; Bayston, R; Birchall, J P

    2013-01-01

    Drug delivery to the ear is used to treat conditions of the middle and inner ear such as acute and chronic otitis media, Ménière's disease, sensorineural hearing loss and tinnitus. Drugs used include antibiotics, antifungals, steroids, local anesthetics and neuroprotective agents. A literature review was conducted searching Medline (1966-2012), Embase (1988-2012), the Cochrane Library and Ovid (1966-2012), using search terms 'drug delivery', 'middle ear', 'inner ear' and 'transtympanic'. There are numerous methods of drug delivery to the middle ear, which can be categorized as topical, systemic (intravenous), transtympanic and via the Eustachian tube. Localized treatments to the ear have the advantages of targeted drug delivery allowing higher therapeutic doses and minimizing systemic side effects. The ideal scenario would be a carrier system that could cross the intact tympanic membrane loaded with drugs or biochemical agents for the treatment of middle and inner ear conditions.

  12. [Development of topical drug delivery systems utilizing polymeric materials].

    PubMed

    Machida, Y

    1993-05-01

    Topical drug delivery is important from the view points of improvement of therapeutic effect and reduction of systemic side effects. Utilization of polymeric materials seemed to be as a key for the development of new topical dosage forms including targeting drug delivery systems. Adriamycin ointment for local chemotherapy to breast cancer prepared using polyethylene glycol, ammonium polyacrylate and hydroxypropyl cellulose (HPC) according to an optimum formulation showed an excellent clinical effect in spite of a decreased drug content. Double-layered mucoadhesive sticks for the treatment of uterine cervix cancer were prepared by direct compression of powder mixture of bleomycin, HPC and carboxyvinyl polymer (CP). Drug release property of the sticks could be controlled by the weight of outer layer, drug combining ratio to each layer and coating of core layer. The results suggested a possibility of a "once-a-week" treatment that is preferable for the patients. Magnetic granules for the treatment of esophageal cancer were prepared using ferrite, HPC and CP. Magnetic guidance and retainment of the granules on esophageal mucosa were confirmed using rabbits in vivo. Buoyant sustained release preparations were prepared using chitosan, soybean protein, HPC and other polymers. Usefulness of the buoyant preparations was suggested from the results in vitro and in vivo. Insulin microspheres (IMS) for targeting delivery to the small intestine were prepared by the newly developed method. Employment of enteric coating material (Eudragit) and combination of protease inhibitor protected insulin from enzymatic attack and gave decreased levels of blood glucose by oral administration.

  13. Biocompatible and mucoadhesive bacterial cellulose-g-poly(acrylic acid) hydrogels for oral protein delivery.

    PubMed

    Ahmad, Naveed; Amin, Mohd Cairul Iqbal Mohd; Mahali, Shalela Mohd; Ismail, Ismanizan; Chuang, Victor Tuan Giam

    2014-11-01

    Stimuli-responsive bacterial cellulose-g-poly(acrylic acid) hydrogels were investigated for their potential use as an oral delivery system for proteins. These hydrogels were synthesized using electron beam irradiation without any cross-linking agents, thereby eliminating any potential toxic effects associated with cross-linkers. Bovine serum albumin (BSA), a model protein drug, was loaded into the hydrogels, and the release profile in simulated gastrointestinal fluids was investigated. Cumulative release of less than 10% in simulated gastric fluid (SGF) demonstrated the potential of these hydrogels to protect BSA from the acidic environment of the stomach. Subsequent conformational stability analyses of released BSA by SDS-PAGE, circular dichroism, and an esterase activity assay indicated that the structural integrity and bioactivity of BSA was maintained and preserved by the hydrogels. Furthermore, an increase in BSA penetration across intestinal mucosa tissue was observed in an ex vivo penetration experiment. Our fabricated hydrogels exhibited excellent cytocompatibility and showed no sign of toxicity, indicating the safety of these hydrogels for in vivo applications.

  14. Bioresponsive matrices in drug delivery

    PubMed Central

    2010-01-01

    For years, the field of drug delivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli. PMID:21114841

  15. Nanoencapsulation for drug delivery

    PubMed Central

    Kumari, Avnesh; Singla, Rubbel; Guliani, Anika; Yadav, Sudesh Kumar

    2014-01-01

    Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology. PMID:26417260

  16. A novel in situ gel for sustained drug delivery and targeting.

    PubMed

    Ganguly, Sudipta; Dash, Alekha K

    2004-05-19

    The objective of this study was to develop a novel chitosan-glyceryl monooleate (GMO) in situ gel system for sustained drug delivery and targeting. The delivery system consisted of 3% (w/v) chitosan and 3% (w/v) GMO in 0.33M citric acid. In situ gel was formed at a biological pH. In vitro release studies were conducted in Sorensen's phosphate buffer (pH 7.4) and drugs were analyzed either by HPLC or spectrophotometry. Characterization of the gel included the effect of cross-linker, determination of diffusion coefficient and water uptake by thermogravimetric analysis (TGA). Mucoadhesive property of the gel was evaluated in vitro using an EZ-Tester. Incorporation of a cross-linker (glutaraldehyde) retarded the rate and extent of drug release. The in vitro release can further be sustained by replacing the free drug with drug-encapsulated microspheres. Drug release from the gel followed a matrix diffusion controlled mechanism. Inclusion of GMO enhanced the mucoadhesive property of chitosan by three- to sevenfold. This novel in situ gel system can be useful in the sustained delivery of drugs via oral as well as parenteral routes.

  17. Microchip technology in drug delivery.

    PubMed

    Santini, J T; Richards, A C; Scheidt, R A; Cima, M J; Langer, R S

    2000-09-01

    The realization that the therapeutic efficacy of certain drugs can be affected dramatically by the way in which they are delivered has created immense interest in controlled drug delivery systems. Much previous work in drug delivery focused on achieving sustained drug release rates over time, while a more recent trend is to make devices that allow the release rate to be varied over time. Advances in microfabrication technology have made an entirely new type of drug delivery device possible. Proof-of-principle experiments have shown that silicon microchips have the ability to store and release multiple chemicals on demand. Future integration of active control electronics, such as microprocessors, remote control units, or biosensors, could lead to the development of a 'pharmacy on a chip,' ie 'smart' microchip implants or tablets that release drugs into the body automatically when needed.

  18. Photoresponsive nanoparticles for drug delivery

    PubMed Central

    Rwei, Alina Y.; Wang, Weiping; Kohane, Daniel S.

    2015-01-01

    Summary Externally triggerable drug delivery systems provide a strategy for the delivery of therapeutic agents preferentially to a target site, presenting the ability to enhance therapeutic efficacy while reducing side effects. Light is a versatile and easily tuned external stimulus that can provide spatiotemporal control. Here we will review the use of nanoparticles in which light triggers drug release or induces particle binding to tissues (phototargeting). PMID:26644797

  19. Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

    NASA Astrophysics Data System (ADS)

    Ensign-Hodges, Laura

    A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations

  20. Enema ion compositions for enhancing colorectal drug delivery.

    PubMed

    Maisel, Katharina; Chattopadhyay, Sumon; Moench, Thomas; Hendrix, Craig; Cone, Richard; Ensign, Laura M; Hanes, Justin

    2015-07-10

    Delivering drugs to the colorectum by enema has advantages for treating or preventing both local and systemic diseases. However, the properties of the enema itself are not typically exploited for improving drug delivery. Sodium ions are actively pumped out of the lumen of the colon, which is followed by osmotically-driven water absorption, so we hypothesized that this natural mechanism could be exploited to drive nanoparticles and drugs to the colorectal tissue surface. Here, we report that sodium-based, absorption-inducing (hypotonic) enemas rapidly transport hydrophilic drugs and non-mucoadhesive, mucus penetrating nanoparticles (MPP), deep into the colorectal folds to reach virtually the entire colorectal epithelial surface. In contrast, isotonic and secretion-inducing (hypertonic) vehicles led to non-uniform, poor surface coverage. Sodium-based enemas induced rapid fluid absorption even when moderately hyper-osmolal (~350 mOsm) compared to blood (~300 mOsm), which suggests that active sodium absorption plays a key role in osmosis-driven fluid uptake. We then used tenofovir, an antiretroviral drug in clinical trials for preventing HIV, to test the effects of enema composition on local and systemic drug delivery. We found that strongly hypotonic and hypertonic enemas caused rapid systemic drug uptake, whereas moderately hypotonic enemas with ion compositions similar to feces resulted in high local tissue levels with minimal systemic drug exposure. Similarly, moderately hypotonic enemas provided improved local drug retention in colorectal tissue, whereas hypertonic and isotonic enemas provided markedly reduced drug retention in colorectal tissue. Lastly, we found that moderately hypotonic enema formulations caused little to no detectable epithelial damage, while hypertonic solutions caused significant damage, including epithelial sloughing; the epithelial damage caused increased systemic drug absorption and penetration of MPP into colorectal tissue, a potential

  1. Rheological Analysis of Polymer Interactions and Ageing of Poly(Methylvinylether-Co-Maleic Anhydride)/Poly(Vinyl Alcohol) Binary Networks and Their Effects on Mucoadhesion.

    PubMed

    Andrews, Gavin P; Laverty, Thomas P; Jones, David S

    2015-12-01

    Polymer blends of poly(vinylalcohol, PVA) and poly(methylvinylether-co-maleic anhydride, PMVE/MA) were formulated and their viscoelastic and mucoadhesive properties characterised. The viscoelastic and mucoadhesive properties were dependent on polymer concentration, molecular weight of PVA and PVA:PMVE/MA ratio. Alteration of these properties allowed platforms to be designed to offer defined rheological and mucoadhesive properties, properties that could not be achieved using monopolymeric platforms. A strong correlation was noted between the modulus of the polymeric blends and mucoadhesion. After storage, the polymeric blends underwent rheological structuring (ageing) with an attendant enhancement of mucoadhesion. In certain blends containing the highest molecular weight of PVA (146-186 kDa), storage ultimately resulted in an increase and then a significant decrease in the rheological and mucoadhesive properties, the latter phenomenon being accredited to polymer recrystallisation. Ageing of the rheological and mucoadhesive properties was modelled using an exponential growth model, allowing predictions of the storage period associated with the maxima in viscoelastic and mucoadhesive properties. These observations highlight the possible implications whenever interactive polymeric blends are employed in drug delivery. Caution is therefore urged whenever a formulation strategy based on interactive polymer blends is employed to ensure that ageing is fully understood and mathematically characterised. PMID:26502109

  2. Quantitative analysis of drug delivery to the brain via nasal route.

    PubMed

    Kozlovskaya, Luba; Abou-Kaoud, Mohammed; Stepensky, David

    2014-09-10

    The blood-brain barrier (BBB) prevents drugs' permeability into the brain and limits the management of brain diseases. Intranasal delivery is a convenient route of drug administration that can bypass the BBB and lead to a direct delivery of the drug to the brain. Indeed, drug accumulation in the brain following intranasal application of a drug solution, or of a drug encapsulated in specialized delivery systems (DDSs), has been reported in numerous scientific publications. We aimed to analyze the available quantitative data on drug delivery to the brain via the nasal route and to reveal the efficiency of brain drug delivery and targeting by different types of nasally-administered DDSs. We searched for scientific publications published in 1970-2014 that reported delivery of drugs or model compounds to the brain via intranasal and parenteral routes, and contained quantitative data that were sufficient for calculation of brain targeting efficiency. We identified 73 publications (that reported data on 82 compounds) that matched the search criteria and analyzed their experimental settings, formulation types, analytical methods, and the claimed efficiencies of drug brain targeting: drug targeting efficiency (%DTE) and nose-to-brain direct transport (%DTP). Outcomes of this analysis indicate that efficiency of brain delivery by the nasal route differs widely between the studies, and does not correlate with the drug's physicochemical properties. Particle- and gel-based DDSs offer limited advantage for brain drug delivery in comparison to the intranasal administration of drug solution. Nevertheless, incorporation of specialized reagents (e.g., absorption enhancers, mucoadhesive compounds, targeting residues) can increase the efficiency of drug delivery to the brain via the nasal route. More elaborate and detailed methodological and analytical characterizations and standardized reporting of the experimental outcomes are required for reliable quantification of drug targeting

  3. Development and optimisation of mucoadhesive nanoparticles of acyclovir using design of experiments approach.

    PubMed

    Kharia, Ankit Anand; Singhai, Akhlesh Kumar

    2015-01-01

    The aim of our study was to improve the bioavailability of acyclovir (ACV) by delivery of mucoadhesive nanoparticles (NPs) and controlled delivery of drug at its absorption window. Central composite design was used by which the effects of independent variables (gelatin and Pluronic F-68) on various responses such as particle size, polydispersity index, entrapment efficiency, loading efficiency, drug release and mucoadhesive strength were studied. The optimised formulation was evaluated for morphology, stability, pharmacokinetic and gastrointestinal tracking. The optimised NPs were found to be nearly spherical. Changes in characteristics of NPs were not significant after six months of accelerated stability studies. In vivo mucoadhesion study showed significant retention of mucoadhesive NPs in upper gastro-intestinal tract for more than 12 h. Pharmacokinetic study in rats revealed that mucoadhesive NPs could maintain relatively steady plasma concentration of ACV for more than 10 h. The AUC0-∞ and mean residence time of optimised formulation (7527.9 ng h/mL and 12.09 h) were significantly high than tablet dispersion (3841.13 ng h/mL and 7.97 h). PMID:26333938

  4. Chitosan in nasal delivery systems for therapeutic drugs.

    PubMed

    Casettari, Luca; Illum, Lisbeth

    2014-09-28

    There is an obvious need for efficient and safe nasal absorption enhancers for the development of therapeutically efficacious nasal products for small hydrophilic drugs, peptides, proteins, nucleic acids and polysaccharides, which do not easily cross mucosal membranes, including the nasal. Recent years have seen the development of a range of nasal absorption enhancer systems such as CriticalSorb (based on Solutol HS15) (Critical Pharmaceuticals Ltd), Chisys based on chitosan (Archimedes Pharma Ltd) and Intravail based on alkylsaccharides (Aegis Therapeutics Inc.), that is presently being tested in clinical trials for a range of drugs. So far, none of these absorption enhancers have been used in a marketed nasal product. The present review discusses the evaluation of chitosan and chitosan derivatives as nasal absorption enhancers, for a range of drugs and in a range of formulations such as solutions, gels and nanoparticles and finds that chitosan and its derivatives are able to efficiently improve the nasal bioavailability. The revirtew also questions whether chitosan nanoparticles for systemic drug delivery provide any real improvement over simpler chitosan formulations. Furthermore, the review also evaluates the use of chitosan formulations for the improvement of transport of drugs directly from the nasal cavity to the brain, based on its mucoadhesive characteristics and its ability to open tight junctions in the olfactory and respiratory epithelia. It is found that the use of chitosan nanoparticles greatly increases the transport of drugs from nose to brain over and above the effect of simpler chitosan formulations. PMID:24818769

  5. Chitosan in nasal delivery systems for therapeutic drugs.

    PubMed

    Casettari, Luca; Illum, Lisbeth

    2014-09-28

    There is an obvious need for efficient and safe nasal absorption enhancers for the development of therapeutically efficacious nasal products for small hydrophilic drugs, peptides, proteins, nucleic acids and polysaccharides, which do not easily cross mucosal membranes, including the nasal. Recent years have seen the development of a range of nasal absorption enhancer systems such as CriticalSorb (based on Solutol HS15) (Critical Pharmaceuticals Ltd), Chisys based on chitosan (Archimedes Pharma Ltd) and Intravail based on alkylsaccharides (Aegis Therapeutics Inc.), that is presently being tested in clinical trials for a range of drugs. So far, none of these absorption enhancers have been used in a marketed nasal product. The present review discusses the evaluation of chitosan and chitosan derivatives as nasal absorption enhancers, for a range of drugs and in a range of formulations such as solutions, gels and nanoparticles and finds that chitosan and its derivatives are able to efficiently improve the nasal bioavailability. The revirtew also questions whether chitosan nanoparticles for systemic drug delivery provide any real improvement over simpler chitosan formulations. Furthermore, the review also evaluates the use of chitosan formulations for the improvement of transport of drugs directly from the nasal cavity to the brain, based on its mucoadhesive characteristics and its ability to open tight junctions in the olfactory and respiratory epithelia. It is found that the use of chitosan nanoparticles greatly increases the transport of drugs from nose to brain over and above the effect of simpler chitosan formulations.

  6. Tamarind seed polysaccharide-gellan mucoadhesive beads for controlled release of metformin HCl.

    PubMed

    Nayak, Amit Kumar; Pal, Dilipkumar; Santra, Kousik

    2014-03-15

    The paper describes the development, optimization and evaluation of tamarind seed polysaccharide (TSP)-blended gellan gum (GG) mucoadhesive beads containing metformin HCl through Ca(2+)-ion cross-linked ionic gelation for oral drug delivery. Effects of GG to TSP ratio and cross-linker (CaCl2) concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release after 10h (R10h, %) of TSP-GG mucoadhesive beads containing metformin HCl were optimized by 32 factorial design. The optimized mucoadhesive beads (F-O) showed DEE of 95.73 ± 4.02%, R10h of 61.22 ± 3.44% and mean diameter of 1.70 ± 0.24 mm.These beads were characterized by SEM and FTIR analyses. The in vitro drug release from these beads showed controlled-release (zero-order) pattern over a period of 10h.The optimized TSP-GG mucoadhesive beads also exhibited pH-dependent swelling, good mucoadhesivity with biological mucosal membrane and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration.

  7. Tamarind seed polysaccharide-gellan mucoadhesive beads for controlled release of metformin HCl.

    PubMed

    Nayak, Amit Kumar; Pal, Dilipkumar; Santra, Kousik

    2014-03-15

    The paper describes the development, optimization and evaluation of tamarind seed polysaccharide (TSP)-blended gellan gum (GG) mucoadhesive beads containing metformin HCl through Ca(2+)-ion cross-linked ionic gelation for oral drug delivery. Effects of GG to TSP ratio and cross-linker (CaCl2) concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release after 10h (R10h, %) of TSP-GG mucoadhesive beads containing metformin HCl were optimized by 32 factorial design. The optimized mucoadhesive beads (F-O) showed DEE of 95.73 ± 4.02%, R10h of 61.22 ± 3.44% and mean diameter of 1.70 ± 0.24 mm.These beads were characterized by SEM and FTIR analyses. The in vitro drug release from these beads showed controlled-release (zero-order) pattern over a period of 10h.The optimized TSP-GG mucoadhesive beads also exhibited pH-dependent swelling, good mucoadhesivity with biological mucosal membrane and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration. PMID:24528714

  8. Mucoadhesive system formed by liquid crystals for buccal administration of poly(hexamethylene biguanide) hydrochloride.

    PubMed

    Souza, Carla; Watanabe, Evandro; Borgheti-Cardoso, Livia Neves; De Abreu Fantini, Márcia Carvalho; Lara, Marilisa Guimarães

    2014-12-01

    Antimicrobial approaches are valuable in controlling the development of buccal diseases, but some antibacterial agents have a short duration of activity. Therefore, the development of prolonged delivery systems would be advantageous. Liquid crystalline systems comprising monoolein (GMO)/water have been considered to be a potential vehicle to deliver drugs to the buccal mucosa because of the phase properties that allow for controlled drug release as well as its mucoadhesive properties. Therefore, the aim of this study was to develop a GMO/water system for the slow release of poly(hexamethylene biguanide) hydrochloride (PHMB) on the buccal mucosa and test the properties of this system with regard to swelling, release profile, antimicrobial activity, and strength of mucoadhesion, with the overall goal of treating buccal infections. The tested systems were capable of modulating drug release, which is controlled by diffusion of the drug throughout the system. Furthermore, PHMB appeared to improve the mucoadhesive properties of the system and may synergistically act with the drug to promote antimicrobial activity against S. mutas and C. albicans, indicating that liquid crystals may be suitable for the administration of PHMB on the buccal mucosa. Therefore, this system could be proposed as a novel system for mucoadhesive drug delivery.

  9. Formulation and Evaluation of In-vitro Characterization of Gastic-Mucoadhesive Microparticles/Discs Containing Metformin Hydrochloride

    PubMed Central

    Khonsari, Fatemeh; Zakeri-Milani, Parvin; Jelvehgari, Mitra

    2014-01-01

    The present study involves preparation and evaluation of gastric-mucoadhesive microparticles with Metformin Hydrochloride as model drug for prolongation of gastric residence time. The microparticles were prepared by the emulsification solvent evaporation technique using polymers of Carbomer 934p (CP) and Ethylcellulose (EC). The microparticles were prepared by emulsion solvent evaporation method (O1/O2). Disc formulations were prepared by direct compression technique from microparticles. In the current study, gastric-mucoadhesive microparticles with different polymers ratios (CP:EC) were prepared and were characterized by encapsulation efficiency, particle size, flowability, mucoadhesive property and drug release studies. The best polymers ratio was 1:3 (F2) with Carbomer 934p (as mucoadhesive polymer) and ethylcellulose (as retardant polymer), respectively. The production yield microparticles F2 showed 98.80%, mean particle size 933.25 µm and loading efficiency %98.44. The results were found that microparticle discs prepared had slower release than microparticles (p > o.o5). The microparticles exhibited very good percentage of mucoadhesion and flowability properties. The release of drug was prolonged to 8 h (71.65-82.22%) when incorporated into mucoadhesive microparticles. The poor bioavailability of metformine is attributed to short retention of its dosage form at the absorption sites (in upper gastrointestinal tract). The results of mucoadhesion study showed better retention of metformine microparticles (8 h) in duodenal and jejunum regions of intestine (F1, 1:2 ratio of CP:EC). Therefore, it may be concluded that drug loaded gastric-mucoadhesive microparticles are a suitable delivery system for metformin hydrochloride, and may be used for effective management of NIDDM (Non Insulin Dependent Diabetes Mellitus). PMID:24734057

  10. Nanoparticles for Brain Drug Delivery

    PubMed Central

    Masserini, Massimo

    2013-01-01

    The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood-brain barrier (BBB) regulating its homeostasis. BBB is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted number of macromolecules from the blood to the brain, protecting it from injuries and diseases. However, the BBB also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders. As a consequence, several strategies are currently being sought after to enhance the delivery of drugs across the BBB. Within this review, the recently born strategy of brain drug delivery based on the use of nanoparticles, multifunctional drug delivery systems with size in the order of one-billionth of meters, is described. The review also includes a brief description of the structural and physiological features of the barrier and of the most utilized nanoparticles for medical use. Finally, the potential neurotoxicity of nanoparticles is discussed, and future technological approaches are described. The strong efforts to allow the translation from preclinical to concrete clinical applications are worth the economic investments. PMID:25937958

  11. Formulation and Characterization of Oral Mucoadhesive Chlorhexidine Tablets Using Cordia myxa Mucilage

    PubMed Central

    Moghimipour, Eskandar; Aghel, Nasrin; Adelpour, Akram

    2012-01-01

    Background The dilution and rapid elimination of topically applied drugs due to the flushing action of saliva is a major difficulty in the effort to eradicate infections of oral cavity. Utilization a proper delivery system for incorporation of drugs has a major impact on drug delivery and such a system should be formulated for prolonged drug retention in oral cavity. Objectives The aim of the present study was the use of mucilage of Cordia myxa as a mucoadhesive material in production of chlorhexidine buccal tablets and its substitution for synthetic polymers such as HPMC. Materials and Methods The influence of mucilage concentration on the physicochemical responses (hardness, friability, disintegration time, dissolution, swelling, and muco-adhesiveness strength) was studied and swelling of mucilage and HPMC were compared. The evaluated responses included pharmacopoeial characteristics of tablets, the force needed to separate tablets from mucosa, and the amount of water absorbed by tablets. Results In comparison to HPMC, the rise of mucilage concentration in the formulations increased disintegration time, drug dissolution rate, and reduced MDT. Also, compared to 30% HPMC, muco-adhesiveness strength of buccal tablets containing 20% mucilage was significantly higher. Conclusions It can be concluded that the presence of Cordia myxa powdered mucilage may significantly affect the tablet characteristics, and increasing in muco-adhesiveness may be achieved by using 20% w/w mucilage. PMID:24624170

  12. Bionanocomposites based on layered double hydroxides as drug delivery systems

    NASA Astrophysics Data System (ADS)

    Aranda, Pilar; Alcântara, Ana C. S.; Ribeiro, Ligia N. M.; Darder, Margarita; Ruiz-Hitzky, Eduardo

    2012-10-01

    The present work introduces new biohybrid materials involving layered double hydroxides (LDH) and biopolymers to produce bionanocomposites, able to act as effective drug delivery systems (DDS). Ibuprofen (IBU) and 5-aminosalicylic acid (5-ASA) have been chosen as model drugs, being intercalated in a Mg-Al LDH matrix. On the one side, the LDHIBU intercalation compound prepared by ion-exchange reaction was blended with the biopolymers zein, a highly hydrophobic protein, and alginate, a polysaccharide widely applied for encapsulating drugs. On the other side, the LDH- 5-ASA intercalation compound prepared by co-precipitation was assembled to the polysaccharides chitosan and pectin, which show mucoadhesive properties and resistance to acid pH values, respectively. Characterization of the intercalation compounds and the resulting bionanocomposites was carried out by means of different experimental techniques: X-ray diffraction, infrared spectroscopy, chemical and thermal analysis, as well as optical and scanning electron microscopies. Data on the swelling behavior and drug release under different pH conditions are also reported.

  13. Microfabricated injectable drug delivery system

    DOEpatents

    Krulevitch, Peter A.; Wang, Amy W.

    2002-01-01

    A microfabricated, fully integrated drug delivery system capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.

  14. Crosslinked chitosan-dextran sulfate nanoparticle for improved topical ocular drug delivery

    PubMed Central

    Chaiyasan, Wanachat; Srinivas, Sangly P.

    2015-01-01

    Purpose To examine the benefits of chitosan-dextran sulfate nanoparticles (CDNs) as a topical ocular delivery system with lutein as a model drug. Methods CDNs were developed by polyelectrolyte complexation of positively charged chitosan (CS) and negatively charged dextran sulfate (DS). 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and polyethylene glycol 400 (PEG400) were used as co-crosslinking and stabilizing agents, respectively. The influence of these on the properties of CDNs, including drug release and mucoadhesiveness, was examined. The chemical stability of lutein in CDNs (LCDNs) was also examined. Results Typically, LCDNs showed a spherical shape, possessing a mean size of ~400 nm with a narrow size distribution. The entrapment efficiency of lutein was in the range of 60%–76%. LCDNs possessing a positive surface charge (+46 mV) were found to be mucoadhesive. The release profile of LCDNs followed Higuchi’s square root model, suggesting drug release by diffusion from the polymer matrix. Lutein in LCDNs showed increased chemical stability during storage compared to its solution form. Conclusions These characteristics of CDNs make them suitable for drug delivery to the ocular surface. PMID:26604662

  15. Protease-mediated drug delivery

    NASA Astrophysics Data System (ADS)

    Dickson, Eva F.; Goyan, Rebecca L.; Kennedy, James C.; Mackay, M.; Mendes, M. A. K.; Pottier, Roy H.

    2003-12-01

    Drugs used in disease treatment can cause damage to both malignant and normal tissue. This toxicity limits the maximum therapeutic dose. Drug targeting is of high interest to increase the therapeutic efficacy of the drug without increasing systemic toxicity. Certain tissue abnormalities, disease processes, cancers, and infections are characterized by high levels of activity of specific extracellular and/or intracellular proteases. Abnormally high activity levels of specific proteases are present at sites of physical or chemical trauma, blood clots, malignant tumors, rheumatoid arthritis, inflammatory bowel disease, gingival disease, glomerulonerphritis, and acute pancreatitis. Abnormal protease activity is suspected in development of liver thrombosis, pulmonary emphysema, atherosclerosis, and muscular dystrophy. Inactiviating disease-associated proteases by the administration of appropriate protease inhibitors has had limited success. Instead, one could use such proteases to target drugs to treat the condition. Protease mediated drug delivery offers such a possibility. Solubilizing groups are attached to insoluble drugs via a polypeptide chain which is specifically cleavable by certian proteases. When the solubilized drug enounters the protease, the solubilizing moieties are cleaved, and the drug precipitates at the disease location. Thus, a smaller systemic dosage could result in a therapeutic drug concentration at the treatment site with less systemic toxicity.

  16. Mucoadhesive Hydrogel Films of Econazole Nitrate: Formulation and Optimization Using Factorial Design

    PubMed Central

    Gajra, Balaram; Pandya, Saurabh S.; Singh, Sanjay; Rabari, Haribhai A.

    2014-01-01

    The mucoadhesive hydrogel film was prepared and optimized for the purpose of local drug delivery to oral cavity for the treatment of oral Candidiasis. The mucoadhesive hydrogel film was prepared with the poly(vinyl alcohol) by freeze/thaw crosslinking technique. 32 full factorial design was employed to optimize the formulation. Number of freeze/thaw cycles (4, 6, and 8 cycles) and the concentration of the poly(vinyl alcohol) (10, 15, and 20%) were used as the independent variables whereas time required for 50% drug release, cumulative percent of drug release at 8th hour, and “k” of zero order equation were used as the dependent variables. The films were evaluated for mucoadhesive strength, in vitro residence time, swelling study, in vitro drug release, and effectiveness against Candida albicans. The concentration of poly(vinyl alcohol) and the number of freeze/thaw cycles both decrease the drug release rate. Mucoadhesive hydrogel film with 15% poly(vinyl alcohol) and 7 freeze/thaw cycles was optimized. The optimized batch exhibited the sustained release of drug and the antifungal studies revealed that the drug released from the film could inhibit the growth of Candida albicans for 12 hours. PMID:25006462

  17. Ultrasound mediated nanoparticle drug delivery

    NASA Astrophysics Data System (ADS)

    Mullin, Lee B.

    Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

  18. Perispinal Delivery of CNS Drugs.

    PubMed

    Tobinick, Edward Lewis

    2016-06-01

    Perispinal injection is a novel emerging method of drug delivery to the central nervous system (CNS). Physiological barriers prevent macromolecules from efficiently penetrating into the CNS after systemic administration. Perispinal injection is designed to use the cerebrospinal venous system (CSVS) to enhance delivery of drugs to the CNS. It delivers a substance into the anatomic area posterior to the ligamentum flavum, an anatomic region drained by the external vertebral venous plexus (EVVP), a division of the CSVS. Blood within the EVVP communicates with the deeper venous plexuses of the CSVS. The anatomical basis for this method originates in the detailed studies of the CSVS published in 1819 by the French anatomist Gilbert Breschet. By the turn of the century, Breschet's findings were nearly forgotten, until rediscovered by American anatomist Oscar Batson in 1940. Batson confirmed the unique, linear, bidirectional and retrograde flow of blood between the spinal and cerebral divisions of the CSVS, made possible by the absence of venous valves. Recently, additional supporting evidence was discovered in the publications of American neurologist Corning. Analysis suggests that Corning's famous first use of cocaine for spinal anesthesia in 1885 was in fact based on Breschet's anatomical findings, and accomplished by perispinal injection. The therapeutic potential of perispinal injection for CNS disorders is highlighted by the rapid neurological improvement in patients with otherwise intractable neuroinflammatory disorders that may ensue following perispinal etanercept administration. Perispinal delivery merits intense investigation as a new method of enhanced delivery of macromolecules to the CNS and related structures.

  19. Opportunities in respiratory drug delivery.

    PubMed

    Pritchard, John N; Giles, Rachael D

    2014-12-01

    A wide range of asthma and chronic obstructive pulmonary disease products are soon to be released onto the inhaled therapies market and differentiation between these devices will help them to gain market share over their competitors. Current legislation is directing healthcare towards being more efficient and cost-effective in order to continually provide quality care despite the challenges of aging populations and fewer resources. Devices and drugs that can be differentiated by producing improved patient outcomes would, therefore, be likely to win market share. In this perspective article, the current and potential opportunities for the successful delivery and differentiation of new inhaled drug products are discussed.

  20. Polymeric Nanoparticle Drug Delivery Technologies for Oral Delivery Applications

    PubMed Central

    Pridgen, Eric M.; Alexis, Frank; Farokhzad, Omid C.

    2016-01-01

    Introduction Many therapeutics are limited to parenteral administration. Oral administration is a desirable alternative because of the convenience and increased compliance by patients, especially for chronic diseases that require frequent administration. Polymeric nanoparticles are one technology being developed to enable clinically feasible oral delivery. Areas covered This review discusses the challenges associated with oral delivery. Strategies used to overcome gastrointestinal barriers using polymeric nanoparticles will be considered, including mucoadhesive biomaterials and targeting of nanoparticles to transcytosis pathways associated with M cells and enterocytes. Applications of oral delivery technologies will also be discussed, such as oral chemotherapies, oral insulin, treatment of inflammatory bowel disease, and mucosal vaccinations. Expert opinion There have been many approaches used to overcome the transport barriers presented by the gastrointestinal tract, but most have been limited by low bioavailability. Recent strategies targeting nanoparticles to transcytosis pathways present in the intestines have demonstrated that it is feasible to efficiently transport both therapeutics and nanoparticles across the intestines and into systemic circulation after oral administration. Further understanding of the physiology and pathophysiology of the intestines could lead to additional improvements in oral polymeric nanoparticle technologies and enable the translation of these technologies to clinical practice. PMID:25813361

  1. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods

    PubMed Central

    Chinna Reddy, P; Chaitanya, K.S.C.; Madhusudan Rao, Y.

    2011-01-01

    Owing to the ease of the administration, the oral cavity is an attractive site for the delivery of drugs. Through this route it is possible to realize mucosal (local effect) and transmucosal (systemic effect) drug administration. In the first case, the aim is to achieve a site-specific release of the drug on the mucosa, whereas the second case involves drug absorption through the mucosal barrier to reach the systemic circulation. The main obstacles that drugs meet when administered via the buccal route derive from the limited absorption area and the barrier properties of the mucosa. The effective physiological removal mechanisms of the oral cavity that take the formulation away from the absorption site are the other obstacles that have to be considered. The strategies studied to overcome such obstacles include the employment of new materials that, possibly, combine mucoadhesive, enzyme inhibitory and penetration enhancer properties and the design of innovative drug delivery systems which, besides improving patient compliance, favor a more intimate contact of the drug with the absorption mucosa. This presents a brief description of advantages and limitations of buccal drug delivery and the anatomical structure of oral mucosa, mechanisms of drug permeation followed by current formulation design in line with developments in buccal delivery systems and methodology in evaluating buccal formulations. PMID:23008684

  2. Superhydrophobic materials for drug delivery

    NASA Astrophysics Data System (ADS)

    Yohe, Stefan Thomas

    Superhydrophobicity is a property of material surfaces reflecting the ability to maintain air at the solid-liquid interface when in contact with water. These surfaces have characteristically high apparent contact angles, by definition exceeding 150°, as a result of the composite material-air surface formed under an applied water droplet. Superhydrophobic surfaces were first discovered on naturally occurring substrates, and have subsequently been fabricated in the last several decades to harness these favorable surface properties for a number of emerging applications, including their use in biomedical settings. This work describes fabrication and characterization of superhydrophobic 3D materials, as well as their use as drug delivery devices. Superhydrophobic 3D materials are distinct from 2D superhydrophobic surfaces in that air is maintained not just at the surface of the material, but also within the bulk. When the superhydrophobic 3D materials are submerged in water, water infiltrates slowly and continuously as a new water-air-material interface is formed with controlled displacement of air. Electrospinning and electrospraying are used to fabricate superhydrophobic 3D materials utilizing blends of the biocompatible polymers poly(epsilon-caprolactone) and poly(caprolactone-co-glycerol monostearate) (PGC-C18). PGC-C18 is significantly more hydrophobic than PCL (contact angle of 116° versus 83° for flat materials), and further additions of PGC-C18 into electrospun meshes and electrosprayed coatings affords increased stability of the entrapped air layer. For example, PCL meshes alone (500 mum thick) take 10 days to fully wet, and with 10% or 30% PGC-C18 addition wetting rates are dramatically slowed to 60% wetted by 77 days and 4% by 75 days, respectively. Stability of the superhydrophobic materials can be further probed with a variety of physio-chemical techniques, including pressure, surfactant containing solutions, and solvents of varying surface tension

  3. Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.

    PubMed

    Lemieux, Marc; Gosselin, Patrick; Mateescu, Mircea Alexandru

    2015-12-30

    Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms.

  4. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye. PMID:26501994

  5. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye.

  6. Phospholipid-chitosan hybrid nanoliposomes promoting cell entry for drug delivery against cervical cancer.

    PubMed

    Saesoo, Somsak; Bunthot, Suphawadee; Sajomsang, Warayuth; Gonil, Pattarapond; Phunpee, Sarunya; Songkhum, Patsaya; Laohhasurayotin, Kritapas; Wutikhun, Tuksadon; Yata, Teerapong; Ruktanonchai, Uracha Rungsardthong; Saengkrit, Nattika

    2016-10-15

    This study emphasizes the development of a novel surface modified liposome as an anticancer drug nanocarrier. Quaternized N,O-oleoyl chitosan (QCS) was synthesized and incorporated into liposome vesicles, generating QCS-liposomes (Lip-QCS). The Lip-QCS liposomes were spherical in shape (average size diameter 171.5±0.8nm), with a narrow size distribution (PDI 0.1±0.0) and zeta potential of 11.7±0.7mV. In vitro mucoadhesive tests indicated that Lip-QCS possesses a mucoadhesive property. Moreover, the presence of QCS was able to induce the cationic charge on the surface of liposome. Cellular internalization of Lip-QCS was monitored over time, with the results revealing that the cell entry level of Lip-QCS was elevated at 24h. Following this, Lip-QCS were then employed to load cisplatin, a common platinum-containing anti-cancer drug, with a loading efficiency of 27.45±0.78% being obtained. The therapeutic potency of the loaded Lip-QCS was investigated using a 3D spheroid cervical cancer model (SiHa) which highlighted their cytotoxicity and apoptosis effect, and suitability as a controllable system for sustained drug release. This approach has the potential to assist in development of an effective drug delivery system against cervical cancer. PMID:27442151

  7. Ocular drug delivery systems: An overview

    PubMed Central

    Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

    2014-01-01

    The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

  8. Cubosomes: remarkable drug delivery potential.

    PubMed

    Karami, Zahra; Hamidi, Mehrdad

    2016-05-01

    Cubosomes are nanostructured liquid crystalline particles, made of certain amphiphilic lipids in definite proportions, known as biocompatible carriers in drug delivery. Cubosomes comprise curved bicontinuous lipid bilayers that are organized in three dimensions as honeycombed structures and divided into two internal aqueous channels that can be exploited by various bioactive ingredients, such as chemical drugs, peptides and proteins. Owing to unique properties such as thermodynamic stability, bioadhesion, the ability of encapsulating hydrophilic, hydrophobic and amphiphilic substances, and the potential for controlled release through functionalization, cubosomes are regarded as promising vehicles for different routes of administration. Based on the most recent reports, this review introduces cubosomes focusing on their structure, preparation methods, mechanism of release and potential routes of administration. PMID:26780385

  9. Microemulsion-based drug delivery system for transnasal delivery of Carbamazepine: preliminary brain-targeting study.

    PubMed

    Patel, Rashmin Bharatbhai; Patel, Mrunali Rashmin; Bhatt, Kashyap K; Patel, Bharat G; Gaikwad, Rajiv V

    2016-01-01

    This study reports the development and evaluation of Carbamazepine (CMP)-loaded microemulsions (CMPME) for intranasal delivery in the treatment of epilepsy. The CMPME was prepared by the spontaneous emulsification method and characterized for physicochemical parameters. All formulations were radiolabeled with (99m)Tc (technetium) and biodistribution of CMP in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rats was also performed to determine the uptake of the CMP into the brain. CMPME were found crystal clear and stable with average globule size of 34.11 ± 1.41 nm. (99m)Tc-labeled CMP solution (CMPS)/CMPME/CMP mucoadhesive microemulsion (CMPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMPMME compared to intravenous CMPME was found to be 2- to 3-fold higher signifying larger extent of distribution of the CMP in brain. Drug targeting efficiency and direct drug transport were found to be highest for CMPMME post-intranasal administration compared to intravenous CMP. Rat brain scintigraphy also demonstrated higher intranasal uptake of the CMP into the brain. This investigation demonstrates a prompt and larger extent of transport of CMP into the brain through intranasal CMPMME, which may prove beneficial for treatment of epilepsy.

  10. Heart-targeted nanoscale drug delivery systems.

    PubMed

    Liu, Meifang; Li, Minghui; Wang, Guangtian; Liu, Xiaoying; Liu, Daming; Peng, Haisheng; Wang, Qun

    2014-09-01

    The efficacious delivery of drugs to the heart is an important treatment strategy for various heart diseases. Nanocarriers have shown increasing promise in targeted drug delivery systems. The success of nanocarriers for delivering drugs to therapeutic sites in the heart mainly depends on specific target sites, appropriate drug delivery carriers and effective targeting ligands. Successful targeted drug delivery suggests the specific deposition of a drug in the heart with minimal effects on other organs after administration. This review discusses the pathological manifestations, pathogenesis, therapeutic limitations and new therapeutic advances in various heart diseases. In particular, we summarize the recent advances in heart-targeted nanoscale drug delivery systems, including dendrimers, liposomes, polymer-drug conjugates, microparticles, nanostents, nanoparticles, micelles and microbubbles. Current clinical trials, the commercial market and future perspective are further discussed in the conclusions.

  11. Ungual and transungual drug delivery.

    PubMed

    Shivakumar, H N; Juluri, Abhishek; Desai, B G; Murthy, S Narasimha

    2012-08-01

    Topical therapy is desirable in treatment of nail diseases like onychomycosis (fungal infection of nail) and psoriasis. The topical treatment avoids the adverse effects associated with systemic therapy, thereby enhancing the patient compliance and reducing the treatment cost. However the effectiveness of the topical therapies has been limited due to the poor permeability of the nail plate to topically applied therapeutic agents. Research over the past one decade has been focused on improving the transungual permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods. The present review is an attempt to discuss the different physical and chemical methods employed to increase the permeability of the nail plate. Minimally invasive electrically mediated techniques such as iontophoresis have gained success in facilitating the transungual delivery of actives. In addition drug transport across the nail plate has been improved by filing the dorsal surface of the nail plate prior to application of topical formulation. But attempts to improve the trans-nail permeation using transdermal chemical enhancers have failed so far. Attempts are on to search suitable physical enhancement techniques and chemical transungual enhancers in view to maximize the drug delivery across the nail plate. PMID:22149347

  12. Ungual and transungual drug delivery.

    PubMed

    Shivakumar, H N; Juluri, Abhishek; Desai, B G; Murthy, S Narasimha

    2012-08-01

    Topical therapy is desirable in treatment of nail diseases like onychomycosis (fungal infection of nail) and psoriasis. The topical treatment avoids the adverse effects associated with systemic therapy, thereby enhancing the patient compliance and reducing the treatment cost. However the effectiveness of the topical therapies has been limited due to the poor permeability of the nail plate to topically applied therapeutic agents. Research over the past one decade has been focused on improving the transungual permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods. The present review is an attempt to discuss the different physical and chemical methods employed to increase the permeability of the nail plate. Minimally invasive electrically mediated techniques such as iontophoresis have gained success in facilitating the transungual delivery of actives. In addition drug transport across the nail plate has been improved by filing the dorsal surface of the nail plate prior to application of topical formulation. But attempts to improve the trans-nail permeation using transdermal chemical enhancers have failed so far. Attempts are on to search suitable physical enhancement techniques and chemical transungual enhancers in view to maximize the drug delivery across the nail plate.

  13. Ispaghula mucilage-gellan mucoadhesive beads of metformin HCl: development by response surface methodology.

    PubMed

    Nayak, Amit Kumar; Pal, Dilipkumar; Santra, Kousik

    2014-07-17

    Response surface methodology based on 3(2) factorial design was used to develop ispaghula (Plantago ovata F.) husk mucilage (IHM)-gellan gum (GG) mucoadhesive beads containing metformin HCl through Ca(2+)-ion cross-linked ionotropic-gelation technique for the use in oral drug delivery. GG to IHM ratio and cross-linker (CaCl2) concentration were investigated as independent variables. Drug encapsulation efficiency (DEE, %) and cumulative drug release after 10h (R10h, %) were analyzed as dependent variables. The optimized mucoadhesive beads (F-O) showed DEE of 94.24 ± 4.18%, R10h of 59.13 ± 2.27%. These beads were also characterized by SEM and FTIR analyses. The in vitro drug release from these beads showed controlled-release (zero-order) pattern with super case-II transport mechanism over 10h. The optimized beads showed pH-dependent swelling and good mucoadhesivity with the goat intestinal mucosa. The optimized IHM-GG mucoadhesive beads containing metformin HCl exhibited significant antidiabetic effect in alloxan-induced diabetic rats over 10h. PMID:24702916

  14. Polymeric conjugates for drug delivery

    PubMed Central

    Larson, Nate; Ghandehari, Hamidreza

    2012-01-01

    The field of polymer therapeutics has evolved over the past decade and has resulted in the development of polymer-drug conjugates with a wide variety of architectures and chemical properties. Whereas traditional non-degradable polymeric carriers such as poly(ethylene glycol) (PEG) and N-(2-hydroxypropyl methacrylamide) (HPMA) copolymers have been translated to use in the clinic, functionalized polymer-drug conjugates are increasingly being utilized to obtain biodegradable, stimuli-sensitive, and targeted systems in an attempt to further enhance localized drug delivery and ease of elimination. In addition, the study of conjugates bearing both therapeutic and diagnostic agents has resulted in multifunctional carriers with the potential to both “see and treat” patients. In this paper, the rational design of polymer-drug conjugates will be discussed followed by a review of different classes of conjugates currently under investigation. The design and chemistry used for the synthesis of various conjugates will be presented with additional comments on their potential applications and current developmental status. PMID:22707853

  15. Physically facilitating drug-delivery systems

    PubMed Central

    Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

    2012-01-01

    Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

  16. Mucoadhesive Nanostructured Polyelectrolyte Complexes as Potential Carrier to Improve Zidovudine Permeability.

    PubMed

    Pedreiro, Liliane Neves; Stringhetti, Beatriz; Cury, Ferreira; Gremião, Maria Palmira Daflon

    2016-02-01

    Mucoadhesive drug delivery systems have been widely investigated as a strategic to allow the raising of intestinal residence time of drugs and the intimate contact with the intestinal mucosa, both factors that increase the local concentration gradient. Zidovudine (AZT) mucoadhesive nanostructured polyelectrolyte complexes were obtained by chitosan (CS)-hypromellose phthalate (HP) interactions in order to favor the permeability through biological membranes and the AZT absorption. Particle size and morphology analyses showed the obtaining of nanoparticulate delivery systems, with AZT loaded about of 65%. The characterization by DSC, X-ray diffraction and FTIR showed a new crystalline structure formed in which the drug remained molecularly dispersed, without changing this structure. The reduced release rates in the simulated gastric medium and the control of release rates in simulated intestinal medium of AZT were demonstrated by in vitro release studies. The nanoparticles liquid uptake ability associated to the mucoadhesiveness by electronic interaction between the particles and mucus revealed that the drug delivery system developed in this work is a promising approach to improve the permeation of this drug throughout the intestinal mucosa. PMID:27433574

  17. Novel central nervous system drug delivery systems.

    PubMed

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.

  18. Alginate Particles as Platform for Drug Delivery by the Oral Route: State-of-the-Art

    PubMed Central

    2014-01-01

    Pharmaceutical research and development aims to design products with ensured safety, quality, and efficacy to treat disease. To make the process more rational, coherent, efficient, and cost-effective, the field of Pharmaceutical Materials Science has emerged as the systematic study of the physicochemical properties and behavior of materials of pharmaceutical interest in relation to product performance. The oral route is the most patient preferred for drug administration. The presence of a mucus layer that covers the entire gastrointestinal tract has been exploited to expand the use of the oral route by developing a mucoadhesive drug delivery system that showed a prolonged residence time. Alginic acid and sodium and potassium alginates have emerged as one of the most extensively explored mucoadhesive biomaterials owing to very good cytocompatibility and biocompatibility, biodegradation, sol-gel transition properties, and chemical versatility that make possible further modifications to tailor their properties. The present review overviews the most relevant applications of alginate microparticles and nanoparticles for drug administration by the oral route and discusses the perspectives of this biomaterial in the future. PMID:25101184

  19. Polymers for Colon Targeted Drug Delivery

    PubMed Central

    Rajpurohit, H.; Sharma, P.; Sharma, S.; Bhandari, A.

    2010-01-01

    The colon targeted drug delivery has a number of important implications in the field of pharmacotherapy. Oral colon targeted drug delivery systems have recently gained importance for delivering a variety of therapeutic agents for both local and systemic administration. Targeting of drugs to the colon via oral administration protect the drug from degradation or release in the stomach and small intestine. It also ensures abrupt or controlled release of the drug in the proximal colon. Various drug delivery systems have been designed that deliver the drug quantitatively to the colon and then trigger the release of drug. This review will cover different types of polymers which can be used in formulation of colon targeted drug delivery systems. PMID:21969739

  20. Preparation and evaluation of glyceryl monooleate-coated hollow-bioadhesive microspheres for gastroretentive drug delivery.

    PubMed

    Liu, Yuanfen; Zhang, Jianjun; Gao, Yuan; Zhu, Jiabi

    2011-07-15

    The purpose of this study was to produce hollow and bioadhesive microspheres to lengthen drug retention time in the stomach. In these microspheres, ethylcellulose was used as the matrix, Eudragit EPO was employed to modulate the release rate, and glyceryl monooleate (GMO) was the bioadhesive polymer in situ. The morphological characteristics of the microspheres were defined using scanning electron microscopy. The in vitro release test showed that the release rate of drug from the microspheres was pH-dependent, and was not influenced by the GMO coating film. The prepared microspheres demonstrated strong mucoadhesive properties with good buoyancy both in vitro and in vivo. Pharmacokinetic analysis indicated that the elimination half-life time of the hollow-bioadhesive microspheres was prolonged, and that the elimination rate was decreased. In conclusion, the hollow-bioadhesive synergic drug delivery system may be advantageous in the treatment of stomach diseases.

  1. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery

    PubMed Central

    Ahmed, Tarek A; Aljaeid, Bader M

    2016-01-01

    Naturally occurring polymers, particularly of the polysaccharide type, have been used pharmaceutically for the delivery of a wide variety of therapeutic agents. Chitosan, the second abundant naturally occurring polysaccharide next to cellulose, is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of micro-as well as nanoparticles. The prepared particles have been exploited as a potential carrier for different therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and nonparenteral administration. Therapeutic agent-loaded chitosan micro- or nanoparticles were found to be more stable, permeable, and bioactive. In this review, we are highlighting the different methods of preparation and characterization of chitosan micro- and nanoparticles, while reviewing the pharmaceutical applications of these particles in drug delivery. Moreover, the roles of chitosan derivatives and chitosan metal nanoparticles in drug delivery have been illustrated. PMID:26869768

  2. Drug delivery systems: An updated review

    PubMed Central

    Tiwari, Gaurav; Tiwari, Ruchi; Sriwastawa, Birendra; Bhati, L; Pandey, S; Pandey, P; Bannerjee, Saurabh K

    2012-01-01

    Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time. PMID:23071954

  3. Collagen macromolecular drug delivery systems

    SciTech Connect

    Gilbert, D.L.

    1988-01-01

    The objective of this study was to examine collagen for use as a macromolecular drug delivery system by determining the mechanism of release through a matrix. Collagen membranes varying in porosity, crosslinking density, structure and crosslinker were fabricated. Collagen characterized by infrared spectroscopy and solution viscosity was determined to be pure and native. The collagen membranes were determined to possess native vs. non-native quaternary structure and porous vs. dense aggregate membranes by electron microscopy. Collagen monolithic devices containing a model macromolecule (inulin) were fabricated. In vitro release rates were found to be linear with respect to t{sup {1/2}} and were affected by crosslinking density, crosslinker and structure. The biodegradation of the collagen matrix was also examined. In vivo biocompatibility, degradation and {sup 14}C-inulin release rates were evaluated subcutaneously in rats.

  4. Nanodisks: hydrophobic drug delivery vehicles.

    PubMed

    Ryan, Robert O

    2008-03-01

    Members of the class of exchangeable apolipoproteins possess the unique capacity to transform phospholipid vesicle substrates into nanoscale disk-shaped bilayers. This reaction can proceed in the presence of exogenous hydrophobic biomolecules, resulting in the formation of novel transport vehicles termed nanodisks (NDs). The objective of this study is to describe the structural organization of NDs and evaluate the utility of these complexes as hydrophobic biomolecule transport vehicles. The topics presented focus on two distinct water insoluble drugs, amphotericin B (AMB) and all trans retinoic acid (ATRA). In vitro and in vivo studies reveal that AMB-ND display potent anti-fungal and anti-protozoal activity, while ATRA-ND show promise in the treatment of cancer. The versatility conferred by the presence of a polypeptide component provides opportunities for targeted delivery of ND to cells.

  5. Implantable Devices for Sustained, Intravesical Drug Delivery

    PubMed Central

    2016-01-01

    In clinical settings, intravesical instillation of a drug bolus is often performed for the treatment of bladder diseases. However, it requires repeated instillations to extend drug efficacy, which may result in poor patient compliance. To alleviate this challenge, implantable devices have been developed for the purpose of sustained, intravesical drug delivery. In this review, we briefly summarize the current trend in the development of intravesical drug-delivery devices. We also introduce the most recently developed devices with strong potential for intravesical drug-delivery applications. PMID:27377941

  6. Immune response induced by conjunctival immunization with polymeric antigen BLSOmp31 using a thermoresponsive and mucoadhesive in situ gel as vaccine delivery system for prevention of ovine brucellosis.

    PubMed

    Díaz, Alejandra Graciela; Quinteros, Daniela Alejandra; Gutiérrez, Silvina Elena; Rivero, Mariana Alejandra; Palma, Santiago Daniel; Allemandi, Daniel Alberto; Pardo, Romina Paola; Zylberman, Vanesa; Goldbaum, Fernando Alberto; Estein, Silvia Marcela

    2016-10-01

    Control of ovine brucellosis with subcellular vaccines can solve some drawbacks associated with the use of Brucella melitensis Rev.1. Previous studies have demonstrated that the polymeric antigen BLSOmp31 administered by parenteral route was immunogenic and conferred significant protection against B. ovis in rams. Immunization with BLSOmp31 by conjunctival route could be efficient for the induction of mucosal and systemic immune responses. In this work, we evaluated the conjunctival immunization using a thermoresponsive and mucoadhesive in situ gel composed of Poloxamer 407 (P407) and chitosan (Ch) as vaccine delivery system for BLSOmp31 in rams. Serum samples, saliva, lacrimal, preputial and nasal secretions were analyzed to measure specific IgG and IgA antibodies. Cellular immune response was evaluated in vivo and in vitro. Immunization with BLSOmp31-P407-Ch induced high IgG antibody levels in serum and preputial secretions which remained at similar levels until the end of the experiment. Levels of IgG in saliva, lacrimal and nasal secretions were also higher compared to unvaccinated control group but decreased more rapidly. IgA antibodies were only detected in nasal and preputial secretions. BLSOmp31-P407-Ch stimulated a significant cellular immune response in vivo and in vitro. The induction of systemic and local immune responses indicates a promising potential of P407-Ch for the delivery of BLSOmp31 by conjunctival route.

  7. Immune response induced by conjunctival immunization with polymeric antigen BLSOmp31 using a thermoresponsive and mucoadhesive in situ gel as vaccine delivery system for prevention of ovine brucellosis.

    PubMed

    Díaz, Alejandra Graciela; Quinteros, Daniela Alejandra; Gutiérrez, Silvina Elena; Rivero, Mariana Alejandra; Palma, Santiago Daniel; Allemandi, Daniel Alberto; Pardo, Romina Paola; Zylberman, Vanesa; Goldbaum, Fernando Alberto; Estein, Silvia Marcela

    2016-10-01

    Control of ovine brucellosis with subcellular vaccines can solve some drawbacks associated with the use of Brucella melitensis Rev.1. Previous studies have demonstrated that the polymeric antigen BLSOmp31 administered by parenteral route was immunogenic and conferred significant protection against B. ovis in rams. Immunization with BLSOmp31 by conjunctival route could be efficient for the induction of mucosal and systemic immune responses. In this work, we evaluated the conjunctival immunization using a thermoresponsive and mucoadhesive in situ gel composed of Poloxamer 407 (P407) and chitosan (Ch) as vaccine delivery system for BLSOmp31 in rams. Serum samples, saliva, lacrimal, preputial and nasal secretions were analyzed to measure specific IgG and IgA antibodies. Cellular immune response was evaluated in vivo and in vitro. Immunization with BLSOmp31-P407-Ch induced high IgG antibody levels in serum and preputial secretions which remained at similar levels until the end of the experiment. Levels of IgG in saliva, lacrimal and nasal secretions were also higher compared to unvaccinated control group but decreased more rapidly. IgA antibodies were only detected in nasal and preputial secretions. BLSOmp31-P407-Ch stimulated a significant cellular immune response in vivo and in vitro. The induction of systemic and local immune responses indicates a promising potential of P407-Ch for the delivery of BLSOmp31 by conjunctival route. PMID:27496742

  8. Combinatorial Approach of Antigen Delivery Using M Cell-Homing Peptide and Mucoadhesive Vehicle to Enhance the Efficacy of Oral Vaccine.

    PubMed

    Singh, Bijay; Maharjan, Sushila; Jiang, Tao; Kang, Sang-Kee; Choi, Yun-Jaie; Cho, Chong-Su

    2015-11-01

    Orally ingested pathogens or antigens are taken up by microfold cells (M cells) in Peyer's patches of intestine to initiate protective immunity against infections. However, the uptake of orally delivered protein antigens through M cells is very low due to lack of specificity of proteins toward M cells and degradation of proteins in the harsh environment of gastrointestinal (GI) tract. To overcome these limitations, here we developed a pH-sensitive and mucoadhesive vehicle of thiolated eudragit (TE) microparticles to transport an M cell-targeting peptide-fused model protein antigen. Particularly, TE prolonged the particles transit time through the GI tract and predominantly released the proteins in ileum where M cells are abundant. Thus, oral delivery of TE microparticulate antigens exhibited high transcytosis of antigens through M cells resulting in strong protective sIgA as well as systemic IgG antibody responses. Importantly, the delivery system not only induced CD4(+) T cell immune responses but also generated strong CD8(+) T cell responses with enhanced production of IFN-γ in spleen. Given that M cells are considered a promising target for oral vaccination, this study could provide a new combinatorial method for the development of M-cell-targeted mucosal vaccines. PMID:26394158

  9. Applications of Important Polysaccharides in Drug Delivery.

    PubMed

    Huang, Gangliang; Mei, Xinya; Xiao, Feng; Chen, Xin; Tang, Qilin; Peng, Daquan

    2015-01-01

    Polysaccharide is a kind of biological material, which has good biocompatibility, non-toxicity, and non-immunogenicity. So, the polysaccharide has widely been applied in drug delivery system. The applications of chitosan, hyaluronic acid and dextran in drug delivery have been summarized herein. PMID:25578889

  10. Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain.

    PubMed

    Hussain, Amjad; Syed, Muhammad Ali; Abbas, Nasir; Hanif, Sana; Arshad, Muhammad Sohail; Bukhari, Nadeem Irfan; Hussain, Khalid; Akhlaq, Muhammad; Ahmad, Zeeshan

    2016-06-01

    A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach. PMID:27279067

  11. Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain.

    PubMed

    Hussain, Amjad; Syed, Muhammad Ali; Abbas, Nasir; Hanif, Sana; Arshad, Muhammad Sohail; Bukhari, Nadeem Irfan; Hussain, Khalid; Akhlaq, Muhammad; Ahmad, Zeeshan

    2016-06-01

    A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.

  12. Ocular Drug Delivery - New Strategies for Targeting Anterior and Posterior Segments of the Eye.

    PubMed

    Fangueiro, Joana F; Veiga, Francisco; Silva, Amelia M; Souto, Eliana B

    2016-01-01

    The ocular delivery of drugs encounters several limitations because of the dynamic and static barriers of the human's eye anatomy and physiology. The poor bioavailability of drugs are mainly related to the topical administration, i.e. eye drops which is the most common drug dosage form for the treatment of eye pathologies. Precorneal factors and drug limitations related to its solubility and susceptibility for physicochemical degradation could be the main reasons for the poor permeation and uptake in the ocular mucosa. Pathologies affecting the anterior and posterior segment of the eye are thereafter difficult to be treated and, given the chronic and degenerative nature of some of these injuries, it is crucial to improve drugs therapeutic effect. Nanotechnology-based delivery systems could be a suitable approach to overcome these limitations. Some of the most important colloidal systems are highlighted in this review, such as the use of mucoadhesive polymers, prodrugs, nanogels, liposomes, microemulsions, lipid and polymeric nanoparticles, cyclodextrins, dendrimers and nanocrystals, along with their clinical and therapeutic relevance for the administration of drugs for ocular delivery. PMID:26675225

  13. Nanoparticles for intracellular-targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Paulo, Cristiana S. O.; Pires das Neves, Ricardo; Ferreira, Lino S.

    2011-12-01

    Nanoparticles (NPs) are very promising for the intracellular delivery of anticancer and immunomodulatory drugs, stem cell differentiation biomolecules and cell activity modulators. Although initial studies in the area of intracellular drug delivery have been performed in the delivery of DNA, there is an increasing interest in the use of other molecules to modulate cell activity. Herein, we review the latest advances in the intracellular-targeted delivery of short interference RNA, proteins and small molecules using NPs. In most cases, the drugs act at different cellular organelles and therefore the drug-containing NPs should be directed to precise locations within the cell. This will lead to the desired magnitude and duration of the drug effects. The spatial control in the intracellular delivery might open new avenues to modulate cell activity while avoiding side-effects.

  14. Recent advances in ocular drug delivery.

    PubMed

    Achouri, Djamila; Alhanout, Kamel; Piccerelle, Philippe; Andrieu, Véronique

    2013-11-01

    Amongst the various routes of drug delivery, the field of ocular drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. Recent research has focused on the characteristic advantages and limitations of the various drug delivery systems, and further research will be required before the ideal system can be developed. Administration of drugs to the ocular region with conventional delivery systems leads to short contact time of the formulations on the epithelium and fast elimination of drugs. This transient residence time involves poor bioavailability of drugs which can be explained by the tear production, non-productive absorption and impermeability of corneal epithelium. Anatomy of the eye is shortly presented and is connected with ophthalmic delivery and bioavailability of drugs. In the present update on ocular dosage forms, chemical delivery systems such as prodrugs, the use of cyclodextrins to increase solubility of various drugs, the concept of penetration enhancers and other ocular drug delivery systems such as polymeric gels, bioadhesive hydrogels, in-situ forming gels with temperature-, pH-, or osmotically induced gelation, combination of polymers and colloidal systems such as liposomes, niosomes, cubosomes, microemulsions, nanoemulsions and nanoparticles are discussed. Novel ophthalmic delivery systems propose the use of many excipients to increase the viscosity or the bioadhesion of the product. New formulations like gels or colloidal systems have been tested with numerous active substances by in vitro and in vivo studies. Sustained drug release and increase in drug bioavailability have been obtained, offering the promise of innovation in drug delivery systems for ocular administration. Combining different properties of pharmaceutical formulations appears to offer a genuine synergy in bioavailability and sustained release. Promising results are obtained with colloidal systems which present very comfortable

  15. Formulation, optimization and evaluation of spray-dried mucoadhesive microspheres as intranasal carriers for Valsartan.

    PubMed

    Pardeshi, Chandrakant V; Rajput, Pravin V; Belgamwar, Veena S; Tekade, Avinash R

    2012-01-01

    This investigation deals with the intranasal delivery of Valsartan, encapsulated in HPMC-based spray-dried mucoadhesive microspheres, with an aim to provide rapid absorption and quick onset of action for treating hypertension. A 2³-factorial design has been employed for the assessment of influence of three independent variables, namely inlet temperature, feed-flow rate and drug-polymer ratio on production yield, particle size and in vitro drug diffusion of the prepared microspheres. Microspheres were evaluated for particle size, entrapment efficiency, swelling property, in vitro mucoadhesion, in vitro drug diffusion, ex vivo drug permeation, histopathological examination and stability studies. The results of differential scanning calorimetry, X-ray diffraction and scanning electron microscopy revealed molecular dispersion of Valsartan into microspheres with spherical shape and smooth surface. Optimized formulation indicated good mucoadhesion with no severe sign of damage on nasal mucosa. Results of the non-invasive animal studies in dexamethasone-induced hypertensive rat model suggested the suitability of investigated drug delivery system for intranasal administration.

  16. Colloidal microgels in drug delivery applications

    PubMed Central

    Vinogradov, Serguei V.

    2005-01-01

    Colloidal microgels have recently received attention as environmentally responsive systems and now are increasingly used in applications as carriers for therapeutic drugs and diagnostic agents. Synthetic microgels consist of a crosslinked polymer network that provides a depot for loaded drugs, protection against environmental hazards and template for post-synthetic modification or vectorization of the drug carriers. The aim of this manuscript is to review recent attempts to develop new microgel formulations for oral drug delivery, to design metal-containing microgels for diagnostic and therapeutic applications, and to advance approaches including the systemic administration of microgels. Novel nanogel drug delivery systems developed in the authors’ laboratory are discussed in details including aspects of their synthesis, vectorization and recent applications for encapsulation of low molecular weight drugs or formulation of biological macromolecules. The findings reviewed here are encouraging for further development of the nanogels as intelligent drug carriers with such features as targeted delivery and triggered drug release. PMID:17168773

  17. Magnetic nanoparticles for gene and drug delivery

    PubMed Central

    McBain, Stuart C; Yiu, Humphrey HP; Dobson, Jon

    2008-01-01

    Investigations of magnetic micro- and nanoparticles for targeted drug delivery began over 30 years ago. Since that time, major progress has been made in particle design and synthesis techniques, however, very few clinical trials have taken place. Here we review advances in magnetic nanoparticle design, in vitro and animal experiments with magnetic nanoparticle-based drug and gene delivery, and clinical trials of drug targeting. PMID:18686777

  18. Nanomedicine and drug delivery: a mini review

    NASA Astrophysics Data System (ADS)

    Mirza, Agha Zeeshan; Siddiqui, Farhan Ahmed

    2014-02-01

    The field of nanotechnology now has pivotal roles in electronics, biology and medicine. Its application can be appraised, as it involves the materials to be designed at atomic and molecular level. Due to the advantage of their size, nanospheres have been shown to be robust drug delivery systems and may be useful for encapsulating drugs and enabling more precise targeting with a controlled release. In this review specifically, we highlight the recent advances of this technology for medicine and drug delivery systems.

  19. Biologically responsive polymeric nanoparticles for drug delivery.

    PubMed

    Colson, Yolonda L; Grinstaff, Mark W

    2012-07-24

    Responsive nanoparticles that release their drug cargo in accordance with a change in pH or oxidative stress are of significant clinical interest as this approach offers the opportunity to link drug delivery to a specific location or disease state. This research news article reviews the current state of this field by examining a series of published articles that highlight the novelty and benefits of using responsive polymeric particles to achieve functionally-targeted drug delivery. PMID:22988558

  20. Nanotechnology-based drug delivery systems

    PubMed Central

    Suri, Sarabjeet Singh; Fenniri, Hicham; Singh, Baljit

    2007-01-01

    Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA) and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF) receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression. PMID:18053152

  1. Magnetizable implants for targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Forbes, Zachary Graham

    The capability to deliver high effective dosages to specific sites in the human body has become the holy grail of drug delivery research. Drugs with proven effectiveness under in vitro investigation often reach a major roadblock under in vivo testing due to a lack of an effective delivery strategy. In addition, many clinical scenarios require delivery of agents that are therapeutic at the desired delivery point, but otherwise systemically toxic. This project proposes a method for targeted drug delivery by applying high magnetic field gradients within the body to an injected superparamagnetic colloidal fluid carrying a drug, with the aid of modest uniform magnetic field. The design involves patterning of endovascular implants, such as coronary stents, with soft magnetic coatings capable of applying high local magnetic field gradients within the body. Examination of the feasibility of the design has been focused around the treatment of coronary restenosis following angioplasty. Drug-eluting stents, which have debuted in hospitals over the past two years, have thus far reduced restenosis rates to below 10%. Our local drug delivery system is a viable alternative or enhancement to drug-eluting stents, offering increased clinician control of dose size, the ability to treat a site repeatedly, and a wide array of applications for treatment of other pathologies. The theoretical models, parallel plate and pipe flow analysis, and cell culture models presented give insight into the use of micron and sub-micron scale magnetic particles for site-specific delivery of pharmaceuticals and magnetically labeled cells.

  2. Preparation of ibuprofen-loaded chitosan films for oral mucosal drug delivery using supercritical solution impregnation.

    PubMed

    Tang, Chuan; Guan, Yi-Xin; Yao, Shan-Jing; Zhu, Zi-Qiang

    2014-10-01

    Drug-loaded chitosan films suitable for oral mucosal drug delivery were prepared using supercritical solution impregnation (SSI) technology. Firstly, chitosan films were obtained via casting method, and the film properties including water-uptake, erosion and mucoadhesive were characterized. SSI process was then employed to load the drug of ibuprofen onto the prepared chitosan films, and the effects of impregnation pressure and temperature on morphologies of the ibuprofen-loaded chitosan films and drug loading capacity (DLC) were studied. The SEM and X-ray diffraction patterns suggested that distinct ibuprofen shapes such as microparticles, flake, rod-like and needle-like occurred after impregnation at different pressures, and DLC varied from 7.9% to 130.4% during the SSI process. The ex vivo release profiles showed that ibuprofen-loaded chitosan films could deliver the drug across the rabbit buccal mucosa, and up to 70% of the ibuprofen was released from the matrix in 460 min. SSI process is a promising method to prepare drug-loaded film formulations for oral mucosal drug delivery, which provides the advantages of low solvent residual and sustained- and controlled- release behavior.

  3. Fabrication and in vitro evaluation of mucoadhesive ondansetron hydrochloride beads for the management of emesis in chemotherapy

    PubMed Central

    Malik, Raj Kaur; Malik, Prashant; Gulati, Neha; Nagaich, Upendra

    2013-01-01

    Background Mucoadhesive beads were fabricated and evaluated for controlled release of an antiemetic drug ‘Ondansetron Hydrochloride’. Ondansetron hydrochloride is a serotonin 5-HT3 receptor antagonist mainly used for the treatment of emesis, which occurs as a side effect of chemotherapy. Materials and Methods: The present work was to fabricate and evaluate ondansetron-loaded microbeads by using chitosan as mucoadhesive and sustained release polymer. Sodium tripolyphosphate (Na-TPP) was used as a cross-linking agent. The microbeads were successfully prepared by ionotropic gelation technique. The particle size, entrapment efficiency, and mucoadhesive strength of drug-loaded formulations was measured by an optical microscope, direct crushing method, and in vitro wash-off method, respectively. Results: Particle size, entrapment efficiency, mucoadhesive strength, and in vitro drug release of optimized formulation was found to be 760.11 ± 1.02 μm, 75.09 ± 2.40%, 95.14 ± 0.27% and 87.45 ± 1.21%, respectively. The data was fitted to different kinetic models to illustrate its anomalous (non-Fickian) diffusion. Conclusions: The results revealed that ondansetron HCl loaded microbeads are most suitable mode of drug delivery for promising therapeutic action. Ondansetron HCl-loaded microbeads can prove to be potential pharmaceutical dosage forms for sustaining the drug release and reducing the dose frequency. PMID:23799204

  4. Inorganic Nanomaterials as Carriers for Drug Delivery.

    PubMed

    Chen, Shizhu; Hao, Xiaohong; Liang, Xingjie; Zhang, Qun; Zhang, Cuimiao; Zhou, Guoqiang; Shen, Shigang; Jia, Guang; Zhang, Jinchao

    2016-01-01

    For safe and effective therapy, drugs must be delivered efficiently and with minimal systemic side effects. Nanostructured drug carriers enable the delivery of small-molecule drugs as well as nucleic acids and proteins. Inorganic nanomaterials are ideal for drug delivery platforms due to their unique physicochemical properties, such as facile preparation, good storage stability and biocompatibility. Many inorganic nanostructure-based drug delivery platforms have been prepared. Although there are still many obstacles to overcome, significant advances have been made in recent years. This review focuses on the status and development of inorganic nanostructures, including silica, quantum dots, gold, carbon-based and magnetic iron oxide-based nanostructures, as carriers for chemical and biological drugs. We specifically highlight the extensive use of these inorganic drug carriers for cancer therapy. Finally, we discuss the most important areas in the field that urgently require further study. PMID:27301169

  5. Radiation sterilization of new drug delivery systems

    PubMed Central

    Abuhanoğlu, Gürhan

    2014-01-01

    Radiation sterilization has now become a commonly used method for sterilization of several active ingredients in drugs or drug delivery systems containing these substances. In this context, many applications have been performed on the human products that are required to be sterile, as well as on pharmaceutical products prepared to be developed. The new drug delivery systems designed to deliver the medication to the target tissue or organ, such as microspheres, nanospheres, microemulsion, and liposomal systems, have been sterilized by gamma (γ) and beta (β) rays, and more recently, by e-beam sterilization. In this review, the sterilization of new drug delivery systems was discussed other than conventional drug delivery systems by γ irradiation. PMID:24936306

  6. Development and evaluation of tamarind seed xyloglucan-based mucoadhesive buccal films of rizatriptan benzoate.

    PubMed

    Avachat, Amelia M; Gujar, Kishore N; Wagh, Kishor V

    2013-01-16

    Mucoadhesive buccal films were developed using tamarind seed xyloglucan (TSX) as novel mucoadhesive polysaccharide polymer for systemic delivery of rizatriptan benzoate through buccal route. Formulations were prepared based on 3(2) factorial design with concentrations of TSX and carbopol 934P (CP) as independent variables. Three dependent variables considered were tensile strength, bioadhesion force and drug release. DSC analysis revealed no interaction between drug and polymers. Ex vivo diffusion studies were carried out using Franz diffusion cell, while bioadhesive properties were evaluated using texture analyzer with porcine buccal mucosa as model tissue. Results revealed that bilayer film containing 4% (w/v) TSX and 0.5% (w/v) CP in the drug layer and 1% (w/v) ethyl cellulose in backing layer demonstrated diffusion of 93.45% through the porcine buccal mucosa. Thus, this study suggests that tamarind seed polysaccharide can act as a potential mucoadhesive polymer for buccal delivery of a highly soluble drug like rizatriptan benzoate. PMID:23121942

  7. 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

  8. Recent Advances in Ocular Drug Delivery, with Special Emphasis on Lipid Based Nanocarriers.

    PubMed

    Sah, Abhishek K; Suresh, Preeti K

    2015-01-01

    Eye is a vital sense organ of our body and any disorder can lead to serious medical implications that may put great financial burden on patient and their family. Effective drug delivery to the eye is a challenging proposition for the pharmaceutical scientist. Eye drops have been globally accepted as a formulation for anterior segment applications. On one hand it is widely used owing to its convenience but is also associated with some limitations in terms of desired pharmacological and pharmacokinetic profile, dosing frequency, systemic untoward effects, patient noncompliance, low drug bioavailability due to transient contact time, rapid washout by tearing and nasolacrimal drainage. The need to overcome these major issues related to ocular pharmacotherapy has been long recognized. Several novel nanocarriers including nanolipid based carrier systems have been widely explored and investigated for ophthalmic applications. These include solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), liposomes, in situ gels, niosomes, mucoadhesive systems and discomes. Since lipids have similar structure to human cell lipids, their biodegradable, non-toxic and biocompatible profile are particularly useful. Additionally, they also offer protection against drug degradation, impart controlled drug release characteristics and site specific delivery. This review explores the potential feasibility of lipid component in formulation of nanomedicine for ophthalmic delivery and reports the clinical findings in order to improve the ocular pharmacotherapy. Here, we also discussed for patents related to the topic. PMID:27009124

  9. Nanoparticulate devices for brain drug delivery.

    PubMed

    Celia, Christian; Cosco, Donato; Paolino, Donatella; Fresta, Massimo

    2011-09-01

    The blood-brain barrier (BBB) limits the transport of therapeutic molecules from the blood compartment into the brain, thus greatly reducing the species of therapeutic compounds that can be efficiently accumulated in the central nervous system (CNS). Various strategies have been proposed for improving the delivery of drugs to this tissue, and numerous invasive and noninvasive methods have been proposed by different scientists in an attempt to circumvent the BBB and to increase the delivery of drug compounds into the brain. An interesting alternative, in the solution of this problem and also that of reaching a suitable target in the CNS, has recently been provided through the use of nanoparticulate colloidal devices as a noninvasive technique for brain drug delivery. These systems offer diverse advantages over invasive strategies, because (1) they are designed using biocompatible and biodegradable materials; (2) they avoid the disruption and/or modification of the BBB; and (3) they modulate the biopharmaceutical properties of the entrapped drugs. Moreover, the possibility of targeting specific brain tissue, thanks to ligands linked to the surface of the nanoparticulate colloidal devices, confers the necessary characteristics for the treatment of CNS pathologies to these drug carriers. The aim of this review is to focus on describing the main strategies in use for designing nanoparticulate colloidal devices for CNS delivery, their potentiality as noninvasive strategies in the delivery of drugs to the cerebral tissues, and their biological and clinical applications in cerebral drug delivery.

  10. Synthetic micro/nanomotors in drug delivery

    NASA Astrophysics Data System (ADS)

    Gao, Wei; Wang, Joseph

    2014-08-01

    Nanomachines offer considerable promise for the treatment of diseases. The ability of man-made nanomotors to rapidly deliver therapeutic payloads to their target destination represents a novel nanomedicine approach. Synthetic nanomotors, based on a multitude of propulsion mechanisms, have been developed over the past decade toward diverse biomedical applications. In this review article, we journey from the use of chemically powered drug-delivery nanovehicles to externally actuated (fuel-free) drug-delivery nanomachine platforms, and conclude with future prospects and challenges for such practical propelling drug-delivery systems. As future micro/nanomachines become more powerful and functional, these tiny devices are expected to perform more demanding biomedical tasks and benefit different drug delivery applications.

  11. Adaptations and innovations in drug delivery.

    PubMed

    Cavalla, D

    2001-10-01

    The most recent meeting organized by the Society for Medicines Research, entitled Improving Medicines Through Drug Delivery, was held at the National Heart and Lung Institute in London on July 5, 2001. Drug delivery is increasingly becoming a central technology in the research and development of better medicines. This is so for at least three reasons. First, new drugs are being derived from complex biological molecules that are not readily amenable to oral delivery. Second, improved medicine is recognized as requiring better dosing regimens for the patient. Both compliance and preference are improved by reduced dosing frequency, and it is rare for new products to require three-times-daily administration. Lastly, drug delivery technology has come a long way in the past 20 years, beyond controlled-release pharmaceuticals to polymer conjugates and dry powder-inhaled proteins. PMID:12806435

  12. Chitosan Microspheres in Novel Drug Delivery Systems

    PubMed Central

    Mitra, Analava; Dey, Baishakhi

    2011-01-01

    The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. PMID:22707817

  13. Development and in vitro evaluation of a buccal drug delivery system based on preactivated thiolated pectin.

    PubMed

    Hauptstein, Sabine; Hintzen, Fabian; Müller, Christiane; Ohm, Moritz; Bernkop-Schnürch, Andreas

    2014-11-01

    The aim of this study was to evaluate the potential of preactivated thiolated pectin (Pec-Cys-MNA) for buccal drug delivery. Therefore, a gel formulation containing this novel polymer and the model drug lidocaine was prepared and investigated in vitro in terms of rheology, mucoadhesion, swelling behavior and drug release in comparison to formulations based on pectin (Pec) and thiolated pectin (Pec-Cys). Both pectin derivatives showed gel formation without addition of any other excipient due to self-crosslinking thiol groups. Under same conditions, pectin did not show gel formation. Viscosity of Pec-Cys-based formulation increased 92-fold and viscosity of Pec-Cys-MNA-based formulations by 4958-fold compared to pectin-based formulation. Gels did not dissolve in aqueous environment during several hours and were able to take up water. Mucoadhesion of pectin on buccal tissue could be improved significantly, value of total work of adhesion increased in the following rank order: Pec-Cys-MNA > Pec-Cys > Pec. The retention time of a model drug incorporated in gel formulations on buccal mucosa under continuous rinsing with phosphate-buffered saline was prolonged, after 1.5 h 3-fold higher amount of a model drug was to be found on tissue after application of Pec-Cys-MNA-based formulation compared to pectin-based and 2-fold compared to Pec-Cys-based formulation. The Pec-Cys-MNA-based gel showed a more sustained release of lidocaine than Pec-Cys-based gel, whereas pectin solution revealed an immediate release. According to these results, the self-crosslinking pectin-derivative is a promising tool for buccal application.

  14. Methods of Drug Delivery in Neurotrauma.

    PubMed

    Deng-Bryant, Ying; Readnower, Ryan; Leung, Lai Yee; Tortella, Frank; Shear, Deborah

    2016-01-01

    The central nervous system (CNS) is protected by blood-brain barrier (BBB) and blood-cerebrospinal-fluid (CSF) barrier that limit toxic agents and most molecules from penetrating the brain and spinal cord. However, these barriers also prevent most pharmaceuticals from entering into the CNS. Drug delivery to the CNS following neurotrauma is complicated. Although studies have shown BBB permeability increases in various TBI models, it remains as the key mitigating factor for delivering drugs into the CNS. The commonly used methods for drug delivery in preclinical neurotrauma studies include intraperitoneal, subcutaneous, intravenous, and intracerebroventricular delivery. It should be noted that for a drug to be successfully translated into the clinic, it needs to be administered preclinically as it would be anticipated to be administered to patients. And this likely leads to better dose selection of the drug, as well as recognition of any possible side effects, prior to transition into a clinical trial. Additionally, novel approach that is noninvasive and yet circumvents BBB, such as drug delivery through nerve pathways innervating the nasal passages, needs to be investigated in animal models, as it may provide a viable drug delivery method for patients who sustain mild CNS injury or require chronic treatments. Therefore, the focus of this chapter is to present rationales and methods for delivering drugs by IV infusion via the jugular vein, and intranasally in preclinical studies. PMID:27604714

  15. Role of microemuslsions in advanced drug delivery.

    PubMed

    Sharma, Aman Kumar; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-06-01

    Microemulsions have gained significant attention from formulation scientists since the time they have been discovered, because of their excellent properties related to their stability, solubility, simplicity, and formulation aspects. The application of microemulsions is not limited to drug delivery via the oral, topical or ocular routes, but may also be seen in cosmetics, immunology, sensor devices, coating, textiles, analytical chemistry, and spermicide. Finally, the objective of this review is to discuss briefly the applications of microemulsions in advanced drug delivery. PMID:25711493

  16. Determination of ofloxacin in tear by HPLC-ESI-MS/MS method: comparison of ophthalmic drug release between a new mucoadhesive chitosan films and a conventional eye drop formulation in rabbit model.

    PubMed

    Byrro, Ricardo Martins Duarte; de Oliveira Fulgêncio, Gustavo; da Silva Cunha, Armando; César, Isabela Costa; Chellini, Paula Rocha; Pianetti, Gerson Antônio

    2012-11-01

    Ofloxacin, second-generation fluoroquinolone derivative, is one of the most commonly used to treat and prevent superficial ocular infection in animals and human beings. However, poor bioavailability, rapid elimination, and non compliance by patients are several problems associated with ocular route. Ophthalmic controlled drug delivery offers the potential to enhance the efficacy of treatment for pathological conditions, while reducing the side effects and the toxicity associated with frequent applications. Specific analytical methods to determine drugs in eye are needed to analyze and compare the new controlled release ocular devices with those conventional eye drops. The topical eye administration of ophthalmic drugs induces lachrymation, and the tear promotes a drug wash out. Quantify drugs in tear is a good tool to study their kinetic comportment in the eye. A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for quantitation of ofloxacin in rabbits' tears was developed and validated. The tear was collected with tear strips, extracted by a liquid extraction procedure and then separated on an ACE C(18) column with a mobile phase composed of 0.15% aqueous formic acid and methanol (60:40, v/v). Calibration curve was constructed over the range of 10-5000 ng/mL for ofloxacin. The mean R.S.D. values for the intra-run and inter-run precision were 5.15% and 4.35%, respectively. The mean accuracy value was 100.16%. The validated method was successfully applied to determine the ofloxacin concentration in tears of rabbits treated with a mucoadhesive chitosan films and a conventional eye drop formulation.

  17. Progress in antiretroviral drug delivery using nanotechnology.

    PubMed

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-08-09

    There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV). More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatment and prevention of this disease, the use of nanocarriers to achieve more efficient delivery of antiretroviral drugs has been studied. Various forms of nanocarriers, such as nanoparticles (polymeric, inorganic, and solid lipid), liposomes, polymeric micelles, dendrimers, cyclodextrins, and cell-based nanoformulations have been studied for delivery of drugs intended for HIV prevention or therapy. The aim of this review is to provide a summary of the application of nanocarrier systems to the delivery of anti-HIV drugs, specifically antiretrovirals. For anti-HIV drugs to be effective, adequate distribution to specific sites in the body must be achieved, and effective drug concentrations must be maintained at those sites for the required period of time. Nanocarriers provide a means to overcome cellular and anatomical barriers to drug delivery. Their application in the area of HIV prevention and therapy may lead to the development of more effective drug products for combating this pandemic disease.

  18. Progress in antiretroviral drug delivery using nanotechnology

    PubMed Central

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-01-01

    There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV). More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatment and prevention of this disease, the use of nanocarriers to achieve more efficient delivery of antiretroviral drugs has been studied. Various forms of nanocarriers, such as nanoparticles (polymeric, inorganic, and solid lipid), liposomes, polymeric micelles, dendrimers, cyclodextrins, and cell-based nanoformulations have been studied for delivery of drugs intended for HIV prevention or therapy. The aim of this review is to provide a summary of the application of nanocarrier systems to the delivery of anti-HIV drugs, specifically antiretrovirals. For anti-HIV drugs to be effective, adequate distribution to specific sites in the body must be achieved, and effective drug concentrations must be maintained at those sites for the required period of time. Nanocarriers provide a means to overcome cellular and anatomical barriers to drug delivery. Their application in the area of HIV prevention and therapy may lead to the development of more effective drug products for combating this pandemic disease. PMID:20957115

  19. Microneedles for drug and vaccine delivery.

    PubMed

    Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R

    2012-11-01

    Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990's when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. PMID:22575858

  20. Microneedles for drug and vaccine delivery

    PubMed Central

    Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R.

    2012-01-01

    Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990’s when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. PMID:22575858

  1. Intracellular Drug Delivery: Mechanisms for Cell Entry.

    PubMed

    Garnacho, Carmen

    2016-01-01

    Over the last half century, the delivery of pharmacologically active substances, such as synthetic drugs, natural compounds, gene material and many other pharmaceutical products, has been widely studied. Understanding the interactions of drug carriers with cells and how these interactions influence the cellular uptake is of paramount importance, since targets for many therapeutic agents against several disorders are localized in the subcellular compartments. Besides, the route of drug carrier entry (direct or via endocytosis) often defines the efficiency, kinetics and final destination of the drug itself. Although classical endocytic pathways such as phagocytosis, macropinocytosis, clathrin-mediated and caveola-dependent pathways are well characterized, their control for pharmaceutical drug delivery applications is still a challenging issue. Also, better knowledge of non-classical endocytic pathways may help optimize targeted drug delivery systems for intracellular delivery. Therefore, this review focuses on mechanisms of intracellular delivery, including direct internalization and endocytosis, as well as factors such as targeting moiety, target receptor, and size, shape, and surface properties of the drug carrier that can influence uptake process. PMID:26675221

  2. Transpapillary Drug Delivery to the Breast

    PubMed Central

    Dave, Kaushalkumar; Averineni, Ranjith; Sahdev, Preety; Perumal, Omathanu

    2014-01-01

    The study was aimed at investigating localized topical drug delivery to the breast via mammary papilla (nipple). 5-fluorouracil (5-FU) and estradiol (EST) were used as model hydrophilic and hydrophobic compounds respectively. Porcine and human nipple were used for in-vitro penetration studies. The removal of keratin plug enhanced the drug transport through the nipple. The drug penetration was significantly higher through the nipple compared to breast skin. The drug’s lipophilicity had a significant influence on drug penetration through nipple. The ducts in the nipple served as a major transport pathway to the underlying breast tissue. Results showed that porcine nipple could be a potential model for human nipple. The topical application of 5-FU on the rat nipple resulted in high drug concentration in the breast and minimal drug levels in plasma and other organs. Overall, the findings from this study demonstrate the feasibility of localized drug delivery to the breast through nipple. PMID:25545150

  3. Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

    PubMed Central

    Voltan, Aline Raquel; Quindós, Guillermo; Alarcón, Kaila P Medina; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares; Chorilli, Marlus

    2016-01-01

    Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis. PMID:27540288

  4. Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

    PubMed

    Voltan, Aline Raquel; Quindós, Guillermo; Alarcón, Kaila P Medina; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares; Chorilli, Marlus

    2016-01-01

    Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis.

  5. Microfluidic device for drug delivery

    NASA Technical Reports Server (NTRS)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2010-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  6. Implication of nanofibers in oral drug delivery.

    PubMed

    Kapahi, Himani; Khan, Nikhat Mansoor; Bhardwaj, Ankur; Mishra, Neeraj

    2015-01-01

    Nanofibers has gained significant prominence in recent years due to its wide applications in medicinal pharmacy, textile, tissue engineering and in various drug delivery system. In oral drug delivery system (DDS), nanofibers can be delivered as Nanofiber scaffolds, electrosponge nanofibers as oral fast delivery system, multilayered nanofiber loaded mashes, surface modified cross-linked electrospun nanofibers. Nanofibers are of 50- 1000 nm size fibres having large surface area, high porosity, small pore size, low density. Various approaches for formulation of nanofibers are molecular assembly, thermally induced phase separation, electrospining. Most commonly used by using electrospining polymer nanofibres with different range can be produced collective usage of electro spinning with pharmaceutical polymers offers novel tactics for developing drug delivery system (DDS). Different polymers used in preparation of nanofibers include biodegradable hydrophilic polymers, hydrophobic polymers and amphiphilic polymers. Electrospun nanofibers are often used to load insoluble drugs for enhancing their dissolution properties due to their high surface area per unit mass. Besides the water insoluble drugs freely water soluble sodium can also spun into the fibers. The most commonly polymers used for nanofibers are gelatin, dextran, nylon, polystyrene, polyacrylonitrile, polycarbonate, polyimides, poly vinyl alchol, polybenzimidazole. Delivery systems reviewed rely on temporal control, changes in pH along the GIT, the action of local enzymes to trigger drug release, and changes in intraluminal pressure. Dissolution of enteric polymer coatings due to a change in local pH and reduction of azo-bonds to release an active agent are both used in commercially marketed products. In vitro and in vivo studies have demonstrated that the release rates of drugs from these nanofiber formulations are enhanced compared to those from original drug substance. This review is focused on the different

  7. Hp-β-CD-Voriconazole In Situ Gelling System for Ocular Drug Delivery: In Vitro, Stability, and Antifungal Activities Assessment

    PubMed Central

    Pawar, Pravin; Kashyap, Heena; Malhotra, Sakshi; Sindhu, Rakesh

    2013-01-01

    The objective of the present study was to design ophthalmic delivery systems based on polymeric carriers that undergo sol-to-gel transition upon change in temperature or in the presence of cations so as to prolong the effect of HP-β-CD Voriconazole (VCZ) in situ gelling formulations. The in situ gelling formulations of Voriconazole were prepared by using pluronic F-127 (PF-127) or with combination of pluronic F-68 (PF-68) and sodium alginate by cold method technique. The prepared formulations were evaluated for their physical appearance, drug content, gelation temperature (Tgel), in vitro permeation studies, rheological properties, mucoadhesion studies, antifungal studies, and stability studies. All batches of in situ formulations had satisfactory pH ranging from 6.8 to 7.4, drug content between 95% and 100%, showing uniform distribution of drug. As the concentration of each polymeric component was increased, that is, PF-68 and sodium alginate, there was a decrease in Tgel with increase in viscosity and mucoadhesive strength. The in vitro drug release decreased with increase in polymeric concentrations. The stability data concluded that all formulations showed the low degradation and maximum shelf life of 2 years. The antifungal efficiency of the selected formulation against Candida albicans and Asperigillus fumigatus confirmed that designed formulation has prolonged effect and retained its properties against fungal infection. PMID:23762839

  8. A wireless actuating drug delivery system

    NASA Astrophysics Data System (ADS)

    Jo, Won-Jun; Baek, Seung-Ki; Park, Jung-Hwan

    2015-04-01

    A wireless actuating drug delivery system was devised. The system is based on induction heating for drug delivery. In this study, thermally generated nitrogen gas produced by induction heating of azobisisobutyronitrile (AIBN) was utilized for pressure-driven release of the drug. The delivery device consists of an actuator chamber, a drug reservoir, and a microchannel. A semicircular copper disc (5 and 6 mm in diameter and 100 µm thick), and thermal conductive tape were integrated as the heating element in the actuator chamber. The final device was 2.7 mm thick. 28 µl of drug solution were placed in the reservoir and the device released the drug quickly at the rate of 6 µl s-1 by induction heating at 160 µT of magnetic intensity. The entire drug solution was released and dispersed after subcutaneous implantation under identical experimental condition. This study demonstrates that the device was simply prepared and drug delivery could be achieved by wireless actuation of a thin, pressure-driven actuator.

  9. Electroresponsive nanoparticles for drug delivery on demand

    NASA Astrophysics Data System (ADS)

    Samanta, Devleena; Hosseini-Nassab, Niloufar; Zare, Richard N.

    2016-04-01

    The potential of electroresponsive conducting polymer nanoparticles to be used as general drug delivery systems that allow electrically pulsed, linearly scalable, and on demand release of incorporated drugs is demonstrated. As examples, facile release from polypyrrole nanoparticles is shown for fluorescein, a highly water-soluble model compound, piroxicam, a lipophilic small molecule drug, and insulin, a large hydrophilic peptide hormone. The drug loading is about 13 wt% and release is accomplished in a few seconds by applying a weak constant current or voltage. To identify the parameters that should be finely tuned to tailor the carrier system for the release of the therapeutic molecule of interest, a systematic study of the factors that affect drug delivery is performed, using fluorescein as a model compound. The parameters studied include current, time, voltage, pH, temperature, particle concentration, and ionic strength. Results indicate that there are several degrees of freedom that can be optimized for efficient drug delivery. The ability to modulate linearly drug release from conducting polymers with the applied stimulus can be utilized to design programmable and minimally invasive drug delivery devices.

  10. Electroresponsive nanoparticles for drug delivery on demand.

    PubMed

    Samanta, Devleena; Hosseini-Nassab, Niloufar; Zare, Richard N

    2016-04-28

    The potential of electroresponsive conducting polymer nanoparticles to be used as general drug delivery systems that allow electrically pulsed, linearly scalable, and on demand release of incorporated drugs is demonstrated. As examples, facile release from polypyrrole nanoparticles is shown for fluorescein, a highly water-soluble model compound, piroxicam, a lipophilic small molecule drug, and insulin, a large hydrophilic peptide hormone. The drug loading is about 13 wt% and release is accomplished in a few seconds by applying a weak constant current or voltage. To identify the parameters that should be finely tuned to tailor the carrier system for the release of the therapeutic molecule of interest, a systematic study of the factors that affect drug delivery is performed, using fluorescein as a model compound. The parameters studied include current, time, voltage, pH, temperature, particle concentration, and ionic strength. Results indicate that there are several degrees of freedom that can be optimized for efficient drug delivery. The ability to modulate linearly drug release from conducting polymers with the applied stimulus can be utilized to design programmable and minimally invasive drug delivery devices. PMID:27088543

  11. Microfabrication Technologies for Oral Drug Delivery

    PubMed Central

    Sant, Shilpa; Tao, Sarah L.; Fisher, Omar; Xu, Qiaobing; Peppas, Nicholas A.; Khademhosseini, Ali

    2012-01-01

    Micro-/nanoscale technologies such as lithographic techniques and microfluidics offer promising avenues to revolutionalize the fields of tissue engineering, drug discovery, diagnostics and personalized medicine. Microfabrication techniques are being explored for drug delivery applications due to their ability to combine several features such as precise shape and size into a single drug delivery vehicle. They also offer to create unique asymmetrical features incorporated into single or multiple reservoir systems maximizing contact area with the intestinal lining. Combined with intelligent materials, such microfabricated platforms can be designed to be bioadhesive and stimuli-responsive. Apart from drug delivery devices, microfabrication technologies offer exciting opportunities to create biomimetic gastrointestinal tract models incorporating physiological cell types, flow patterns and brush-border like structures. Here we review the recent developments in this field with a focus on the applications of microfabrication in the development of oral drug delivery devices and biomimetic gastrointestinal tract models that can be used to evaluate the drug delivery efficacy. PMID:22166590

  12. A pulsed mode electrolytic drug delivery device

    NASA Astrophysics Data System (ADS)

    Yi, Ying; Buttner, Ulrich; Carreno, Armando A. A.; Conchouso, David; Foulds, Ian G.

    2015-10-01

    This paper reports the design of a proof-of-concept drug delivery device that is actuated using the bubbles formed during electrolysis. The device uses a platinum (Pt) coated nickel (Ni) metal foam and a solid drug in reservoir (SDR) approach to improve the device’s performance. This electrochemically-driven pump has many features that are unlike conventional drug delivery devices: it is capable of pumping periodically and being refilled automatically; it features drug release control; and it enables targeted delivery. Pt-coated metal foam is used as a catalytic reforming element, which reduces the period of each delivery cycle. Two methods were used for fabricating the Pt-coated metal: sputtering and electroplating. Of these two methods, the sputtered Pt-coated metal foam has a higher pumping rate; it also has a comparable recombination rate when compared to the electroplated Pt-coated metal foam. The only drawback of this catalytic reformer is that it consumes nickel scaffold. Considering long-term applications, the electroplated Pt metal foam was selected for drug delivery, where a controlled drug release rate of 2.2 μg  ±  0.3 μg per actuation pulse was achieved using 4 mW of power.

  13. Nanomedicine-nanoscale drugs and delivery systems.

    PubMed

    Singh, Surya

    2010-12-01

    Significant progress has been made in nanoscale drugs and delivery systems employing diverse chemical formulations to facilitate the rate of drug delivery and release from the human body. The biocompatible nanomaterials have been used in biological markers, contrast agents for biological imaging, healthcare products, pharmaceuticals, drug-delivery systems as well as in detection, diagnosis and treatment of various types of diseases. Nanomedicines offer delivery of potential drugs to human organs which were previously beyond reach of microscale drugs due to specific biological barriers. The nanoscale systems work as nanocarriers for the delivery of drugs. The nanocarriers are made of biocompatible and biodegradable materials such as synthetic proteins, peptides, lipids, polysaccharides, biodegradable polymers and fibers. This review article reports the recent developments in the field of nanomedicine covering biodegradable polymers, nanoparticles, cyclodextrin, dendrimeres, liposomes and lipid-based nanocarriers, nanofibers, nanowires and carbon nanotubes and their chemical functionalization for distribution to different organs, their solubility, surface, chemical and biological properties, stability and release systems. The toxicity and safety of nanomaterials on human health is also briefly discussed.

  14. Nanoparticles for drug delivery to the lungs.

    PubMed

    Sung, Jean C; Pulliam, Brian L; Edwards, David A

    2007-12-01

    The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. Incorporating therapeutics with polymeric nanoparticles offers additional degrees of manipulation for delivery systems, providing sustained release and the ability to target specific cells and organs. However, nanoparticle delivery to the lungs has many challenges including formulation instability due to particle-particle interactions and poor delivery efficiency due to exhalation of low-inertia nanoparticles. Thus, novel methods formulating nanoparticles into the form of micron-scale dry powders have been developed. These carrier particles exhibit improved handling and delivery, while releasing nanoparticles upon deposition in the lungs. This review covers the development of nanoparticle formulations for pulmonary delivery as both individual nanoparticles and encapsulated within carrier particles.

  15. Mucoadhesive polyethylenimine-dextran sulfate nanoparticles containing Punica granatum peel extract as a novel sustained-release antimicrobial.

    PubMed

    Tiyaboonchai, Waree; Rodleang, Ingdao; Ounaroon, Anan

    2015-06-01

    Mucoadhesive polyethylenimine-dextran sulfate nanoparticles (PDNPs) were developed for local oral mucosa delivery. Punica granatum peel extract (PGE) was loaded into PDNPs for oral malodor reduction and caries prevention. PDNPs were constructed using the polyelectrolyte complexation technique employing oppositely charged polymers polyethylenimine (PEI) and dextran sulfate (DS), with PEG 400 as a stabilizer. Under optimal conditions, spherical particles of ∼ 500 nm with a zeta potential of ∼+28 mV were produced. Up to 98%, drug entrapment efficiency was observed. The mass ratio of PEI:DS played a significant role in controlling particle size and entrapment efficacy. PDNPs shown to be a good mucoadhesive drug delivery system as confirmed by ex vivo wash off test. In vitro dissolution studies revealed that PGE-loaded PDNPs manifested a prolong release characteristic with a burst release within 5 min. In addition, they remained effectively against oral bacteria. PMID:24438035

  16. Liposome-like Nanostructures for Drug Delivery

    PubMed Central

    Gao, Weiwei; Hu, Che-Ming J.; Fang, Ronnie H.; Zhang, Liangfang

    2013-01-01

    Liposomes are a class of well-established drug carriers that have found numerous therapeutic applications. The success of liposomes, together with recent advancements in nanotechnology, has motivated the development of various novel liposome-like nanostructures with improved drug delivery performance. These nanostructures can be categorized into five major varieties, namely: (1) polymer-stabilized liposomes, (2) nanoparticle-stabilized liposomes, (3) core-shell lipid-polymer hybrid nanoparticles, (4) natural membrane-derived vesicles, and (5) natural membrane coated nanoparticles. They have received significant attention and have become popular drug delivery platforms. Herein, we discuss the unique strengths of these liposome-like platforms in drug delivery, with a particular emphasis on how liposome-inspired novel designs have led to improved therapeutic efficacy, and review recent progress made by each platform in advancing healthcare. PMID:24392221

  17. Brain drug delivery systems for neurodegenerative disorders.

    PubMed

    Garbayo, E; Ansorena, E; Blanco-Prieto, M J

    2012-09-01

    Neurodegenerative disorders (NDs) are rapidly increasing as population ages. However, successful treatments for NDs have so far been limited and drug delivery to the brain remains one of the major challenges to overcome. There has recently been growing interest in the development of drug delivery systems (DDS) for local or systemic brain administration. DDS are able to improve the pharmacological and therapeutic properties of conventional drugs and reduce their side effects. The present review provides a concise overview of the recent advances made in the field of brain drug delivery for treating neurodegenerative disorders. Examples include polymeric micro and nanoparticles, lipidic nanoparticles, pegylated liposomes, microemulsions and nanogels that have been tested in experimental models of Parkinson's, Alzheimer's and Huntington's disease. Overall, the results reviewed here show that DDS have great potential for NDs treatment. PMID:23016644

  18. Effect of a novel mucoadhesive polysaccharide obtained from tamarind seeds on the intraocular penetration of gentamicin and ofloxacin in rabbits.

    PubMed

    Ghelardi, E; Tavanti, A; Celandroni, F; Lupetti, A; Blandizzi, C; Boldrini, E; Campa, M; Senesi, S

    2000-11-01

    This report describes the efficacy of a novel mucoadhesive polymer, the tamarind seed polysaccharide, as a delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics. Healthy rabbits were subjected to repeated ocular instillations with either conventional gentamicin or ofloxacin or these agents viscosified with the tamarind seed polysaccharide. Administration of viscosified preparations produced antibiotic concentrations both in the aqueous humour and cornea that were significantly higher than those achieved with the drugs alone. The increased drug absorption and the prolonged drug elimination phase obtained with the viscosified formulations indicate the usefulness of the tamarind seed polysaccharide as an ophthalmic delivery system for topical administration of antibiotics.

  19. Inhaled nano- and microparticles for drug delivery

    PubMed Central

    El-Sherbiny, Ibrahim M.; El-Baz, Nancy M.; Yacoub, Magdi H.

    2015-01-01

    The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems. PMID:26779496

  20. Spray Drying Tenofovir Loaded Mucoadhesive and pH-Sensitive Microspheres Intended for HIV Prevention

    PubMed Central

    Zhang, Tao; Zhang, Chi; Agrahari, Vivek; Murowchick, James B.; Oyler, Nathan A.; Youan, Bi-Botti C.

    2013-01-01

    Purpose To develop spray dried mucoadhesive and pH-sensitive microspheres (MS) based on polymethacrylate salt intended for vaginal delivery of tenofovir (a model HIV microbicide) and assess their critical biological responses. Methods The formulation variables and process parameters are screened and optimized using a 24-1 fractional factorial design. The MS are characterized for size, zeta potential, yield, encapsulation efficiency, Carr’s index, drug loading, in vitro release, cytotoxicity, inflammatory responses and mucoadhesion. Results The optimal MS formulation has an average size of 4.73 µm, Zeta potential of −26.3 mV, 68.9% yield, encapsulation efficiency of 88.7%, Carr’s index of 28.3 and drug loading of 2% (w/w). The MS formulation can release 90% of its payload in the presence of simulated human semen. At a concentration of 1 mg/ml, the MS are noncytotoxic to vaginal endocervical/epithelial cells and Lactobacillus crispatus when compared to control media. There is also no statistically significant level of inflammatory cytokine (IL1-α, IL-1β, IL-6, IL-8, and IP-10) release triggered by MS. The mucoadhesive property of MS formulation is 2-fold higher than that of 1% HEC gel formulation. Conclusion These data suggest the promise of using such MS as an alternative controlled microbicide delivery template by intravaginal route for HIV prevention. PMID:23274788

  1. Applications of chitosan nanoparticles in drug delivery.

    PubMed

    Tajmir-Riahi, H A; Nafisi, Sh; Sanyakamdhorn, S; Agudelo, D; Chanphai, P

    2014-01-01

    We have reviewed the binding affinities of several antitumor drugs doxorubicin (Dox), N-(trifluoroacetyl) doxorubicin (FDox), tamoxifen (Tam), 4-hydroxytamoxifen (4-Hydroxytam), and endoxifen (Endox) with chitosan nanoparticles of different sizes (chitosan-15, chitosan-100, and chitosan-200 KD) in order to evaluate the efficacy of chitosan nanocarriers in drug delivery systems. Spectroscopic and molecular modeling studies showed the binding sites and the stability of drug-polymer complexes. Drug-chitosan complexation occurred via hydrophobic and hydrophilic contacts as well as H-bonding network. Chitosan-100 KD was the more effective drug carrier than the chitosan-15 and chitosan-200 KD. PMID:24567139

  2. Functional Cyclodextrin Polyrotaxanes for Drug Delivery

    NASA Astrophysics Data System (ADS)

    Yui, Nobuhiko; Katoono, Ryo; Yamashita, Atsushi

    The mobility of cyclodextrins (CDs) threaded onto a linear polymeric chain and the dethreading of the CDs from the chain are the most fascinating features seen in polyrotaxanes. These structural characteristics are very promising for their possible applications in drug delivery. Enhanced multivalent interaction between ligand-receptor systems by using ligand-conjugated polyrotaxanes would be just one of the excellent properties related to the CD mobility. Gene delivery using cytocleavable polyrotaxanes is a more practical but highly crucial issue in drug delivery. Complexation of the polyrotaxanes with DNA and its intracellular DNA release ingeniously utilizes both CD mobility and polyrotaxane dissociation to achieve effective gene delivery. Such a supramolecular approach using CD-containing polyrotaxanes is expected to exploit a new paradigm of biomaterials.

  3. Trojan Microparticles for Drug Delivery

    PubMed Central

    Anton, Nicolas; Jakhmola, Anshuman; Vandamme, Thierry F.

    2012-01-01

    During the last decade, the US Food and Drug Administration (FDA) have regulated a wide range of products, (foods, cosmetics, drugs, devices, veterinary, and tobacco) which may utilize micro and nanotechnology or contain nanomaterials. Nanotechnology allows scientists to create, explore, and manipulate materials in nano-regime. Such materials have chemical, physical, and biological properties that are quite different from their bulk counterparts. For pharmaceutical applications and in order to improve their administration (oral, pulmonary and dermal), the nanocarriers can be spread into microparticles. These supramolecular associations can also modulate the kinetic releases of drugs entrapped in the nanoparticles. Different strategies to produce these hybrid particles and to optimize the release kinetics of encapsulated drugs are discussed in this review. PMID:24300177

  4. Nanoparticles and nanofibers for topical drug delivery

    PubMed Central

    Goyal, Ritu; Macri, Lauren K.; Kaplan, Hilton M.; Kohn, Joachim

    2016-01-01

    This review provides the first comprehensive overview of the use of both nanoparticles and nanofibers for topical drug delivery. Researchers have explored the use of nanotechnology, specifically nanoparticles and nanofibers, as drug delivery systems for topical and transdermal applications. This approach employs increased drug concentration in the carrier, in order to increase drug flux into and through the skin. Both nanoparticles and nanofibers can be used to deliver hydrophobic and hydrophilic drugs and are capable of controlled release for a prolonged period of time. The examples presented provide significant evidence that this area of research has—and will continue to have — a profound impact on both clinical outcomes and the development of new products. PMID:26518723

  5. Engineered inorganic nanoparticles for drug delivery applications.

    PubMed

    Ojea-Jiménez, Isaac; Comenge, Joan; García-Fernández, Lorena; Megson, Zoë A; Casals, Eudald; Puntes, Victor F

    2013-06-01

    Inorganic nanoparticles (NPs) currently have immense potential as drug delivery vectors due to their unique physicochemical properties such as high surface area per unit volume, their optical and magnetic uniqueness and the ability to be functionalized with a large number of ligands to enhance their affinity towards target molecules. These features, together with the therapeutic activity of some drugs, render the combination of these two entities (NP-drug) as an attractive alternative in the area of drug delivery. One of the major advantages of these conjugates is the possibility to have a local delivery of the drug, thus reducing systemic side effects and enabling a higher efficiency of the therapeutic molecule. This review highlights the direct implications of nanoscale particles in the development of drug delivery systems. In more detail, it is also remarked the extensive use of inorganic NPs for targeted cancer therapies. As the range of nanoparticles and their applications continues to increase, human safety concerns are gaining importance, which makes it necessary to better understand the potential toxicity hazards of these materials.

  6. Engineered inorganic nanoparticles for drug delivery applications.

    PubMed

    Ojea-Jiménez, Isaac; Comenge, Joan; García-Fernández, Lorena; Megson, Zoë A; Casals, Eudald; Puntes, Victor F

    2013-06-01

    Inorganic nanoparticles (NPs) currently have immense potential as drug delivery vectors due to their unique physicochemical properties such as high surface area per unit volume, their optical and magnetic uniqueness and the ability to be functionalized with a large number of ligands to enhance their affinity towards target molecules. These features, together with the therapeutic activity of some drugs, render the combination of these two entities (NP-drug) as an attractive alternative in the area of drug delivery. One of the major advantages of these conjugates is the possibility to have a local delivery of the drug, thus reducing systemic side effects and enabling a higher efficiency of the therapeutic molecule. This review highlights the direct implications of nanoscale particles in the development of drug delivery systems. In more detail, it is also remarked the extensive use of inorganic NPs for targeted cancer therapies. As the range of nanoparticles and their applications continues to increase, human safety concerns are gaining importance, which makes it necessary to better understand the potential toxicity hazards of these materials. PMID:23116108

  7. Genetically engineered nanocarriers for drug delivery

    PubMed Central

    Shi, Pu; Gustafson, Joshua A; MacKay, J Andrew

    2014-01-01

    Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins. PMID:24741309

  8. Functional physico-chemical, ex vivo permeation and cell viability characterization of omeprazole loaded buccal films for paediatric drug delivery.

    PubMed

    Khan, Sajjad; Trivedi, Vivek; Boateng, Joshua

    2016-03-16

    Buccal films were prepared from aqueous and ethanolic Metolose gels using the solvent casting approach (40°C). The hydration (PBS and simulated saliva), mucoadhesion, physical stability (20°C, 40°C), in vitro drug (omeprazole) dissolution (PBS and simulated saliva), ex vivo permeation (pig buccal mucosa) in the presence of simulated saliva, ex vivo bioadhesion and cell viability using MTT of films were investigated. Hydration and mucoadhesion results showed that swelling capacity and adhesion was higher in the presence of PBS than simulated saliva (SS) due to differences in ionic strength. Omeprazole was more stable at 20°C than 40°C whilst omeprazole release reached a plateau within 1h and faster in PBS than in SS. Fitting release data to kinetic models showed that Korsmeyer-Peppas equation best fit the dissolution data. Drug release in PBS was best described by zero order via non-Fickian diffusion but followed super case II transport in SS attributed to drug diffusion and polymer erosion. The amount of omeprazole permeating over 2h was 275 ug/cm(2) whilst the formulations and starting materials showed cell viability values greater than 95%, confirming their safety for potential use in paediatric buccal delivery. PMID:26802493

  9. Barriers to drug delivery in solid tumors.

    PubMed

    Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

    2014-01-01

    Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic. PMID:25068098

  10. Barriers to drug delivery in solid tumors

    PubMed Central

    Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

    2014-01-01

    Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic. PMID:25068098

  11. Ultrasound-mediated gastrointestinal drug delivery.

    PubMed

    Schoellhammer, Carl M; Schroeder, Avi; Maa, Ruby; Lauwers, Gregory Yves; Swiston, Albert; Zervas, Michael; Barman, Ross; DiCiccio, Angela M; Brugge, William R; Anderson, Daniel G; Blankschtein, Daniel; Langer, Robert; Traverso, Giovanni

    2015-10-21

    There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn's and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.

  12. Ultrasound-mediated gastrointestinal drug delivery

    PubMed Central

    Schoellhammer, Carl M.; Schroeder, Avi; Maa, Ruby; Lauwers, Gregory Yves; Swiston, Albert; Zervas, Michael; Barman, Ross; DiCiccio, Angela M.; Brugge, William R.; Anderson, Daniel G.; Blankschtein, Daniel; Langer, Robert; Traverso, Giovanni

    2016-01-01

    There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn’s and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease. PMID:26491078

  13. Light induced drug delivery into cancer cells.

    PubMed

    Shamay, Yosi; Adar, Lily; Ashkenasy, Gonen; David, Ayelet

    2011-02-01

    Cell-penetrating peptides (CPPs) can be used for intracellular delivery of a broad variety of cargoes, including various nanoparticulate pharmaceutical carriers. However, the cationic nature of all CPP sequences, and thus lack of cell specificity, limits their in vivo use for drug delivery applications. Here, we have devised and tested a strategy for site-specific delivery of dyes and drugs into cancer cells by using polymers bearing a light activated caged CPP (cCPP). The positive charge of Lys residues on the minimum sequence of the CPP penetratin ((52)RRMKWKK(58)) was masked with photo-cleavable groups to minimize non-specific adsorption and cellular uptake. Once illuminated by UV light, these protecting groups were cleaved, the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the polymer-dye or polymer-drug conjugates into cancer cells. We have found that a 10-min light illumination time was sufficient to enhance the penetration of the polymer-CPP conjugates bearing the proapoptotic peptide, (D)(KLAKLAK)(2), into 80% of the target cells, and to promote a 'switch' like cytotoxic activity resulting a shift from 100% to 10% in cell viability after 2 h. This report provides an example for tumor targeting by means of light activation of cell-penetrating peptides for intracellular drug delivery. PMID:21074848

  14. Light induced drug delivery into cancer cells.

    PubMed

    Shamay, Yosi; Adar, Lily; Ashkenasy, Gonen; David, Ayelet

    2011-02-01

    Cell-penetrating peptides (CPPs) can be used for intracellular delivery of a broad variety of cargoes, including various nanoparticulate pharmaceutical carriers. However, the cationic nature of all CPP sequences, and thus lack of cell specificity, limits their in vivo use for drug delivery applications. Here, we have devised and tested a strategy for site-specific delivery of dyes and drugs into cancer cells by using polymers bearing a light activated caged CPP (cCPP). The positive charge of Lys residues on the minimum sequence of the CPP penetratin ((52)RRMKWKK(58)) was masked with photo-cleavable groups to minimize non-specific adsorption and cellular uptake. Once illuminated by UV light, these protecting groups were cleaved, the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the polymer-dye or polymer-drug conjugates into cancer cells. We have found that a 10-min light illumination time was sufficient to enhance the penetration of the polymer-CPP conjugates bearing the proapoptotic peptide, (D)(KLAKLAK)(2), into 80% of the target cells, and to promote a 'switch' like cytotoxic activity resulting a shift from 100% to 10% in cell viability after 2 h. This report provides an example for tumor targeting by means of light activation of cell-penetrating peptides for intracellular drug delivery.

  15. Drug delivery and nanoparticles: Applications and hazards

    PubMed Central

    De Jong, Wim H; Borm, Paul JA

    2008-01-01

    The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells

  16. Transungual drug delivery: current status.

    PubMed

    Elkeeb, Rania; AliKhan, Ali; Elkeeb, Laila; Hui, Xiaoying; Maibach, Howard I

    2010-01-15

    Topical therapy is highly desirable in treating nail disorders due to its localized effects, which results in minimal adverse systemic events and possibly improved adherence. However, the effectiveness of topical therapies is limited by minimal drug permeability through the nail plate. Current research on nail permeation that focuses on altering the nail plate barrier by means of chemical treatments, penetration enhancers as well as physical and mechanical methods is reviewed. A new method of nail sampling is examined. Finally limitations of current ungual drug permeability studies are briefly discussed. PMID:19819318

  17. Transungual drug delivery: current status.

    PubMed

    Elkeeb, Rania; AliKhan, Ali; Elkeeb, Laila; Hui, Xiaoying; Maibach, Howard I

    2010-01-15

    Topical therapy is highly desirable in treating nail disorders due to its localized effects, which results in minimal adverse systemic events and possibly improved adherence. However, the effectiveness of topical therapies is limited by minimal drug permeability through the nail plate. Current research on nail permeation that focuses on altering the nail plate barrier by means of chemical treatments, penetration enhancers as well as physical and mechanical methods is reviewed. A new method of nail sampling is examined. Finally limitations of current ungual drug permeability studies are briefly discussed.

  18. Recent technologies in pulsatile drug delivery systems

    PubMed Central

    Jain, Deepika; Raturi, Richa; Jain, Vikas; Bansal, Praveen; Singh, Ranjit

    2011-01-01

    Pulsatile drug delivery systems (PDDS) have attracted attraction because of their multiple benefits over conventional dosage forms. They deliver the drug at the right time, at the right site of action and in the right amount, which provides more benefit than conventional dosages and increased patient compliance. These systems are designed according to the circadian rhythm of the body, and the drug is released rapidly and completely as a pulse after a lag time. These products follow the sigmoid release profile characterized by a time period. These systems are beneficial for drugs with chronopharmacological behavior, where nocturnal dosing is required, and for drugs that show the first-pass effect. This review covers methods and marketed technologies that have been developed to achieve pulsatile delivery. Marketed technologies, such as PulsincapTM, Diffucaps®, CODAS®, OROS® and PULSYSTM, follow the above mechanism to render a sigmoidal drug release profile. Diseases wherein PDDS are promising include asthma, peptic ulcers, cardiovascular ailments, arthritis and attention deficit syndrome in children and hypercholesterolemia. Pulsatile drug delivery systems have the potential to bring new developments in the therapy of many diseases. PMID:23507727

  19. Plasmon resonant liposomes for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Knights-Mitchell, Shellie S.; Romanowski, Marek

    2015-03-01

    Nanotechnology use in drug delivery promotes a reduction in systemic toxicity, improved pharmacokinetics, and better drug bioavailability. Liposomes continue to be extensively researched as drug delivery systems (DDS) with formulations such as Doxil® and Ambisome® approved by FDA and successfully marketed in the United States. However, the limited ability to precisely control release of active ingredients from these vesicles continues to challenge the broad implementation of this technology. Moreover, the full potential of the carrier to sequester drugs until it can reach its intended target has yet to be realized. Here, we describe a liposomal DDS that releases therapeutic doses of an anticancer drug in response to external stimulus. Earlier, we introduced degradable plasmon resonant liposomes. These constructs, obtained by reducing gold on the liposome surface, facilitate spatial and temporal release of drugs upon laser light illumination that ultimately induces an increase in temperature. In this work, plasmon resonant liposomes have been developed to stably encapsulate and retain doxorubicin at physiological conditions represented by isotonic saline at 37o C and pH 7.4. Subsequently, they are stimulated to release contents either by a 5o C increase in temperature or by laser illumination (760 nm and 88 mW/cm2 power density). Successful development of degradable plasmon resonant liposomes responsive to near-infrared light or moderate hyperthermia can provide a new delivery method for multiple lipophilic and hydrophilic drugs with pharmacokinetic profiles that limit clinical utility.

  20. Drug delivery system and breast cancer cells

    NASA Astrophysics Data System (ADS)

    Colone, Marisa; Kaliappan, Subramanian; Calcabrini, Annarica; Tortora, Mariarosaria; Cavalieri, Francesca; Stringaro, Annarita

    2016-06-01

    Recently, nanomedicine has received increasing attention for its ability to improve the efficacy of cancer therapeutics. Nanosized polymer therapeutic agents offer the advantage of prolonged circulation in the blood stream, targeting to specific sites, improved efficacy and reduced side effects. In this way, local, controlled delivery of the drug will be achieved with the advantage of a high concentration of drug release at the target site while keeping the systemic concentration of the drug low, thus reducing side effects due to bioaccumulation. Various drug delivery systems such as nanoparticles, liposomes, microparticles and implants have been demonstrated to significantly enhance the preventive/therapeutic efficacy of many drugs by increasing their bioavailability and targetability. As these carriers significantly increase the therapeutic effect of drugs, their administration would become less cost effective in the near future. The purpose of our research work is to develop a delivery system for breast cancer cells using a microvector of drugs. These results highlight the potential uses of these responsive platforms suited for biomedical and pharmaceutical applications. At the request of all authors of the paper an updated version was published on 12 July 2016. The manuscript was prepared and submitted without Dr. Francesca Cavalieri's contribution and her name was added without her consent. Her name has been removed in the updated and re-published article.

  1. Aptamers for Targeted Drug Delivery

    PubMed Central

    Ray, Partha; White, Rebekah R.

    2010-01-01

    Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX). SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery. PMID:27713328

  2. Aptamers for Targeted Drug Delivery

    PubMed Central

    Ray, Partha; White, Rebekah R.

    2010-01-01

    Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX). SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

  3. Tuberculosis chemotherapy: current drug delivery approaches

    PubMed Central

    du Toit, Lisa Claire; Pillay, Viness; Danckwerts, Michael Paul

    2006-01-01

    Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance. PMID:16984627

  4. Nanocarriers for delivery of platinum anticancer drugs.

    PubMed

    Oberoi, Hardeep S; Nukolova, Natalia V; Kabanov, Alexander V; Bronich, Tatiana K

    2013-11-01

    Platinum based anticancer drugs have revolutionized cancer chemotherapy, and continue to be in widespread clinical use especially for management of tumors of the ovary, testes, and the head and neck. However, several dose limiting toxicities associated with platinum drug use, partial anti-tumor response in most patients, development of drug resistance, tumor relapse, and many other challenges have severely limited the patient quality of life. These limitations have motivated an extensive research effort towards development of new strategies for improving platinum therapy. Nanocarrier-based delivery of platinum compounds is one such area of intense research effort beginning to provide encouraging preclinical and clinical results and may allow the development of the next generation of platinum chemotherapy. This review highlights current understanding on the pharmacology and limitations of platinum compounds in clinical use, and provides a comprehensive analysis of various platinum-polymer complexes, micelles, dendrimers, liposomes and other nanoparticles currently under investigation for delivery of platinum drugs.

  5. Drug delivery applications with ethosomes.

    PubMed

    Ainbinder, D; Paolino, D; Fresta, M; Touitou, E

    2010-10-01

    Ethosomes are specially tailored vesicular carriers able to efficiently deliver various molecules with different physicochemical properties into deep skin layers and across the skin. This paper reviews the unique characteristics of the ethosomal carriers, focusing on work carried out with drug containing ethosomal systems in animal models and in clinical studies. The paper concludes with a discussion on the safety of the ethosomal system applications.

  6. Drug delivery applications with ethosomes.

    PubMed

    Ainbinder, D; Paolino, D; Fresta, M; Touitou, E

    2010-10-01

    Ethosomes are specially tailored vesicular carriers able to efficiently deliver various molecules with different physicochemical properties into deep skin layers and across the skin. This paper reviews the unique characteristics of the ethosomal carriers, focusing on work carried out with drug containing ethosomal systems in animal models and in clinical studies. The paper concludes with a discussion on the safety of the ethosomal system applications. PMID:21329048

  7. Preparation and pharmaceutical evaluation of glibenclamide slow release mucoadhesive buccal film

    PubMed Central

    Bahri-Najafi, R.; Tavakoli, N.; Senemar, M.; Peikanpour, M.

    2014-01-01

    Buccal mucoadhesive systems among novel drug delivery systems have attracted great attention in recent years due to their ability to adhere and remain on the oral mucosa and to release their drug content gradually. Buccal mucoadhesive films can improve the drug therapeutic effect by enhancement of drug absorption through oral mucosa increasing the drug bioavailability via reducing the hepatic first pass effect. The aim of the current study was to formulate the drug as buccal bioadhesive film, which releases the drug at sufficient concentration with a sustain manner reducing the frequency of the dosage form administration. One of the advantagees of this formulation is better patient compliances due to the ease of administration with no water to swallow the product. The mucoadhesive films of glibenclamide were prepared using hydroxypropyl methylcellulose (HPMC) K4M, K15M and Eudragit RL100 polymers and propylene glycol as plasticizer and co-solvent. Films were prepared using solvent casting method, and were evaluated with regard to drug content, thickness, weight variations, swelling index, tensile strength, ex vivo adhesion force and percentage of in vitro drug release. Films with high concentrations of HPMC K4M and K15M did not have favorable appearance and uniformity. The formulations prepared from Eudragit were transparent, uniform, flexible, and without bubble. The highest and the lowest percentages of swelling were observed for the films containing HPMC K15M and Eudragit RL100, respectively. Films made of HPMC K15M had adhesion force higher than those containing Eudragit RL100. Formulations with Eudragit RL100 showed the highest mean dissolution time (MDT). Drug release kinetics of all formulations followed Higuchi's model and the mechanism of diffusion was considered non-Fickian type. It was concluded that formulations containing Eudragit RL100 were more favorable than others with regard to uniformity, flexibility, rate and percentage of drug release. PMID

  8. Maximized mucoadhesion and skin permeation of anti-AIDS-loaded niosomal gels.

    PubMed

    Zidan, Ahmed S; Habib, Muhammad J

    2014-03-01

    The low permeability of the anti-AIDS, tenofovir, limits its antiretroviral clinical potency. The proposed study aimed at assessing the critical biological responses of tenofovir through the development and optimization of its surfactant-based niosomal gels intended for vaginal delivery. Fatty acid chain length of the amphiphile and cholesterol loading were optimized using a 3² full factorial design. Vesicular size, shape and surface charge, drug entrapment efficiency, in vitro release, and skin permeation were used to assess the gels. In addition, their biological performance on Lactobacillus crispatus viability and mucoadhesion to porcine vaginal tissue was also assessed. Within the design space, mucoadhesion percentage ranged from 6.2% to 28.6% and increased nonlinearly by decreasing niosomal vesicular size and linearly by increasing surface charge. Moreover, these gels were not cytotoxic to Lactobacillus crispatus for 48 h. For maximizing tenofovir entrapment, percutaneous permeation, and mucoadhesion while achieving sustained-release features, an optimum formulation was proposed with the shortest length of fatty chain and 0.48 mM cholesterol content. Overall, applying quality by design paradigm to the development of tenofovir niosomal gels not only offered a promising nanomedicine for the vaginal microbicide delivery but also unveiled the critical formulation interactions influencing its biological performance.

  9. Optically generated ultrasound for enhanced drug delivery

    DOEpatents

    Visuri, Steven R.; Campbell, Heather L.; Da Silva, Luiz

    2002-01-01

    High frequency acoustic waves, analogous to ultrasound, can enhance the delivery of therapeutic compounds into cells. The compounds delivered may be chemotherapeutic drugs, antibiotics, photodynamic drugs or gene therapies. The therapeutic compounds are administered systemically, or preferably locally to the targeted site. Local delivery can be accomplished through a needle, cannula, or through a variety of vascular catheters, depending on the location of routes of access. To enhance the systemic or local delivery of the therapeutic compounds, high frequency acoustic waves are generated locally near the target site, and preferably near the site of compound administration. The acoustic waves are produced via laser radiation interaction with an absorbing media and can be produced via thermoelastic expansion, thermodynamic vaporization, material ablation, or plasma formation. Acoustic waves have the effect of temporarily permeabilizing the membranes of local cells, increasing the diffusion of the therapeutic compound into the cells, allowing for decreased total body dosages, decreased side effects, and enabling new therapies.

  10. Local drug and gene delivery through microbubbles.

    PubMed

    Unger, E C; Hersh, E; Vannan, M; Matsunaga, T O; McCreery, T

    2001-01-01

    Ultrasound contrast agents (microbubbles) lower the threshold for cavitation by ultrasound energy. Ultrasound microbubbles may be used as cavitation nuclei for drug and gene delivery. By tailoring the physical properties of microbubbles and coating materials, drugs and genetic drugs can be incorporated into ultrasound contrast agents. As the microbubbles enter the region of insonation, the microbubbles cavitate, locally releasing the therapeutic agents. Cavitation also causes a local shockwave that improves cellular uptake of the therapeutic agent. As a result of the human genome project and continuing advances in molecular biology, many therapeutic genes have been discovered. In the cardiovascular system, gene therapy has the potential to improve myocardial vascularization and ameliorate congestive heart failure. For successful development of clinical gene therapy, however, effective gene delivery vectors are needed. Ultrasound contrast agents can be used to develop new, more effective vectors for gene delivery. Transthoracic ultrasound can be focused on the heart so that an intravenous injection of gene-bearing microbubbles will deliver genes relatively selectively to the myocardium. Using this technique, we have produced high levels of transgene expression in the insonated region of the myocardium. This new technology, using microbubbles and ultrasound for drug and gene delivery, merits further study and development.

  11. Intravesical drug delivery for dysfunctional bladder.

    PubMed

    Hsu, Chun-Chien; Chuang, Yao-Chi; Chancellor, Michael B

    2013-06-01

    The bladder is a hollow organ that can be treated locally by transurethral catheter for intravesical drug instillation or cystoscopy for intravesical drug injection. With advancing technology, local organ-specific therapy and drug delivery is of expanding interest for treating dysfunctional bladder, including interstitial cystitis/bladder pain syndrome, overactive bladder and sterile hemorrhagic cystitis after chemotherapy or pelvic radiation. Intravesical therapy has shown varying degrees of efficacy and safety in treating interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with new modalities being developed. Intravesical (regional) therapy has several advantages than oral (systemic) therapy, including high local concentration and less systemic toxicity. In recent years, intravesical delivery of biotechnological products including neurotoxins and immunosuppressive agents, and delivery platform including liposomes has shown promise for lower urinary tract symptoms. This review considers the current status of intravesical therapy in dysfunctional bladder including interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with special attention to lipid based novel drug-delivery.

  12. Recent Perspectives in Ocular Drug Delivery

    PubMed Central

    Gaudana, Ripal; Jwala, J.; Boddu, Sai H. S.; Mitra, Ashim K.

    2015-01-01

    Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders. PMID:18758924

  13. Inhalation delivery of asthma drugs.

    PubMed

    Matthys, H

    1990-01-01

    In the immediate future, metered-dose inhalers (MDIs) with spacers remain the aerosol application of choice for topical steroids, mainly to reduce side effects. For beta 2-agonist, anticholinergics and prophylactic drugs, MDI (with or without demand valve), dry powder inhalers (multidose inhalers), ultrasonic or jet aerosol generators (with or without mechanical breathing assistance [IPPB]) are chosen according to the preference or the ability of the patients to perform the necessary breathing maneuvers as well as the availability of different products in different countries.

  14. Strategies for antimicrobial drug delivery to biofilm.

    PubMed

    Martin, Claire; Low, Wan Li; Gupta, Abhishek; Amin, Mohd Cairul Iqbal Mohd; Radecka, Iza; Britland, Stephen T; Raj, Prem; Kenward, Ken M A

    2015-01-01

    Biofilms are formed by the attachment of single or mixed microbial communities to a variety of biological and/or synthetic surfaces. Biofilm micro-organisms benefit from many advantages of the polymicrobial environment including increased resistance against antimicrobials and protection against the host organism's defence mechanisms. These benefits stem from a number of structural and physiological differences between planktonic and biofilm-resident microbes, but two main factors are the presence of extracellular polymeric substances (EPS) and quorum sensing communication. Once formed, biofilms begin to synthesise EPS, a complex viscous matrix composed of a variety of macromolecules including proteins, lipids and polysaccharides. In terms of drug delivery strategies, it is the EPS that presents the greatest barrier to diffusion for drug delivery systems and free antimicrobial agents alike. In addition to EPS synthesis, biofilm-based micro-organisms can also produce small, diffusible signalling molecules involved in cell density-dependent intercellular communication, or quorum sensing. Not only does quorum sensing allow microbes to detect critical cell density numbers, but it also permits co-ordinated behaviour within the biofilm, such as iron chelation and defensive antibiotic activities. Against this backdrop of microbial defence and cell density-specific communication, a variety of drug delivery systems have been developed to deliver antimicrobial agents and antibiotics to extracellular and/or intracellular targets, or more recently, to interfere with the specific mechanisms of quorum sensing. Successful delivery strategies have employed lipidic and polymeric-based formulations such as liposomes and cyclodextrins respectively, in addition to inorganic carriers e.g. metal nanoparticles. This review will examine a range of drug delivery systems and their application to biofilm delivery, as well as pharmaceutical formulations with innate antimicrobial properties

  15. Mucoadhesive glycol chitosan nanoparticles for intranasal delivery of hepatitis B vaccine: enhancement of mucosal and systemic immune response.

    PubMed

    Pawar, Dilip; Jaganathan, K S

    2016-01-01

    In this study, for the first time, glycol chitosan (GC) nanoparticles (NPs) were prepared and evaluated to obtain systemic and mucosal immune responses against nasally administered hepatitis B surface antigen (HBsAg). Size, zeta potential and morphology of the NPs were investigated as a function of preparation method. NPs with high loading efficacy ( > 95%) and positively charged surface were obtained with an average particle size of approximately 200 nm. The structural integrity of HBsAg in NPs was evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis and further confirmed by measuring the in vitro antigenicity using an enzyme immunoassay. During in vivo studies, GC NPs showed the lowest nasal clearance rate and better mucosal uptake when compared with chitosan (CS) NPs. The immunogenicity of NPs-based delivery system(s) was assessed by measuring anti-HBsAg antibody titer in mice serum and secretions after intranasal administration. The alum-based HBsAg vaccine injected subcutaneously was used as positive control. Results indicated that alum-based HBsAg induced strong humoral but negligible mucosal immunity. However, GC NPs induced stronger immune response at both of the fronts as compared to generated by CS NPs. This study demonstrates that this newly developed system has potential for mucosal administration of vaccines.

  16. Structural DNA nanotechnology for intelligent drug delivery.

    PubMed

    Chao, Jie; Liu, Huajie; Su, Shao; Wang, Lianhui; Huang, Wei; Fan, Chunhai

    2014-11-01

    Drug delivery carriers have been popularly employed to improve solubility, stability, and efficacy of chemical and biomolecular drugs. Despite the rapid progress in this field, it remains a great challenge to develop an ideal carrier with minimal cytotoxicity, high biocompatibility and intelligence for targeted controlled release. The emergence of DNA nanotechnology offers unprecedented opportunities in this regard. Due to the unparalleled self-recognition properties of DNA molecules, it is possible to create numerous artificial DNA nanostructures with well-defined structures and DNA nanodevices with precisely controlled motions. More importantly, recent studies have proven that DNA nanostructures possess greater permeability to the membrane barrier of cells, which pave the way to developing new drug delivery carriers with nucleic acids, are summarized. In this Concept, recent advances on the design and fabrication of both static and dynamic DNA nanostructures, and the use of these nanostructures for the delivery of various types of drugs, are highlighted. It is also demonstrated that dynamic DNA nanostructures provide the required intelligence to realize logically controlled drug release.

  17. Advanced materials and nanotechnology for drug delivery.

    PubMed

    Yan, Li; Yang, Yang; Zhang, Wenjun; Chen, Xianfeng

    2014-08-20

    Many biological barriers are of great importance. For example, stratum corneum, the outmost layer of skin, effectively protects people from being invaded by external microorganisms such as bacteria and viruses. Cell membranes help organisms maintain homeostasis by controlling substances to enter and leave cells. However, on the other hand, these biological barriers seriously restrict drug delivery. For instance, stratum corneum has a very dense structure and only allows very small molecules with a molecular weight of below 500 Da to permeate whereas most drug molecules are much larger than that. A wide variety of drugs including genes needs to enter cells for proper functioning but cell membranes are not permeable to them. To overcome these biological barriers, many drug-delivery routes are being actively researched and developed. In this research news, we will focus on two advanced materials and nanotechnology approaches for delivering vaccines through the skin for painless and efficient immunization and transporting drug molecules to cross cell membranes for high-throughput intracellular delivery.

  18. Tight junction modulator and drug delivery.

    PubMed

    Matsuhisa, Koji; Kondoh, Masuo; Takahashi, Azusa; Yagi, Kiyohito

    2009-05-01

    Recent progress in pharmaceutical technology based on genomic and proteomic research has provided many drug candidates, including not only chemicals but peptides, antibodies and nucleic acids. These candidates do not show pharmaceutical activity without their absorption into systemic flow and movement from the systemic flow into the target tissue. Epithelial and endothelial cell sheets play a pivotal role in the barrier between internal and external body and tissues. Tight junctions (TJs) between adjacent epithelial cells limit the movement of molecules through the intercellular space in epithelial and endothelial cell sheets. Thus, a promising strategy for drug delivery is the modulation of TJ components to allow molecules to pass through the TJ-based cellular barriers. In this review, we discuss recent progress in the development of TJ modulators and the possibility of absorption enhancers and drug-delivery systems based on TJ components.

  19. A Molecular Communications Model for Drug Delivery.

    PubMed

    Femminella, Mauro; Reali, Gianluca; Vasilakos, Athanasios V

    2015-12-01

    This paper considers the scenario of a targeted drug delivery system, which consists of deploying a number of biological nanomachines close to a biological target (e.g., a tumor), able to deliver drug molecules in the diseased area. Suitably located transmitters are designed to release a continuous flow of drug molecules in the surrounding environment, where they diffuse and reach the target. These molecules are received when they chemically react with compliant receptors deployed on the receiver surface. In these conditions, if the release rate is relatively high and the drug absorption time is significant, congestion may happen, essentially at the receiver site. This phenomenon limits the drug absorption rate and makes the signal transmission ineffective, with an undesired diffusion of drug molecules elsewhere in the body. The original contribution of this paper consists of a theoretical analysis of the causes of congestion in diffusion-based molecular communications. For this purpose, it is proposed a reception model consisting of a set of pure loss queuing systems. The proposed model exhibits an excellent agreement with the results of a simulation campaign made by using the Biological and Nano-Scale communication simulator version 2 (BiNS2), a well-known simulator for molecular communications, whose reliability has been assessed through in vitro experiments. The obtained results can be used in rate control algorithms to optimally determine the optimal release rate of molecules in drug delivery applications.

  20. A new brain drug delivery strategy: focused ultrasound-enhanced intranasal drug delivery.

    PubMed

    Chen, Hong; Chen, Cherry C; Acosta, Camilo; Wu, Shih-Ying; Sun, Tao; Konofagou, Elisa E

    2014-01-01

    Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (i.n.) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+i.n.) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After i.n. administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (i.v.) drug injection is employed, FUS was also applied after i.v. injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+i.n. enhanced drug delivery within the targeted region compared with that achieved by i.n. only. Despite the fact that the i.n. route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+i.n. was not significantly different from that of FUS+i.v.. As a new drug delivery platform, the FUS+i.n. technique is potentially useful for treating CNS diseases.

  1. Assessment of test methods evaluating mucoadhesive polymers and dosage forms: an overview.

    PubMed

    Woertz, Christina; Preis, Maren; Breitkreutz, Jörg; Kleinebudde, Peter

    2013-11-01

    Oral mucoadhesive preparations have gained increasing importance in the last decades, by reason of numerous advantages like easy application, discrete handling and no swallowing of the drug product. Pharmacopoeial methods to study mucoadhesion are not available so far, despite the new monograph for oromucosal preparations is valid since the European Pharmacopoeia 7.4 (2012) including a chapter on mucoadhesive preparations. Several mucoadhesion test methods are reviewed concerning the applicability for various polymers, different drug dosage forms and comparability of experimental set-ups. Different test methods and experimental set-ups lead to huge differences regarding the results. PMID:23851076

  2. Assessment of test methods evaluating mucoadhesive polymers and dosage forms: an overview.

    PubMed

    Woertz, Christina; Preis, Maren; Breitkreutz, Jörg; Kleinebudde, Peter

    2013-11-01

    Oral mucoadhesive preparations have gained increasing importance in the last decades, by reason of numerous advantages like easy application, discrete handling and no swallowing of the drug product. Pharmacopoeial methods to study mucoadhesion are not available so far, despite the new monograph for oromucosal preparations is valid since the European Pharmacopoeia 7.4 (2012) including a chapter on mucoadhesive preparations. Several mucoadhesion test methods are reviewed concerning the applicability for various polymers, different drug dosage forms and comparability of experimental set-ups. Different test methods and experimental set-ups lead to huge differences regarding the results.

  3. Ultrasound-Mediated Polymeric Micelle Drug Delivery.

    PubMed

    Xia, Hesheng; Zhao, Yue; Tong, Rui

    2016-01-01

    The synthesis of multi-functional nanocarriers and the design of new stimuli-responsive means are equally important for drug delivery. Ultrasound can be used as a remote, non-invasive and controllable trigger for the stimuli-responsive release of nanocarriers. Polymeric micelles are one kind of potential drug nanocarrier. By combining ultrasound and polymeric micelles, a new modality (i.e., ultrasound-mediated polymeric micelle drug delivery) has been developed and has recently received increasing attention. A major challenge remaining in developing ultrasound-responsive polymeric micelles is the improvement of the sensitivity or responsiveness of polymeric micelles to ultrasound. This chapter reviews the recent advance in this field. In order to understand the interaction mechanism between ultrasound stimulus and polymeric micelles, ultrasound effects, such as thermal effect, cavitation effect, ultrasound sonochemistry (including ultrasonic degradation, ultrasound-initiated polymerization, ultrasonic in-situ polymerization and ultrasound site-specific degradation), as well as basic micellar knowledge are introduced. Ultrasound-mediated polymeric micelle drug delivery has been classified into two main streams based on the different interaction mechanism between ultrasound and polymeric micelles; one is based on the ultrasound-induced physical disruption of the micelle and reversible release of payload. The other is based on micellar ultrasound mechanochemical disruption and irreversible release of payload.

  4. BioMEMS in drug delivery.

    PubMed

    Nuxoll, Eric

    2013-11-01

    The drive to design micro-scale medical devices which can be reliably and uniformly mass produced has prompted many researchers to adapt processing technologies from the semiconductor industry. By operating at a much smaller length scale, the resulting biologically-oriented microelectromechanical systems (BioMEMS) provide many opportunities for improved drug delivery: Low-dose vaccinations and painless transdermal drug delivery are possible through precisely engineered microneedles which pierce the skin's barrier layer without reaching the nerves. Low-power, low-volume BioMEMS pumps and reservoirs can be implanted where conventional pumping systems cannot. Drug formulations with geometrically complex, extremely uniform micro- and nano-particles are formed through micromolding or with microfluidic devices. This review describes these BioMEMS technologies and discusses their current state of implementation. As these technologies continue to develop and capitalize on their simpler integration with other MEMS-based systems such as computer controls and telemetry, BioMEMS' impact on the field of drug delivery will continue to increase.

  5. Pharmaceutical technology, biopharmaceutics and drug delivery.

    PubMed

    Youn, Yu Seok; Lee, Beom-Jin

    2011-03-01

    The 40th annual international conference of the Korean Society of Pharmaceutical Sciences and Technology on Pharmaceutical Technology, Biopharmaceutics and Drug Delivery was held on 2-3 December 2010 in Jeju Special Self-Governing Providence, Korea, to celebrate its 40th anniversary. A comprehensive review of a wide spectrum of recent topics on pharmaceutical technology, biopharmaceutics and drug delivery was presented. Invited lectures and poster presentations over 2 days were divided into six parallel sessions covering areas such as biotechnology, biopharmaceutics, drug delivery, formulation/manufacture, regulatory science and frontier science. Among these, there were two sessions related to regulatory science and biopharmaceutics that were co-sponsored by the Korea Food and Drug Administration. In fact, this conference provided an opportunity for many investigators to discuss their research, collect new information and to promote the advancement of knowledge in each pharmaceutical area. This conference report summarizes the keynote podium presentations provided by many distinguished speakers, including Gordon L Amidon of the University of Michigan.

  6. Drug delivery nanoparticles in skin cancers.

    PubMed

    Dianzani, Chiara; Zara, Gian Paolo; Maina, Giovanni; Pettazzoni, Piergiorgio; Pizzimenti, Stefania; Rossi, Federica; Gigliotti, Casimiro Luca; Ciamporcero, Eric Stefano; Daga, Martina; Barrera, Giuseppina

    2014-01-01

    Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported.

  7. Drug Delivery Nanoparticles in Skin Cancers

    PubMed Central

    Dianzani, Chiara; Zara, Gian Paolo; Maina, Giovanni; Pettazzoni, Piergiorgio; Pizzimenti, Stefania; Rossi, Federica; Gigliotti, Casimiro Luca; Ciamporcero, Eric Stefano; Daga, Martina; Barrera, Giuseppina

    2014-01-01

    Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported. PMID:25101298

  8. ATP-triggered anticancer drug delivery

    NASA Astrophysics Data System (ADS)

    Mo, Ran; Jiang, Tianyue; Disanto, Rocco; Tai, Wanyi; Gu, Zhen

    2014-03-01

    Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 μM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.

  9. Pectin-coated chitosan-LDH bionanocomposite beads as potential systems for colon-targeted drug delivery.

    PubMed

    Ribeiro, Lígia N M; Alcântara, Ana C S; Darder, Margarita; Aranda, Pilar; Araújo-Moreira, Fernando M; Ruiz-Hitzky, Eduardo

    2014-03-10

    This work introduces results on a new drug delivery system (DDS) based on the use of chitosan/layered double hydroxide (LDH) biohybrid beads coated with pectin for controlled release in the treatment of colon diseases. Thus, the 5-aminosalicylic acid (5ASA), the most used non-steroid-anti-inflammatory drug (NSAID) in the treatment of ulcerative colitis and Crohn's disease, was chosen as model drug aiming to a controlled and selective delivery in the colon. The pure 5ASA drug and the hybrid material prepared by intercalation in a layered double hydroxide of Mg2Al using the co-precipitation method, were incorporated in a chitosan matrix in order to profit from its mucoadhesiveness. These compounds processed as beads were further treated with the polysaccharide pectin to create a protective coating that ensures the stability of both chitosan and layered double hydroxide at the acid pH of the gastric fluid. The resulting composite beads presenting the pectin coating are stable to water swelling and procure a controlled release of the drug along their passage through the simulated gastrointestinal tract in in vitro experiments, due to their resistance to pH changes. Based on these results, the pectin@chitosan/LDH-5ASA bionanocomposite beads could be proposed as promising candidates for the colon-targeted delivery of 5ASA, with the aim of acting only in the focus of the disease and minimizing side effects.

  10. Limited Efficiency of Drug Delivery to Specific Intracellular Organelles Using Subcellularly "Targeted" Drug Delivery Systems.

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2016-01-01

    Many drugs have been designed to act on intracellular targets and to affect intracellular processes inside target cells. For the desired effects to be exerted, these drugs should permeate target cells and reach specific intracellular organelles. This subcellular drug targeting approach has been proposed for enhancement of accumulation of these drugs in target organelles and improved efficiency. This approach is based on drug encapsulation in drug delivery systems (DDSs) and/or their decoration with specific targeting moieties that are intended to enhance the drug/DDS accumulation in the intracellular organelle of interest. During recent years, there has been a constant increase in interest in DDSs targeted to specific intracellular organelles, and many different approaches have been proposed for attaining efficient drug delivery to specific organelles of interest. However, it appears that in many studies insufficient efforts have been devoted to quantitative analysis of the major formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and endosomal escape, intracellular trafficking, and efficiency of DDS delivery to the target organelle) and of the resulting pharmacological effects. Thus, in many cases, claims regarding efficient delivery of drug/DDS to a specific organelle and efficient subcellular targeting appear to be exaggerated. On the basis of the available experimental data, it appears that drugs/DDS decoration with specific targeting residues can affect their intracellular fate and result in preferential drug accumulation within an organelle of interest. However, it is not clear whether these approaches will be efficient in in vivo settings and be translated into preclinical and clinical applications. Studies that quantitatively assess the mechanisms, barriers, and efficiencies of subcellular drug delivery and of the associated toxic effects are required to determine the therapeutic potential of subcellular DDS targeting.

  11. Polymeric multilayer capsules in drug delivery.

    PubMed

    De Cock, Liesbeth J; De Koker, Stefaan; De Geest, Bruno G; Grooten, Johan; Vervaet, Chris; Remon, Jean Paul; Sukhorukov, Gleb B; Antipina, Maria N

    2010-09-17

    Recent advances in medicine and biotechnology have prompted the need to develop nanoengineered delivery systems that can encapsulate a wide variety of novel therapeutics such as proteins, chemotherapeutics, and nucleic acids. Moreover, these delivery systems should be "intelligent", such that they can deliver their payload at a well-defined time, place, or after a specific stimulus. Polymeric multilayer capsules, made by layer-by-layer (LbL) coating of a sacrificial template followed by dissolution of the template, allow the design of microcapsules in aqueous conditions by using simple building blocks and assembly procedures, and provide a previously unmet control over the functionality of the microcapsules. Polymeric multilayer capsules have recently received increased interest from the life science community, and many interesting systems have appeared in the literature with biodegradable components and biospecific functionalities. In this Review we give an overview of the recent breakthroughs in their application for drug delivery.

  12. Ultraviolet light-mediated drug delivery: Principles, applications, and challenges.

    PubMed

    Barhoumi, Aoune; Liu, Qian; Kohane, Daniel S

    2015-12-10

    UV light has been extensively employed in drug delivery because of its versatility, ease of manipulation, and ability to induce chemical changes on the therapeutic carrier. Here we review the mechanisms by which UV light affects drug delivery systems. We will present the challenges facing UV-induced drug delivery and some of the proposed solutions.

  13. Nanotechnology Approaches for Ocular Drug Delivery

    PubMed Central

    Xu, Qingguo; Kambhampati, Siva P.; Kannan, Rangaramanujam M.

    2013-01-01

    Blindness is a major health concern worldwide that has a powerful impact on afflicted individuals and their families, and is associated with enormous socio-economical consequences. The Middle East is heavily impacted by blindness, and the problem there is augmented by an increasing incidence of diabetes in the population. An appropriate drug/gene delivery system that can sustain and deliver therapeutics to the target tissues and cells is a key need for ocular therapies. The application of nanotechnology in medicine is undergoing rapid progress, and the recent developments in nanomedicine-based therapeutic approaches may bring significant benefits to address the leading causes of blindness associated with cataract, glaucoma, diabetic retinopathy and retinal degeneration. In this brief review, we highlight some promising nanomedicine-based therapeutic approaches for drug and gene delivery to the anterior and posterior segments. PMID:23580849

  14. Diatomite silica nanoparticles for drug delivery

    NASA Astrophysics Data System (ADS)

    Ruggiero, Immacolata; Terracciano, Monica; Martucci, Nicola M.; De Stefano, Luca; Migliaccio, Nunzia; Tatè, Rosarita; Rendina, Ivo; Arcari, Paolo; Lamberti, Annalisa; Rea, Ilaria

    2014-07-01

    Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery.

  15. Inhalation drug delivery devices: technology update

    PubMed Central

    Ibrahim, Mariam; Verma, Rahul; Garcia-Contreras, Lucila

    2015-01-01

    The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler device, and the patient. However, the biggest single problem that accounts for the lack of desired effect or adverse outcomes is the incorrect use of the device due to lack of training in how to use the device or how to coordinate actuation and aerosol inhalation. This review summarizes the structural and mechanical features of aerosol delivery devices with respect to mechanisms of aerosol generation, their use with different formulations, and their advantages and limitations. A technological update of the current state-of-the-art designs proposed to overcome current challenges of existing devices is also provided. PMID:25709510

  16. Nanogel Carrier Design for Targeted Drug Delivery

    PubMed Central

    Eckmann, D. M.; Composto, R. J.; Tsourkas, A.; Muzykantov, V. R.

    2014-01-01

    Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions. PMID:25485112

  17. Intratumoral Drug Delivery with Nanoparticulate Carriers

    PubMed Central

    Holback, Hillary

    2011-01-01

    Stiff extracellular matrix, elevated interstitial fluid pressure, and the affinity for the tumor cells in the peripheral region of a solid tumor mass have long been recognized as significant barriers to diffusion of small-molecular-weight drugs and antibodies. However, their impacts on nanoparticle-based drug delivery have begun to receive due attention only recently. This article reviews biological features of many solid tumors that influence transport of drugs and nanoparticles and properties of nanoparticles relevant to their intratumoral transport, studied in various tumor models. We also discuss several experimental approaches employed to date for enhancement of intratumoral nanoparticle penetration. The impact of nanoparticle distribution on the effectiveness of chemotherapy remains to be investigated and should be considered in the design of new nanoparticulate drug carriers. PMID:21213021

  18. Injected nanocrystals for targeted drug delivery

    PubMed Central

    Lu, Yi; Li, Ye; Wu, Wei

    2016-01-01

    Nanocrystals are pure drug crystals with sizes in the nanometer range. Due to the advantages of high drug loading, platform stability, and ease of scaling-up, nanocrystals have been widely used to deliver poorly water-soluble drugs. Nanocrystals in the blood stream can be recognized and sequestered as exogenous materials by mononuclear phagocytic system (MPS) cells, leading to passive accumulation in MPS-rich organs, such as liver, spleen and lung. Particle size, morphology and surface modification affect the biodistribution of nanocrystals. Ligand conjugation and stimuli-responsive polymers can also be used to target nanocrystals to specific pathogenic sites. In this review, the progress on injected nanocrystals for targeted drug delivery is discussed following a brief introduction to nanocrystal preparation methods, i.e., top-down and bottom-up technologies. PMID:27006893

  19. Microneedle Coating Techniques for Transdermal Drug Delivery

    PubMed Central

    Haj-Ahmad, Rita; Khan, Hashim; Arshad, Muhammad Sohail; Rasekh, Manoochehr; Hussain, Amjad; Walsh, Susannah; Li, Xiang; Chang, Ming-Wei; Ahmad, Zeeshan

    2015-01-01

    Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates. PMID:26556364

  20. Zwitterionic drug nanocarriers: a biomimetic strategy for drug delivery.

    PubMed

    Jin, Qiao; Chen, Yangjun; Wang, Yin; Ji, Jian

    2014-12-01

    Nanomaterials self-assembled from amphiphilic functional copolymers have emerged as safe and efficient nanocarriers for delivery of therapeutics. Surface engineering of the nanocarriers is extremely important for the design of drug delivery systems. Bioinspired zwitterions are considered as novel nonfouling materials to construct biocompatible and bioinert nanocarriers. As an alternative to poly(ethylene glycol) (PEG), zwitterions exhibit some unique properties that PEG do not have. In this review, we highlight recent progress of the design of drug nanocarriers using a zwitterionic strategy. The possible mechanism of stealth properties of zwitterions was proposed. The advantages of zwitterionic drug nanocarriers deriving from phosphorylcholine (PC), carboxybetaine (CB), and sulfobetaine (SB) are also discussed. PMID:25092584

  1. Preparation and in vitro characterization of mucoadhesive hydroxypropyl guar microspheres containing amlodipine besylate for nasal administration.

    PubMed

    Swamy, N G N; Abbas, Z

    2011-11-01

    Amlodipine besylate microspheres for intranasal administration were prepared with an aim to avoid first-pass metabolism, to achieve controlled blood level profiles and to improve therapeutic efficacy. Hydroxypropyl Guar, a biodegradable polymer, was used in the preparation of microspheres by employing water in oil emulsification solvent evaporation technique. The formulation variables were drug concentration, emulsifier concentration, temperature, agitation speed and polymer concentration. All the formulations were evaluated for particle size, particle shape and surface morphology by scanning electron microscopy, percentage yield, drug entrapment efficiency, in vitro mucoadhesion test, degree of swelling and in vitro drug diffusion through sheep nasal mucosa. The microspheres obtained were free flowing, spherical and the particles ranged in size from 13.4±2.38 μm to 43.4±1.92 μm very much suitable for nasal delivery. Increasing polymer concentration resulted in increased drug entrapment efficiency and increased particle size. Amlodipine besylate was entrapped into the microspheres with an efficiency of 67.2±1.18 % to 81.8±0.64 %. The prepared microspheres showed good mucoadhesion properties, swellability and sustained the release of the drug over a period of 8 h. The data obtained were analysed by fitment into various kinetic models; it was observed that the drug release was matrix diffusion controlled and the release mechanism was found to be non-Fickian. Stability studies were carried out on selected formulations at 5±3°, 25±2°/60±5% RH and 40±2°/75±5% RH for 90 days. The drug content was observed to be within permissible limits and there were no significant deviations in the in vitro mucoadhesion and in vitro drug diffusion characteristics. PMID:23112393

  2. PEGylated Silk Nanoparticles for Anticancer Drug Delivery.

    PubMed

    Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew J; Seib, F Philipp

    2015-11-01

    Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of "stealth" design principals is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system. We first generated B. mori derived silk nanoparticles by driving β-sheet assembly (size 104 ± 1.7 nm, zeta potential -56 ± 5.6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using clinically established and emerging anticancer drugs. Overall, PEGylated silk nanoparticles showed high encapsulation efficiency (>93%) and a pH-dependent release over 14 days. Finally, we demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied as single and combination nanomedicines to human breast cancer cells. In conclusion, these results, taken together with prior silk nanoparticle data, support a viable future for silk-based nanomedicines. PMID:26418537

  3. PEGylated Silk Nanoparticles for Anticancer Drug Delivery.

    PubMed

    Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew J; Seib, F Philipp

    2015-11-01

    Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of "stealth" design principals is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system. We first generated B. mori derived silk nanoparticles by driving β-sheet assembly (size 104 ± 1.7 nm, zeta potential -56 ± 5.6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using clinically established and emerging anticancer drugs. Overall, PEGylated silk nanoparticles showed high encapsulation efficiency (>93%) and a pH-dependent release over 14 days. Finally, we demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied as single and combination nanomedicines to human breast cancer cells. In conclusion, these results, taken together with prior silk nanoparticle data, support a viable future for silk-based nanomedicines.

  4. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

    A novel ultrasound-mediated drug delivery system has been developed for treatment of a nail fungal disorder (onychomycosis) by improving delivery to the nail bed using ultrasound to increase the permeability of the nail. The slip-in device consists of ultrasound transducers and drug delivery compartments above each toenail. The device is connected to a computer, where a software interface allows users to select their preferred course of treatment. In in vitro testing, canine nails were exposed to 3 energy levels (acoustic power of 1.2 W and exposure durations of 30, 60, and 120 seconds). A stereo -microscope was used to determine how much of a drug-mimicking compound was delivered through the nail layers by measuring brightness on the cross section of each nail tested at each condition, where brightness level decreases coincide with increases in permeability. Each of the 3 energy levels tested showed statistical significance when compared to the control (P < .05) with a permeability factor of 1.3 after 30 seconds of exposure, 1.3 after 60 seconds, and 1.5 after 120 seconds, where a permeability factor of 1 shows no increase in permeability. Current treatments for onychomycosis include systemic, topical, and surgical. Even when used all together, these treatments typically take a long time to result in nail healing, thus making this ultrasound-mediated device a promising alternative. PMID:22124008

  5. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

    A novel ultrasound-mediated drug delivery system has been developed for treatment of a nail fungal disorder (onychomycosis) by improving delivery to the nail bed using ultrasound to increase the permeability of the nail. The slip-in device consists of ultrasound transducers and drug delivery compartments above each toenail. The device is connected to a computer, where a software interface allows users to select their preferred course of treatment. In in vitro testing, canine nails were exposed to 3 energy levels (acoustic power of 1.2 W and exposure durations of 30, 60, and 120 seconds). A stereo -microscope was used to determine how much of a drug-mimicking compound was delivered through the nail layers by measuring brightness on the cross section of each nail tested at each condition, where brightness level decreases coincide with increases in permeability. Each of the 3 energy levels tested showed statistical significance when compared to the control (P < .05) with a permeability factor of 1.3 after 30 seconds of exposure, 1.3 after 60 seconds, and 1.5 after 120 seconds, where a permeability factor of 1 shows no increase in permeability. Current treatments for onychomycosis include systemic, topical, and surgical. Even when used all together, these treatments typically take a long time to result in nail healing, thus making this ultrasound-mediated device a promising alternative.

  6. Controlled ocular drug delivery with nanomicelles.

    PubMed

    Vaishya, Ravi D; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K

    2014-01-01

    Many vision threatening ocular diseases such as age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and proliferative vitreoretinopathy may result in blindness. Ocular drug delivery specifically to the intraocular tissues remains a challenging task due to the presence of various physiological barriers. Nonetheless, recent advancements in the field of nanomicelle-based novel drug delivery system could fulfil these unmet needs. Nanomicelles consists of amphiphilic molecules that self-assemble in aqueous media to form organized supramolecular structures. Micelles can be prepared in various sizes (10-1000 nm) and shapes depending on the molecular weights of the core and corona forming blocks. Nanomicelles have been an attractive carrier for their potential to solubilize hydrophobic molecules in aqueous solution. In addition, small size in nanometer range and highly modifiable surface properties have been reported to be advantageous in ocular drug delivery. In this review, various factors influencing rationale design of nanomicelles formulation and disposition are discussed along with case studies. Despite the progress in the field, influence of various properties of nanomicelles such as size, shape, surface charge, rigidity of structure on ocular disposition need to be studied in further details to develop an efficient nanocarrier system.

  7. Controlled Ocular Drug Delivery with Nanomicelles

    PubMed Central

    Vaishya, Ravi D.; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K.

    2014-01-01

    Many vision threatening ocular diseases such as age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and proliferative vitreoretinopathy may result in blindness. Ocular drug delivery specifically to the intraocular tissues remains a challenging task due to the presence of various physiological barriers. Nonetheless, recent advancements in the field of nanomicelle based novel drug delivery system could fulfil these unmet needs. Nanomicelles consists of amphiphilic molecules that self-assemble in aqueous media to form organized supramolecular structures. Micelles can be prepared in various sizes (10 to 1000nm) and shapes depending on the molecular weights of the core and corona forming blocks. Nanomicelles have been an attractive carriers for their potential to solubilize hydrophobic molecules in aqueous solution. In addition, small size in nanometer range and highly modifiable surface properties have been reported to be advantageous in ocular drug delivery. In the present review various factors influencing rationale design of nanomicelles formulation and disposition are discussed along with case studies. Despite the progress in the field, influence of various properties of nanomicelles such as size, shape, surface charge, rigidity of structure on ocular disposition need to be studied in further details to develop an efficient nanocarrier system. PMID:24888969

  8. Approaches for drug delivery with intracortical probes.

    PubMed

    Spieth, Sven; Schumacher, Axel; Trenkle, Fabian; Brett, Olivia; Seidl, Karsten; Herwik, Stanislav; Kisban, Sebastian; Ruther, Patrick; Paul, Oliver; Aarts, Arno A A; Neves, Hercules P; Rich, P Dylan; Theobald, David E; Holtzman, Tahl; Dalley, Jeffrey W; Verhoef, Bram-Ernst; Janssen, Peter; Zengerle, Roland

    2014-08-01

    Intracortical microprobes allow the precise monitoring of electrical and chemical signaling and are widely used in neuroscience. Microelectromechanical system (MEMS) technologies have greatly enhanced the integration of multifunctional probes by facilitating the combination of multiple recording electrodes and drug delivery channels in a single probe. Depending on the neuroscientific application, various assembly strategies are required in addition to the microprobe fabrication itself. This paper summarizes recent advances in the fabrication and assembly of micromachined silicon probes for drug delivery achieved within the EU-funded research project NeuroProbes. The described fabrication process combines a two-wafer silicon bonding process with deep reactive ion etching, wafer grinding, and thin film patterning and offers a maximum in design flexibility. By applying this process, three general comb-like microprobe designs featuring up to four 8-mm-long shafts, cross sections from 150×200 to 250×250 µm², and different electrode and fluidic channel configurations are realized. Furthermore, we discuss the development and application of different probe assemblies for acute, semichronic, and chronic applications, including comb and array assemblies, floating microprobe arrays, as well as the complete drug delivery system NeuroMedicator for small animal research.

  9. A model of axonal transport drug delivery

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Andrey V.

    2012-04-01

    In this paper a model of targeted drug delivery by means of active (motor-driven) axonal transport is developed. The model is motivated by recent experimental research by Filler et al. (A.G. Filler, G.T. Whiteside, M. Bacon, M. Frederickson, F.A. Howe, M.D. Rabinowitz, A.J. Sokoloff, T.W. Deacon, C. Abell, R. Munglani, J.R. Griffiths, B.A. Bell, A.M.L. Lever, Tri-partite complex for axonal transport drug delivery achieves pharmacological effect, Bmc Neuroscience 11 (2010) 8) that reported synthesis and pharmacological efficiency tests of a tri-partite complex designed for axonal transport drug delivery. The developed model accounts for two populations of pharmaceutical agent complexes (PACs): PACs that are transported retrogradely by dynein motors and PACs that are accumulated in the axon at the Nodes of Ranvier. The transitions between these two populations of PACs are described by first-order reactions. An analytical solution of the coupled system of transient equations describing conservations of these two populations of PACs is obtained by using Laplace transform. Numerical results for various combinations of parameter values are presented and their physical significance is discussed.

  10. Immobilization of coacervate microcapsules in multilayer sodium alginate beads for efficient oral anticancer drug delivery.

    PubMed

    Feng, Chao; Song, Ruixi; Sun, Guohui; Kong, Ming; Bao, Zixian; Li, Yang; Cheng, Xiaojie; Cha, Dongsu; Park, Hyunjin; Chen, Xiguang

    2014-03-10

    We have designed and evaluated coacervate microcapsules-immobilized multilayer sodium alginate beads (CMs-M-ALG-Beads) for oral drug delivery. The CMs-M-ALG-Beads were prepared by immobilization of doxorubicin hydrochloride (DOX) loaded chitosan/carboxymethyl coacervate microcapsules (DOX:CS/CMCS-CMs) in the core and layers of the multilayer sodium alginate beads. The obtained CMs-M-ALG-beads exhibited layer-by-layer structure and rough surface with many nanoscale particles. The swelling characteristic and drug release results indicated that 4-layer CMs-M-ALG-Beads possessed favorable gastric acid tolerance (the swelling rate <5%, the cumulative drug release rate <3.8%). In small intestine, the intact DOX:CS/CMCS-CMs were able to rapidly release from CMs-M-ALG-Beads with the dissolution of ALG matrix. Ex vivo intestinal mucoadhesive and permeation showed that CMs-M-ALG-Beads exhibited continued growth for P(app) values of DOX, which was 1.07-1.15 folds and 1.28-1.38 folds higher than DOX:CS:CMCS-CMs in rat jejunum and ileum, respectively, demonstrating that CMs-M-ALG-Beads were able to enhance the absorption of DOX by controlled releasing DOX:CS/CMCS-CMs and prolonging the contact time between the DOX:CS/CMCS-CMs and small intestinal mucosa.

  11. Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization.

    PubMed

    Shah, Brijesh M; Misra, Manju; Shishoo, Chamanlal J; Padh, Harish

    2015-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to irreversible loss of neurons, cognition and formation of abnormal protein aggregates. Rivastigmine, a reversible cholinesterase inhibitor used for the treatment of AD, undergoes extensive first-pass metabolism, thus limiting its absolute bioavailability to only 36% after 3-mg dose. Due to extreme aqueous solubility, rivastigmine shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. This investigation was aimed to formulate microemulsion (ME) and mucoadhesive microemulsions (MMEs) of rivastigmine for nose to brain delivery and to compare percentage drug diffused for both systems using in-vitro and ex-vivo study. Rivastigmine-loaded ME and MMEs were prepared by titration method and characterized for drug content, globule size distribution, zeta potential, pH, viscosity and nasal ciliotoxicity study. Rivastigmine-loaded ME system containing 8% w/w Capmul MCM EP, 44% w/w Labrasol:Transcutol-P (1:1) and 48% w/w distilled water was formulated, whereas 0.3% w/w chitosan (CH) and cetyl trimethyl ammonium bromide (as mucoadhesive agents) were used to formulate MMEs, respectively. ME and MMEs formulations were transparent with drug content, globule size and zeta potential in the range of 98.59% to 99.43%, 53.8 nm to 55.4 nm and -2.73 mV to 6.52 mV, respectively. MME containing 0.3% w/w CH followed Higuchi model (r(2) = 0.9773) and showed highest diffusion coefficient. It was free from nasal ciliotoxicity and stable for three months. However, the potential of developed CH-based MME for nose to brain delivery of rivastigmine can only be established after in-vivo and biodistribution study.

  12. Drug Delivery to the Ischemic Brain

    PubMed Central

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  13. Protein-Based Nanomedicine Platforms for Drug Delivery

    SciTech Connect

    Ma Ham, Aihui; Tang, Zhiwen; Wu, Hong; Wang, Jun; Lin, Yuehe

    2009-08-03

    Drug delivery systems have been developed for many years, however some limitations still hurdle the pace of going to clinical phase, for example, poor biodistribution, drug molecule cytotoxicity, tissue damage, quick clearance from the circulation system, solubility and stability of drug molecules. To overcome the limitations of drug delivery, biomaterials have to be developed and applied to drug delivery to protect the drug molecules and to enhance the drug’s efficacy. Protein-based nanomedicine platforms for drug delivery are platforms comprised of naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They are ideal for drug delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug delivery systems including the ferritin/apoferritin protein cage, plant derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms including the various protein cages, microspheres, nanoparticles, hydrogels, films, minirods and minipellets. There are over 30 therapeutic compounds that have been investigated with protein-based drug delivery platforms for the potential treatment of various cancers, infectious diseases, chronic diseases, autoimmune diseases. In protein-based drug delivery platforms, protein cage is the most newly developed biomaterials for drug delivery and therapeutic applications. Their uniform sizes, multifunctions, and biodegradability push them to the frontier for drug delivery. In this review, the recent strategic development of drug delivery has been discussed with a special emphasis upon the polymer based, especially protein-based nanomedicine platforms for drug delivery. The advantages and disadvantages are also

  14. Phospholipid nanodisc engineering for drug delivery systems.

    PubMed

    Murakami, Tatsuya

    2012-06-01

    Biocompatible mesoscale nanoparticles (5-100 nm in diameter) are attractive tools for drug delivery. Among them are several types of liposomes and polymer micelles already in clinical trial or use. Generally, biocompatibility of such particles is achieved by coating them with polyethylene glycol (PEG). Without PEG coating, particles are quickly trapped in the reticuloendothelial system when intravenously administered. However, recent studies have revealed several potential problems with PEG coating, including antigenicity and restriction of cellular uptake. This has motivated the development of alternative drug and gene delivery vehicles, including chemically and genetically engineered high-density lipoprotein (HDL)-like nanodiscs or "bicelles". HDL is a naturally occurring mesoscale nanoparticle that normally ferries cholesterol around in the body. Its initial "nascent" form is thought to be a simple 10 nm disc of phospholipids in a bilayer, and can be easily synthesized in vitro by mixing recombinant apoA-I proteins with various phospholipids. In this review, the use of synthetic HDL-like phospholipid nanodiscs as biocompatible drug carriers is summarized, focussing on manufacturing, size-control, drug loading and cell targeting.

  15. Silk Electrogel Based Gastroretentive Drug Delivery System

    NASA Astrophysics Data System (ADS)

    Wang, Qianrui

    Gastric cancer has become a global pandemic and there is imperative to develop efficient therapies. Oral dosing strategy is the preferred route to deliver drugs for treating the disease. Recent studies suggested silk electro hydrogel, which is pH sensitive and reversible, has potential as a vehicle to deliver the drug in the stomach environment. The aim of this study is to establish in vitro electrogelation e-gel based silk gel as a gastroretentive drug delivery system. We successfully extended the duration of silk e-gel in artificial gastric juice by mixing silk solution with glycerol at different ratios before the electrogelation. Structural analysis indicated the extended duration was due to the change of beta sheet content. The glycerol mixed silk e-gel had good doxorubicin loading capability and could release doxorubicin in a sustained-release profile. Doxorubicin loaded silk e-gels were applied to human gastric cancer cells. Significant cell viability decrease was observed. We believe that with further characterization as well as functional analysis, the silk e-gel system has the potential to become an effective vehicle for gastric drug delivery applications.

  16. Microemulsions based transdermal drug delivery systems.

    PubMed

    Vadlamudi, Harini C; Narendran, Hyndavi; Nagaswaram, Tejeswari; Yaga, Gowri; Thanniru, Jyotsna; Yalavarthi, Prasanna R

    2014-01-01

    Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored. PMID:25466399

  17. Surface modification of PLGA nanoparticles by carbopol to enhance mucoadhesion and cell internalization.

    PubMed

    Surassmo, Suvimol; Saengkrit, Nattika; Ruktanonchai, Uracha Rungsardthong; Suktham, Kunat; Woramongkolchai, Noppawan; Wutikhun, Tuksadon; Puttipipatkhachorn, Satit

    2015-06-01

    Mucoadhesive poly (lactic-co-glycolic acid) (PLGA) nanoparticles having a modified shell-matrix derived from polyvinyl alcohol (PVA) and Carbopol (CP), a biodegradable polymer coating, to improve the adhesion and cell transfection properties were developed. The optimum formulations utilized a CP concentration in the range of 0.05-0.2%w/v, and were formed using modified emulsion-solvent evaporation technique. The resulting CP-PLGA nanoparticles were characterized in terms of their physical and chemical properties. The absorbed CP on the PLGA shell-matrix was found to affect the particle size and surface charge, with 0.05% CP giving rise to smooth spherical particles (0.05CP-PLGA) with the smallest size (285.90 nm), and strong negative surface charge (-25.70 mV). The introduction of CP results in an enhancement of the mucoadhesion between CP-PLGA nanoparticles and mucin particles. In vitro cell internalization studies highlighted the potential of 0.05CP-PLGA nanoparticles for transfection into SiHa cells, with uptake being time dependent. Additionally, cytotoxicity studies of CP-PLGA nanoparticles against SiHa cancer cells indicated that low concentrations of the nanoparticles were non-toxic to cells (cell viability >80%). From the various formulations studied, 0.05CP-PLGA nanoparticles proved to be the optimum model carrier having the required mucoadhesive profile and could be an alternative therapeutic efficacy carrier for targeted mucosal drug delivery systems with biodegradable polymer.

  18. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery.

    PubMed

    Islam, Nazrul; Ferro, Vito

    2016-08-14

    The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

  19. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

    NASA Astrophysics Data System (ADS)

    Islam, Nazrul; Ferro, Vito

    2016-07-01

    The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

  20. Topical Drug Delivery for Chronic Rhinosinusitis

    PubMed Central

    Liang, Jonathan; Lane, Andrew P.

    2013-01-01

    Chronic rhinosinusitis is a multifactorial disorder that may be heterogeneous in presentation and clinical course. While the introduction of endoscopic sinus surgery revolutionized surgical management and has led to significantly improved patient outcomes, medical therapy remains the foundation of long-term care of chronic rhinosinusitis, particularly in surgically recalcitrant cases. A variety of devices and pharmaceutical agents have been developed to apply topical medical therapy to the sinuses, taking advantage of the access provided by endoscopic surgery. The goal of topical therapy is to address the inflammation, infection, and mucociliary dysfunction that underlies the disease. Major factors that impact success include the patient’s sinus anatomy and the dynamics of the delivery device. Despite a growing number of topical treatment options, the evidence-based literature to support their use is limited. In this article, we comprehensively review current delivery methods and the available topical agents. We also discuss biotechnological advances that promise enhanced delivery in the future, and evolving pharmacotherapeutical compounds that may be added to rhinologist’s armamentarium. A complete understand of topical drug delivery is increasingly essential to the management of chronic rhinosinusitis when traditional forms of medical therapy and surgery have failed. PMID:23525506

  1. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    PubMed Central

    Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

    2012-01-01

    Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

  2. Drug transport and drug delivery--the Midnight Sun meeting.

    PubMed

    Uchegbu, Ijeoma F

    2004-08-01

    The Midnight Sun Meeting on Drug Transport and Drug Delivery was held on the island of Tromso in northern Norway, where the sun does not set for 2 months during the summer. The meeting was hosted by the University of Tromso's newly established Institute of Pharmacy and the Controlled Release Society (Nordic Chapter). The meeting, attended by approximately 80 delegates from across Europe, showcased recent advances in drug transport through biological barriers, solid-state pharmaceuticals and particulate drug delivery systems. This report will focus on the particulate and solid-state pharmaceuticals sessions, in which lectures were given to demonstrate the benefits in cognitive function associated with omega-3 fish oils, the increase in drug release rates observed on the processing-induced deformation of tablet granules, and the size of polymeric particulates being directly and linearly related to the molecular weight of a polymer. The meeting was held as a single-session event, giving delegates the opportunity to attend all presentations. There was a small poster and exhibitor display, and the meeting attracted sponsorship from a number of companies, namely Polypure AS, Weifa AS, ProBioNeutraceuticals AS, Lipoid GmbH, Clavis Pharma AS and Thermometric AB.

  3. Synthesis of thiolated alginate and evaluation of mucoadhesiveness, cytotoxicity and release retardant properties.

    PubMed

    Jindal, A B; Wasnik, M N; Nair, Hema A

    2010-11-01

    Modification of polymers by covalent attachment of thiol bearing pendant groups is reported to impart many beneficial properties to them. Hence in the present study, sodium alginate-cysteine conjugate was synthesized by carbodiimide mediated coupling under varying reaction conditions and the derivatives characterized for thiol content. The thiolated alginate species synthesized had bound thiol content ranging from 247.8±11.03-324.54±10.107 ΅mol/g of polymer depending on the reaction conditions. Matrix tablets based on sodium alginate-cysteine conjugate and native sodium alginate containing tramadol hydrochloride as a model drug were prepared and mucoadhesive strength and in vitro drug release from the tablets were compared. Tablets containing 75 mg sodium alginate-cysteine conjugate could sustain release of 10 mg of model drug for 3 h, whereas 90% of the drug was released within 1 h from corresponding tablets prepared using native sodium alginate. An approximately 2-fold increase in the minimal detachment force of the tablets from an artificial mucin film was observed for sodium alginate-cysteine conjugate as compared to native sodium alginate. In vitro cytotoxicity studies in L-929 mouse fibroblast cells studied using an MTT assay revealed that at low concentrations of polymer, sodium alginate-cysteine conjugate was less toxic to L-929 mouse fibroblast cell line when compared to native sodium alginate. Hence, thiolation is found to be a simple route to improving polymer performance. The combination of improved controlled drug release and mucoadhesive properties coupled with the low toxicity of these new excipients builds up immense scope for the use of thiolated polymers in mucoadhesive drug delivery systems. PMID:21969750

  4. Adenovirus Dodecahedron, as a Drug Delivery Vector

    PubMed Central

    Zochowska, Monika; Paca, Agnieszka; Schoehn, Guy; Andrieu, Jean-Pierre; Chroboczek, Jadwiga; Dublet, Bernard; Szolajska, Ewa

    2009-01-01

    Background Bleomycin (BLM) is an anticancer antibiotic used in many cancer regimens. Its utility is limited by systemic toxicity and dose-dependent pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 50% of the total patient population, out of which 3% will die. We propose to improve BLM delivery by tethering it to an efficient delivery vector. Adenovirus (Ad) dodecahedron base (DB) is a particulate vector composed of 12 copies of a pentameric viral protein responsible for virus penetration. The vector efficiently penetrates the plasma membrane, is liberated in the cytoplasm and has a propensity to concentrate around the nucleus; up to 300000 particles can be observed in one cell in vitro. Principal Findings Dodecahedron (Dd) structure is preserved at up to about 50°C at pH 7–8 and during dialysis, freezing and drying in the speed-vac in the presence of 150 mM ammonium sulfate, as well as during lyophilization in the presence of cryoprotectants. The vector is also stable in human serum for 2 h at 37°C. We prepared a Dd-BLM conjugate which upon penetration induced death of transformed cells. Similarly to free bleomycin, Dd-BLM caused dsDNA breaks. Significantly, effective cytotoxic concentration of BLM delivered with Dd was 100 times lower than that of free bleomycin. Conclusions/Significance Stability studies show that Dds can be conveniently stored and transported, and can potentially be used for therapeutic purposes under various climates. Successful BLM delivery by Ad Dds demonstrates that the use of virus like particle (VLP) results in significantly improved drug bioavailability. These experiments open new vistas for delivery of non-permeant labile drugs. PMID:19440379

  5. Micro- and nano-fabricated implantable drug-delivery systems

    PubMed Central

    Meng, Ellis; Hoang, Tuan

    2013-01-01

    Implantable drug-delivery systems provide new means for achieving therapeutic drug concentrations over entire treatment durations in order to optimize drug action. This article focuses on new drug administration modalities achieved using implantable drug-delivery systems that are enabled by micro- and nano-fabrication technologies, and microfluidics. Recent advances in drug administration technologies are discussed and remaining challenges are highlighted. PMID:23323562

  6. Computational Study of Nanosized Drug Delivery from Cyclodextrins, Crown Ethers and Hyaluronan in Pharmaceutical Formulations.

    PubMed

    Torrens, Francisco; Castellano, Gloria

    2015-01-01

    The problem in this work is the computational characterization of cyclodextrins, crown ethers and hyaluronan (HA) as hosts of inclusion complexes for nanosized drug delivery vehicles in pharmaceutical formulations. The difficulty is addressed through a computational study of some thermodynamic, geometric and topological properties of the hosts. The calculated properties of oligosaccharides of D-glucopyranoses allow these to act as co-solvents of polyanions in water. In crown ethers, the central channel is computed. Mucoadhesive polymer HA in formulations releases drugs in mucosas. Geometric, topological and fractal analyses are carried out with code TOPO. Reference calculations are performed with code GEPOL. From HA to HA·3Ca and hydrate, the hydrophilic solvent-accessible surface varies with the count of H-bonds. The fractal dimension rises. The dimension of external atoms rises resulting 1.725 for HA. It rises going to HA·3Ca and hydrate. Nonburied minus molecular dimension rises and decays. Hydrate globularity is lower than O(water), Ca(2+) and O(HA). Ca(2+) rugosity is smaller than for hydrate, O(HA) and O(water). Ca(2+) and O(water) accessibilities are greater than hydrate. Conclusions are drawn on: (1) the relative stability of linear/cyclic and shorter/larger polymers; (2) the atomic analysis of properties allows determining the atoms with maximum reactivity.

  7. Biomedical Imaging in Implantable Drug Delivery Systems

    PubMed Central

    Zhou, Haoyan; Hernandez, Christopher; Goss, Monika; Gawlik, Anna; Exner, Agata A.

    2015-01-01

    Implantable drug delivery systems (DDS) provide a platform for sustained release of therapeutic agents over a period of weeks to months and sometimes years. Such strategies are typically used clinically to increase patient compliance by replacing frequent administration of drugs such as contraceptives and hormones to maintain plasma concentration within the therapeutic window. Implantable or injectable systems have also been investigated as a means of local drug administration which favors high drug concentration at a site of interest, such as a tumor, while reducing systemic drug exposure to minimize unwanted side effects. Significant advances in the field of local DDS have led to increasingly sophisticated technology with new challenges including quantification of local and systemic pharmacokinetics and implant-body interactions. Because many of these sought-after parameters are highly dependent on the tissue properties at the implantation site, and rarely represented adequately with in vitro models, new nondestructive techniques that can be used to study implants in situ are highly desirable. Versatile imaging tools can meet this need and provide quantitative data on morphological and functional aspects of implantable systems. The focus of this review article is an overview of current biomedical imaging techniques, including magnetic resonance imaging (MRI), ultrasound imaging, optical imaging, X-ray and computed tomography (CT), and their application in evaluation of implantable DDS. PMID:25418857

  8. Provesicles as novel drug delivery systems.

    PubMed

    Bayindir, Zerrin S; Yuksel, Nilufer

    2015-01-01

    Vesicular systems exhibit many attractive properties such as controlled drug release, ability to carry both hydrophilic and hydrophobic drugs, targetability and good biocompatibility. With these unique properties they can provide improved drug bioavailability and reduced side effects. Until now, many vesicular formulations have been studied in clinical and preclinical stages. Nevertheless, the major concern about these systems is their low physicochemical stability and high manufacturing expenses. The stability problems (fusion, aggregation, sedimentation, swelling, and drug leakage during storage) associated with the aqueous nature of vesicular systems hinders their effective usage. The advances on improving the stability of vesicular systems led to the emergence of provesicular systems, which are commonly described as dry, free flowing preformulations of vesicular drug delivery systems. Provesicles form vesicular systems upon hydratation with water and exhibit the advantages of vesicular systems with improved stability. The present article briefly reviews vesicular systems (particularly liposomes and niosomes) and enlightens about the innovations in the field. Overall investigations are reviewed and the provesicle approach is explained by giving detailed information on the composition, preparation, administration and characterization methods of provesicular systems (proliposomes and proniosomes). The scope of this article is expected to give insight to the researchers and industrialists to perform further research in this area. PMID:25658383

  9. Laser assisted Drug Delivery: Grundlagen und Praxis.

    PubMed

    Braun, Stephan Alexander; Schrumpf, Holger; Buhren, Bettina Alexandra; Homey, Bernhard; Gerber, Peter Arne

    2016-05-01

    Die topische Applikation von Wirkstoffen ist eine zentrale Therapieoption der Dermatologie. Allerdings mindert die effektive Barrierefunktion der Haut die Bioverfügbarkeit der meisten Externa. Fraktionierte ablative Laser stellen ein innovatives Verfahren dar, um die epidermale Barriere standardisiert, kontaktfrei zu überwinden. Die Bioverfügbarkeit im Anschluss applizierter Externa wird im Sinne einer laser assisted drug delivery (LADD) signifikant gesteigert. Das Prinzip der LADD wird bereits in einigen Bereichen der Dermatologie erfolgreich eingesetzt. Die vorliegende Übersichtsarbeit soll einen Überblick über die aktuellen aber auch perspektivischen Einsatzmöglichkeiten der LADD bieten. PMID:27119467

  10. Dendrimer based nanotherapeutics for ocular drug delivery

    NASA Astrophysics Data System (ADS)

    Kambhampati, Siva Pramodh

    PAMAM dendrimers are a class of well-defined, hyperbranched polymeric nanocarriers that are being investigated for ocular drug and gene delivery. Their favorable properties such as small size, multivalency and water solubility can provide significant opportunities for many biologically unstable drugs and allows potentially favorable ocular biodistribution. This work exploits hydroxyl terminated dendrimers (G4-OH) as drug/gene delivery vehicles that can target retinal microglia and pigment epithelium via systemic delivery with improved efficacy at much lower concentrations without any side effects. Two different drugs Triamcinolone acetonide (TA) and N-Acetyl Cysteine (NAC) conjugated to G4-OH dendrimers showed tailorable sustained release in physiological relevant solutions and were evaluated in-vitro and in-vivo. Dendrimer-TA conjugates enhanced the solubility of TA and were 100 fold more effective at lower concentrations than free TA in its anti-inflammatory activity in activated microglia and in suppressing VEGF production in hypoxic RPE cells. Dendrimers targeted activated microglia/macrophages and RPE and retained for a period of 21 days in I/R mice model. The relative retention of intravitreal and intravenous dendrimers was comparable, if a 30-fold intravenous dose is used; suggesting intravenous route targeting retinal diseases are possible with dendrimers. D-NAC when injected intravenously attenuated retinal and choroidal inflammation, significantly reduced (˜73%) CNV growth at early stage of AMD in rat model of CNV. A combination therapy of D-NAC + D-TA significantly suppressed microglial activation and promoted CNV regression in late stages of AMD without causing side-effects. G4-OH was modified with linker having minimal amine groups and incorporation of TA as a nuclear localization enhancer resulted in compact gene vectors with favorable safety profile and achieved high levels of transgene expression in hard to transfect human retinal pigment

  11. Stability of nanosuspensions in drug delivery.

    PubMed

    Wang, Yancai; Zheng, Ying; Zhang, Ling; Wang, Qiwei; Zhang, Dianrui

    2013-12-28

    Nanosuspensions are nanosized colloidal dispersion systems that are stabilized by surfactants and/or polymers. Because nanosizing results in the creation of new interfaces and in a positive Gibbs free energy change, nanosuspensions are thermodynamically unstable systems with a tendency toward agglomeration or crystal growth. Despite extensive research on nanosuspension technology, stability remains a limitation for pharmaceutical or industrial applications of nanosuspensions. Furthermore, the empirical relationship between stabilizer efficacy and nanosuspension stability has not been well characterized. This review focuses on the issue of nanosuspension stability in drug delivery to present the state of the art of nanosuspensions. Therefore, this review will discuss unstable suspensions, methods and guidelines for selecting and optimizing stabilizers, approaches for enhancing stability, and other factors that influence nanosuspension stability. This review could serve as a reference for the educated selection of a stabilizer for a specific drug candidate and the optimization of the operational parameters for nanosuspension formulation, rather than the currently practiced trial-and-error approach.

  12. Implantable microchip: the futuristic controlled drug delivery system.

    PubMed

    Sutradhar, Kumar Bishwajit; Sumi, Chandra Datta

    2016-01-01

    There is no doubt that controlled and pulsatile drug delivery system is an important challenge in medicine over the conventional drug delivery system in case of therapeutic efficacy. However, the conventional drug delivery systems often offer a limited by their inability to drug delivery which consists of systemic toxicity, narrow therapeutic window, complex dosing schedule for long term treatment etc. Therefore, there has been a search for the drug delivery system that exhibit broad enhancing activity for more drugs with less complication. More recently, some elegant study has noted that, a new type of micro-electrochemical system or MEMS-based drug delivery systems called microchip has been improved to overcome the problems related to conventional drug delivery. Moreover, micro-fabrication technology has enabled to develop the implantable controlled released microchip devices with improved drug administration and patient compliance. In this article, we have presented an overview of the investigations on the feasibility and application of microchip as an advanced drug delivery system. Commercial manufacturing materials and methods, related other research works and current advancement of the microchips for controlled drug delivery have also been summarized.

  13. Ultrasound-Propelled Nanocups for Drug Delivery

    PubMed Central

    Kwan, James J; Myers, Rachel; Coviello, Christian M; Graham, Susan M; Shah, Apurva R; Stride, Eleanor; Carlisle, Robert C; Coussios, Constantin C

    2015-01-01

    Ultrasound-induced bubble activity (cavitation) has been recently shown to actively transport and improve the distribution of therapeutic agents in tumors. However, existing cavitation-promoting agents are micron-sized and cannot sustain cavitation activity over prolonged time periods because they are rapidly destroyed upon ultrasound exposure. A novel ultrasound-responsive single-cavity polymeric nanoparticle (nanocup) capable of trapping and stabilizing gas against dissolution in the bloodstream is reported. Upon ultrasound exposure at frequencies and intensities achievable with existing diagnostic and therapeutic systems, nanocups initiate and sustain readily detectable cavitation activity for at least four times longer than existing microbubble constructs in an in vivo tumor model. As a proof-of-concept of their ability to enhance the delivery of unmodified therapeutics, intravenously injected nanocups are also found to improve the distribution of a freely circulating IgG mouse antibody when the tumor is exposed to ultrasound. Quantification of the delivery distance and concentration of both the nanocups and coadministered model therapeutic in an in vitro flow phantom shows that the ultrasound-propelled nanocups travel further than the model therapeutic, which is itself delivered to hundreds of microns from the vessel wall. Thus nanocups offer considerable potential for enhanced drug delivery and treatment monitoring in oncological and other biomedical applications. PMID:26296985

  14. Preparation and characterization of mucoadhesive nanoparticles of poly (methyl vinyl ether-co-maleic anhydride) containing glycyrrhizic acid intended for vaginal administration.

    PubMed

    Aguilar-Rosas, Irene; Alcalá-Alcalá, Sergio; Llera-Rojas, Viridiana; Ganem-Rondero, Adriana

    2015-01-01

    Traditional vaginal preparations reside in the vaginal cavity for relatively a short period of time, requiring multiple doses in order to attain the desired therapeutic effect. Therefore, mucoadhesive systems appear to be appropriate to prolong the residence time in the vaginal cavity. In the current study, mucoadhesive nanoparticles based on poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) intended for vaginal delivery of glycyrrhizic acid (GA) (a drug with well-known antiviral properties) were prepared and characterized. Nanoparticles were generated by a solvent displacement method. Incorporation of GA was performed during nanoprecipitation, followed by adsorption of drug once nanoparticles were formed. The prepared nanoparticles were characterized in terms of size, Z-potential, morphology, drug loading, interaction of GA with PVM/MA (by differential scanning calorimetry) and the in vitro interaction of nanoparticles with pig mucin (at two pH values, 3.6 and 5; with and without GA adsorbed). The preparation method led to nanoparticles of a mean diameter of 198.5 ± 24.3 nm, zeta potential of -44.8 ± 2.8 mV and drug loading of 15.07 ± 0.86 µg/mg polymer. The highest mucin interaction resulted at pH 3.6 for nanoparticles without GA adsorbed. The data obtained suggest the promise of using mucoadhesive nanoparticles of PVM/MA for intravaginal delivery of GA.

  15. Smart Nanoparticles for Drug Delivery: Boundaries and Opportunities

    PubMed Central

    Lee, Byung Kook; Yun, Yeon Hee; Park, Kinam

    2014-01-01

    Various pharmaceutical particles have been used in developing different drug delivery systems ranging from traditional tablets to state-of-the-art nanoparticle formulations. Nanoparticle formulations are unique in that the small size with huge surface area sometimes provides unique properties that larger particles and bulk materials do not have. Nanoparticle formulations have been used in improving the bioavailability of various drugs, in particular, poorly soluble drugs. Nanoparticle drug delivery systems have found their unique applications in targeted drug delivery to tumors. While nanoparticle formulations have been successful in small animal xenograft models, their translation to clinical applications has been very rare. Developing nanoparticle systems designed for targeted drug delivery, e.g., treating tumors in humans, requires clear understanding of the uniqueness of nanoparticles, as well as limitations and causes of failures in clinical applications. It also requires designing novel smart nanoparticle delivery systems that can increase the drug bioavailability and at the same time reduce the drug's side effects. PMID:25684780

  16. Vascular Permeability and Drug Delivery in Cancers

    PubMed Central

    Azzi, Sandy; Hebda, Jagoda K.; Gavard, Julie

    2013-01-01

    The endothelial barrier strictly maintains vascular and tissue homeostasis, and therefore modulates many physiological processes such as angiogenesis, immune responses, and dynamic exchanges throughout organs. Consequently, alteration of this finely tuned function may have devastating consequences for the organism. This is particularly obvious in cancers, where a disorganized and leaky blood vessel network irrigates solid tumors. In this context, vascular permeability drives tumor-induced angiogenesis, blood flow disturbances, inflammatory cell infiltration, and tumor cell extravasation. This can directly restrain the efficacy of conventional therapies by limiting intravenous drug delivery. Indeed, for more effective anti-angiogenic therapies, it is now accepted that not only should excessive angiogenesis be alleviated, but also that the tumor vasculature needs to be normalized. Recovery of normal state vasculature requires diminishing hyperpermeability, increasing pericyte coverage, and restoring the basement membrane, to subsequently reduce hypoxia, and interstitial fluid pressure. In this review, we will introduce how vascular permeability accompanies tumor progression and, as a collateral damage, impacts on efficient drug delivery. The molecular mechanisms involved in tumor-driven vascular permeability will next be detailed, with a particular focus on the main factors produced by tumor cells, especially the emblematic vascular endothelial growth factor. Finally, new perspectives in cancer therapy will be presented, centered on the use of anti-permeability factors and normalization agents. PMID:23967403

  17. Challenges in modelling nanoparticles for drug delivery

    NASA Astrophysics Data System (ADS)

    Barnard, Amanda S.

    2016-01-01

    Although there have been significant advances in the fields of theoretical condensed matter and computational physics, when confronted with the complexity and diversity of nanoparticles available in conventional laboratories a number of modeling challenges remain. These challenges are generally shared among application domains, but the impacts of the limitations and approximations we make to overcome them (or circumvent them) can be more significant one area than another. In the case of nanoparticles for drug delivery applications some immediate challenges include the incompatibility of length-scales, our ability to model weak interactions and solvation, the complexity of the thermochemical environment surrounding the nanoparticles, and the role of polydispersivity in determining properties and performance. Some of these challenges can be met with existing technologies, others with emerging technologies including the data-driven sciences; some others require new methods to be developed. In this article we will briefly review some simple methods and techniques that can be applied to these (and other) challenges, and demonstrate some results using nanodiamond-based drug delivery platforms as an exemplar.

  18. Diatomite silica nanoparticles for drug delivery

    PubMed Central

    2014-01-01

    Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery. PACS 87.85.J81.05.Rm; 61.46. + w PMID:25024689

  19. Cooperative assembly in targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Auguste, Debra

    2012-02-01

    Described as cell analogues, liposomes are self-assembled lipid bilayer spheres that encapsulate aqueous volumes. Liposomes offer several drug delivery advantages due to their structural versatility related to size, composition, bilayer fluidity, and ability to encapsulate a large variety of compounds non-covalently. However, liposomes lack the structural information embedded within cell membranes. Partitioning of unsaturated and saturated lipids into liquid crystalline (Lα) and gel phase (Lβ) domains, respectively, affects local molecular diffusion and elasticity. Liposome microdomains may be used to pattern molecules, such as antibodies, on the liposome surface to create concentrated, segregated binding regions. We have synthesized, characterized, and evaluated a series of homogeneous and heterogeneous liposomal vehicles that target inflamed endothelium. These drug delivery vehicles are designed to complement the heterogeneous presentation of lipids and receptors on endothelial cells (ECs). EC surfaces are dynamic; they segregate receptors within saturated lipid microdomains on the cell surface to regulate binding and signaling events. We have demonstrated that cooperative binding of two antibodies enhances targeting by multiple fold. Further, we have shown that organization of these antibodies on the surface can further enhance cell uptake. The data suggest that EC targeting may be enhanced by designing liposomes that mirror the segregated structure of lipid and receptor molecules involved in neutrophil-EC adhesion. This strategy is employed in an atherosclerotic mouse model in vivo.

  20. Collagen interactions: Drug design and delivery.

    PubMed

    An, Bo; Lin, Yu-Shan; Brodsky, Barbara

    2016-02-01

    Collagen is a major component in a wide range of drug delivery systems and biomaterial applications. Its basic physical and structural properties, together with its low immunogenicity and natural turnover, are keys to its biocompatibility and effectiveness. In addition to its material properties, the collagen triple-helix interacts with a large number of molecules that trigger biological events. Collagen interactions with cell surface receptors regulate many cellular processes, while interactions with other ECM components are critical for matrix structure and remodeling. Collagen also interacts with enzymes involved in its biosynthesis and degradation, including matrix metalloproteinases. Over the past decade, much information has been gained about the nature and specificity of collagen interactions with its partners. These studies have defined collagen sequences responsible for binding and the high-resolution structures of triple-helical peptides bound to its natural binding partners. Strategies to target collagen interactions are already being developed, including the use of monoclonal antibodies to interfere with collagen fibril formation and the use of triple-helical peptides to direct liposomes to melanoma cells. The molecular information about collagen interactions will further serve as a foundation for computational studies to design small molecules that can interfere with specific interactions or target tumor cells. Intelligent control of collagen biological interactions within a material context will expand the effectiveness of collagen-based drug delivery.

  1. Polymeric micelles for acyclovir drug delivery.

    PubMed

    Sawdon, Alicia J; Peng, Ching-An

    2014-10-01

    Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of ɛ-caprolactone to form ACV-polycaprolactone (ACV-PCL). Through conjugation of hydrophobic ACV-PCL with hydrophilic methoxy poly(ethylene glycol) (MPEG) or chitosan, polymeric micelles for drug delivery were formed. (1)H NMR, FTIR, and gel permeation chromatography were employed to show successful conjugation of MPEG or chitosan to hydrophobic ACV-PCL. Through dynamic light scattering, zeta potential analysis, transmission electron microscopy, and critical micelle concentration (CMC), the synthesized ACV-tagged polymeric micelles were characterized. It was found that the average size of the polymeric micelles was under 200nm and the CMCs of ACV-PCL-MPEG and ACV-PCL-chitosan were 2.0mgL(-1) and 6.6mgL(-1), respectively. The drug release kinetics of ACV was investigated and cytotoxicity assay demonstrates that ACV-tagged polymeric micelles were non-toxic.

  2. Surface-modified PLGA nanosphere with chitosan improved pulmonary delivery of calcitonin by mucoadhesion and opening of the intercellular tight junctions.

    PubMed

    Yamamoto, Hiromitsu; Kuno, Yoshio; Sugimoto, Shohei; Takeuchi, Hirofumi; Kawashima, Yoshiaki

    2005-02-01

    Surface-modified DL-lactide/glycolide copolymer (PLGA) nanospheres with chitosan (CS) were prepared by the emulsion solvent diffusion method for pulmonary delivery of peptide, i.e., elcatonin. The nanosphere suspension was successfully aerosolized with a nebulizer similar to the drug solution, whereas the microsphere suspensions could not be aerosolized. After pulmonary administration, CS-modified PLGA nanospheres were more slowly eliminated from the lungs than unmodified PLGA nanospheres. CS-modified PLGA nanospheres loaded with elcatonin reduced blood calcium levels to 80% of the initial calcium concentration and prolonged the pharmacological action to 24 h, which was a significantly longer duration of action than that by CS-unmodified nanospheres. These results were attributed to the retention of nanospheres adhered to the bronchial mucus and lung tissue and sustained drug release at the adherence site. In addition, CS and CS on the surface of the nanospheres enhanced the absorption of drug. The rank order of the absorption of the model drugs with CS solution was carboxyfluorescein>FITC-dextran-4 (FD-4; Mw. 4000)>FD-21 (Mw. 21,000)>FD70 (Mw. 70,000), which corresponded to the molecular weights ([Mw.] given in parentheses). The absorption-enhancing effect may have been caused by opening the intercellular tight junctions.

  3. Nanoscale coordination polymers for anticancer drug delivery

    NASA Astrophysics Data System (ADS)

    Phillips, Rachel Huxford

    This dissertation reports the synthesis and characterization of nanoscale coordination polymers (NCPs) for anticancer drug delivery. Nanoparticles have been explored in order to address the limitations of small molecule chemotherapeutics. NCPs have been investigated as drug delivery vehicles as they can exhibit the same beneficial properties as the bulk metal-organic frameworks as well as interesting characteristics that are unique to nanomaterials. Gd-MTX (MTX = methotrexate) NCPs with a MTX loading of 71.6 wt% were synthesized and stabilized by encapsulation within a lipid bilayer containing anisamide (AA), a small molecule that targets sigma receptors which are overexpressed in many cancer tissues. Functionalization with AA allows for targeted delivery and controlled release to cancer cells, as shown by enhanced efficacy against leukemia cells. The NCPs were doped with Ru(bpy)32+ (bpy = 2,2'-bipyridine), and this formulation was utilized as an optical imaging agent by confocal microscopy. NCPs containing the chemotherapeutic pemetrexed (PMX) were synthesized using different binding metals. Zr-based materials could not be stabilized by encapsulation with a lipid bilayer, and Gd-based materials showed that PMX had degraded during synthesis. However, Hf-based NCPs containing 19.7 wt% PMX were stabilized by a lipid coating and showed in vitro efficacy against non-small cell lung cancer (NSCLC) cell lines. Enhanced efficacy was observed for formulations containing AA. Additionally, NCP formulations containing the cisplatin prodrug disuccinatocisplatin were prepared; one of these formulations could be stabilized by encapsulation within a lipid layer. Coating with a lipid layer doped with AA rendered this formulation an active targeting agent. The resulting formulation proved more potent than free cisplatin in NSCLC cell lines. Improved NCP uptake was demonstrated by confocal microscopy and competitive binding assays. Finally, a Pt(IV) oxaliplatin prodrug was

  4. Gellan gum-based mucoadhesive microspheres of almotriptan for nasal administration: Formulation optimization using factorial design, characterization, and in vitro evaluation

    PubMed Central

    Abbas, Zaheer; Marihal, Sachin

    2014-01-01

    Background: Almotriptan malate (ALM), indicated for the treatment of migraine in adults is not a drug candidate feasible to be administered through the oral route during the attack due to its associated symptoms such as nausea and vomiting. This obviates an alternative dosage form and nasal drug delivery is a good substitute to oral and parenteral administration. Materials and Methods: Gellan gum (GG) microspheres of ALM, for intranasal administration were prepared by water-in-oil emulsification cross-linking technique employing a 23 factorial design. Drug to polymer ratio, calcium chloride concentration and cross-linking time were selected as independent variables, while particle size and in vitro mucoadhesion of the microspheres were investigated as dependent variables. Regression analysis was performed to identify the best formulation conditions. The microspheres were evaluated for characteristics such as practical percentage yield, particle size, percentage incorporation efficiency, swellability, zeta potential, in vitro mucoadhesion, thermal analysis, X-ray diffraction study, and in vitro drug diffusion studies. Results: The shape and surface characteristics of the microspheres were determined by scanning electron microscopy, which revealed spherical nature and nearly smooth surface with drug incorporation efficiency in the range of 71.65 ± 1.09% – 91.65 ± 1.13%. In vitro mucoadhesion was observed the range of 79.45 ± 1.69% – 95.48 ± 1.27%. Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of drug in the microspheres. In vitro drug diffusion was Higuchi matrix controlled and the release mechanism was found to be non-Fickian. Stability studies indicated that there were no significant deviations in the drug content, in vitro mucoadhesion and in vitro drug diffusion characteristics. Conclusion: The investigation revealed promising potential of GG microspheres for delivering ALM intranasally for the

  5. Dendrimeric micelles for controlled drug release and targeted delivery

    PubMed Central

    Ambade, Ashootosh V.; Savariar, Elamprakash N.; Thayumanavan, S.

    2008-01-01

    This review highlights the developments in dendrimer-based micelles for drug delivery. Dendrimers, the perfectly branched monodisperse macromolecules, have certain structural advantages that make them attractive candidates as drug carriers for controlled release or targeted delivery. As polymeric micelle-based approaches precede the work in dendrimers, these are also discussed briefly. The review concludes with a perspective on possible applications of biaryl-based dendrimeric micelles that exhibit environment-dependent conformations, in drug delivery. PMID:16053329

  6. Two Important Polysaccharides as Carriers for Drug Delivery.

    PubMed

    Huang, Gangliang; Chen, Yingli; Li, Yue; Huang, Dan; Han, Jie; Yang, Min

    2015-01-01

    Chitosan can be used to prepare the carriers, such as nanoparticles (NPs), intelligent gels, microspheres, nano/microencapsulation, and so on. Its applications in the drug delivery are more broad. Dextran can be combined with drugs by non-covalent crosslinking method or covalent modification mode in the course of delivery. The applications of chitosan and dextran as carriers for drug delivery were summed up herein. PMID:26156418

  7. Intrathecal Drug Delivery (ITDD) systems for cancer pain

    PubMed Central

    Bhatia, Gaurav; Lau, Mary E; Koury, Katharine M; Gulur, Padma

    2014-01-01

    Intrathecal drug delivery is an effective pain management option for patients with chronic and cancer pain. The delivery of drugs into the intrathecal space provides superior analgesia with smaller doses of analgesics to minimize side effects while significantly improving quality of life. This article aims to provide a general overview of the use of intrathecal drug delivery to manage pain, dosing recommendations, potential risks and complications, and growing trends in the field. PMID:24555051

  8. Lipoidal Soft Hybrid Biocarriers of Supramolecular Construction for Drug Delivery

    PubMed Central

    Kumar, Dinesh; Sharma, Deepak; Singh, Gurmeet; Singh, Mankaran; Rathore, Mahendra Singh

    2012-01-01

    Lipid-based innovations have achieved new heights during the last few years as an essential component of drug development. The current challenge of drug delivery is liberation of drug agents at the right time in a safe and reproducible manner to a specific target site. A number of novel drug delivery systems has emerged encompassing various routes of administration, to achieve controlled and targeted drug delivery. Microparticulate lipoidal vesicular system represents a unique technology platform suitable for the oral and systemic administration of a wide variety of molecules with important therapeutic biological activities, including drugs, genes, and vaccine antigens. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. Also, novel lipid carrier-mediated vesicular systems are originated. This paper has focused on the lipid-based supramolecular vesicular carriers that are used in various drug delivery and drug targeting systems. PMID:22888455

  9. Engineering bioceramic microstructure for customized drug delivery

    NASA Astrophysics Data System (ADS)

    Pacheco Gomez, Hernando Jose

    One of the most efficient approaches to treat cancer and infection is to use biomaterials as a drug delivery system (DDS). The goal is for the material to provide a sustained release of therapeutic drug dose locally to target the ill tissue without affecting other organs. Silica Calcium Phosphate nano composite (SCPC) is a drug delivery platform that successfully demonstrated the ability to bind and release several therapeutics including antibiotics, anticancer drugs, and growth factors. The aim of the present work is to analyze the role of SCPC microstructure on drug binding and release kinetics. The main crystalline phases of SCPC are alpha-cristobalite (SiO2, Cris) and beta-rhenanite (NaCaPO4, Rhe); therefore, these two phases were prepared and characterized separately. Structural and compositional features of Cris, Rhe and SCPC bioceramics demonstrated a significant influence on the loading capacity and release kinetics profile of Vancomycin (Vanc) and Cisplatin (Cis). Fourier Transform Infrared (FTIR) spectroscopy analyses demonstrated that the P-O functional group in Rhe and SCPC has high affinity to the (C=O and N-H) of Vanc and (N-H and O-H) of Cis. By contrast, a weak chemical interaction between the Si-O functional group in Cris and SCPC and the two drugs was observed. Vanc loading per unit surface area increased in the order 8.00 microg Vanc/m2 for Rhe > 4.49 microg Vanc /m2 for SCPC>3.01 microg Vanc /m2 for Cris (p<0.05). Cis loading capacity increased in the order 8.59 microg Vanc /m2 for Cris, 17.8 microg Vanc/m2 for Rhe and 6.03 microg Vanc /m2 for SCPC (p<0.05). Drug release kinetics was dependent on the carrier as well as on the kind of drug. Different burst release and sustained release rates were measured for Vanc and Cis from the same carrier. The percentages of drug amount released from Cris, Rhe and SCPC during the burst stage (the first 2h) were: 50%, 50%, and 46% of Vanc; and 53.4%, 36.6%, and 30.6 % of Cis, respectively. Burst release was

  10. Local arterial wall drug delivery using balloon catheter system.

    PubMed

    Tesfamariam, Belay

    2016-09-28

    Balloon-based drug delivery systems allow localized application of drugs to a vascular segment to reduce neointimal hyperplasia and restenosis. Drugs are coated onto balloons using excipients as drug carriers to facilitate adherence and release of drug during balloon inflation. Drug-coated balloon delivery system is characterized by a rapid drug transfer that achieves high drug concentration along the vessel wall surface, intended to correspond to the balloon dilation-induced vascular injury and healing processes. The balloon catheter system allows homogenous drug delivery to the vessel wall, such that the drug release per unit surface area is kept constant along balloons of different lengths. Optimization of the balloon coating matrix is essential for efficient drug transfer and tissue retention until the artery remodels to a normal set point. Challenges in the development of balloon-based drug delivery to the arterial wall include finding suitable excipients for drug formulation to enable drug release to a targeted lesion site effectively, maintain coating integrity during transit, prolong tissue retention and reduce particulate generation. This review highlights various factors involved in the successful design of balloon-based delivery systems, including drug release kinetics, matrix coating transfer, transmural drug partitioning, dissolution rate and release of unbound active drug. PMID:27473765

  11. Polymeric carriers: role of geometry in drug delivery

    PubMed Central

    Simone, Eric A; Dziubla, Thomas D; Muzykantov, Vladimir R

    2009-01-01

    The unique properties of synthetic nanostructures promise a diverse set of applications as carriers for drug delivery, which are advantageous in terms of biocompatibility, pharmacokinetics, targeting and controlled drug release. Historically, more traditional drug delivery systems have focused on spherical carriers. However, there is a growing interest in pursuing non-spherical carriers, such as elongated or filamentous morphologies, now available due to novel formulation strategies. Unique physiochemical properties of these supramolecular structures offer distinct advantages as drug delivery systems. In particular, results of recent studies in cell cultures and lab animals indicate that rational design of carriers of a given geometry (size and shape) offers an unprecedented control of their longevity in circulation and targeting to selected cellular and subcellular locations. This article reviews drug delivery aspects of non-spherical drug delivery systems, including material selection and formulation, drug loading and release, biocompatibility, circulation behavior, targeting and subcellular addressing. PMID:19040392

  12. Extended Release Drug Delivery Strategies in Psychiatry

    PubMed Central

    2005-01-01

    Objective: An overview of the emerging field of long-term delivery strategies for improved convenience and adherence with psychiatric medications is provided. This review is motivated by the hypothesis that adherence to treatment is an important determinant of clinical outcomes in a wide range of settings and is particularly important in psychiatry practice where patients require treatment for months or years and premature discontinuation can have serious consequences for patient health and quality of life. Design: The author reviews the relevant literature and highlights several approaches to providing improved access to continuous medication through new and innovative delivery strategies ranging from days to annual intervals. Benefits and Disadvantages: Several solutions to the problem of discontinuous access to pharmacotherapy are being developed in the form of new, long-acting drug-delivery systems, which gradually release medication over a period of several days or weeks with a single application. Long-acting formulations of psychiatric medications offer a number of potential benefits in comparison with conventional immediate-release agents, including improved safety and effectiveness. Potential limitations to using long-acting formulations may include pain and discomfort at the injection site, perceived inconvenience of a new treatment method, preference for oral medications, and length of time to titrate down to the lowest effective dose. Conclusions: The introduction of new, long-acting drug formulations could provide significant improvements in clinical outcomes and patient satisfaction for many patients, including those with affective disorders, schizophrenia, and alcohol dependence. Switching from oral administration to these new agents requires careful monitoring to reach the optimal dose, and patient concerns regarding the use of new delivery methods must be addressed. Long-acting formulations are not intended to be a sole form of treatment, and the

  13. Controlled drug delivery systems: past forward and future back.

    PubMed

    Park, Kinam

    2014-09-28

    Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology.

  14. Oro-dental mucoadhesive proniosomal gel formulation loaded with lornoxicam for management of dental pain.

    PubMed

    Abdelbary, Ghada Ahmed; Aburahma, Mona Hassan

    2015-01-01

    Oro-dental diseases are generally associated with pain that is controlled using oral tablets containing NSAIDs. Lornoxicam, a relatively new NSAID, is effective in relieving pain accompanying different oro-dental problems. The aim of the current research is to prepare oro-dental analgesic and anti-inflammatory gel using provesicular approach to deliver lornoxicam directly to the site of action in the oral cavity. Local administration of lornoxicam is expected to be superior to systemic delivery in pain relieving and poses less GIT adverse effects. Different surfactants were utilized to prepare the proniosomal gels that rapidly transform into nano-sized niosomes after hydration with the oral saliva. The effect of the surfactant structure on vesicles size distribution and entrapment efficiency percentage (EE%) was investigated. The proniosomal formulations were incorporated into carbopol hydrogels that were characterized regarding rheological and mucoadhesion properties. Moreover, ex-vivo mucosal membrane permeation studies were conducted for selected proniosomal gels to quantify the permeation parameters and assess the amount of drug deposited within the oral mucosa. Results revealed that mucoadhesive proniosomes formulation prepared using Span 60 was optimal as it was nano-sized and also showed the highest EE%. The transmucosal flux of lornoxicam, from these proniosomal formulations, across the oral mucosa was significantly higher (p < 0.05) than lornoxicam containing carbopol gel and the percent drug diffused increased more than twofolds. The results collectively suggest that the mucoadhesive proniosomal gels can be assertively considered as a promising carrier for transmucosal delivery of lornoxicam into the oral cavity. PMID:25058447

  15. Engineering bioceramic microstructure for customized drug delivery

    NASA Astrophysics Data System (ADS)

    Pacheco Gomez, Hernando Jose

    One of the most efficient approaches to treat cancer and infection is to use biomaterials as a drug delivery system (DDS). The goal is for the material to provide a sustained release of therapeutic drug dose locally to target the ill tissue without affecting other organs. Silica Calcium Phosphate nano composite (SCPC) is a drug delivery platform that successfully demonstrated the ability to bind and release several therapeutics including antibiotics, anticancer drugs, and growth factors. The aim of the present work is to analyze the role of SCPC microstructure on drug binding and release kinetics. The main crystalline phases of SCPC are alpha-cristobalite (SiO2, Cris) and beta-rhenanite (NaCaPO4, Rhe); therefore, these two phases were prepared and characterized separately. Structural and compositional features of Cris, Rhe and SCPC bioceramics demonstrated a significant influence on the loading capacity and release kinetics profile of Vancomycin (Vanc) and Cisplatin (Cis). Fourier Transform Infrared (FTIR) spectroscopy analyses demonstrated that the P-O functional group in Rhe and SCPC has high affinity to the (C=O and N-H) of Vanc and (N-H and O-H) of Cis. By contrast, a weak chemical interaction between the Si-O functional group in Cris and SCPC and the two drugs was observed. Vanc loading per unit surface area increased in the order 8.00 microg Vanc/m2 for Rhe > 4.49 microg Vanc /m2 for SCPC>3.01 microg Vanc /m2 for Cris (p<0.05). Cis loading capacity increased in the order 8.59 microg Vanc /m2 for Cris, 17.8 microg Vanc/m2 for Rhe and 6.03 microg Vanc /m2 for SCPC (p<0.05). Drug release kinetics was dependent on the carrier as well as on the kind of drug. Different burst release and sustained release rates were measured for Vanc and Cis from the same carrier. The percentages of drug amount released from Cris, Rhe and SCPC during the burst stage (the first 2h) were: 50%, 50%, and 46% of Vanc; and 53.4%, 36.6%, and 30.6 % of Cis, respectively. Burst release was

  16. Advances in Lymphatic Imaging and Drug Delivery

    SciTech Connect

    Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.; Thallapally, Praveen K.; Laird, Forrest M.

    2011-09-10

    Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastly improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.

  17. Bioinspired Nanonetworks for Targeted Cancer Drug Delivery.

    PubMed

    Raz, Nasibeh Rady; Akbarzadeh-T, Mohammad-R; Tafaghodi, Mohsen

    2015-12-01

    A biomimicry approach to nanonetworks is proposed here for targeted cancer drug delivery (TDD). The swarm of bioinspired nanomachines utilizes the blood distribution network and chemotaxis to carry drug through the vascular system to the cancer site, recognized by a high concentration of vascular endothelial growth factor (VEGF). Our approach is multi-scale and includes processes that occur both within cells and with their neighbors. The proposed bionanonetwork takes advantage of several organic processes, some of which already occur within the human body, such as a plate-like structure similar to those of red blood cells for more environmental contact; a berry fruit architecture for its internal multi-foams architecture; the penetrable structure of cancer cells, tissue, as well as the porous structure of the capillaries for drug penetration; state of glycocalyx for ligand-receptor adhesion; as well as changes in pH state of blood and O 2 release for nanomachine communication. For a more appropriate evaluation, we compare our work with a conventional chemotherapy approach using a mathematical model of cancer under actual experimental parameter settings. Simulation results show the merits of the proposed method in targeted cancer therapy by improving the densities of the relevant cancer cell types and VEGF concentration, while following more organic and natural processes.

  18. Bioinspired Nanonetworks for Targeted Cancer Drug Delivery.

    PubMed

    Raz, Nasibeh Rady; Akbarzadeh-T, Mohammad-R; Tafaghodi, Mohsen

    2015-12-01

    A biomimicry approach to nanonetworks is proposed here for targeted cancer drug delivery (TDD). The swarm of bioinspired nanomachines utilizes the blood distribution network and chemotaxis to carry drug through the vascular system to the cancer site, recognized by a high concentration of vascular endothelial growth factor (VEGF). Our approach is multi-scale and includes processes that occur both within cells and with their neighbors. The proposed bionanonetwork takes advantage of several organic processes, some of which already occur within the human body, such as a plate-like structure similar to those of red blood cells for more environmental contact; a berry fruit architecture for its internal multi-foams architecture; the penetrable structure of cancer cells, tissue, as well as the porous structure of the capillaries for drug penetration; state of glycocalyx for ligand-receptor adhesion; as well as changes in pH state of blood and O 2 release for nanomachine communication. For a more appropriate evaluation, we compare our work with a conventional chemotherapy approach using a mathematical model of cancer under actual experimental parameter settings. Simulation results show the merits of the proposed method in targeted cancer therapy by improving the densities of the relevant cancer cell types and VEGF concentration, while following more organic and natural processes. PMID:26529771

  19. Microencapsulation: A promising technique for controlled drug delivery

    PubMed Central

    Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.

    2010-01-01

    Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed. PMID:21589795

  20. Approaches to Neural Tissue Engineering Using Scaffolds for Drug Delivery

    PubMed Central

    Willerth, Stephanie M.; Sakiyama-Elbert, Shelly E.

    2007-01-01

    This review seeks to give an overview of the current approaches to drug delivery from scaffolds for neural tissue engineering applications. The challenges presented by attempting to replicate the three types of nervous tissue (brain, spinal cord, and peripheral nerve) are summarized. Potential scaffold materials (both synthetic and natural) and target drugs are discussed with the benefits and drawbacks given. Finally, common methods of drug delivery, including degradable/diffusion-based delivery systems, affinity-based delivery systems, immobilized drug delivery systems, and electrically controlled drug delivery systems, are examined and critiqued. Based on the current body of work, suggestions for future directions of research in the field of neural tissue engineering are presented. PMID:17482308

  1. Nanomicellar formulations for sustained drug delivery: strategies and underlying principles

    PubMed Central

    Trivedi, Ruchit; Kompella, Uday B

    2010-01-01

    Micellar delivery systems smaller than 100 nm can be readily prepared. While micelles allow a great depth of tissue penetration for targeted drug delivery, they usually disintegrate rapidly in the body. Thus, sustained drug delivery from micellar nanocarriers is a challenge. This article summarizes various key strategies and underlying principles for sustained drug delivery using micellar nanocarriers. Comparisons are made with other competing delivery systems such as polymeric microparticles and nanoparticles. Amphiphilic molecules self-assemble in appropriate liquid media to form nanoscale micelles. Strategies for sustained release nanomicellar carriers include use of prodrugs, drug polymer conjugates, novel polymers with low critical micellar concentration or of a reverse thermoresponsive nature, reverse micelles, multi-layer micelles with layer by layer assembly, polymeric films capable of forming micelles in vivo and micelle coats on a solid support. These new micellar systems are promising for sustained drug delivery. PMID:20394539

  2. Click chemistry for drug delivery nanosystems.

    PubMed

    Lallana, Enrique; Sousa-Herves, Ana; Fernandez-Trillo, Francisco; Riguera, Ricardo; Fernandez-Megia, Eduardo

    2012-01-01

    The purpose of this Expert Review is to discuss the impact of click chemistry in nanosized drug delivery systems. Since the introduction of the click concept by Sharpless and coworkers in 2001, numerous examples of click reactions have been reported for the preparation and functionalization of polymeric micelles and nanoparticles, liposomes and polymersomes, capsules, microspheres, metal and silica nanoparticles, carbon nanotubes and fullerenes, or bionanoparticles. Among these click processes, Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has attracted most attention based on its high orthogonality, reliability, and experimental simplicity for non-specialists. A renewed interest in the use of efficient classical transformations has been also observed (e.g., thiol-ene coupling, Michael addition, Diels-Alder). Special emphasis is also devoted to critically discuss the click concept, as well as practical aspects of application of CuAAC to ensure efficient and harmless bioconjugation.

  3. Drug delivery by organ-specific immunoliposomes

    SciTech Connect

    Maruyama, Kazuo; Mori, Atsuhide; Hunag, Leaf . Dept. of Biochemistry); Kennel, S.J. )

    1990-01-01

    Monoclonal antibodies highly specific to the mouse pulmonary endothelial cells were conjugated to liposomes. The resulting immunoliposomes showed high levels of lung accumulation when injected intravenously into mice. Optimal target binding and retention were achieved if the lipid composition included ganglioside GM{sub 1} to reduce the uptake of immunoliposomes by the reticuloendothelial system. Details of the construction and optimization of these organ-specific immunoliposomes are reviewed. The drug delivery potential of this novel liposome system was demonstrated in an experimental pulmonary metastasis model. Immunoliposomes containing a lipophilic prodrug of deoxyfluorouridine effectively prolonged the survival time of the tumor-bearing mice. This and other therapeutic applications of the immunoliposomes are discussed. 25 refs., 5 figs.

  4. Advances in Nanocarriers for Anticancer Drugs Delivery.

    PubMed

    Ali, Imran; Lone, Mohammad Nadeem; Suhail, Mohammad; Mukhtar, Sofi Danish; Asnin, Leonid

    2016-01-01

    Cancer is the most dangerous disease to haunt the mankind in the world today. Generally, the overall cancer mortality rates are similar in both the sexes. The reasons for most of these deaths are inefficacy and failure of the current methods of treatments or the unavailability of treatment options. The researchers of the world are actively integrating nanotechnology of treating of various cancers. The development of smart nanocarriers is one of the most important innovations in this direction. The nanocarriers of the different materials are being developed to improve the efficacy of current treatments. The present article describes the role of nanotechnology in cancer treatment emphasizing cancer nanotherapy, nanocarriers for drug delivery, types and the mechanisms of the nanocarriers. Besides, the efforts are made to discuss the recent advances in the nanocarriers, current challenges and the future prospective. PMID:27048343

  5. Effect of nanoparticles on transdermal drug delivery.

    PubMed

    Cappel, M J; Kreuter, J

    1991-01-01

    The purpose of the present study was to assess by in vitro means the effect of poly (methylmethacrylate) nanoparticles and poly (butylcyanoacrylate) nanoparticles on transdermal drug delivery. Methanol and octanol were chosen as test permeants. In order to distinguish between thermodynamic effect and those due to biological consequences, two different membranes were employed, i.e., full thickness hairless mouse skin and silicone elastomer sheeting (175 microns). It is evident that poly (methylmethacrylate) nanoparticles and poly (butylcyanoacrylate) nanoparticles increase the permeability of methanol through hairless mouse skin by a factor of 1.2-2. The permeability of lipophilic octanol is either unaffected by nanoparticles or decreases as a function of nanoparticle concentration depending on the lipophilicity of the polymer material.

  6. Enzyme-responsive nanomaterials for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Hu, Quanyin; Katti, Prateek S.; Gu, Zhen

    2014-10-01

    Enzymes underpin physiological function and exhibit dysregulation in many disease-associated microenvironments and aberrant cell processes. Exploiting altered enzyme activity and expression for diagnostics, drug targeting, and drug release is tremendously promising. When combined with booming research in nanobiotechnology, enzyme-responsive nanomaterials used for controlled drug release have achieved significant development and have been studied as an important class of drug delivery strategies in nanomedicine. In this review, we describe enzymes such as proteases, phospholipases and oxidoreductases that serve as delivery triggers. Subsequently, we explore recently developed enzyme-responsive nanomaterials with versatile applications for extracellular and intracellular drug delivery. We conclude by discussing future opportunities and challenges in this area.

  7. Enzyme-Responsive Nanomaterials for Controlled Drug Delivery

    PubMed Central

    Hu, Quanyin; Katti, Prateek S.; Gu, Zhen

    2015-01-01

    Enzymes underpin physiological function and exhibit dysregulation in many disease-associated microenvironments and aberrant cell processes. Exploiting altered enzyme activity and expression for diagnostics, drug targeting, and drug release is tremendously promising. When combined with booming research in nanobiotechnology, enzyme-responsive nanomaterials for controlled drug release have achieved significant development and been studied as an important class of drug delivery devices in nanomedicine. In this review, we describe enzymes such as proteases, phospholipase and oxidoreductases that serve as delivery triggers. Subsequently, we explore recently developed enzyme-responsive nanomaterials with versatile applications for extracellular and intracellular drug delivery. We conclude by discussing future opportunities and challenges in this area. PMID:25251024

  8. Formulation and evalution of montelukast sodium - chitosan based spray dried microspheres for pulmonary drug delivery.

    PubMed

    Panchal, Rushi; Patel, Harsha; Patel, Vishnu; Joshi, Pratik; Parikh, Ankit

    2012-03-01

    The objective of present work was to prepare microspheres of montelukast sodium using a natural polymer- chitosan by spray drying method by using glutaraldehyde as a cross linking agent. The microspheres were characterized for size, shape, dissolution, swelling and mucoadhesion. It was observed that, all microspheres were spherical in shape with narrow size distribution. Microspheres had mean particle size of 7-12 μm, with % encapsulation efficiency of 78-86%. The % yield was 32-49% and drug load was 48-53%. With the increase in proportion of chitosan in formulation mucoadhesive strength was increase and also increased in particle size of microspheres. As the drug:polymer ratio increase drug loading was increase and % encapsulation efficiency was also increase.

  9. Preparation and in vitro antibacterial evaluation of gatifloxacin mucoadhesive gellan system

    PubMed Central

    Kesavan, K.; Nath, G.; Pandit, JK.

    2010-01-01

    Background and the purpose of the study The poor bioavailability and therapeutic response exhibited by the conventional ophthalmic solutions due to precorneal elimination of the drug may be overcome by the use of mucoadhesive in situ gel forming systems that are instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac and have good mucoadhesion with ocular mucus layers. The objective of this study was to formulate ophthalmic mucoadhesive system of gatifloxacin (GTN) and to evaluate its in vitro antibacterial potential against, Staphylococcus aureus and Escherichia coli. Methods : Mucoadhesive systems were prepared using gellan combined with sodium carboxymethylcellulose (NaCMC) or sodium alginate to enhance the gel bioadhesion properties. The prepared formulations were evaluated for their gelation, and rheological behaviors, mucoadhesion force, in vitro drug release, and antibacterial activity. Results All formulations in non-physiological or physiological conditions showed pseudoplastic behaviors. Increase in the concentration of mucoadhesive agent enhanced the mucoadhesive force significantly. In vitro release of gatifloxacin from the mucoadhesive system in simulated tear fluid (STF, pH of 7.4) was influenced significantly by the properties and concentration of gellan, sodium carboxymethyl cellulose and sodium alginate. Significant reduction in the total bacterial count was observed between drug solution (control) and mucoadhesive batches against both tested organisms. Major conclusion The developed mucoadhesive system is a viable alternative to conventional eye drops of GTN due to its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain the release of the drug. PMID:22615622

  10. Laminated sponges as challenging solid hydrophilic matrices for the buccal delivery of carvedilol microemulsion systems: Development and proof of concept via mucoadhesion and pharmacokinetic assessments in healthy human volunteers.

    PubMed

    Abd-Elbary, Ahmed; Makky, Amna M A; Tadros, Mina Ibrahim; Alaa-Eldin, Ahmed Adel

    2016-01-20

    Carvedilol (CVD) suffers from low absolute bioavailability (25%) due to its limited aqueous solubility and hepatic first-pass metabolism. Hydroxypropyl methylcellulose (HPMC) laminated buccal sponges loaded with CVD microemulsions (CVD-ME) were exploited to surmount such limitations. Six pseudoternary-phase diagrams were constructed using Capmul® MCM C8/Capmul® PG8, Tween® 80, propylene glycol and water. Six CVD-ME systems (0.625% w/v) were incorporated into HPMC core sponges backed with Ethocel® layers. The sponges were preliminary evaluated via FT-IR, DSC and XRD. The surface pH, morphology and in vitro drug release studies were evaluated. In vivo mucoadhesion and absorption studies of the best achieved laminated sponges (F4) were assessed in healthy volunteers. CVD-ME systems displayed nano-spherical clear droplets. The sponges showed interconnecting porous matrices through which CVD was dispersed in amorphous state. No intermolecular interaction was detected between CVD and HPMC. The surface pH values were almost neutral. The sponges loaded with CVD-ME systems showed more sustained-release profiles than those loaded with CVD-powder. Compared to Dilatrend® tablets, the significantly (P<0.05) higher bioavailability (1.5 folds), delayed Tmax and prolonged MRT(0-∞) unraveled the dual-potential of F4 sponges for water-insoluble drugs, like CVD, in improving drug oral bioavailability and in controlling drug release kinetics via buccal mucosa. PMID:26546947

  11. Engineered microparticles based on drug-polymer coprecipitates for ocular-controlled delivery of Ciprofloxacin: influence of technological parameters.

    PubMed

    Gavini, Elisabetta; Bonferoni, Maria Cristina; Rassu, Giovanna; Sandri, Giuseppina; Rossi, Silvia; Salis, Andrea; Porcu, Elena Piera; Giunchedi, Paolo

    2016-01-01

    Ciprofloxacin is a drug active against a broad spectrum of aerobic Gram-positive and Gram-negative bacteria, for the therapy of ocular infections. It requires frequent administrations owing to rapid ocular clearance and it is a good candidate for ocular controlled release formulations. The preparation of such drug release systems is still a challenge. Ionic interactions between ciprofloxacin and the polyelectrolytes chondroitin sulfate or lambda carrageenan result in coprecipitates that can act as microparticulate controlled release systems from which the drug is released after being displaced by the medium's ions. In some formulations, Carbopol was added to improve the mucoadhesive properties. The aim of this research was the study of the influence of the technological parameters of the preparation method of coprecipitates on their particle size, with the goal of achieving particles engineered with a size suitable for the ocular administration. Technological parameters taken into account were: concentration of drug and polymer solutions utilized for the preparation of interaction products, possible use of surfactants (kind and concentration), temperature of the solutions and stirring during the process of preparation of the coprecipitates. Preliminary stability study tests were carried out to further characterize the leader formulation. Particle size in suspensions for ocular drug delivery is a critical parameter influencing the quality of the formulation. The results obtained from this study show that chondroitin sulfate coprecipitates present the best characteristics in terms of particle size suitable for ocular administration. A further improvement of the particle size characteristics has been obtained with the addition of surfactants.

  12. Detection and drug delivery from superhydrophobic materials

    NASA Astrophysics Data System (ADS)

    Falde, Eric John

    The wetting of a rough material is controlled by surface chemistry and morphology, the liquid phase, solutes, and surfactants that affect the surface tension with the gas phase, and environmental conditions such as temperature and pressure. Materials with high (>150°) apparent contact angles are known as superhydrophobic and are very resistant to wetting. However, in complex biological mixtures eventually protein adsorbs, fouling the surface and facilitating wetting on time scales from seconds to months. The work here uses the partially-wetted (Cassie-Baxter) to fully-wetted (Wenzel) state transition to control drug delivery and to perform surfactant detection via surface tension using hydrophobic and superhydrophobic materials. First there is an overview of the physics of the non-wetting state and the transition to wetting. Then there is a review of how wetting can be controlled by outside stimuli and applications of these materials. Next there is work presented on controlling drug release using superhydrophobic materials with controlled wetting rates, with both in vitro and in vivo results. Then there is work on developing a sensor based on this wetting state transition and its applications toward detecting solute levels in biological fluids for point-of-care diagnosis. Finally, there is work presented on using these sensors for detecting the alcohol content in wine and spirits.

  13. Programmable biomaterials for dynamic and responsive drug delivery

    PubMed Central

    Stejskalová, Anna; Kiani, Mehrdad T

    2016-01-01

    Biomaterials are continually being designed that enable new methods for interacting dynamically with cell and tissues, in turn unlocking new capabilities in areas ranging from drug delivery to regenerative medicine. In this review, we explore some of the recent advances being made in regards to programming biomaterials for improved drug delivery, with a focus on cancer and infection. We begin by explaining several of the underlying concepts that are being used to design this new wave of drug delivery vehicles, followed by examining recent materials systems that are able to coordinate the temporal delivery of multiple therapeutics, dynamically respond to changing tissue environments, and reprogram their bioactivity over time. PMID:27190245

  14. Oral Drug Delivery with Polymeric Nanoparticles: The Gastrointestinal Mucus Barriers

    PubMed Central

    Ensign, Laura M.; Cone, Richard; Hanes, Justin

    2012-01-01

    Oral delivery is the most common method for drug administration. However, poor solubility, stability, and bioavailability of many drugs make achieving therapeutic levels via the gastrointestinal (GI) tract challenging. Drug delivery must overcome numerous hurdles, including the acidic gastric environment and the continuous secretion of mucus that protects the GI tract. Nanoparticle drug carriers that can shield drugs from degradation and deliver them to intended sites within the GI tract may enable more efficient and sustained drug delivery. However, the rapid secretion and shedding of GI tract mucus can significantly limit the effectiveness of nanoparticle drug delivery systems. Many types of nanoparticles are efficiently trapped in and rapidly removed by mucus, making controlled release in the GI tract difficult. This review addresses the protective barrier properties of mucus secretions, how mucus affects the fate of orally administered nanoparticles, and recent developments in nanoparticles engineered to penetrate the mucus barrier. PMID:22212900

  15. Nanoparticle-based drug delivery to the vagina: a review

    PubMed Central

    Ensign, Laura M.; Cone, Richard; Hanes, Justin

    2014-01-01

    Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, including sexually transmitted diseases, fungal and bacterial infections, and cancer. However, achieving sustained local drug concentrations in the vagina can be challenging, due to the high permeability of the vaginal epithelium and expulsion of conventional soluble drug dosage forms. Nanoparticle-based drug delivery platforms have received considerable attention for vaginal drug delivery, as nanoparticles can provide sustained release, cellular targeting, and even intrinsic antimicrobial or adjuvant properties that can improve the potency and/or efficacy of prophylactic and therapeutic modalities. Here, we review the use of polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles for vaginal drug delivery. Although most of the work toward nanoparticle-based drug delivery in the vagina has been focused on HIV prevention, strategies for treatment and prevention of other sexually transmitted infections, treatment for reproductive tract cancer, and treatment of fungal and bacterial infections are also highlighted. PMID:24830303

  16. Hydrogels for ocular drug delivery and tissue engineering

    PubMed Central

    Fathi, Marzieh; Barar, Jaleh; Aghanejad, Ayuob; Omidi, Yadollah

    2015-01-01

    Hydrogels, as crosslinked polymeric three dimensional networks, possess unique structure and behavior in response to the internal and/or external stimuli. As a result, they offer great prospective applications in drug delivery, cell therapy and human tissue engineering. Here, we highlight the potential of hydrogels in prolonged intraocular drug delivery and ocular surface therapy using stem cells incorporated hydrogels. PMID:26929918

  17. Clinical applications of biomedical microdevices for controlled drug delivery.

    PubMed

    Gurman, Pablo; Miranda, Oscar R; Clayton, Kevin; Rosen, Yitzhak; Elman, Noel M

    2015-01-01

    Miniaturization of devices to micrometer and nanometer scales, combined with the use of biocompatible and functional materials, has created new opportunities for the implementation of drug delivery systems. Advances in biomedical microdevices for controlled drug delivery platforms promise a new generation of capabilities for the treatment of acute conditions and chronic illnesses, which require high adherence to treatment, in which temporal control over the pharmacokinetic profiles is critical. In addition, clinical conditions that require a combination of drugs with specific pharmacodynamic profiles and local delivery will benefit from drug delivery microdevices. This review provides a summary of various clinical applications for state-of-the-art controlled drug delivery microdevices, including cancer, endocrine and ocular disorders, and acute conditions such as hemorrhagic shock. Regulatory considerations for clinical translation of drug delivery microdevices are also discussed. Drug delivery microdevices promise a remarkable gain in clinical outcomes and a substantial social impact. A review of articles covering the field of microdevices for drug delivery was performed between January 1, 1990, and January 1, 2014, using PubMed as a search engine.

  18. Drug Delivery Approaches for the Treatment of Cervical Cancer

    PubMed Central

    Ordikhani, Farideh; Erdem Arslan, Mustafa; Marcelo, Raymundo; Sahin, Ilyas; Grigsby, Perry; Schwarz, Julie K.; Azab, Abdel Kareem

    2016-01-01

    Cervical cancer is a highly prevalent cancer that affects women around the world. With the availability of new technologies, researchers have increased their efforts to develop new drug delivery systems in cervical cancer chemotherapy. In this review, we summarized some of the recent research in systematic and localized drug delivery systems and compared the advantages and disadvantages of these methods. PMID:27447664

  19. Nano- and microfabrication for overcoming drug delivery challenges

    PubMed Central

    Kam, Kimberly R.

    2013-01-01

    This highlight article describes current nano- and microfabrication techniques for creating drug delivery devices. We first review the main physiological barriers to delivering therapeutic agents. Then, we describe how novel fabrication methods can be utilized to combine many features into a single physiologically relevant device to overcome drug delivery challenges. PMID:23730504

  20. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    PubMed

    Alimoradi, Houman; Matikonda, Siddharth S; Gamble, Allan B; Giles, Gregory I; Greish, Khaled

    2016-01-01

    Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems.

  1. Electrically Controlled Drug Delivery from Graphene Oxide Nanocomposite Films

    PubMed Central

    2015-01-01

    On-demand, local delivery of drug molecules to target tissues provides a means for effective drug dosing while reducing the adverse effects of systemic drug delivery. This work explores an electrically controlled drug delivery nanocomposite composed of graphene oxide (GO) deposited inside a conducting polymer scaffold. The nanocomposite is loaded with an anti-inflammatory molecule, dexamethasone, and exhibits favorable electrical properties. In response to voltage stimulation, the nanocomposite releases drug with a linear release profile and a dosage that can be adjusted by altering the magnitude of stimulation. No drug passively diffuses from the composite in the absence of stimulation. In vitro cell culture experiments demonstrate that the released drug retains its bioactivity and that no toxic byproducts leach from the film during electrical stimulation. Decreasing the size and thickness of the GO nanosheets, by means of ultrasonication treatment prior to deposition into the nanocomposite, alters the film morphology, drug load, and release profile, creating an opportunity to fine-tune the properties of the drug delivery system to meet a variety of therapeutic needs. The high level of temporal control and dosage flexibility provided by the electrically controlled GO nanocomposite drug delivery platform make it an exciting candidate for on-demand drug delivery. PMID:24428340

  2. Pharmacosomes: An Emerging Novel Vesicular Drug Delivery System for Poorly Soluble Synthetic and Herbal Drugs

    PubMed Central

    2013-01-01

    In the arena of solubility enhancement, several problems are encountered. A novel approach based on lipid drug delivery system has evolved, pharmacosomes. Pharmacosomes are colloidal, nanometric size micelles, vesicles or may be in the form of hexagonal assembly of colloidal drug dispersions attached covalently to the phospholipid. They act as befitting carrier for delivery of drugs quite precisely owing to their unique properties like small size, amphiphilicity, active drug loading, high entrapment efficiency, and stability. They help in controlled release of drug at the site of action as well as in reduction in cost of therapy, drug leakage and toxicity, increased bioavailability of poorly soluble drugs, and restorative effects. There has been advancement in the scope of this delivery system for a number of drugs used for inflammation, heart diseases, cancer, and protein delivery along with a large number of herbal drugs. Hence, pharmacosomes open new challenges and opportunities for improved novel vesicular drug delivery system. PMID:24106615

  3. Nanobiotechnology-based drug delivery in brain targeting.

    PubMed

    Dinda, Subas C; Pattnaik, Gurudutta

    2013-01-01

    Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery to brain in combating the central nervous system (CNS) disorders. Such limiting physiological factors include the reticuloendothelial system and protein opsonization, which present across BBB, play major role in reducing the passage of drug. Several approaches employed to improve the drug delivery across the BBB. Nanoparticles (NP) are the solid colloidal particle ranges from 1 to 1000 nm in size utilized as career for drug delivery. At present NPs are found to play a significant advantage over the other methods of available drug delivery systems to deliver the drug across the BBB. Nanoparticles may be because of its size and functionalization characteristics able to penetrate and facilitate the drug delivery through the barrier. There are number of mechanisms and strategies found to be involved in this process, which are based on the type of nanomaterials used and its combination with therapeutic agents, such materials include liposomes, polymeric nanoparticles and non-viral vectors of nano-sizes for CNS gene therapy, etc. Nanotechnology is expected to reduce the need for invasive procedures for delivery of therapeutics to the CNS. Some devices such as implanted catheters and reservoirs however will still be needed to overcome the problems in effective drug delivery to the CNS. Nanomaterials are found to improve the safety and efficacy level of drug delivery devices in brain targeting. Nanoegineered devices are found to be delivering the drugs at cellular levels through nono-fluidic channels. Different drug delivery systems such as liposomes, microspheres, nanoparticles, nonogels and nonobiocapsules have been used to improve the bioavailability of the drug in the brain, but microchips and biodegradable polymeric nanoparticulate careers are found to be more effective therapeutically in treating brain tumor. The physiological approaches also utilized to improve the transcytosis capacity

  4. Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

    PubMed Central

    Lee, Chun-Ting; Huang, Yen-Wei; Yang, Chih-Hui; Huang, Keng-Shiang

    2015-01-01

    Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed. PMID:25877096

  5. Pulmonary drug delivery systems: recent developments and prospects.

    PubMed

    Courrier, H M; Butz, N; Vandamme, Th F

    2002-01-01

    Targeting drug delivery into the lungs has become one of the most important aspects of systemic or local drug delivery systems. Consequently, in the last few years, techniques and new drug delivery devices intended to deliver drugs into the lungs have been widely developed. Currently, the main drug targeting regimens include direct application of a drug into the lungs, mostly by inhalation therapy using either pressurized metered dose inhalers (pMDI) or dry powder inhalers (DPI). Intratracheal administration is commonly used as a first approach in lung drug delivery in vivo. To convey a sufficient dose of drug to the lungs, suitable drug carriers are required. These can be either solid, liquid, or gaseous excipients. Liposomes, nano- and microparticles, cyclodextrins, microemulsions, micelles, suspensions, or solutions are all examples of this type of pharmaceutical carrier that have been successfully used to target drugs into the lungs. The use of microreservoir-type systems offers clear advantages, such as high loading capacity and the possibility of controlling size and permeability, and thus of controlling the release kinetics of the drugs from the carrier systems. These systems make it possible to use relatively small numbers of vector molecules to deliver substantial amounts of a drug to the target. This review discusses the drug carriers administered or intended to be administered into the lungs. The transition to CFC-free inhalers and drug delivery systems formulated with new propellants are also discussed. Finally, in addition to the various advances made in the field of pulmonary-route administration, we describe new systems based on perfluorooctyl bromide, which guarantee oxygen delivery in the event of respiratory distress and drug delivery into the lungs.

  6. Novel Approaches in Formulation and Drug Delivery using Contact Lenses.

    PubMed

    Singh, Kishan; Nair, Anroop B; Kumar, Ashok; Kumria, Rachna

    2011-03-01

    The success of ocular delivery relies on the potential to enhance the drug bioavailability by controlled and extended release of drug on the eye surface. Several new approaches have been attempted to augment the competence and diminish the intrinsic side effects of existing ocular drug delivery systems. In this contest, progress has been made to develop drug-eluting contact lens using different techniques, which have the potential to control and sustain the delivery of drug. Further, the availability of novel polymers have facilitated and promoted the utility of contact lenses in ocular drug delivery. Several research groups have already explored the feasibility and potential of contact lens using conventional drugs for the treatment of periocular and intraocular diseases. Contact lenses formulated using modern technology exhibits high loading, controlled drug release, apposite thickness, water content, superior mechanical and optical properties as compared to commercial lenses. In general, this review discus various factors and approaches designed and explored for the successful delivery of ophthalmic drugs using contact lenses as drug delivery device.

  7. Nanofibers based antibacterial drug design, delivery and applications.

    PubMed

    Ulubayram, Kezban; Calamak, Semih; Shahbazi, Reza; Eroglu, Ipek

    2015-01-01

    Infections caused by microorganisms like bacteria, fungi, etc. are the main obstacle in healing processes. Conventional antibacterial administration routes can be listed as oral, intravenous/intramuscular, topical and inhalation. These kinds of drug administrations are faced with critical vital issues such as; more rapid delivery of the drug than intended which can result in bacterial resistance, dose related systemic toxicity, tissue irritation and finally delayed healing process that need to be tackled. Recently, studies have been focused on new drug delivery systems, overcoming resistance and toxicological problems and finally localizing the molecules at the site of action in a proper dose. In this regard, many nanotechnological approaches such as nanoparticulate therapeutic systems have been developed to address accompanying problems mentioned above. Among them, drug loaded electrospun nanofibers propose main advantages like controlled drug delivery, high drug loading capacity, high encapsulation efficiency, simultaneous delivery of multiple drugs, ease of production and cost effectiveness for pharmaceutical and biomedical applications. Therefore, some particular attention has been devoted to the design of electrospun nanofibers as promising antibacterial drug carrier systems. A variety of antibacterials e.g., biocides, antibiotics, quaternary ammonium salts, triclosan, metallic nanoparticles (silver, titanium dioxide, and zinc oxide) and antibacterial polymers (chitosan, polyethyleneimine, etc.) have been impregnated by various techniques into nanofibers that exhibit strong antibacterial activity in standard assays. This review highlights the design and delivery of antibacterial drug loaded nanofibers with particular focus on their function in the fields of drug delivery, wound healing, tissue engineering, cosmetics and other biomedical applications.

  8. Novel Approaches in Formulation and Drug Delivery using Contact Lenses

    PubMed Central

    Singh, Kishan; Nair, Anroop B; Kumar, Ashok; Kumria, Rachna

    2011-01-01

    The success of ocular delivery relies on the potential to enhance the drug bioavailability by controlled and extended release of drug on the eye surface. Several new approaches have been attempted to augment the competence and diminish the intrinsic side effects of existing ocular drug delivery systems. In this contest, progress has been made to develop drug-eluting contact lens using different techniques, which have the potential to control and sustain the delivery of drug. Further, the availability of novel polymers have facilitated and promoted the utility of contact lenses in ocular drug delivery. Several research groups have already explored the feasibility and potential of contact lens using conventional drugs for the treatment of periocular and intraocular diseases. Contact lenses formulated using modern technology exhibits high loading, controlled drug release, apposite thickness, water content, superior mechanical and optical properties as compared to commercial lenses. In general, this review discus various factors and approaches designed and explored for the successful delivery of ophthalmic drugs using contact lenses as drug delivery device PMID:24826007

  9. Nanofibers based antibacterial drug design, delivery and applications.

    PubMed

    Ulubayram, Kezban; Calamak, Semih; Shahbazi, Reza; Eroglu, Ipek

    2015-01-01

    Infections caused by microorganisms like bacteria, fungi, etc. are the main obstacle in healing processes. Conventional antibacterial administration routes can be listed as oral, intravenous/intramuscular, topical and inhalation. These kinds of drug administrations are faced with critical vital issues such as; more rapid delivery of the drug than intended which can result in bacterial resistance, dose related systemic toxicity, tissue irritation and finally delayed healing process that need to be tackled. Recently, studies have been focused on new drug delivery systems, overcoming resistance and toxicological problems and finally localizing the molecules at the site of action in a proper dose. In this regard, many nanotechnological approaches such as nanoparticulate therapeutic systems have been developed to address accompanying problems mentioned above. Among them, drug loaded electrospun nanofibers propose main advantages like controlled drug delivery, high drug loading capacity, high encapsulation efficiency, simultaneous delivery of multiple drugs, ease of production and cost effectiveness for pharmaceutical and biomedical applications. Therefore, some particular attention has been devoted to the design of electrospun nanofibers as promising antibacterial drug carrier systems. A variety of antibacterials e.g., biocides, antibiotics, quaternary ammonium salts, triclosan, metallic nanoparticles (silver, titanium dioxide, and zinc oxide) and antibacterial polymers (chitosan, polyethyleneimine, etc.) have been impregnated by various techniques into nanofibers that exhibit strong antibacterial activity in standard assays. This review highlights the design and delivery of antibacterial drug loaded nanofibers with particular focus on their function in the fields of drug delivery, wound healing, tissue engineering, cosmetics and other biomedical applications. PMID:25732666

  10. Microemulsion: New Insights into the Ocular Drug Delivery

    PubMed Central

    Hegde, Rahul Rama; Verma, Anurag; Ghosh, Amitava

    2013-01-01

    Delivery of drugs into eyes using conventional drug delivery systems, such as solutions, is a considerable challenge to the treatment of ocular diseases. Drug loss from the ocular surface by lachrymal fluid secretion, lachrymal fluid-eye barriers, and blood-ocular barriers are main obstacles. A number of ophthalmic drug delivery carriers have been made to improve the bioavailability and to prolong the residence time of drugs applied topically onto the eye. The potential use of microemulsions as an ocular drug delivery carrier offers several favorable pharmaceutical and biopharmaceutical properties such as their excellent thermodynamic stability, phase transition to liquid-crystal state, very low surface tension, and small droplet size, which may result in improved ocular drug retention, extended duration of action, high ocular absorption, and permeation of loaded drugs. Further, both lipophilic and hydrophilic characteristics are present in microemulsions, so that the loaded drugs can diffuse passively as well get significantly partitioned in the variable lipophilic-hydrophilic corneal barrier. This review will provide an insight into previous studies on microemulsions for ocular delivery of drugs using various nonionic surfactants, cosurfactants, and associated irritation potential on the ocular surface. The reported in vivo experiments have shown a delayed effect of drug incorporated in microemulsion and an increase in the corneal permeation of the drug. PMID:23936681

  11. Microemulsion: new insights into the ocular drug delivery.

    PubMed

    Hegde, Rahul Rama; Verma, Anurag; Ghosh, Amitava

    2013-01-01

    Delivery of drugs into eyes using conventional drug delivery systems, such as solutions, is a considerable challenge to the treatment of ocular diseases. Drug loss from the ocular surface by lachrymal fluid secretion, lachrymal fluid-eye barriers, and blood-ocular barriers are main obstacles. A number of ophthalmic drug delivery carriers have been made to improve the bioavailability and to prolong the residence time of drugs applied topically onto the eye. The potential use of microemulsions as an ocular drug delivery carrier offers several favorable pharmaceutical and biopharmaceutical properties such as their excellent thermodynamic stability, phase transition to liquid-crystal state, very low surface tension, and small droplet size, which may result in improved ocular drug retention, extended duration of action, high ocular absorption, and permeation of loaded drugs. Further, both lipophilic and hydrophilic characteristics are present in microemulsions, so that the loaded drugs can diffuse passively as well get significantly partitioned in the variable lipophilic-hydrophilic corneal barrier. This review will provide an insight into previous studies on microemulsions for ocular delivery of drugs using various nonionic surfactants, cosurfactants, and associated irritation potential on the ocular surface. The reported in vivo experiments have shown a delayed effect of drug incorporated in microemulsion and an increase in the corneal permeation of the drug. PMID:23936681

  12. NanoART, neuroAIDS and CNS drug delivery

    PubMed Central

    Nowacek, Ari; Gendelman, Howard E

    2009-01-01

    A broad range of nanomedicines is being developed to improve drug delivery for CNS disorders. The structure of the blood–brain barrier (BBB), the presence of efflux pumps and the expression of metabolic enzymes pose hurdles for drug-brain entry. Nanoformulations can circumvent the BBB to improve CNS-directed drug delivery by affecting such pumps and enzymes. Alternatively, they can be optimized to affect their size, shape, and protein and lipid coatings to facilitate drug uptake, release and ingress across the barrier. This is important as the brain is a sanctuary for a broad range of pathogens including HIV-1. Improved drug delivery to the CNS would affect pharmacokinetic and drug biodistribution properties. This article focuses on how nanotechnology can serve to improve the delivery of antiretroviral medicines, termed nanoART, across the BBB and affect the biodistribution and clinical benefit for HIV-1 disease. PMID:19572821

  13. Facing the Truth about Nanotechnology in Drug Delivery

    PubMed Central

    Park, Kinam

    2013-01-01

    Nanotechnology in drug delivery has been manifested into nanoparticles that can have unique properties both in vitro and in vivo, especially in targeted drug delivery to tumors. Numerous nanoparticle formulations have been designed and tested to great effect in small animal models, but the translation of the small animal results to clinical success has been limited. Successful translation requires revisiting the meaning of nanotechnology in drug delivery, understanding the limitations of nanoparticles, identifying the misconceptions pervasive in the field, and facing inconvenient truths. Nanoparticle approaches can have real impact in improving drug delivery by focusing on the problems at hand, such as enhancing their drug loading capacity, affinity to target cells, and spatiotemporal control of drug release. PMID:24490875

  14. Facing the truth about nanotechnology in drug delivery.

    PubMed

    Park, Kinam

    2013-09-24

    Nanotechnology in drug delivery has been manifested into nanoparticles that can have unique properties both in vitro and in vivo, especially in targeted drug delivery to tumors. Numerous nanoparticle formulations have been designed and tested to great effect in small animal models, but the translation of the small animal results to clinical success has been limited. Successful translation requires revisiting the meaning of nanotechnology in drug delivery, understanding the limitations of nanoparticles, identifying the misconceptions pervasive in the field, and facing inconvenient truths. Nanoparticle approaches can have real impact in improving drug delivery by focusing on the problems at hand, such as enhancing their drug loading capacity, affinity to target cells, and spatiotemporal control of drug release. PMID:24490875

  15. Silk-Based Biomaterials for Sustained Drug Delivery

    PubMed Central

    Yucel, Tuna; Lovett, Michael L.; Kaplan, David L.

    2014-01-01

    Silk presents a rare combination of desirable properties for sustained drug delivery, including aqueous-based purification and processing options without chemical cross-linkers, compatibility with common sterilization methods, controllable and surface-mediated biodegradation into non-inflammatory by-products, biocompatibility, utility in drug stabilization, and robust mechanical properties. A versatile silk-based toolkit is currently available for sustained drug delivery formulations of small molecule through macromolecular drugs, with a promise to mitigate several drawbacks associated with other degradable sustained delivery technologies in the market. Silk-based formulations utilize silk’s well-defined nano- through microscale structural hierarchy, stimuli-responsive self-assembly pathways and crystal polymorphism, as well as sequence and genetic modification options towards targeted pharmaceutical outcomes. Furthermore, by manipulating the interactions between silk and drug molecules, near-zero order sustained release may be achieved through diffusion- and degradation-based release mechanisms. Because of these desirable properties, there has been increasing industrial interest in silk-based drug delivery systems currently at various stages of the developmental pipeline from pre-clinical to FDA-approved products. Here, we discuss the unique aspects of silk technology as a sustained drug delivery platform and highlight the current state of the art in silk-based drug delivery. We also offer a potential early development pathway for silk-based sustained delivery products. PMID:24910193

  16. Controlled release for local delivery of drugs: barriers and models.

    PubMed

    Weiser, Jennifer R; Saltzman, W Mark

    2014-09-28

    Controlled release systems are an effective means for local drug delivery. In local drug delivery, the major goal is to supply therapeutic levels of a drug agent at a physical site in the body for a prolonged period. A second goal is to reduce systemic toxicities, by avoiding the delivery of agents to non-target tissues remote from the site. Understanding the dynamics of drug transport in the vicinity of a local drug delivery device is helpful in achieving both of these goals. Here, we provide an overview of controlled release systems for local delivery and we review mathematical models of drug transport in tissue, which describe the local penetration of drugs into tissue and illustrate the factors - such as diffusion, convection, and elimination - that control drug dispersion and its ultimate fate. This review highlights the important role of controlled release science in development of reliable methods for local delivery, as well as the barriers to accomplishing effective delivery in the brain, blood vessels, mucosal epithelia, and the skin.

  17. Advances and Challenges of Liposome Assisted Drug Delivery

    PubMed Central

    Sercombe, Lisa; Veerati, Tejaswi; Moheimani, Fatemeh; Wu, Sherry Y.; Sood, Anil K.; Hua, Susan

    2015-01-01

    The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented. PMID:26648870

  18. Kontrollierte therapeutische Systeme (Controlled drug delivery systems)

    NASA Astrophysics Data System (ADS)

    Ha, Suk-Woo; Wintermantel, Erich

    Es gibt eine grosse Anzahl von Arzneistoffen, die nicht mit der höchsten Effizienz eingesetzt werden können, weil das geeignete therapeutische System (drug delivery system) für die optimale Applikation fehlt. Viele Arzneistoffe setzen eine häufige Anwendung voraus und sind oft mit mehr oder weniger starken Nebenwirkungen oder aber mit Beeinträchtigungen von Arbeits- und Lebensrhythmus der Patienten verbunden. Der therapeutische Erfolg einer medikamentösen Behandlung setzt eine korrekte Diagnose, die Wahl der richtigen Wirksubstanz sowie ihr Vorliegen in geeigneter Darreichungsform voraus. Zudem muss ein genauer Verabreichungsplan erstellt werden, dessen Einhaltung seitens der Patienten eine wesentliche Voraussetzung für die optimale Wirkung des Arzneistoffes ist. Das Mass, mit dem eine Wirksubstanz therapeutisch voll genutzt werden kann, korreliert direkt mit der Darreichungsform, in der sie angewandt wird. Da viele hochwirksame Arzneimittel bereits existieren, hat sich, neben Neuentwicklungen, das Interesse im vergangenen Jahrzehnt der Optimierung von Arzneimittelwirkungen durch neue Darreichungsformen zugewandt.

  19. Marine Origin Polysaccharides in Drug Delivery Systems

    PubMed Central

    Cardoso, Matias J.; Costa, Rui R.; Mano, João F.

    2016-01-01

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine. PMID:26861358

  20. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

    PubMed Central

    Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

    2012-01-01

    This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

  1. Cell membrane-camouflaged nanoparticles for drug delivery.

    PubMed

    Luk, Brian T; Zhang, Liangfang

    2015-12-28

    Nanoparticles can preferentially accumulate at sites of action and hold great promise to improve the therapeutic index of many drugs. While conventional methods of nanocarrier-mediated drug delivery have focused on primarily synthetic approaches, engineering strategies that combine synthetic nanoparticles with natural biomaterials have recently gained much attention. In particular, cell membrane-camouflaged nanoparticles are a new class of biomimetic nanoparticles that combine the unique functionalities of cellular membranes and engineering versatility of synthetic nanomaterials for effective delivery of therapeutic agents. Herein, we report on the recent progress on cell membrane-coated nanoparticles for drug delivery. In particular, we highlight three areas: (i) prolonging systemic circulation via cell membrane coating, (ii) cell-specific targeting via cell membrane coating, and (iii) applications of cell membrane coating for drug delivery. The cell membrane-camouflaged nanoparticle platform has emerged as a novel delivery strategy with the potential to improve the therapeutic efficacy for the treatment of a variety of diseases.

  2. Progress and perspectives on targeting nanoparticles for brain drug delivery.

    PubMed

    Gao, Huile

    2016-07-01

    Due to the ability of the blood-brain barrier (BBB) to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood-brain tumor barrier (BBTB), and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed. PMID:27471668

  3. Bioavailability of phytochemicals and its enhancement by drug delivery systems

    PubMed Central

    Aqil, Farrukh; Munagala, Radha; Jeyabalan, Jeyaprakash; Vadhanam, Manicka V.

    2013-01-01

    Issues of poor oral bioavailability of cancer chemopreventives have hindered progress in cancer prevention. Novel delivery systems that modulate the pharmacokinetics of existing drugs, such as nanoparticles, cyclodextrins, niosomes, liposomes and implants, could be used to enhance the delivery of chemopreventive agents to target sites. The development of new approaches in prevention and treatment of cancer could encompass new delivery systems for approved and newly investigated compounds. In this review, we discuss some of the delivery approaches that have already made an impact by either delivering a drug to target tissue or increasing its bioavailability by many fold. PMID:23435377

  4. Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s

    PubMed Central

    Shelate, Pragna; Dave, Divyang

    2016-01-01

    The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients.

  5. Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s

    PubMed Central

    Shelate, Pragna; Dave, Divyang

    2016-01-01

    The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients. PMID:27610247

  6. Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s.

    PubMed

    Patel, Apurv; Dodiya, Hitesh; Shelate, Pragna; Shastri, Divyesh; Dave, Divyang

    2016-01-01

    The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients. PMID:27610247

  7. Layered Double Hydroxide-Based Nanocarriers for Drug Delivery

    PubMed Central

    Bi, Xue; Zhang, Hui; Dou, Liguang

    2014-01-01

    Biocompatible clay materials have attracted particular attention as the efficient drug delivery systems (DDS). In this article, we review developments in the use of layered double hydroxides (LDHs) for controlled drug release and delivery. We show how advances in the ability to synthesize intercalated structures have a significant influence on the development of new applications of these materials. We also show how modification and/or functionalization can lead to new biotechnological and biomedical applications. This review highlights the most recent progresses in research on LDH-based controlled drug delivery systems, focusing mainly on: (i) DDS with cardiovascular drugs as guests; (ii) DDS with anti-inflammatory drugs as guests; and (iii) DDS with anti-cancer drugs as guests. Finally, future prospects for LDH-based drug carriers are also discussed. PMID:24940733

  8. Colloidal drug delivery systems: current status and future directions.

    PubMed

    Garg, Tarun; Rath, Goutam; Goyal, Amit Kumar

    2015-01-01

    In this paper, we provide an overview an extensive range of colloidal drug delivery systems with special focus on vesicular and particulates systems that are being used in research or might be potentially useful as carriers systems for drug or active biomolecules or as cell carriers with application in the therapeutic field. We present some important examples of commercially available drug delivery systems with applications in research or in clinical fields. This class of systems is widely used due to excellent drug targeting, sustained and controlled release behavior, higher entrapment efficiency of drug molecules, prevention of drug hydrolysis or enzymatic degradation, and improvement of therapeutic efficacy. These characteristics help in the selection of suitable carrier systems for drug, cell, and gene delivery in different fields.

  9. Recent advances of cocktail chemotherapy by combination drug delivery systems.

    PubMed

    Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

    2016-03-01

    Combination chemotherapy is widely exploited for enhanced cancer treatment in the clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end.

  10. Dendrimeric systems and their applications in ocular drug delivery.

    PubMed

    Yavuz, Burçin; Pehlivan, Sibel Bozdağ; Unlü, Nurşen

    2013-01-01

    Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed. PMID:24396306

  11. Dendrimeric Systems and Their Applications in Ocular Drug Delivery

    PubMed Central

    Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

    2013-01-01

    Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed. PMID:24396306

  12. Cyclodextrin nanoassemblies: a promising tool for drug delivery.

    PubMed

    Bonnet, Véronique; Gervaise, Cédric; Djedaïni-Pilard, Florence; Furlan, Aurélien; Sarazin, Catherine

    2015-09-01

    Among the biodegradable and nontoxic compounds that can form nanoparticles for drug delivery, amphiphilic cyclodextrins are very promising. Apart from ionic cyclodextrins, which have been extensively studied and reviewed because of their application in gene delivery, our purpose is to provide a clear description of the supramolecular assemblies of nonionic amphiphilic cyclodextrins, which can form nanoassemblies for controlled drug release. Moreover, we focus on the relationship between their structure and physicochemical characteristics, which is crucial for self assembly and drug delivery. We also highlight the importance of the nanoparticle technology preparation for the stability and application of this nanodevice. PMID:26037681

  13. Porous silicon advances in drug delivery and immunotherapy

    PubMed Central

    Savage, D; Liu, X; Curley, S; Ferrari, M; Serda, RE

    2013-01-01

    Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators. PMID:23845260

  14. Chondroitin sulfate derived theranostic nanoparticles for targeted drug delivery.

    PubMed

    Varghese, Oommen P; Liu, Jianping; Sundaram, Karthi; Hilborn, Jöns; Oommen, Oommen P

    2016-08-16

    Glycosaminoglycan derived nanoparticles are a promising delivery system owing to their unique tumour targeting ability. Exploiting fluorescein for inducing amphiphilicity in these biopolymers provides inherent imaging and drug stabilization capabilities by π-π stacking interactions with aromatic antineoplastic agents. This offers a versatile and highly customizable nanocarrier with narrow size distribution and high drug loading efficiency (80%) with sustained drug release. PMID:27431007

  15. A Controlled Drug-Delivery Experiment Using Alginate Beads

    ERIC Educational Resources Information Center

    Farrell, Stephanie; Vernengo, Jennifer

    2012-01-01

    This paper describes a simple, cost-effective experiment which introduces students to drug delivery and modeling using alginate beads. Students produce calcium alginate beads loaded with drug and measure the rate of release from the beads for systems having different stir rates, geometries, extents of cross-linking, and drug molecular weight.…

  16. [Development of drug delivery systems for targeting to macrophages].

    PubMed

    Chono, Sumio

    2007-09-01

    Drug delivery systems (DDS) using liposomes as drug carriers for targeting to macrophages have been developed for the treatment of diseases that macrophages are related to their progress. Initially, DDS for the treatment of atherosclerosis are described. The influence of particle size on the drug delivery to atherosclerotic lesions that macrophages are richly present and antiatherosclerotic effects following intravenous administration of liposomes containing dexamethasone (DXM-liposomes) was investigated in atherogenic mice. Both the drug delivery efficacy of DXM-liposomes (particle size, 200 nm) to atherosclerotic lesions and their antiatherosclerotic effects were greater than those of 70 and 500 nm. These results indicate that there is an optimal particle size for drug delivery to atherosclerotic lesions. DDS for the treatment of respiratory infections are then described. The influence of particle size and surface mannosylation on the drug delivery to alveolar macrophages (AMs) and antibacterial effects following pulmonary administration of liposomes containing ciprofloxacin (CPFX-liposomes) was investigated in rats. The drug delivery efficacy of CPFX-liposomes to AMs was particle size-dependent over the range 100-1000 nm and then became constant at over 1000 nm. These results indicate that the most effective size is 1000 nm. Both the drug delivery efficacy of mannosylated CPFX-liposomes (particle size, 1000 nm) to AMs and their antibacterial effects were significantly greater than those of unmodified CPFX-liposomes. These results indicate that the surface mannosylation is useful method for drug delivery to AMs. This review provides useful information to help in the development of novel pharmaceutical formulations aimed at drug targeting to macrophages.

  17. Pectin-cysteine conjugate: synthesis and in-vitro evaluation of its potential for drug delivery.

    PubMed

    Majzoob, Sayeh; Atyabi, Fatemeh; Dorkoosh, Farid; Kafedjiiski, Krum; Loretz, Brigitta; Bernkop-Schnürch, Andreas

    2006-12-01

    This study was aimed at improving certain properties of pectin by introduction of thiol moieties on the polymer. Thiolated pectin was synthesized by covalent attachment of cysteine. Pectin-cysteine conjugate was evaluated for its ability to be degraded by pectinolytic enzyme. The toxicity profile of the thiolated polymer in Caco-2-cells, its permeation enhancing effect and its mucoadhesive and swelling properties were studied. Moreover insulin-loaded hydrogel beads of the new polymer were examined for their stability in simulated gastrointestinal conditions and their drug release profile. The new polymer displayed 892.27 +/- 68.68 micromol thiol groups immobilized per g polymer, and proved to have retained its biodegradability, upon addition of Pectinex Ultra SPL in-vitro, determined by viscosity measurements and titration method. Pectin-cysteine showed no severe toxicity in Caco-2 cells, as tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Moreover, the synthesized polymer exhibited a relative permeation enhancement ratio of 1.61 for sodium fluorescein, compared to unmodified pectin. Pectin-cysteine conjugate exhibited approximately 5-fold increased in in-vitro adhesion duration and significantly improved cohesive properties. Zinc pectin-cysteine beads showed improved stability in simulated gastrointestinal media; however, insulin release from these beads followed the same profile as unmodified zinc pectinate beads. Due to favourable safety and biodegradability profile, and improved cohesive and permeation-enhancing properties, pectin-cysteine might be a promising excipient in various transmucosal drug delivery systems.

  18. 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

  19. 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.

  20. Nasal Drug Delivery in Traditional Persian Medicine

    PubMed Central

    Zarshenas, Mohammad Mehdi; Zargaran, Arman; Müller, Johannes; Mohagheghzadeh, Abdolali

    2013-01-01

    Background Over one hundred different pharmaceutical dosage forms have been recorded in literatures of Traditional Persian Medicine among which nasal forms are considerable. Objectives This study designed to derive the most often applied nasal dosage forms together with those brief clinical administrations. Materials and Methods In the current study remaining pharmaceutical manuscripts of Persia during 9th to 18th century AD have been studied and different dosage forms related to nasal application of herbal medicines and their therapeutic effects were derived. Results By searching through pharmaceutical manuscripts of medieval Persia, different nasal dosage forms involving eleven types related to three main groups are found. These types could be derived from powder, solution or liquid and gaseous forms. Gaseous form were classified into fumigation (Bakhoor), vapor bath (Enkebab), inhalation (Lakhlakheh), aroma agents (Ghalieh) and olfaction or smell (Shomoom). Nasal solutions were as drops (Ghatoor), nasal snuffing drops (Saoot) and liquid snuff formulations (Noshoogh). Powders were as nasal insufflation or snorting agents (Nofookh) and errhine or sternutator medicine (Otoos). Nasal forms were not applied only for local purposes. Rather systemic disorders and specially CNS complications were said to be a target for these dosage forms. Discussion While this novel type of drug delivery is known as a suitable substitute for oral and parenteral administration, it was well accepted and extensively mentioned in Persian medical and pharmaceutical manuscripts and other traditional systems of medicine as well. Accordingly, medieval pharmaceutical standpoints on nasal dosage forms could still be an interesting subject of study. Therefore, the current work can briefly show the pharmaceutical knowledge on nasal formulations in medieval Persia and clarify a part of history of traditional Persian pharmacy. PMID:24624204

  1. Nanotechnology approaches for pain therapy through transdermal drug delivery.

    PubMed

    Peptu, Cristian; Rotaru, Razvan; Ignat, Leonard; Humelnicu, Andra Cristina; Harabagiu, Valeria; Peptu, Catalina Anisoara; Leon, Maria-Magdalena; Mitu, Florin; Cojocaru, Elena; Boca, Andreea; Tamba, Bogdan Ionel

    2015-01-01

    The paper focuses on the advances in the field of pain treatment by transdermal delivery of specific drugs. Starting from a short description of the skin barrier, the pharmacodynamics and pharmacokinetics including absorption, distribution, action mechanism, metabolism and toxicity, aspects related to the use of pain therapy drugs are further discussed. Most recent results on topical anesthetic agents as well as the methods proved to overcome the skin barrier and to provide efficient delivery of the drug are also discussed. The present review is proposing to summarize the recent literature on the pharmacotherapeutic principles of local anesthetics and non-steroidal anti-inflammatory drugs, generally used to alleviate pain but also the drugs as nanoformulations with potential applications in transdermal delivery. A special attention is given to efficient formulations meant for transdermal penetration enhancement of anesthetics where the drug is encapsulated into macrocyclic molecules (cyclodextrins, cyclodextrin derivatives), liposomes or polymer nanoparticles and hydrogels. PMID:26503147

  2. Microneedles: a valuable physical enhancer to increase transdermal drug delivery.

    PubMed

    Escobar-Chávez, José Juan; Bonilla-Martínez, Dalia; Villegas-González, Martha Angélica; Molina-Trinidad, Eva; Casas-Alancaster, Norma; Revilla-Vázquez, Alma Luisa

    2011-07-01

    Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Recently, the use of micron-scale needles in increasing skin permeability has been proposed and shown to dramatically increase transdermal delivery. Microneedles have been fabricated with a range of sizes, shapes, and materials. Most in vitro drug delivery studies have shown these needles to increase skin permeability to a broad range of drugs that differ in molecular size and weight. In vivo studies have demonstrated satisfactory release of oligonucleotides and insulin and the induction of immune responses from protein and DNA vaccines. Microneedles inserted into the skin of human subjects were reported to be painless. For all these reasons, microneedles are a promising technology to deliver drugs into the skin. This review presents the main findings concerning the use of microneedles in transdermal drug delivery. It also covers types of microneedles, their advantages and disadvantages, enhancement mechanisms, and trends in transdermal drug delivery.

  3. Recent advancement of gelatin nanoparticles in drug and vaccine delivery.

    PubMed

    Sahoo, Nityananda; Sahoo, Ranjan Ku; Biswas, Nikhil; Guha, Arijit; Kuotsu, Ketousetuo

    2015-11-01

    Novel drug delivery system using nanoscale materials with a broad spectrum of applications provides a new therapeutic foundation for technological integration and innovation. Nanoparticles are suitable drug carrier for various routes of administration as well as rapid recognition by the immune system. Gelatin, the biological macromolecule is a versatile drug/vaccine delivery carrier in pharmaceutical field due to its biodegradable, biocompatible, non-antigenicity and low cost with easy availability. The surface of gelatin nanoparticles can be modified with site-specific ligands, cationized with amine derivatives or, coated with polyethyl glycols to achieve targeted and sustained release drug delivery. Compared to other colloidal carriers, gelatin nanoparticles are better stable in biological fluids to provide the desired controlled and sustained release of entrapped drug molecules. The current review highlights the different formulation aspects of gelatin nanoparticles which affect the particle characteristics like zeta potential, polydispersity index, entrapment efficacy and drug release properties. It has also given emphasis on the major applications of gelatin nanoparticles in drug and vaccine delivery, gene delivery to target tissues and nutraceutical delivery for improving the poor bioavailabity of bioactive phytonutrients.

  4. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs: I. Formulation development.

    PubMed

    Rao, Sripriya Venkata Ramana; Shao, Jun

    2008-10-01

    The global aim of this research project was to develop a self-nanoemulsifying drug delivery system (SNEDDS) for non-invasive delivery of protein drugs. The specific aim of this study was to develop SNEDDS formulations. An experimental design was adopted to develop SNEDDS. Fluorescent labeled beta-lactamase (FITC-BLM), a model protein, was loaded into SNEDDS through solid dispersion technique. The experimental design provided 720 compositions of different oil, surfactant, and co-surfactant at various ratios, of which 33 SNEDDS prototypes were obtained. Solid dispersion of FITC-BLM in SoyPC prepared was able to dissolve in 16 SNEDDS prototypes (approximately 2200 mU BLM in 1g SNEDDS). SNEDDS NE-12-7 (composition: Lauroglycol FCC, Cremophor EL and Transcutol; ratio: 5:4:3) formed O/W nanoemulsion with mean droplet size in the range of 22-50 nm when diluted with various pH media and different dilution factor with PBS (pH 7.4). The phase diagram of NE-12-7 indicated a broad region of nanoemulsion. BLM-loaded SNEDDS (NE-12-7) stored at 4 degrees C for 12 weeks indicated 10% loss of BLM activity. A SNEDDS was developed to load FITC-BLM into the oil phase which can spontaneously form O/W nanoemulsion upon the addition of water.

  5. Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety

    PubMed Central

    Donnelly, Ryan F.; Raj Singh, Thakur Raghu; Woolfson, A. David

    2010-01-01

    Many promising therapeutic agents are limited by their inability to reach the systemic circulation, due to the excellent barrier properties of biological membranes, such as the stratum corneum (SC) of the skin or the sclera/cornea of the eye and others. The outermost layer of the skin, the SC, is the principal barrier to topically-applied medications. The intact SC thus provides the main barrier to exogenous substances, including drugs. Only drugs with very specific physicochemical properties (molecular weight < 500 Da, adequate lipophilicity, and low melting point) can be successfully administered transdermally. Transdermal delivery of hydrophilic drugs and macromolecular agents of interest, including peptides, DNA, and small interfering RNA is problematic. Therefore, facilitation of drug penetration through the SC may involve by-pass or reversible disruption of SC molecular architecture. Microneedles (MNs), when used to puncture skin, will by-pass the SC and create transient aqueous transport pathways of micron dimensions and enhance the transdermal permeability. These micropores are orders of magnitude larger than molecular dimensions, and, therefore, should readily permit the transport of hydrophilic macromolecules. Various strategies have been employed by many research groups and pharmaceutical companies worldwide, for the fabrication of MNs. This review details various types of MNs, fabrication methods and, importantly, investigations of clinical safety of MN. PMID:20297904

  6. Coacervate delivery systems for proteins and small molecule drugs

    PubMed Central

    Johnson, Noah R; Wang, Yadong

    2015-01-01

    Coacervates represent an exciting new class of drug delivery vehicles, developed in the past decade as carriers of small molecule drugs and proteins. This review summarizes several well-described coacervate systems, including Elastin-like peptides for delivery of anti-cancer therapeutics,Heparin-based coacervates with synthetic polycations for controlled growth factor delivery,Carboxymethyl chitosan aggregates for oral drug delivery,Mussel adhesive protein and hyaluronic acid coacervates. Coacervates present advantages in their simple assembly and easy incorporation into tissue engineering scaffolds or as adjuncts to cell therapies. They are also amenable to functionalization such as for targeting or for enhancing the bioactivity of their cargo. These new drug carriers are anticipated to have broad applications and noteworthy impact in the near future. PMID:25138695

  7. Coacervate delivery systems for proteins and small molecule drugs.

    PubMed

    Johnson, Noah R; Wang, Yadong

    2014-12-01

    Coacervates represent an exciting new class of drug delivery vehicles, developed in the past decade as carriers of small molecule drugs and proteins. This review summarizes several well-described coacervate systems, including: i) elastin-like peptides for delivery of anticancer therapeutics; ii) heparin-based coacervates with synthetic polycations for controlled growth factor delivery; iii) carboxymethyl chitosan aggregates for oral drug delivery; iv) Mussel adhesive protein and hyaluronic acid coacervates. Coacervates present advantages in their simple assembly and easy incorporation into tissue engineering scaffolds or as adjuncts to cell therapies. They are also amenable to functionalization such as for targeting or for enhancing the bioactivity of their cargo. These new drug carriers are anticipated to have broad applications and noteworthy impact in the near future.

  8. Carbon nanotubes for delivery of small molecule drugs.

    PubMed

    Wong, Bin Sheng; Yoong, Sia Lee; Jagusiak, Anna; Panczyk, Tomasz; Ho, Han Kiat; Ang, Wee Han; Pastorin, Giorgia

    2013-12-01

    In the realm of drug delivery, carbon nanotubes (CNTs) have gained tremendous attention as promising nanocarriers, owing to their distinct characteristics, such as high surface area, enhanced cellular uptake and the possibility to be easily conjugated with many therapeutics, including both small molecules and biologics, displaying superior efficacy, enhanced specificity and diminished side effects. While most CNT-based drug delivery system (DDS) had been engineered to combat cancers, there are also emerging reports that employ CNTs as either the main carrier or adjunct material for the delivery of various non-anticancer drugs. In this review, the delivery of small molecule drugs is expounded, with special attention paid to the current progress of in vitro and in vivo research involving CNT-based DDSs, before finally concluding with some consideration on inevitable complications that hamper successful disease intervention with CNTs. PMID:23954402

  9. Drug Delivery via Cell Membrane Fusion Using Lipopeptide Modified Liposomes

    PubMed Central

    2016-01-01

    Efficient delivery of drugs to living cells is still a major challenge. Currently, most methods rely on the endocytotic pathway resulting in low delivery efficiency due to limited endosomal escape and/or degradation in lysosomes. Here, we report a new method for direct drug delivery into the cytosol of live cells in vitro and invivo utilizing targeted membrane fusion between liposomes and live cells. A pair of complementary coiled-coil lipopeptides was embedded in the lipid bilayer of liposomes and cell membranes respectively, resulting in targeted membrane fusion with concomitant release of liposome encapsulated cargo including fluorescent dyes and the cytotoxic drug doxorubicin. Using a wide spectrum of endocytosis inhibitors and endosome trackers, we demonstrate that the major site of cargo release is at the plasma membrane. This method thus allows for the quick and efficient delivery of drugs and is expected to have many invitro, ex vivo, and invivo applications. PMID:27725960

  10. Functionalized nanofibers as drug-delivery systems for osteochondral regeneration.

    PubMed

    Amler, Evžen; Filová, Eva; Buzgo, Matej; Prosecká, Eva; Rampichová, Michala; Nečas, Alois; Nooeaid, Patcharakamon; Boccaccini, Aldo R

    2014-05-01

    A wide range of drug-delivery systems are currently attracting the attention of researchers. Nanofibers are very interesting carriers for drug delivery. This is because nanofibers are versatile, flexible, nanobiomimetic and similar to extracellular matrix components, possible to be functionalized both on their surface as well as in their core, and also because they can be produced easily and cost effectively. There have been increasing attempts to use nanofibers in the construction of a range of tissues, including cartilage and bone. Nanofibers have also been favorably engaged as a drug-delivery system in cell-free scaffolds. This short overview is devoted to current applications and to further perspectives of nanofibers as drug-delivery devices in the field of cartilage and bone regeneration, and also in osteochondral reconstruction. PMID:24978465

  11. Multifunctional inverse opal particles for drug delivery and monitoring

    NASA Astrophysics Data System (ADS)

    Zhang, Bin; Cheng, Yao; Wang, Huan; Ye, Baofen; Shang, Luoran; Zhao, Yuanjin; Gu, Zhongze

    2015-06-01

    Particle-based delivery systems have a demonstrated value for drug discovery and development. Here, we report a new type of particle-based delivery system that has controllable release and is self-monitoring. The particles were composed of poly(N-isopropylacrylamide) (pNIPAM) hydrogel with an inverse opal structure. The presence of macropores in the particles provides channels for active drug loading and release from the materials.Particle-based delivery systems have a demonstrated value for drug discovery and development. Here, we report a new type of particle-based delivery system that has controllable release and is self-monitoring. The particles were composed of poly(N-isopropylacrylamide) (pNIPAM) hydrogel with an inverse opal structure. The presence of macropores in the particles provides channels for active drug loading and release from the materials. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02324f

  12. Carbon nanotubes for delivery of small molecule drugs.

    PubMed

    Wong, Bin Sheng; Yoong, Sia Lee; Jagusiak, Anna; Panczyk, Tomasz; Ho, Han Kiat; Ang, Wee Han; Pastorin, Giorgia

    2013-12-01

    In the realm of drug delivery, carbon nanotubes (CNTs) have gained tremendous attention as promising nanocarriers, owing to their distinct characteristics, such as high surface area, enhanced cellular uptake and the possibility to be easily conjugated with many therapeutics, including both small molecules and biologics, displaying superior efficacy, enhanced specificity and diminished side effects. While most CNT-based drug delivery system (DDS) had been engineered to combat cancers, there are also emerging reports that employ CNTs as either the main carrier or adjunct material for the delivery of various non-anticancer drugs. In this review, the delivery of small molecule drugs is expounded, with special attention paid to the current progress of in vitro and in vivo research involving CNT-based DDSs, before finally concluding with some consideration on inevitable complications that hamper successful disease intervention with CNTs.

  13. Formulation and characterization of mucoadhesive microparticles of cinnarizine hydrochloride using supercritical fluid technique.

    PubMed

    Patel, Jayvadan K; Patil, Priyanka S; Sutariya, Vijaykumar B

    2013-06-01

    The mucoadhesive microparticles (CHCNZ) composed of chitosan (CH) and cinnarizine (CNZ) hydrochloride were successfully prepared, in a process of solution-enhanced dispersion, by supercritical CO₂ (SEDS) technique. Scanning electron microscopy was used to reveal the morphological characteristics of mucoadhesive microparticles. The average particle size of microparticles was in the range from 1.9 to 12.8 µm. In vitro and in vivo mucoadhesive tests showed that CHCNZ mucoadhesive microparticles adhered more strongly to gastric mucous layer. Thereby retaining in gastrointestinal tract for an extended period of time and exhibiting good mucoadhesive properties. The X-ray powder diffractometry and differential scanning calorimetry analysis demonstrated that the SEDS process was an efficient physical coating process to produce CHCNZ composite microparticles. It also suggests that CNZ did not undergo chemical changes during the production of microparticles. The optimized batch exhibited a high drug entrapment efficiency of 67% with particle size of 3.9 µm. A sustained pattern of drug release was obtained for more than 20 h. In vivo studies were carried out by administering orally cinnarizine HCl (CNZ) suspension and mucoadhesive microparticles to rabbits under fasted (for 12 h) conditions. The results showed that CNZ mucoadhesive microparticles had a better bioavailability than CNZ suspension due to longer retention in the gastric environment of the test animals. PMID:23286919

  14. Micro/nanofabricated platforms for oral drug delivery.

    PubMed

    Fox, Cade B; Kim, Jean; Le, Long V; Nemeth, Cameron L; Chirra, Hariharasudhan D; Desai, Tejal A

    2015-12-10

    The oral route of drug administration is most preferred due to its ease of use, low cost, and high patient compliance. However, the oral uptake of many small molecule drugs and biotherapeutics is limited by various physiological barriers, and, as a result, drugs suffer from issues with low solubility, low permeability, and degradation following oral administration. The flexibility of micro- and nanofabrication techniques has been used to create drug delivery platforms designed to address these barriers to oral drug uptake. Specifically, micro/nanofabricated devices have been designed with planar, asymmetric geometries to promote device adhesion and unidirectional drug release toward epithelial tissue, thereby prolonging drug exposure and increasing drug permeation. Furthermore, surface functionalization, nanotopography, responsive drug release, motion-based responses, and permeation enhancers have been incorporated into such platforms to further enhance drug uptake. This review will outline the application of micro/nanotechnology to specifically address the physiological barriers to oral drug delivery and highlight technologies that may be incorporated into these oral drug delivery systems to further enhance drug uptake.

  15. Formulation and Evaluation of a Mucoadhesive Thermoresponsive System Containing Brazilian Green Propolis for the Treatment of Lesions Caused by Herpes Simplex Type I.

    PubMed

    Mazia, Renata Sespede; de Araújo Pereira, Raphaela Regina; de Francisco, Lizziane Maria Belloto; Natali, Maria Raquel Marçal; Dias Filho, Benedito Prado; Nakamura, Celso Vataru; Bruschi, Marcos Luciano; Ueda-Nakamura, Tânia

    2016-01-01

    The aim of the present work was to develop a topical delivery system that contains Brazilian green propolis extract (PE-8) to increase efficiency and convenience when applied to herpetic lesions. The cytotoxicity and antiherpetic activity was determined in vitro and in vivo. The PE-8 was added to a system that contained poloxamer 407 and carbopol 934P. The in vitro characterization of the system included rheological studies, texture profile analysis, and mucoadhesion analysis. The PE-8 inhibited the virus during the phase of viral infection, induced virion damage, and exhibited an ability to protect cells from viral infection. The system had advantageous mucoadhesive properties, including a suitable gelation temperature of approximately 25°C for topical delivery, a desirable textural profile, and pseudoplastic behavior. The in vitro release study showed a rapid initial release of the PE-8 in the first 3 h, and the rate of drug release remained constant for up to 24 h. The system appeared to be macroscopically and microscopically innocuous to skin tissue. Therefore, the mucoadhesive thermoresponsive system that contained the PE-8 appears to be promising for increasing bioavailability and achieving prolonged release of the PE-8 when applied to skin lesions caused by herpes simplex virus type 1.

  16. Contact lenses: promising devices for ocular drug delivery.

    PubMed

    Guzman-Aranguez, Ana; Colligris, Basilio; Pintor, Jesús

    2013-03-01

    In the ocular pharmacology market, there is a noteworthy unmet demand for more efficacious delivery of ocular therapeutics. Contact lenses are emerging as an alternative ophthalmic drug delivery system to resolve the drawbacks of the conventional topical application methods. Thus, contact lenses drug delivery systems have been developed to provide an increased residence time of the drug at the surface of the eye leading to enhanced bioavailability and more convenient and efficacious therapy. Several research groups have already explored the feasibility and potential of contact lenses loading conventional drugs used to treat anterior eye disorders. Drug incorporation to the lens body is achieved with techniques, like simple soaking, inclusion of drug-loaded colloidal nanoparticles, or molecular imprinting. Regardless of the technique used, key properties of the contact lens, such as transparency and oxygen permeability, should be preserved. In this article, we reviewed the different techniques used for drug delivery through contact lenses, analyzing their advantages and disadvantages, and focused on articles describing contact lens-based ophthalmic drug delivery systems with significant potential to use in ocular therapeutics.

  17. Formulation and Stability Aspects of Nanosized Solid Drug Delivery Systems.

    PubMed

    Szabo, Peter; Zelko, Romana

    2015-01-01

    Nano drug delivery systems are considered as useful means to remedy the problems of drugs of poor solubility, permeability and bioavailability, which became one of the most troublesome questions of the pharmaceutical industry. Different types of nanosized drug delivery systems have been developed and investigated for oral administration, providing auspicious solutions for drug development. In this paper nanosized drug delivery systems intended for oral administration are discussed based on the chemical nature of the carrier of drug molecules. Lipid nanoparticles comprising solid lipid nanoparticles, improved nanostructured lipid carriers and nanostructured silica- lipid hybrid particles have become popular in the formulation of lipophilic drugs of poor oral bioavailability. Polymeric nanoparticles including nanospheres and nanocapsules and polymeric fibrous systems have also emerged as potential drug delivery systems owing to their unique structure. The feasibility of surface functionalization of mesoporous materials and gold nanoparticles enables high level of control over particle characteristics making inorganic nanoparticles an exceptional formulation approach. The authors paid particular attention to the functionality-related stability of the reviewed delivery systems. PMID:26027571

  18. Improving drug delivery to solid tumors: priming the tumor microenvironment.

    PubMed

    Khawar, Iftikhar Ali; Kim, Jung Ho; Kuh, Hyo-Jeong

    2015-03-10

    Malignant transformation and growth of the tumor mass tend to induce changes in the surrounding microenvironment. Abnormality of the tumor microenvironment provides a driving force leading not only to tumor progression, including invasion and metastasis, but also to acquisition of drug resistance, including pharmacokinetic (drug delivery-related) and pharmacodynamic (sensitivity-related) resistance. Drug delivery systems exploiting the enhanced permeability and retention (EPR) effect and active targeting moieties were expected to be able to cope with delivery-related drug resistance. However, recent evidence supports a considerable barrier role of tumors via various mechanisms, which results in imperfect or inefficient EPR and/or targeting effect. The components of the tumor microenvironment such as abnormal tumor vascular system, deregulated composition of the extracellular matrix, and interstitial hypertension (elevated interstitial fluid pressure) collectively or cooperatively hinder the drug distribution, which is prerequisite to the efficacy of nanoparticles and small-molecule drugs used in cancer medicine. Hence, the abnormal tumor microenvironment has recently been suggested to be a promising target for the improvement of drug delivery to improve therapeutic efficacy. Strategies to modulate the abnormal tumor microenvironment, referred to here as "solid tumor priming" (vascular normalization and/or solid stress alleviation leading to improvement in blood perfusion and convective molecular movement), have shown promising results in the enhancement of drug delivery and anticancer efficacy. These strategies may provide a novel avenue for the development of new chemotherapeutics and combination chemotherapeutic regimens as well as reassessment of previously ineffective agents. PMID:25526702

  19. Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

    PubMed Central

    Zhao, Shan; Lv, Yan; Zhang, Jian-Bin; Wang, Bing; Lv, Guo-Jun; Ma, Xiao-Jun

    2014-01-01

    Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections. PMID:25071326

  20. Nanoparticle hardness controls the internalization pathway for drug delivery

    NASA Astrophysics Data System (ADS)

    Li, Ye; Zhang, Xianren; Cao, Dapeng

    2015-01-01

    Nanoparticle (NP)-based drug delivery systems offer fundamental advantages over current therapeutic agents that commonly display a longer circulation time, lower toxicity, specific targeted release, and greater bioavailability. For successful NP-based drug delivery it is essential that the drug-carrying nanocarriers can be internalized by the target cells and transported to specific sites, and the inefficient internalization of nanocarriers is often one of the major sources for drug resistance. In this work, we use the dissipative particle dynamics simulation to investigate the effect of NP hardness on their internalization efficiency. Three simplified models of NP platforms for drug delivery, including polymeric NP, liposome and solid NP, are designed here to represent increasing nanocarrier hardness. Simulation results indicate that NP hardness controls the internalization pathway for drug delivery. Rigid NPs can enter the cell by a pathway of endocytosis, whereas for soft NPs the endocytosis process can be inhibited or frustrated due to wrapping-induced shape deformation and non-uniform ligand distribution. Instead, soft NPs tend to find one of three penetration pathways to enter the cell membrane via rearranging their hydrophobic and hydrophilic segments. Finally, we show that the interaction between nanocarriers and drug molecules is also essential for effective drug delivery.

  1. Albumin-based nanocomposite spheres for advanced drug delivery systems.

    PubMed

    Misak, Heath E; Asmatulu, Ramazan; Gopu, Janani S; Man, Ka-Poh; Zacharias, Nora M; Wooley, Paul H; Yang, Shang-You

    2014-01-01

    A novel drug delivery system incorporating human serum albumin, poly(lactic-co-glycolic acid, magnetite nanoparticles, and therapeutic agent(s) was developed for potential application in the treatment of diseases such as rheumatoid arthritis and skin cancer. An oil-in-oil emulsion/solvent evaporation (O/OSE) method was modified to produce a drug delivery system with a diameter of 0.5–2 μm. The diameter was mainly controlled by adjusting the viscosity of albumin in the discontinuous phase of the O/OSE method. The drug-release study showed that the release of drug and albumin was mostly dependent on the albumin content of the drug delivery system, which is very similar to the drug occlusion-mesopore model. Cytotoxicity tests indicated that increasing the albumin content in the drug delivery system increased cell viability, possibly due to the improved biocompatibility of the system. Overall, these studies show that the proposed system could be a viable option as a drug delivery system in the treatment of many illnesses, such as rheumatoid arthritis, and skin and breast cancers. PMID:24106002

  2. A smart multifunctional drug delivery nanoplatform for targeting cancer cells.

    PubMed

    Hoop, M; Mushtaq, F; Hurter, C; Chen, X-Z; Nelson, B J; Pané, S

    2016-07-01

    Wirelessly guided magnetic nanomachines are promising vectors for targeted drug delivery, which have the potential to minimize the interaction between anticancer agents and healthy tissues. In this work, we propose a smart multifunctional drug delivery nanomachine for targeted drug delivery that incorporates a stimuli-responsive building block. The nanomachine consists of a magnetic nickel (Ni) nanotube that contains a pH-responsive chitosan hydrogel in its inner cavity. The chitosan inside the nanotube serves as a matrix that can selectively release drugs in acidic environments, such as the extracellular space of most tumors. Approximately a 2.5 times higher drug release from Ni nanotubes at pH = 6 is achieved compared to that at pH = 7.4. The outside of the Ni tube is coated with gold. A fluorescein isothiocyanate (FITC) labeled thiol-ssDNA, a biological marker, was conjugated on its surface by thiol-gold click chemistry, which enables traceability. The Ni nanotube allows the propulsion of the device by means of external magnetic fields. As the proposed nanoarchitecture integrates different functional building blocks, our drug delivery nanoplatform can be employed for carrying molecular drug conjugates and for performing targeted combinatorial therapies, which can provide an alternative and supplementary solution to current drug delivery technologies. PMID:27297037

  3. Micelles and Nanoparticles for Ultrasonic Drug and Gene Delivery

    PubMed Central

    Husseini, Ghaleb A.; Pitt, William G.

    2008-01-01

    Drug delivery research employing micelles and nanoparticles has expanded in recent years. Of particular interest is the use of these nanovehicles that deliver high concentrations of cytotoxic drugs to diseased tissues selectively, thus reducing the agent’s side effects on the rest of the body. Ultrasound, traditionally used in diagnostic medicine, is finding a place in drug delivery in connection with these nanoparticles. In addition to their non-invasive nature and the fact that they can be focused on targeted tissues, acoustic waves have been credited with releasing pharmacological agents from nanocarriers, as well as rendering cell membranes more permeable. In this article, we summarize new technologies that combine the use of nanoparticles with acoustic power both in drug and gene delivery. Ultrasonic drug delivery from micelles usually employs polyether block copolymers, and has been found effective in vivo for treating tumors. Ultrasound releases drug from micelles, most probably via shear stress and shock waves from collapse of cavitation bubbles. Liquid emulsions and solid nanoparticles are used with ultrasound to deliver genes in vitro and in vivo. The small packaging allows nanoparticles to extravasate into tumor tissues. Ultrasonic drug and gene delivery from nano-carriers has tremendous potential because of the wide variety of drugs and genes that could be delivered to targeted tissues by fairly non-invasive means. PMID:18486269

  4. Formulation and Stability Aspects of Nanosized Solid Drug Delivery Systems.

    PubMed

    Szabo, Peter; Zelko, Romana

    2015-01-01

    Nano drug delivery systems are considered as useful means to remedy the problems of drugs of poor solubility, permeability and bioavailability, which became one of the most troublesome questions of the pharmaceutical industry. Different types of nanosized drug delivery systems have been developed and investigated for oral administration, providing auspicious solutions for drug development. In this paper nanosized drug delivery systems intended for oral administration are discussed based on the chemical nature of the carrier of drug molecules. Lipid nanoparticles comprising solid lipid nanoparticles, improved nanostructured lipid carriers and nanostructured silica- lipid hybrid particles have become popular in the formulation of lipophilic drugs of poor oral bioavailability. Polymeric nanoparticles including nanospheres and nanocapsules and polymeric fibrous systems have also emerged as potential drug delivery systems owing to their unique structure. The feasibility of surface functionalization of mesoporous materials and gold nanoparticles enables high level of control over particle characteristics making inorganic nanoparticles an exceptional formulation approach. The authors paid particular attention to the functionality-related stability of the reviewed delivery systems.

  5. Multifunctional inverse opal particles for drug delivery and monitoring.

    PubMed

    Zhang, Bin; Cheng, Yao; Wang, Huan; Ye, Baofen; Shang, Luoran; Zhao, Yuanjin; Gu, Zhongze

    2015-06-28

    Particle-based delivery systems have a demonstrated value for drug discovery and development. Here, we report a new type of particle-based delivery system that has controllable release and is self-monitoring. The particles were composed of poly(N-isopropylacrylamide) (pNIPAM) hydrogel with an inverse opal structure. The presence of macropores in the particles provides channels for active drug loading and release from the materials.

  6. Multifunctional inverse opal particles for drug delivery and monitoring.

    PubMed

    Zhang, Bin; Cheng, Yao; Wang, Huan; Ye, Baofen; Shang, Luoran; Zhao, Yuanjin; Gu, Zhongze

    2015-06-28

    Particle-based delivery systems have a demonstrated value for drug discovery and development. Here, we report a new type of particle-based delivery system that has controllable release and is self-monitoring. The particles were composed of poly(N-isopropylacrylamide) (pNIPAM) hydrogel with an inverse opal structure. The presence of macropores in the particles provides channels for active drug loading and release from the materials. PMID:26035621

  7. Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation

    PubMed Central

    Rajan, Reshmy; Jose, Shoma; Mukund, V. P. Biju; Vasudevan, Deepa T.

    2011-01-01

    Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era. PMID:22171309

  8. Surface modification of PLGA nanoparticles by carbopol to enhance mucoadhesion and cell internalization.

    PubMed

    Surassmo, Suvimol; Saengkrit, Nattika; Ruktanonchai, Uracha Rungsardthong; Suktham, Kunat; Woramongkolchai, Noppawan; Wutikhun, Tuksadon; Puttipipatkhachorn, Satit

    2015-06-01

    Mucoadhesive poly (lactic-co-glycolic acid) (PLGA) nanoparticles having a modified shell-matrix derived from polyvinyl alcohol (PVA) and Carbopol (CP), a biodegradable polymer coating, to improve the adhesion and cell transfection properties were developed. The optimum formulations utilized a CP concentration in the range of 0.05-0.2%w/v, and were formed using modified emulsion-solvent evaporation technique. The resulting CP-PLGA nanoparticles were characterized in terms of their physical and chemical properties. The absorbed CP on the PLGA shell-matrix was found to affect the particle size and surface charge, with 0.05% CP giving rise to smooth spherical particles (0.05CP-PLGA) with the smallest size (285.90 nm), and strong negative surface charge (-25.70 mV). The introduction of CP results in an enhancement of the mucoadhesion between CP-PLGA nanoparticles and mucin particles. In vitro cell internalization studies highlighted the potential of 0.05CP-PLGA nanoparticles for transfection into SiHa cells, with uptake being time dependent. Additionally, cytotoxicity studies of CP-PLGA nanoparticles against SiHa cancer cells indicated that low concentrations of the nanoparticles were non-toxic to cells (cell viability >80%). From the various formulations studied, 0.05CP-PLGA nanoparticles proved to be the optimum model carrier having the required mucoadhesive profile and could be an alternative therapeutic efficacy carrier for targeted mucosal drug delivery systems with biodegradable polymer. PMID:25937384

  9. Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

    PubMed Central

    Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

    2012-01-01

    The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

  10. Planar bioadhesive microdevices: a new technology for oral drug delivery

    PubMed Central

    Fox, Cade B.; Chirra, Hariharasudhan D.; Desai, Tejal A.

    2014-01-01

    The oral route is the most convenient and least expensive route of drug administration. Yet, it is accompanied by many physiological barriers to drug uptake including low stomach pH, intestinal enzymes and transporters, mucosal barriers, and high intestinal fluid shear. While many drug delivery systems have been developed for oral drug administration, the physiological components of the gastro intestinal tract remain formidable barriers to drug uptake. Recently, microfabrication techniques have been applied to create micron-scale devices for oral drug delivery with a high degree of control over microdevice size, shape, chemical composition, drug release profile, and targeting ability. With precise control over device properties, microdevices can be fabricated with characteristics that provide increased adhesion for prolonged drug exposure, unidirectional release which serves to avoid luminal drug loss and enhance drug permeation, and protection of a drug payload from the harsh environment of the intestinal tract. Here we review the recent developments in microdevice technology and discuss the potential of these devices to overcome unsolved challenges in oral drug delivery. PMID:25219863

  11. Electrohydrodynamics: A facile technique to fabricate drug delivery systems

    PubMed Central

    Chakraborty, Syandan; Liao, I-Chien; Adler, Andrew; Leong, Kam W.

    2009-01-01

    Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drug delivery systems (DDS) through a one-step process. The nano-structured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial-electrospinning/electrospraying, a relatively new technique of fabricating core-shell fibers/particles have added to the versatility of these DDS by affording a near zero-order drug release kinetics, dampening of burst release, and applicability to a wider range of bioactive agents. Controllable electrospinning/spraying of fibers and particles and subsequent drug release from these chiefly polymeric vehicles depends on well-defined solution and process parameters. The additional drug delivery capability from electrospun fibers can further enhance the material’s functionality in tissue engineering applications. This review discusses the state-of-the-art of using electrohydrodynamic technique to generate nano-fiber/particles as drug delivery devices. PMID:19651167

  12. A Review on Composite Liposomal Technologies for Specialized Drug Delivery

    PubMed Central

    Mufamadi, Maluta S.; Pillay, Viness; Choonara, Yahya E.; Du Toit, Lisa C.; Modi, Girish; Naidoo, Dinesh; Ndesendo, Valence M. K.

    2011-01-01

    The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications. PMID:21490759

  13. Oral Dispersible System: A New Approach in Drug Delivery System

    PubMed Central

    Hannan, P. A.; Khan, J. A.; Khan, A.; Safiullah, S.

    2016-01-01

    Dosage form is a mean used for the delivery of drug to a living body. In order to get the desired effect the drug should be delivered to its site of action at such rate and concentration to achieve the maximum therapeutic effect and minimum adverse effect. Since oral route is still widely accepted route but having a common drawback of difficulty in swallowing of tablets and capsules. Therefore a lot of research has been done on novel drug delivery systems. This review is about oral dispersible tablets a novel approach in drug delivery systems that are now a day's more focused in formulation world, and laid a new path that, helped the patients to build their compliance level with the therapy, also reduced the cost and ease the administration especially in case of pediatrics and geriatrics. Quick absorption, rapid onset of action and reduction in drug loss properties are the basic advantages of this dosage form. PMID:27168675

  14. Oral Dispersible System: A New Approach in Drug Delivery System.

    PubMed

    Hannan, P A; Khan, J A; Khan, A; Safiullah, S

    2016-01-01

    Dosage form is a mean used for the delivery of drug to a living body. In order to get the desired effect the drug should be delivered to its site of action at such rate and concentration to achieve the maximum therapeutic effect and minimum adverse effect. Since oral route is still widely accepted route but having a common drawback of difficulty in swallowing of tablets and capsules. Therefore a lot of research has been done on novel drug delivery systems. This review is about oral dispersible tablets a novel approach in drug delivery systems that are now a day's more focused in formulation world, and laid a new path that, helped the patients to build their compliance level with the therapy, also reduced the cost and ease the administration especially in case of pediatrics and geriatrics. Quick absorption, rapid onset of action and reduction in drug loss properties are the basic advantages of this dosage form.

  15. A review of nebulized drug delivery in COPD

    PubMed Central

    Tashkin, Donald P

    2016-01-01

    Current guidelines recommend inhaled pharmacologic therapy as the preferred route of administration for treating COPD. Bronchodilators (β2-agonists and antimuscarinics) are the mainstay of pharmacologic therapy in patients with COPD, with long-acting agents recommended for patients with moderate to severe symptoms or those who are at a higher risk for COPD exacerbations. Dry powder inhalers and pressurized metered dose inhalers are the most commonly used drug delivery devices, but they may be inadequate in various clinical scenarios (eg, the elderly, the cognitively impaired, and hospitalized patients). As more drugs become available in solution formulations, patients with COPD and their caregivers are becoming increasingly satisfied with nebulized drug delivery, which provides benefits similar to drugs delivered by handheld inhalers in both symptom relief and improved quality of life. This article reviews recent innovations in nebulized drug delivery and the important role of nebulized therapy in the treatment of COPD. PMID:27799757

  16. Electrothermally activated microchips for implantable drug delivery and biosensing.

    PubMed

    Maloney, John M; Uhland, Scott A; Polito, Benjamin F; Sheppard, Norman F; Pelta, Christina M; Santini, John T

    2005-12-01

    Novel drug delivery and biosensing devices have the potential to increase the efficacy of drug therapy by providing physicians and patients the ability to precisely control key therapy parameters. Such "intelligent" systems can enable control of dose amount and the time, rate, and location of drug delivery. We have developed and demonstrated the operation of an electrothermal mechanism to precisely control the delivery of drugs and exposure of biosensors. These microchip devices contain an array of individually sealed and actuated reservoirs, each capped by a thin metal membrane comprised of either gold or multiple layers of titanium and platinum. The passage of a threshold level of electric current through the membrane causes it to disintegrate, thereby exposing the protected contents (drugs or biosensors) of the reservoir to the surrounding environment. This paper describes the theory and experimental characterization of the electrothermal method and includes in vitro release results for a model compound.

  17. Using exosomes, naturally-equipped nanocarriers, for drug delivery.

    PubMed

    Batrakova, Elena V; Kim, Myung Soo

    2015-12-10

    Exosomes offer distinct advantages that uniquely position them as highly effective drug carriers. Comprised of cellular membranes with multiple adhesive proteins on their surface, exosomes are known to specialize in cell-cell communications and provide an exclusive approach for the delivery of various therapeutic agents to target cells. In addition, exosomes can be amended through their parental cells to express a targeting moiety on their surface, or supplemented with desired biological activity. Development and validation of exosome-based drug delivery systems are the focus of this review. Different techniques of exosome isolation, characterization, drug loading, and applications in experimental disease models and clinic are discussed. Exosome-based drug formulations may be applied to a wide variety of disorders such as cancer, various infectious, cardiovascular, and neurodegenerative disorders. Overall, exosomes combine benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations.

  18. Targeted electrohydrodynamic printing for micro-reservoir drug delivery systems

    NASA Astrophysics Data System (ADS)

    Hwang, Tae Heon; Kim, Jin Bum; Som Yang, Da; Park, Yong-il; Ryu, WonHyoung

    2013-03-01

    Microfluidic drug delivery systems consisting of a drug reservoir and microfluidic channels have shown the possibility of simple and robust modulation of drug release rate. However, the difficulty of loading a small quantity of drug into drug reservoirs at a micro-scale limited further development of such systems. Electrohydrodynamic (EHD) printing was employed to fill micro-reservoirs with controlled amount of drugs in the range of a few hundreds of picograms to tens of micrograms with spatial resolution of as small as 20 µm. Unlike most EHD systems, this system was configured in combination with an inverted microscope that allows in situ targeting of drug loading at micrometer scale accuracy. Methylene blue and rhodamine B were used as model drugs in distilled water, isopropanol and a polymer solution of a biodegradable polymer and dimethyl sulfoxide (DMSO). Also tetracycline-HCl/DI water was used as actual drug ink. The optimal parameters of EHD printing to load an extremely small quantity of drug into microscale drug reservoirs were investigated by changing pumping rates, the strength of an electric field and drug concentration. This targeted EHD technique was used to load drugs into the microreservoirs of PDMS microfluidic drug delivery devices and their drug release performance was demonstrated in vitro.

  19. Intracellular Delivery System for Antibody–Peptide Drug Conjugates

    PubMed Central

    Berguig, Geoffrey Y; Convertine, Anthony J; Frayo, Shani; Kern, Hanna B; Procko, Erik; Roy, Debashish; Srinivasan, Selvi; Margineantu, Daciana H; Booth, Garrett; Palanca-Wessels, Maria Corinna; Baker, David; Hockenbery, David; Press, Oliver W; Stayton, Patrick S

    2015-01-01

    Antibodies armed with biologic drugs could greatly expand the therapeutic potential of antibody–drug conjugates for cancer therapy, broadening their application to disease targets currently limited by intracellular delivery barriers. Additional selectivity and new therapeutic approaches could be realized with intracellular protein drugs that more specifically target dysregulated pathways in hematologic cancers and other malignancies. A multifunctional polymeric delivery system for enhanced cytosolic delivery of protein drugs has been developed that incorporates endosomal-releasing activity, antibody targeting, and a biocompatible long-chain ethylene glycol component for optimized safety, pharmacokinetics, and tumor biodistribution. The pH-responsive polymeric micelle carrier, with an internalizing anti-CD22 monoclonal targeting antibody, effectively delivered a proapoptotic Bcl-2 interacting mediator (BIM) peptide drug that suppressed tumor growth for the duration of treatment and prolonged survival in a xenograft mouse model of human B-cell lymphoma. Antitumor drug activity was correlated with a mechanistic induction of the Bcl-2 pathway biomarker cleaved caspase-3 and a marked decrease in the Ki-67 proliferation biomarker. Broadening the intracellular target space by more effective delivery of protein/peptide drugs could expand the repertoire of antibody–drug conjugates to currently undruggable disease-specific targets and permit tailored drug strategies to stratified subpopulations and personalized medicines. PMID:25669432

  20. Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

    PubMed Central

    Upadhyay, Ravi Kant

    2014-01-01

    Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID:25136634

  1. Drug delivery systems, CNS protection, and the blood brain barrier.

    PubMed

    Upadhyay, Ravi Kant

    2014-01-01

    Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

  2. Microsystems Technologies for Drug Delivery to the Inner Ear

    PubMed Central

    Leary Pararas, Erin E.; Borkholder, David A.; Borenstein, Jeffrey T.

    2012-01-01

    The inner ear represents one of the most technologically challenging targets for local drug delivery, but its clinical significance is rapidly increasing. The prevalence of sensorineural hearing loss and other auditory diseases, along with balance disorders and tinnitus, has spurred broad efforts to develop therapeutic compounds and regenerative approaches to treat these conditions, necessitating advances in systems capable of targeted and sustained drug delivery. The delicate nature of hearing structures combined with the relative inaccessibility of the cochlea by means of conventional delivery routes together necessitate significant advancements in both the precision and miniaturization of delivery systems, and the nature of the molecular and cellular targets for these therapies suggests that multiple compounds may need to be delivered in a time-sequenced fashion over an extended duration. Here we address the various approaches being developed for inner ear drug delivery, including micropump-based devices, reciprocating systems, and cochlear prosthesis-mediated delivery, concluding with an analysis of emerging challenges and opportunities for the first generation of technologies suitable for human clinical use. These developments represent exciting advances that have the potential to repair and regenerate hearing structures in millions of patients for whom no currently available medical treatments exist, a situation that requires them to function with electronic hearing augmentation devices or to live with severely impaired auditory function. These advances also have the potential for broader clinical applications that share similar requirements and challenges with the inner ear, such as drug delivery to the central nervous system. PMID:22386561

  3. Ocular drug metabolism of the bioactivating antioxidant N-acetylcarnosine for vision in ophthalmic prodrug and codrug design and delivery.

    PubMed

    Babizhayev, Mark A

    2008-10-01

    The basic idea in this study relates to the interesting research problem to employ with the knowledgeable pharmacy staff N-acetylcarnosine (NAC) in the developed suitable compounded prodrug ophthalmic preparations, which are currently used for the treatment of cataract and have antioxidant effect, in order to provide the molecular support to one of the most popular beliefs of the growing market for the treatment of senile cataract in patients and animals with efficacious NAC drug formulations worldwide patented by the author. This work presents the progress in ocular NAC prodrug and codrug design and delivery in light of revealed ocular metabolic activities. There is a considerable interest in the ophthalmic codrug design including NAC prodrug based on the strategies to improve ophthalmic drug delivery of the active peptide principal L-carnosine through the sustained intraocular metabolic activation of a dipeptide while making it resistant to enzymatic hydrolysis. Novel approaches to ocular NAC drug delivery, developed by Innovative Vision Products, Inc. (IVP), aim at enhancing the drug bioavailability by ensuring a prolonged retention of the medication in the eye, and/or by facilitating transcorneal penetration. IVP team studied the effects of lubricant eye drops designed as 1% NAC prodrug of L-carnosine containing a mucoadhesive cellulose-based and corneal absorption promoters in a drug delivery system. The predicted responses of the corneal and conjunctival penetrations to the synergistic promoters are useful in controlling the extent and pathway of the ocular and systemic absorptions of instilled NAC prodrug in designed ophthalmic formulations thereof. Utility of peptidase enzyme inhibitors in the codrug formulation to modulate the transport and metabolism of NAC prodrug appears to be a promising strategy for enhancing dipeptide drug transport across the cornea. The developed and officially CE mark registered by IVP NAC prodrug and codrug lubricating eye drop

  4. Discovery and Delivery of Synergistic Chemotherapy Drug Combinations to Tumors

    NASA Astrophysics Data System (ADS)

    Camacho, Kathryn Militar

    Chemotherapy combinations for cancer treatments harbor immense therapeutic potentials which have largely been untapped. Of all diseases, clinical studies of drug combinations are the most prevalent in oncology, yet their effectiveness is disputable, as complete tumor regressions are rare. Our research has been devoted towards developing delivery vehicles for combinations of chemotherapy drugs which elicit significant tumor reduction yet limit toxicity in healthy tissue. Current administration methods assume that chemotherapy combinations at maximum tolerable doses will provide the greatest therapeutic effect -- a presumption which often leads to unprecedented side effects. Contrary to traditional administration, we have found that drug ratios rather than total cumulative doses govern combination therapeutic efficacy. In this thesis, we have developed nanoparticles to incorporate synergistic ratios of chemotherapy combinations which significantly inhibit cancer cell growth at lower doses than would be required for their single drug counterparts. The advantages of multi-drug incorporation in nano-vehicles are many: improved accumulation in tumor tissue via the enhanced permeation and retention effect, limited uptake in healthy tissue, and controlled exposure of tumor tissue to optimal synergistic drug ratios. To exploit these advantages for polychemotherapy delivery, two prominent nanoparticles were investigated: liposomes and polymer-drug conjugates. Liposomes represent the oldest class of nanoparticles, with high drug loading capacities and excellent biocompatibility. Polymer-drug conjugates offer controlled drug incorporations through reaction stoichiometry, and potentially allow for delivery of precise ratios. Here, we show that both vehicles, when armed with synergistic ratios of chemotherapy drugs, significantly inhibit tumor growth in an aggressive mouse breast carcinoma model. Furthermore, versatile drug incorporation methods investigated here can be broadly

  5. Micro-Fluidic Device for Drug Delivery

    NASA Technical Reports Server (NTRS)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2014-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  6. Liposome-based drug delivery in breast cancer treatment

    PubMed Central

    Park, John W

    2002-01-01

    Drug delivery systems can in principle provide enhanced efficacy and/or reduced toxicity for anticancer agents. Long circulating macromolecular carriers such as liposomes can exploit the 'enhanced permeability and retention' effect for preferential extravasation from tumor vessels. Liposomal anthracyclines have achieved highly efficient drug encapsulation, resulting in significant anticancer activity with reduced cardiotoxicity, and include versions with greatly prolonged circulation such as liposomal daunorubicin and pegylated liposomal doxorubicin. Pegylated liposomal doxorubucin has shown substantial efficacy in breast cancer treatment both as monotherapy and in combination with other chemotherapeutics. Additional liposome constructs are being developed for the delivery of other drugs. The next generation of delivery systems will include true molecular targeting; immunoliposomes and other ligand-directed constructs represent an integration of biological components capable of tumor recognition with delivery technologies. PMID:12052251

  7. Membrane-targeting liquid crystal nanoparticles (LCNPs) for drug delivery

    NASA Astrophysics Data System (ADS)

    Nag, Okhil K.; Naciri, Jawad; Spillmann, Christopher M.; Delehanty, James B.

    2016-03-01

    In addition to maintaining the structural integrity of the cell, the plasma membrane regulates multiple important cellular processes, such as endocytosis and trafficking, apoptotic pathways and drug transport. The modulation or tracking of such cellular processes by means of controlled delivery of drugs or imaging agents via nanoscale delivery systems is very attractive. Nanoparticle-mediated delivery systems that mediate long-term residence (e.g., days) and controlled release of the cargoes in the plasma membrane while simultaneously not interfering with regular cellular physiology would be ideal for this purpose. Our laboratory has developed a plasma membrane-targeted liquid crystal nanoparticle (LCNP) formulation that can be loaded with dyes or drugs which can be slowly released from the particle over time. Here we highlight the utility of these nanopreparations for membrane delivery and imaging.

  8. Coaxial electrohydrodynamic atomization: microparticles for drug delivery applications.

    PubMed

    Davoodi, Pooya; Feng, Fang; Xu, Qingxing; Yan, Wei-Cheng; Tong, Yen Wah; Srinivasan, M P; Sharma, Vijay Kumar; Wang, Chi-Hwa

    2015-05-10

    As cancer takes its toll on human health and well-being, standard treatment techniques such as chemotherapy and radiotherapy often fall short of ideal solutions. In particular, adverse side effects due to excess dosage and collateral damage to healthy cells as well as poor patient compliance due to multiple administrations continue to pose challenges in cancer treatment. Thus, the development of appropriately engineered drug delivery systems (DDS) for effective, controlled and sustained delivery of drugs is of interest for patient treatment. Moreover, the physiopathological characteristics of tumors play an essential role in the success of cancer treatment. Here, we present an overview of the application of double-walled microparticles for local drug delivery with particular focus on the electrohydrodynamic atomization (EHDA) technique and its fabrication challenges. The review highlights the importance of a combination of experimental data and computational simulations for the design of an optimal delivery system. PMID:25483422

  9. An Intravaginal Ring for the Simultaneous Delivery of Multiple Drugs

    PubMed Central

    Baum, Marc M.; Butkyavichene, Irina; Gilman, Joshua; Kennedy, Sean; Kopin, Etana; Malone, Amanda M.; Nguyen, Cali; Smith, Thomas J.; Friend, David R.; Clark, Meredith R.; Moss, John A.

    2013-01-01

    Intravaginal delivery of microbicide combinations is a promising approach for the prevention of sexually transmitted infections, but requires a method of providing simultaneous, independent release of multiple agents into the vaginal compartment. A novel intravaginal ring (IVR) platform has been developed for simultaneous delivery of the reverse-transcriptase inhibitor tenofovir (TFV) and the guanosine analogue antiviral acyclovir (ACV) with independent control of release rate for each drug. The IVR is based on a pod design, with up to 10 individual polymer-coated drug cores embedded in the ring releasing through preformed delivery channels. The release rate from each pod is controlled independently of the others by the drug properties, polymer coating, and size and number of delivery channels. Pseudo-zero-order in vitro release of TFV (144 ± 10 µg day) and ACV (120 ± 19 µg day−1) from an IVR containing both drugs was sustained for 28 days. The mechanical properties of the pod IVR were evaluated and compared with the commercially available Estring® (Pfizer, NY, NY). The pod-IVR design enables the vaginal delivery of multiple microbicides with differing physicochemical properties, and is an attractive approach for the sustained intravaginal delivery of relatively hydrophilic drugs that are difficult to deliver using conventional matrix IVR technology. PMID:22619076

  10. Ultrasonic-Activated Micellar Drug Delivery for Cancer Treatment

    PubMed Central

    Husseini, Ghaleb A.; Pitt, William G.

    2008-01-01

    The use of nanoparticles and ultrasound in medicine continues to evolve. Great strides have been made in the areas of producing micelles, nanoemulsions and solid nanoparticles that can be used in drug delivery. An effective nanocarrier allows for the delivery of a high concentration of potent medications to targeted tissue while minimizing the side effect of the agent to the rest of the body. Polymeric micelles have been shown to encapsulate therapeutic agents and maintain their structural integrity at lower concentrations. Ultrasound is currently being used in drug delivery as well as diagnostics, and has many advantages that elevate its importance in drug delivery. The technique is non-invasive, thus no surgery is needed; the ultrasonic waves can be easily controlled by advanced electronic technology so that they can be focused on the desired target volume. Additionally, the physics of ultrasound are widely used and well understood; thus ultrasonic application can be tailored towards a particular drug delivery system. In this article, we review the recent progress made in research that utilizes both polymeric micelles and ultrasonic power in drug delivery. PMID:18506804

  11. Drug delivery to the brain--realization by novel drug carriers.

    PubMed

    Müller, Rainer H; Keck, Cornelia M

    2004-05-01

    Delivery of drugs to the brain is still a major challenge. Successful delivery across the bloodbrain barrier has only been achieved in some cases, e.g., using pro-drugs. The review describes the delivery to the brain using nanoparticulate drug carriers in combination with the novel targeting principle of "differential protein adsorption" (PathFinder technology). The PathFinder technology exploits proteins in the blood which adsorb onto the surface of intravenously injected carriers for targeting. Apolipoprotein E is the targeting moiety for the delivery of particles to the endothelials of the blood-brain barrier. To reach therapeutic drug level in the brain, nanoparticulate drug carriers with sufficiently high loading capacity are reviewed, including drug nanocrystals (nanosuspensions), lipid drug conjugate (LDC) nanoparticles and lipid nanoparticles (solid lipid nanoparticles-SLN, nanostructured lipid carriers-NLC). The features are described, including regulatory aspects and large scale production. PMID:15503432

  12. Drug delivery to the brain--realization by novel drug carriers.

    PubMed

    Müller, Rainer H; Keck, Cornelia M

    2004-05-01

    Delivery of drugs to the brain is still a major challenge. Successful delivery across the bloodbrain barrier has only been achieved in some cases, e.g., using pro-drugs. The review describes the delivery to the brain using nanoparticulate drug carriers in combination with the novel targeting principle of "differential protein adsorption" (PathFinder technology). The PathFinder technology exploits proteins in the blood which adsorb onto the surface of intravenously injected carriers for targeting. Apolipoprotein E is the targeting moiety for the delivery of particles to the endothelials of the blood-brain barrier. To reach therapeutic drug level in the brain, nanoparticulate drug carriers with sufficiently high loading capacity are reviewed, including drug nanocrystals (nanosuspensions), lipid drug conjugate (LDC) nanoparticles and lipid nanoparticles (solid lipid nanoparticles-SLN, nanostructured lipid carriers-NLC). The features are described, including regulatory aspects and large scale production.

  13. Prolonged Ocular Retention of Mucoadhesive Nanoparticle Eye Drop Formulation Enables Treatment of Eye Diseases Using Significantly Reduced Dosage.

    PubMed

    Liu, Shengyan; Dozois, Matthew D; Chang, Chu Ning; Ahmad, Aaminah; Ng, Deborah L T; Hileeto, Denise; Liang, Huiyuan; Reyad, Matthew-Mina; Boyd, Shelley; Jones, Lyndon W; Gu, Frank X

    2016-09-01

    Eye diseases, such as dry eye syndrome, are commonly treated with eye drop formulations. However, eye drop formulations require frequent dosing with high drug concentrations due to poor ocular surface retention, which leads to poor patient compliance and high risks of side effects. We developed a mucoadhesive nanoparticle eye drop delivery platform to prolong the ocular retention of topical drugs, thus enabling treatment of eye diseases using reduced dosage. Using fluorescent imaging on rabbit eyes, we showed ocular retention of the fluorescent dye delivered through these nanoparticles beyond 24 h while free dyes were mostly cleared from the ocular surface within 3 h after administration. Utilizing the prolonged retention of the nanoparticles, we demonstrated effective treatment of experimentally induced dry eye in mice by delivering cyclosporin A (CsA) bound to this delivery system. The once a week dosing of 0.005 to 0.01% CsA in NP eye drop formulation demonstrated both the elimination of the inflammation signs and the recovery of ocular surface goblet cells after a month. Thrice daily administration of RESTASIS on mice only showed elimination without recovering the ocular surface goblet cells. The mucoadhesive nanoparticle eye drop platform demonstrated prolonged ocular surface retention and effective treatment of dry eye conditions with up to 50- to 100-fold reduction in overall dosage of CsA compared to RESTASIS, which may significantly reduce side effects and, by extending the interdosing interval, improve patient compliance. PMID:27482595

  14. Thiolated nanocarriers for oral delivery of hydrophilic macromolecular drugs.

    PubMed

    Dünnhaupt, S; Barthelmes, J; Köllner, S; Sakloetsakun, D; Shahnaz, G; Düregger, A; Bernkop-Schnürch, A

    2015-03-01

    It was the aim of this study to investigate the effect of unmodified as well as thiolated anionic poly(acrylic acid) (PAA) and cationic chitosan (CS) utilized in free-soluble form and as nanoparticulate system on the absorption of the hydrophilic compound FD4 across intestinal epithelial cell layer with and without a mucus layer. Modifications of these polymers were achieved by conjugation with cysteine to PAA (PAA-Cys) and thioglycolic acid to CS (CS-TGA). Particles were prepared via ionic gelation and characterized based on their amount of thiol groups, particle size and zeta potential. Effects on the cell layer concerning absorption enhancement, transepithelial electrical resistance (TEER) and cytotoxicity were investigated. Permeation enhancement was evaluated with respect to in vitro transport of FD4 across Caco-2 cells, while mucoadhesion was indirectly examined in terms of adsorption behaviour when cells were covered with a mucus layer. Lyophilized particles displayed around 1000 μmol/g of free thiol groups, particle sizes of less than 300 nm and a zeta potential of 18 mV (CS-TGA) and -14 mV (PAA-Cys). Cytotoxicity studies confirmed that all polymer samples were used at nontoxic concentrations (0.5% m/v). Permeation studies revealed that all thiolated formulations had pronounced effects on the paracellular permeability of mucus-free Caco-2 layers and enhanced the permeation of FD4 3.0- to 5.3-fold. Moreover, polymers administered as particles showed a higher permeation enhancement than their corresponding solutions. However, the absorption-enhancing effect of each thiolated formulation was significantly (p<0.05) reduced when cells were covered with mucus layer. In addition, all formulations were able to decrease the TEER of the cell layer significantly (p<0.05). Therefore, both thiolated polymers as nanoparticulate delivery systems represent a promising tool for the oral administration of hydrophilic macromolecules. PMID:25498673

  15. Aptamer-Gated Nanoparticles for Smart Drug Delivery

    PubMed Central

    Ozalp, Veli Cengiz; Eyidogan, Fusun; Oktem, Huseyin Avni

    2011-01-01

    Aptamers are functional nucleic acid sequences which can bind specific targets. An artificial combinatorial methodology can identify aptamer sequences for any target molecule, from ions to whole cells. Drug delivery systems seek to increase efficacy and reduce side-effects by concentrating the therapeutic agents at specific disease sites in the body. This is generally achieved by specific targeting of inactivated drug molecules. Aptamers which can bind to various cancer cell types selectively and with high affinity have been exploited in a variety of drug delivery systems for therapeutic purposes. Recent progress in selection of cell-specific aptamers has provided new opportunities in targeted drug delivery. Especially functionalization of nanoparticles with such aptamers has drawn major attention in the biosensor and biomedical areas. Moreover, nucleic acids are recognized as an attractive building materials in nanomachines because of their unique molecular recognition properties and structural features. A active controlled delivery of drugs once targeted to a disease site is a major research challenge. Stimuli-responsive gating is one way of achieving controlled release of nanoparticle cargoes. Recent reports incorporate the structural properties of aptamers in controlled release systems of drug delivering nanoparticles. In this review, the strategies for using functional nucleic acids in creating smart drug delivery devices will be explained. The main focus will be on aptamer-incorporated nanoparticle systems for drug delivery purposes in order to assess the future potential of aptamers in the therapeutic area. Special emphasis will be given to the very recent progress in controlled drug release based on molecular gating achieved with aptamers.

  16. Porous Carriers for Controlled/Modulated Drug Delivery

    PubMed Central

    Ahuja, G.; Pathak, K.

    2009-01-01

    Considerable research efforts have been directed in recent years towards the development of porous carriers as controlled drug delivery matrices because of possessing several features such as stable uniform porous structure, high surface area, tunable pore size and well-defined surface properties. Owing to wide range of useful properties porous carriers have been used in pharmaceuticals for many purposes including development of floating drug delivery systems, sustained drug delivery systems. Various types of pores like open, closed, transport and blind pores in the porous solid allow them to adsorb drugs and release them in a more reproducible and predictable manner. Pharmaceutically exploited porous adsorbents includes, silica (mesoporous), ethylene vinyl acetate (macroporous), polypropylene foam powder (microporous), titanium dioxide (nanoporous). When porous polymeric drug delivery system is placed in contact with appropriate dissolution medium, release of drug to medium must be preceded by the drug dissolution in the water filled pores or from surface and by diffusion through the water filled channels. The porous carriers are used to improve the oral bioavailability of poorly water soluble drugs, to increase the dissolution of relatively insoluble powders and conversion of crystalline state to amorphous state. PMID:20376211

  17. The potential of magneto-electric nanocarriers for drug delivery

    PubMed Central

    Kaushik, Ajeet; Jayant, Rahul Dev; Sagar, Vidya; Nair, Madhavan

    2015-01-01

    Introduction The development and design of personalized nanomedicine for better health quality is receiving great attention. In order to deliver and release a therapeutic concentration at the target site, novel nanocarriers (NCs) were designed, for example, magneto-electric (ME) which possess ideal properties of high drug loading, site-specificity and precise on-demand controlled drug delivery. Areas covered This review explores the potential of ME-NCs for on-demand and site-specific drug delivery and release for personalized therapeutics. The main features including effect of magnetism, improvement in drug loading, drug transport across blood-brain barriers and on-demand controlled release are also discussed. The future directions and possible impacts on upcoming nanomedicine are highlighted. Expert opinion Numerous reports suggest that there is an urgent need to explore novel NC formulations for safe and targeted drug delivery and release at specific disease sites. The challenges of formulation lie in the development of NCs that improve biocompatibility and surface modifications for optimum drug loading/preservation/transmigration and tailoring of electrical–magnetic properties for on-demand drug release. Thus, the development of novel NCs is anticipated to overcome the problems of targeted delivery of therapeutic agents with desired precision that may lead to better patient compliance. PMID:24986772

  18. Coordination polymer particles as potential drug delivery systems.

    PubMed

    Imaz, Inhar; Rubio-Martínez, Marta; García-Fernández, Lorena; García, Francisca; Ruiz-Molina, Daniel; Hernando, Jordi; Puntes, Victor; Maspoch, Daniel

    2010-07-14

    Micro- and nanoscale coordination polymer particles can be used for encapsulating and delivering drugs. In vitro cancer cell cytotoxicity assays showed that these capsules readily release doxorubicin, which shows anticancer efficacy. The results from this work open up new avenues for metal-organic capsules to be used as potential drug delivery systems.

  19. Coordination polymer particles as potential drug delivery systems.

    PubMed

    Imaz, Inhar; Rubio-Martínez, Marta; García-Fernández, Lorena; García, Francisca; Ruiz-Molina, Daniel; Hernando, Jordi; Puntes, Victor; Maspoch, Daniel

    2010-07-14

    Micro- and nanoscale coordination polymer particles can be used for encapsulating and delivering drugs. In vitro cancer cell cytotoxicity assays showed that these capsules readily release doxorubicin, which shows anticancer efficacy. The results from this work open up new avenues for metal-organic capsules to be used as potential drug delivery systems. PMID:20485835

  20. Porous carriers for controlled/modulated drug delivery.

    PubMed

    Ahuja, G; Pathak, K

    2009-11-01

    Considerable research efforts have been directed in recent years towards the development of porous carriers as controlled drug delivery matrices because of possessing several features such as stable uniform porous structure, high surface area, tunable pore size and well-defined surface properties. Owing to wide range of useful properties porous carriers have been used in pharmaceuticals for many purposes including development of floating drug delivery systems, sustained drug delivery systems. Various types of pores like open, closed, transport and blind pores in the porous solid allow them to adsorb drugs and release them in a more reproducible and predictable manner. Pharmaceutically exploited porous adsorbents includes, silica (mesoporous), ethylene vinyl acetate (macroporous), polypropylene foam powder (microporous), titanium dioxide (nanoporous). When porous polymeric drug delivery system is placed in contact with appropriate dissolution medium, release of drug to medium must be preceded by the drug dissolution in the water filled pores or from surface and by diffusion through the water filled channels. The porous carriers are used to improve the oral bioavailability of poorly water soluble drugs, to increase the dissolution of relatively insoluble powders and conversion of crystalline state to amorphous state.

  1. Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease

    PubMed Central

    Gunay, Mine Silindir; Ozer, A. Yekta; Chalon, Sylvie

    2016-01-01

    Background: Although a variety of therapeutic approaches are available for the treatment of Parkinson’s disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. Methods: This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. Results: It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson’s disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α-synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Conclusion: Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson’s disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson’s Disease therapy and reduce its side effects. PMID:26714584

  2. Basics and recent advances in peptide and protein drug delivery

    PubMed Central

    Bruno, Benjamin J; Miller, Geoffrey D; Lim, Carol S

    2014-01-01

    While the peptide and protein therapeutic market has developed significantly in the past decades, delivery has limited their use. Although oral delivery is preferred, most are currently delivered intravenously or subcutaneously due to degradation and limited absorption in the gastrointestinal tract. Therefore, absorption enhancers, enzyme inhibitors, carrier systems and stability enhancers are being studied to facilitate oral peptide delivery. Additionally, transdermal peptide delivery avoids the issues of the gastrointestinal tract, but also faces absorption limitations. Due to proteases, opsonization and agglutination, free peptides are not systemically stable without modifications. This review discusses oral and transdermal peptide drug delivery, focusing on barriers and solutions to absorption and stability issues. Methods to increase systemic stability and site-specific delivery are also discussed. PMID:24228993

  3. Development of cup shaped microneedle array for transdermal drug delivery.

    PubMed

    Vinayakumar, Kadayar B; Hegde, Gopal M; Ramachandra, Subbaraya G; Nayak, Mangalore M; Dinesh, Narasimhian S; Rajanna, Konandur

    2015-01-01

    Microneedle technology is one of the attractive methods in transdermal drug delivery. However, the clinical applications of this method are limited owing to: complexity in the preparation of multiple coating solutions, drug leakage while inserting the microneedles into the skin and the outer walls of the solid microneedle can hold limited quantity of drug. Here, the authors present the fabrication of an array of rectangular cup shaped silicon microneedles, which provide for reduced drug leakage resulting in improvement of efficiency of drug delivery and possibility of introducing multiple drugs. The fabricated solid microneedles with rectangular cup shaped tip have a total height of 200 μm. These cup shaped tips have dimensions: 60 × 60 μm (length × breadth) with a depth of 60 μm. The cups are filled with drug using a novel in-house built drop coating system. Successful drug dissolution was observed when the coated microneedle was used on mice. Also, using the above method, it is possible to fill the cups selectively with different drugs, which enables simultaneous multiple drug delivery. PMID:25956180

  4. Effect of permeation enhancers in the mucoadhesive buccal patches of salbutamol sulphate for unidirectional buccal drug delivery

    PubMed Central

    Prasanth, V.V.; Puratchikody, A.; Mathew, S.T.; Ashok, K.B.

    2014-01-01

    The purpose of this work was to study the effect of various permeation enhancers on the permeation of salbutamol sulphate (SS) buccal patches through buccal mucosa in order to improve the bioavailability by avoiding the first pass metabolism in the liver and possibly in the gut wall and also achieve a better therapeutic effect. The influence of various permeation enhancers, such as dimethyl sulfoxide (DMSO), linoleic acid (LA), isopropyl myristate (IPM) and oleic acid (OA) on the buccal absorption of SS from buccal patches containing different polymeric combinations such as hydroxypropyl methyl cellulose (HPMC), carbopol, polyvinyl alcohol (PVA), polyvinyl pyrollidone (PVP), sodium carboxymethyl cellulose (NaCMC), acid and water soluble chitosan (CHAS and CHWS) and Eudragit-L100 (EU-L100) was investigated. OA was the most efficient permeation enhancer increasing the flux greater than 8-fold compared with patches without permeation enhancer in HPMC based buccal patches when PEG-400 was used as the plasticizer. LA also exhibited a better permeation enhancing effect of over 4-fold in PVA and HPMC based buccal patches. In PVA based patches, both OA and LA were almost equally effective in improving the SS permeation irrespective of the plasticizer used. DMSO was more effective as a permeation enhancer in HPMC based patches when PG was the plasticizer. IPM showed maximum permeation enhancement of greater than 2-fold when PG was the plasticizer in HPMC based buccal patches. PMID:25657797

  5. Hydrogel-Forming Microneedle Arrays for Enhanced Transdermal Drug Delivery

    PubMed Central

    Donnelly, Ryan F; Singh, Thakur Raghu Raj; Garland, Martin J; Migalska, Katarzyna; Majithiya, Rita; McCrudden, Cian M; Kole, Prashant Laxman; Mahmood, Tuan Mazlelaa Tuan; McCarthy, Helen O; Woolfson, A David

    2012-01-01

    Unique microneedle arrays prepared from crosslinked polymers, which contain no drug themselves, are described. They rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch-type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilized, resist hole closure while in place, and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while electrically modulated delivery is also a unique feature. This technology has the potential to overcome the limitations of conventional microneedle designs and greatly increase the range of the type of drug that is deliverable transdermally, with ensuing benefits for industry, healthcare providers and, ultimately, patients. PMID:23606824

  6. Design of Nanoparticle-Based Carriers for Targeted Drug Delivery

    PubMed Central

    Ren, Muqing; Duval, Kayla; Guo, Xing; Chen, Zi

    2016-01-01

    Nanoparticles have shown promise as both drug delivery vehicles and direct antitumor systems, but they must be properly designed in order to maximize efficacy. Computational modeling is often used both to design new nanoparticles and to better understand existing ones. Modeled processes include the release of drugs at the tumor site and the physical interaction between the nanoparticle and cancer cells. In this article, we provide an overview of three different targeted drug delivery methods (passive targeting, active targeting and physical targeting), compare methods of action, advantages, limitations, and the current stage of research. For the most commonly used nanoparticle carriers, fabrication methods are also reviewed. This is followed by a review of computational simulations and models on nanoparticle-based drug delivery. PMID:27398083

  7. Drug delivery systems improve pharmaceutical profile and facilitate medication adherence.

    PubMed

    Wertheimer, Albert I; Santella, Thomas M; Finestone, Albert J; Levy, Richard A

    2005-01-01

    Innovations in dosage forms and dose delivery systems across a wide range of medications offer substantial clinical advantages, including reduced dosing frequency and improved patient adherence; minimized fluctuation of drug concentrations and maintenance of blood levels within a desired range; localized drug delivery; and the potential for reduced adverse effects and increased safety. The advent of new large-molecule drugs for previously untreatable or only partially treatable diseases is stimulating the development of suitable delivery systems for these agents. Although advanced formulations may be more expensive than conventional dosage forms, they often have a more favorable pharmacologic profile and can be cost-effective. Inclusion of these dosage forms on drug formulary lists may help patients remain on therapy and reduce the economic and social burden of care.

  8. Crystallization Methods for Preparation of Nanocrystals for Drug Delivery System.

    PubMed

    Gao, Yuan; Wang, Jingkang; Wang, Yongli; Yin, Qiuxiang; Glennon, Brian; Zhong, Jian; Ouyang, Jinbo; Huang, Xin; Hao, Hongxun

    2015-01-01

    Low water solubility of drug products causes delivery problems such as low bioavailability. The reduced particle size and increased surface area of nanocrystals lead to the increasing of the dissolution rate. The formulation of drug nanocrystals is a robust approach and has been widely applied to drug delivery system (DDS) due to the significant development of nanoscience and nanotechnology. It can be used to improve drug efficacy, provide targeted delivery and minimize side-effects. Crystallization is the main and efficient unit operation to produce nanocrystals. Both traditional crystallization methods such as reactive crystallization, anti-solvent crystallization and new crystallization methods such as supercritical fluid crystallization, high-gravity controlled precipitation can be used to produce nanocrystals. The current mini-review outlines the main crystallization methods addressed in literature. The advantages and disadvantages of each method were summarized and compared.

  9. Micro and Nanoparticle Drug Delivery Systems for Preventing Allotransplant Rejection

    PubMed Central

    Fisher, James D.; Acharya, Abhinav P.; Little, Steven R.

    2015-01-01

    Despite decades of advances in transplant immunology, tissue damage caused by acute allograft rejection remains the primary cause of morbidity and mortality in the transplant recipient. Moreover, the long-term sequelae of lifelong immunosuppression leaves patients at risk for developing a host of other deleterious conditions. Controlled drug delivery using micro- and nanoparticles (MNPs) is an effective way to deliver higher local doses of a given drug to specific tissues and cells while mitigating systemic effects. Herein, we review several descriptions of MNP immunotherapies aimed at prolonging allograft survival. We also discuss developments in the field of biomimetic drug delivery that use MNP constructs to induce and recruit our bodies' own suppressive immune cells. Finally, we comment on the regulatory pathway associated with these drug delivery systems. Collectively, it is our hope the studies described in this review will help to usher in a new era of immunotherapy in organ transplantation. PMID:25937032

  10. Tissue Bioeffects during Ultrasound-mediated Drug Delivery

    NASA Astrophysics Data System (ADS)

    Sutton, Jonathan

    Ultrasound has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. Vascular effects can be mediated by mechanical oscillations of circulating microbubbles, or ultrasound contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi, or direct drugs to optimal locations for delivery. These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery. This dissertation addresses a fundamental hypothesis in biomedical ultrasound: ultrasound-mediated drug delivery is capable of increasing the penetration of drugs across different physiologic barriers within the cardiovascular system, such as the vascular endothelium, blood clots, and smooth muscle cells.

  11. Smart surface-enhanced Raman scattering traceable drug delivery systems.

    PubMed

    Liu, Lei; Tang, Yonghong; Dai, Sheng; Kleitz, Freddy; Qiao, Shi Zhang

    2016-07-01

    A novel smart nanoparticle-based system has been developed for tracking intracellular drug delivery through surface-enhanced Raman scattering (SERS). This new drug delivery system (DDS) shows targeted cytotoxicity towards cancer cells via pH-cleavable covalent carboxylic hydrazone links and the SERS tracing capability based on gold@silica nanocarriers. Doxorubicin, as a model anticancer drug, was employed to compare SERS with conventional fluorescence tracing approaches. It is evident that SERS demonstrates higher sensitivity and resolution, revealing intracellular details, as the strengths of the original Raman signals can be amplified by SERS. Importantly, non-destructive SERS will provide the designed DDS with great autonomy and potential to study the dynamic procedures of non-fluorescent drug delivery into living cells. PMID:27297745

  12. Recent advances in liposome surface modification for oral drug delivery.

    PubMed

    Nguyen, Thanh Xuan; Huang, Lin; Gauthier, Mario; Yang, Guang; Wang, Qun

    2016-05-01

    Oral delivery via the gastrointestinal (GI) tract is the dominant route for drug administration. Orally delivered liposomal carriers can enhance drug solubility and protect the encapsulated theraputic agents from the extreme conditions found in the GI tract. Liposomes, with their fluid lipid bilayer membrane and their nanoscale size, can significantly improve oral absorption. Unfortunately, the clinical applications of conventional liposomes have been hindered due to their poor stability and availability under the harsh conditions typically presented in the GI tract. To overcome this problem, the surface modification of liposomes has been investigated. Although liposome surface modification has been extensively studied for oral drug delivery, no review exists so far that adequately covers this topic. The purpose of this paper is to summarize and critically analyze emerging trends in liposome surface modification for oral drug delivery. PMID:27074098

  13. Lipid nanocarriers (LNC) and their applications in ocular drug delivery.

    PubMed

    Puglia, Carmelo; Offerta, Alessia; Carbone, Claudia; Bonina, Francesco; Pignatello, Rosario; Puglisi, Giovanni

    2015-01-01

    The peculiar physio-anatomical structure of the eye and the poor physico-chemical properties of many drug molecules are often responsible for the inefficient treatment of ocular diseases by conventio