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Technology Transfer Automated Retrieval System (TEKTRAN)

Two drug delivery systems have been developed from pectin recently in our laboratory. (I) Pectin gel formulations for controlled fragrance release and (II) pectin/zein hydrogels for oral drug delivery. By altering the molecular characteristics or modifying the pectin hydrogel networks, the release ...


Novel central nervous system drug delivery systems.  


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. PMID:24325540

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



Microfabricated injectable drug delivery system  


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.

Krulevitch, Peter A. (Pleasanton, CA); Wang, Amy W. (Oakland, CA)



Packaging for a drug delivery microelectromechanical system  

E-print Network

Local drug delivery is a fast expanding field, and has been a center of attention for researchers in medicine in the last decade. Its advantages over systemic drug delivery are clear in cancer therapy, with localized tumors. ...

Ho Duc, Hong Linh, 1978-



MEMS based system for drug delivery  

Microsoft Academic Search

This paper presents the new design of transdermal drug delivery system. The system consists of integrated control electronics and microelectromechanical (MEMS) devices such as micropump, microneedles, blood pressure sensor and fluid flow sensor. Micropump and microneedles are essential components of proposed drug delivery system. Design, analysis, fabrication and characterization of piezoelectric valveless micropump and hollow out-of-plane silicon microneedles are presented

Muhammad Waseem Ashraf; Shahzadi Tayyaba; Asim Nisar; Nitin Afzulpurkar



Drug delivery systems: An updated review  

PubMed Central

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

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



Nanoparticulate systems for brain delivery of drugs  

Microsoft Academic Search

The blood–brain barrier (BBB) represents an insurmountable obstacle for a large number of drugs, including antibiotics, antineoplastic agents, and a variety of central nervous system (CNS)-active drugs, especially neuropeptides. One of the possibilities to overcome this barrier is a drug delivery to the brain using nanoparticles. Drugs that have successfully been transported into the brain using this carrier include the

Jörg Kreuter



Colloidal systems for CNS drug delivery  

Microsoft Academic Search

The pharmaceutical treatment of central nervous system (CNS) disorders is the second largest area of therapy, following cardiovascular diseases. Nowadays, noninvasive drug delivery systems for CNS are actively studied. The development of these new delivery systems started with the discovery that properly surface-engineered colloidal vectors, and in particular liposomes and polymeric nanoparticles, with a diameter ?200nm, were shown to be

Luca Costantino; Giovanni Tosi; Barbara Ruozi; Lucia Bondioli; Maria Angela Vandelli; Flavio Forni



Nanotechnology-based drug delivery systems.  


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

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



Chitosan Microspheres in Novel Drug Delivery Systems  

PubMed Central

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

Mitra, Analava; Dey, Baishakhi



Novel drug delivery systems for glaucoma  

PubMed Central

Reduction of intraocular pressure (IOP) by pharmaceutical or surgical means has long been the standard treatment for glaucoma. A number of excellent drugs are available that are effective in reducing IOP. These drugs are typically applied as eye drops. However, patient adherence can be poor, thus reducing the clinical efficacy of the drugs. Several novel delivery systems designed to address the issue of adherence and to ensure consistent reduction of IOP are currently under development. These delivery systems include contact lenses-releasing glaucoma medications, injectables such as biodegradable micro- and nanoparticles, and surgically implanted systems. These new technologies are aimed at increasing clinical efficacy by offering multiple delivery options and are capable of managing IOP for several months. There is also a desire to have complementary neuroprotective approaches for those who continue to show progression, despite IOP reduction. Many potential neuroprotective agents are not suitable for traditional oral or drop formulations. Their potential is dependent on developing suitable delivery systems that can provide the drugs in a sustained, local manner to the retina and optic nerve. Drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight for glaucoma patients. In this review, we discuss benefits and limitations of the current systems of delivery and application, as well as those on the horizon. PMID:21475311

Lavik, E; Kuehn, M H; Kwon, Y H



Drug Delivery Systems: Entering the Mainstream  

NASA Astrophysics Data System (ADS)

Drug delivery systems (DDS) such as lipid- or polymer-based nanoparticles can be designed to improve the pharmacological and therapeutic properties of drugs administered parenterally. Many of the early problems that hindered the clinical applications of particulate DDS have been overcome, with several DDS formulations of anticancer and antifungal drugs now approved for clinical use. Furthermore, there is considerable interest in exploiting the advantages of DDS for in vivo delivery of new drugs derived from proteomics or genomics research and for their use in ligand-targeted therapeutics.

Allen, Theresa M.; Cullis, Pieter R.



Nanotechnology in Biomaterials: Nanoparticulates as Drug Delivery Systems  

E-print Network

227 11 Nanotechnology in Biomaterials: Nanoparticulates as Drug Delivery Systems Birsen Demirbag Delivery Systems A drug delivery system (DDS) can be de ned as the system that achieves the administra the concentration, rate, time, and place of release of drugs in the body.1 The primary purpose of drug delivery

Hasýrcý, Vasýf


Cubic phase gels as drug delivery systems.  


Lipids have been used extensively for drug delivery in various forms such as liposomes, and solid-matrices. The focus of this review is evaluation of liquid crystalline cubic phases, spontaneously formed when amphiphilic lipids are placed in aqueous environment, for drug delivery. Cubic phases have an interesting thermodynamically stable structure consisting of curved bicontinuous lipid bilayer in three dimensions, separating two congruent networks of water channels. The unique structure of cubic phase has been extensively studied using various spectroscopic techniques and their resemblance to biomembranes has prompted many scientists to study behavior of proteins in cubic phases. The ability of cubic phase to incorporate and control release of drugs of varying size and polar characteristics, and biodegradability of lipids make it an interesting drug delivery system for various routes of administration. Cubic phases have been shown to deliver small molecule drugs and large proteins by oral and parenteral routes in addition to local delivery in vaginal and periodontal cavity. A number of different proteins in cubic phase appear to retain their native conformation and bioactivity, and are protected from chemical and physical inactivation perhaps due to the reduced activity of water and biomembrane-like structure of cubic phase. Release of drugs from cubic phase typically show diffusion controlled release from a matrix as indicated by Higuchi's square root of time release kinetics. Incorporation of drug in cubic phase can cause phase transformation to lamellar or reversed hexagonal phase depending on the polarity and concentration of the drug, which may affect the release profile. Biodegradability, phase behavior, ability to deliver drugs of varying sizes and polarity and the ability to enhance the chemical and/or physical stability of incorporated drugs and proteins make the cubic phase gel an excellent candidate for use as a drug delivery matrix. However, shorter release duration and the extremely high viscosity may limit its use to specific applications such as periodontal, mucosal, vaginal and short acting oral and parenteral drug delivery. PMID:11311994

Shah, J C; Sadhale, Y; Chilukuri, D M



Colloidal drug delivery system: amplify the ocular delivery.  


Abstract Context: The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. Objective: The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. Methods: This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Conclusion: Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects. PMID:24892625

Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar



Hydrolyticmicroneedles as Transdermal Drug Delivery System  

Microsoft Academic Search

We developed hydrolytic microneedles as a transdermal drug delivery system to overcome the shortcomings of existing microneedle-systems: long-term stay of broken needles in the skin and high cost for safe disposal of used needles. The present microneedles spontaneously dissolve by hydrolysis in human skin as well as in the (boiled) water. We verified their basic utility through experiments.

T. Miyano; T. Miyachi; T. Okanishi; H. Todo; K. Sugibayashi; T. Uemura; N. Takano; S. Konishi



Recent technologies in pulsatile drug delivery systems  

PubMed Central

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

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



Mucoadhesive drug delivery system: An overview  

PubMed Central

Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption. The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT) require increased duration of stay in GIT. Thus, mucoadhesive dosage forms are advantageous in increasing the drug plasma concentrations and also therapeutic activity. In this regard, this review covers the areas of mechanisms and theories of mucoadhesion, factors influencing the mucoadhesive devices and also various mucoadhesive dosage forms. PMID:22247877

Boddupalli, Bindu M.; Mohammed, Zulkar N. K.; Nath, Ravinder A.; Banji, David



Ocular drug delivery systems: An overview  

PubMed Central

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. Also, recent developments with other ocular drug delivery strategies employing in situ gels, implants, contact lens and microneedles have been discussed. PMID:25590022

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



Biomedical Imaging in Implantable Drug Delivery Systems.  


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

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



In Situ Forming Polymeric Drug Delivery Systems  

PubMed Central

In situ forming polymeric formulations are drug delivery systems that are in sol form before administration in the body, but once administered, undergo gelation in situ, to form a gel. The formation of gels depends on factors like temperature modulation, pH change, presence of ions and ultra violet irradiation, from which the drug gets released in a sustained and controlled manner. Various polymers that are used for the formulation of in situ gels include gellan gum, alginic acid, xyloglucan, pectin, chitosan, poly(DL-lactic acid), poly(DL-lactide-co-glycolide) and poly-caprolactone. The choice of solvents like water, dimethylsulphoxide, N-methyl pyrrolidone, triacetin and 2-pyrrolidone for these formulations depends on the solubility of polymer used. Mainly in situ gels are administered by oral, ocular, rectal, vaginal, injectable and intraperitoneal routes. The in situ gel forming polymeric formulations offer several advantages like sustained and prolonged action in comparison to conventional drug delivery systems. The article presents a detailed review of these types of polymeric systems, their evaluation, advancements and their commercial formulations. From a manufacturing point of view, the production of such devices is less complex and thus lowers the investment and manufacturing cost. PMID:20490289

Madan, M.; Bajaj, A.; Lewis, S.; Udupa, N.; Baig, J. A.



Non-viral drug delivery systems for immune modulation  

E-print Network

Biodegradable polymer particles have diverse applications in drug delivery. The main objective of this thesis was to apply these delivery systems to modulating the immune system. We optimized particle formulations for the ...

Fuller, Jason E., Ph. D. Massachusetts Institute of Technology



Expert Review Functionalized Micellar Systems for Cancer Targeted Drug Delivery  

E-print Network

Expert Review Functionalized Micellar Systems for Cancer Targeted Drug Delivery Damon Sutton,1, and general use of micelles as drug delivery systems (4Y13). The purpose of this review is to provide stability, ability to solubilize water insoluble anticancer drugs, and prolonged blood circulation times

Gao, Jinming


Drug accumulation by means of noninvasive magnetic drug delivery system  

NASA Astrophysics Data System (ADS)

The medication is one of the most general treatment methods, but drugs diffuse in the normal tissues other than the target part by the blood circulation. Therefore, side effect in the medication, particularly for a drug with strong effect such as anti-cancer drug, are a serious issue. Drug Delivery System (DDS) which accumulates the drug locally in the human body is one of the techniques to solve the side-effects. Magnetic Drug Delivery System (MDDS) is one of the active DDSs, which uses the magnetic force. The objective of this study is to accumulate the ferromagnetic drugs noninvasively in the deep part of the body by using MDDS. It is necessary to generate high magnetic field and magnetic gradient at the target part to reduce the side-effects to the tissues with no diseases. The biomimetic model was composed, which consists of multiple model organs connected with diverged blood vessel model. The arrangement of magnetic field was examined to accumulate ferromagnetic drug particles in the target model organ by using a superconducting bulk magnet which can generate high magnetic fields. The arrangement of magnet was designed to generate high and stable magnetic field at the target model organ. The accumulation experiment of ferromagnetic particles has been conducted. In this study, rotating HTS bulk magnet around the axis of blood vessels by centering on the target part was suggested, and the model experiment for magnet rotation was conducted. As a result, the accumulation of the ferromagnetic particles to the target model organ in the deep part was confirmed.

Chuzawa, M.; Mishima, F.; Akiyama, Y.; Nishijima, S.



Biodegradable injectable in situ forming drug delivery systems  

Microsoft Academic Search

The ability to inject a drug incorporated into a polymer to a localized site and have the polymer form a semi-solid drug depot has a number of advantages. Among these advantages is ease of application and localized, prolonged drug delivery. For these reasons a large number of in situ setting polymeric delivery systems have been developed and investigated for use

A Hatefi; B Amsden



Controlled drug delivery systems: past forward and future back.  


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. PMID:24794901

Park, Kinam



Design of a Smart Transdermal Insulin Drug Delivery System  

Microsoft Academic Search

In this paper, a micro-needle array combined with transdermal delivery, as well as the detection of micro-sensors intelligent transdermal insulin delivery systems was designed with characteristics of pain-free, smart, timing, positioning, quantitative drug delivery. Transdermal delivery of the requirements for the design of the transdermal delivery of the microneedle array structure, and UV-LIGA process for the production of polymer micro-needle

Zhenqing Hou; Chenghong Lin; Qiqing Zhang



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

PubMed Central

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

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



Microemulsion-based media as novel drug delivery systems  

Microsoft Academic Search

Microemulsions are clear, stable, isotropic mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating a wide range of drug molecules. In order to appreciate the potential of microemulsions as delivery vehicles, this review gives

M. Jayne Lawrence; Gareth D. Rees



Reservoir-Based Drug Delivery Systems Utilizing Microtechnology  

PubMed Central

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

Stevenson, Cynthia L.; Santini, John T.; Langer, Robert



Bioavailability of phytochemicals and its enhancement by drug delivery systems  

PubMed Central

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

Aqil, Farrukh; Munagala, Radha; Jeyabalan, Jeyaprakash; Vadhanam, Manicka V.



Niosomes: a controlled and novel drug delivery system.  


During the past decade formulation of vesicles as a tool to improve drug delivery, has created a lot of interest amongst the scientist working in the area of drug delivery systems. Vesicular system such as liposomes, niosomes, transferosomes, pharmacosomes and ethosomes provide an alternative to improve the drug delivery. Niosomes play an important role owing to their nonionic properties, in such drug delivery system. Design and development of novel drug delivery system (NDDS) has two prerequisites. First, it should deliver the drug in accordance with a predetermined rate and second it should release therapeutically effective amount of drug at the site of action. Conventional dosage forms are unable to meet these requisites. Niosomes are essentially non-ionic surfactant based multilamellar or unilamellar vesicles in which an aqueous solution of solute is entirely enclosed by a membrane resulting from the organization of surfactant macromolecules as bilayer. Niosomes are formed on hydration of non-ionic surfactant film which eventually hydrates imbibing or encapsulating the hydrating aqueous solution. The main aim of development of niosomes is to control the release of drug in a sustained way, modification of distribution profile of drug and for targeting the drug to the specific body site. This paper deals with composition, characterization/evaluation, merits, demerits and applications of niosomes. PMID:21719996

Rajera, Rampal; Nagpal, Kalpana; Singh, Shailendra Kumar; Mishra, Dina Nath



Pharmaceutical approaches to colon targeted drug delivery systems  

Microsoft Academic Search

Purpose. Although oral delivery has become a widely accepted route of administration of therapeutic drugs, the gastrointestinal tract presents several formidable barriers to drug delivery. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon but also for its potential for the delivery of proteins

M. K. Chourasia; S. K. Jain


Pharmacosomes: an emerging novel vesicular drug delivery system for poorly soluble synthetic and herbal drugs.  


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

Pandita, Archana; Sharma, Pooja



Dendrimeric Systems and Their Applications in Ocular Drug Delivery  

PubMed Central

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

Yavuz, Burçin; Bozda? Pehlivan, Sibel; Ünlü, Nur?en



Polymeric nanofibers: targeted gastro-retentive drug delivery systems.  


Abstract Background: Conventional oral dosage forms exhibit poor/low bioavailability due to incomplete release of drug and short residence time at the absorption site. Gastro-retentive drug delivery system (GRDDS) is particularly used to improve bioavailability of the drugs, which have narrow absorption window down in the levels of gastrointestinal tract and also to treat local disorders. Purpose: The purpose of this review is to describe the utility of the nanofibers as gastro-retentive dosage form. From last few decades, formulation scientists have put extensive efforts to develop suitable gastro-retentive drug delivery system, which is appropriate for commercialization. Current approaches used for preparation of gastro-retentive drug delivery system offers limited functional features to control the floating behavior. Recently, an extensive research has been developed to improve the gastric residence time by using nanofibers, which ultimately leads to the increased bioavailability of the drug. Multiple functional features and unique properties of nanofibers improve its gastro retention. Conclusion: Nanofiber system provides stomach-specific drug release for longer duration; moreover, increased local action of the drug due to prolonged contact time with the gastric mucosa. Thus, the nanofiber system promises to be the potential approach for gastric retention drug delivery system. PMID:25268275

Malik, Rafi; Garg, Tarun; Goyal, Amit K; Rath, Goutam



Communications Drug Delivery  

E-print Network

Communications Drug Delivery Z. Zhao, H. Meng, N. Wang, M. J. Donovan, T. Fu, M. You, Z. Chen, X Targeting and Translocation for Drug Delivery This pHLIP is no flop: Functionalizing mesoporous silica nanoparticles (MSNs) with pHLIPss peptide provides a con- trolled-release nanoparticle drug delivery system

Tan, Weihong


Application of plant viruses as nano drug delivery systems.  


Nano-sized drug delivery systems based on virus-derived platforms have promising delivery and targeting efficiencies. To date, much of our understanding of these systems is obtained from studies of animal viruses. Application of plant viruses for drug delivery is in the nascent stage, but it is becoming apparent that plant viral particles can be engineered to possess novel properties to meet the unique requirements of targeted drug delivery. Chemical functionalization of a plant viral particle surface can impart stealth properties to prolong in vivo circulation half-life and/or targeting capability to direct drug delivery to diseased tissues. The amino acid sequence of the viral coat protein can be genetically manipulated to yield protein cages of specific chemistry and morphology, while the conformation of the protein cage can be directed, via the external environment, to disassemble, then reassemble in vitro to exchange native viral genomic material with exogenous cargo. The purpose of this commentary is to evaluate current literature to assess the potential of nano-scale plant-virus-based drug delivery systems for the targeted delivery of chemotherapeutic agents. PMID:20811934

Ren, Yupeng; Wong, Sek Man; Lim, Lee Yong



pH-Responsive Drug-Delivery Systems.  


In many biomedical applications, drugs need to be delivered in response to the pH value in the body. In fact, it is desirable if the drugs can be administered in a controlled manner that precisely matches physiological needs at targeted sites and at predetermined release rates for predefined periods of time. Different organs, tissues, and cellular compartments have different pH values, which makes the pH value a suitable stimulus for controlled drug release. pH-Responsive drug-delivery systems have attracted more and more interest as "smart" drug-delivery systems for overcoming the shortcomings of conventional drug formulations because they are able to deliver drugs in a controlled manner at a specific site and time, which results in high therapeutic efficacy. This focus review is not intended to offer a comprehensive review on the research devoted to pH-responsive drug-delivery systems; instead, it presents some recent progress obtained for pH-responsive drug-delivery systems and future perspectives. There are a large number of publications available on this topic, but only a selection of examples will be discussed. PMID:25303435

Zhu, Ying-Jie; Chen, Feng



Nanotechnology: A Focus on Nanoparticles as a Drug Delivery System  

Microsoft Academic Search

This review will provide an in-depth discussion on the previous development of nanoparticle-based drug delivery systems (DDS) and discuss original research data that includes the therapeutic enhancement of antiretroviral therapy. The use of nanoparticle DDS will allow practitioners to use drugs to target specific areas of the body. In the treatment of malignancies, the use of nanoparticles as a DDS

Jeffrey D. Kingsley; Huanyu Dou; Justin Morehead; Barrett Rabinow; Howard E. Gendelman; Christopher J. Destache



Pulsatile Drug Delivery System Based on Electrohydrodynamic Method  

E-print Network

Electrohydrodynamic (EHD) generation, a commonly used method in BioMEMS, plays a significant role in the pulsatile drug delivery system for a decade. In this paper, an EHD based drug delivery system is well designed, which can be used to generate a single drug droplet as small as 2.83 nL in 8.5 ms with a total device of 2\\times2\\times3 mm^3, and an external supplied voltage of 1500 V. Theoretically, we derive the expressions for the size and the formation time of a droplet generated by EHD method, while taking into account the drug supply rate, properties of liquid, gap between two electrodes, nozzle size, and charged droplet neutralization. This work proves a repeatable, stable and controllable droplet generation and delivery system based on EHD method experimentally as well as theoretically.

Zheng, Yi; Hu, Junqiang; Gao, Wenle



3-dimensional (3D) fabricated polymer based drug delivery systems.  


Drug delivery from 3-dimensional (3D) structures is a rapidly growing area of research. It is essential to achieve structures wherein drug stability is ensured, the drug loading capacity is appropriate and the desired controlled release profile can be attained. Attention must also be paid to the development of appropriate fabrication machinery that allows 3D drug delivery systems (DDS) to be produced in a simple, reliable and reproducible manner. The range of fabrication methods currently being used to form 3D DDSs include electrospinning (solution and melt), wet-spinning and printing (3-dimensional). The use of these techniques enables production of DDSs from the macro-scale down to the nano-scale. This article reviews progress in these fabrication techniques to form DDSs that possess desirable drug delivery kinetics for a wide range of applications. PMID:25020039

Moulton, Simon E; Wallace, Gordon G



An oral-controlled release drug delivery system for liquid and semisolid drug formulations.  


A novel oral drug delivery system for the controlled release of liquid drugs, drug solutions, and semisolid drug preparations is presented that is utilizing the constant vapor pressure of liquefied gas. The system is equipped with a capillary as an element determining the drug delivery rate and contains a liquefied propellant with a suitable boiling point below human body temperature. In the dissolution studies, polyacrylate gels of different viscosities containing paracetamol as model drug were used. Zero-order release kinetics was obtained. The release rates were dependent on the gel viscosity. Besides, by gel viscosity, the drug release rates could also be modified by changing the propellant type and the capillary parameters such as length or diameter. Accordingly, the new system enables a wide range of drug delivery kinetics which can be modified in a case-by-case basis in order to match the desired drug delivery characteristics. PMID:21918919

Haznar-Garbacz, Dorota; Garbacz, Grzegorz; Eisenächer, Friederike; Klein, Sandra; Weitschies, Werner



Biologically erodable microspheres as potential oral drug delivery systems  

Microsoft Academic Search

Biologically adhesive delivery systems offer important advantages1-5 over conventional drug delivery systems6. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium

Edith Mathiowitz; Jules S. Jacob; Yong S. Jong; Gerardo P. Carino; Donald E. Chickering; Pravin Chaturvedi; Camilla A. Santos; Kavita Vijayaraghavan; Sean Montgomery; Michael Bassett; Craig Morrell



Contact lenses as drug reservoirs & delivery systems: the successes & challenges.  


Although conventional eye drops comprise over 90% of the marketed ocular dosage forms, they do have limitations, such as poor ocular drug bioavailability and systemic side effects; contact lenses are amongst the new delivery systems and devices that could overcome some of these problems. The most common approach to load drug molecules into contact lenses includes soaking in a drug solution. This approach had some success, but failed to achieve controlled/sustained drug release to the eye. One the other hand, nanoreservoir systems comprising nanoparticles, cyclodextrins, liposomes or surfactant aggregates being incorporated into the contact lenses could offer a plausible solution. This review highlights the status quo with contact lenses as ocular drug-delivery carriers and identifies possible future directions. PMID:25418268

ElShaer, Amr; Ghatora, Baljit; Mustafa, Shelan; Alany, Raid G



Liposomal drug delivery systems: from concept to clinical applications.  


The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future. PMID:23036225

Allen, Theresa M; Cullis, Pieter R



Nanoscale drug delivery systems and the blood–brain barrier  

PubMed Central

The protective properties of the blood–brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain’s vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual’s age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS. PMID:24550672

Alyautdin, Renad; Khalin, Igor; Nafeeza, Mohd Ismail; Haron, Muhammad Huzaimi; Kuznetsov, Dmitry



Controlled Release of Simvastatin from Biomimetic ?-TCP Drug Delivery System  

PubMed Central

Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin. PMID:23349949

Chou, Joshua; Ito, Tomoko; Bishop, David; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce



Controlled release of simvastatin from biomimetic ?-TCP drug delivery system.  


Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin. PMID:23349949

Chou, Joshua; Ito, Tomoko; Bishop, David; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce



Using DNA nanotechnology to produce a drug delivery system  

NASA Astrophysics Data System (ADS)

Drug delivery to cancer cells in chemotherapy is one of the most advanced research topics. The effectiveness of the current cancer treatment drugs is limited because they are not capable of distinguishing between cancer cells and normal cells so that they kill not only cancer cells but also normal ones. To overcome this disadvantage by profiting from the differences in physical and chemical properties between cancer and normal cells, nanoparticles (NPs) delivering a drug are designed in a specific manner such that they can distinguish the cancer cells from the normal ones and are targeted only to the cancer cells. Currently, there are various drug delivery systems with many advantages, but sharing some common disadvantages such as difficulty with controlling the size, low encapsulation capacity and low stability. With the development and success of DNA nanotechnology, DNA strands are used to create effective drug delivery NPs with precisely controlled size and structure, safety and high stability. This article presents our study on drug encapsulation in DNA nanostructure which loaded docetaxel and curcumin in a desire to create a new and effective drug delivery system with high biological compatibility. Invited talk at the 6th International Workshop on Advanced Materials Science and Nanotechnology, 30 October–2 November, 2012, Ha Long, Vietnam.

Huyen La, Thi; Thu Thuy Nguyen, Thi; Phuc Pham, Van; Huyen Nguyen, Thi Minh; Huan Le, Quang



An emerging platform for drug delivery: aerogel based systems.  


Over the past few decades, advances in "aerogel science" have provoked an increasing interest for these materials in pharmaceutical sciences for drug delivery applications. Because of their high surface areas, high porosities and open pore structures which can be tuned and controlled by manipulation of synthesis conditions, nanostructured aerogels represent a promising class of materials for delivery of various drugs as well as enzymes and proteins. Along with biocompatible inorganic aerogels and biodegradable organic aerogels, more complex systems such as surface functionalized aerogels, composite aerogels and layered aerogels have also been under development and possess huge potential. Emphasis is given to the details of the aerogel synthesis and drug loading methods as well as the influence of synthesis parameters and loading methods on the adsorption and release of the drugs. Owing to their ability to increase the bioavailability of low solubility drugs, to improve both their stability and their release kinetics, there are an increasing number of research articles concerning aerogels in different drug delivery applications. This review presents an up to date overview of the advances in all kinds of aerogel based drug delivery systems which are currently under investigation. PMID:24394377

Ulker, Zeynep; Erkey, Can




E-print Network

COMPUTATIONAL STUDIES OF CONTROLLED NANOPARTICLE AGGLOMERATIONS FOR MRI-GUIDED NANOROBOTIC DRUG-DELIVERY in nanorobotic drug delivery. INTRODUCTION Nanorobotic drug delivery systems guided by Magnetic Resonance Imaging (MRI) scanners have been proposed for localized drug delivery in the human body. The expectation

Mavroidis, Constantinos


Inhaled formulations and pulmonary drug delivery systems for respiratory infections.  


Respiratory infections represent a major global health problem. They are often treated by parenteral administrations of antimicrobials. Unfortunately, systemic therapies of high-dose antimicrobials can lead to severe adverse effects and this calls for a need to develop inhaled formulations that enable targeted drug delivery to the airways with minimal systemic drug exposure. Recent technological advances facilitate the development of inhaled anti-microbial therapies. The newer mesh nebulisers have achieved minimal drug residue, higher aerosolisation efficiencies and rapid administration compared to traditional jet nebulisers. Novel particle engineering and intelligent device design also make dry powder inhalers appealing for the delivery of high-dose antibiotics. In view of the fact that no new antibiotic entities against multi-drug resistant bacteria have come close to commercialisation, advanced formulation strategies are in high demand for combating respiratory 'super bugs'. PMID:25451137

Zhou, Qi Tony; Leung, Sharon Shui Yee; Tang, Patricia; Parumasivam, Thaigarajan; Loh, Zhi Hui; Chan, Hak-Kim



Nanoengineered drug delivery systems for enhancing antibiotic therapy.  


Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:872-905, 2015. PMID:25546108

Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala



Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety  

PubMed Central

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

Donnelly, Ryan F.; Raj Singh, Thakur Raghu; Woolfson, A. David



Carrier-Based Drug Delivery System for Treatment of Acne  

PubMed Central

Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376

Vyas, Amber; Kumar Sonker, Avinesh



Novel drug-delivery systems for patients with chronic rhinosinusitis  

PubMed Central

Chronic rhinosinusitis, one of the most common chronic medical complaints in the United States, seems to be increasing in incidence and prevalence, and has a significant impact on quality of life. Topical forms of medical therapy represent an attractive alternative for drug delivery to the nasal cavity and paranasal sinuses. Topical drug delivery has the advantage of directly acting on the site of inflammation, producing a higher concentration at the target site while avoiding systemic side effects. Although considerable research has been undertaken into improving nasal formulations in order to enhance absorption, little attention has so far been directed to upgrading the delivery devices. The aim of this review is to present current knowledge on the novel drug-delivery devices in use in the management of chronic rhinosinusitis patients, and to present the current available knowledge on topical drug penetration into the sinuses using various delivery devices. Additionally, methods used to enhance fluid sinus deposition are presented and the published clinical studies on the results of nebulized antibiotics in the treatment of chronic rhinosinusitis patients are discussed. PMID:22745531

Albu, Silviu




E-print Network

IMPLANTABLE MEMS DRUG DELIVERY SYSTEMS FOR ADMINISTRATION OF UNALTERED THERAPEUTIC AGENTS Ellis microelectromechanical systems (MEMS) drug delivery device capable of being refilled for targeted intraocular delivery delivery vehicle for treating difficult-to-reach diseases affecting the posterior segment of the eye. Drug

Meng, Ellis


Recent advances in self-emulsifying drug delivery systems (SEDDS).  


One of the biggest challenges confronting the contemporary drug delivery science today is to improve on the oral bioavailability of a vast number of drugs exhibiting poor and inconsistent gastrointestinal absorption. Self-emulsifying drug delivery systems (SEDDS) have been proved as highly useful technological innovations to surmount such bioavailability hiccups by virtue of their diminutive globule size, higher solubilization tendency for hydro-phobic drugs, robust formulation advantages, and easier scalability in the industrial milieu. Besides, these systems are also known to inhibit the P-glycoprotein (P-gp) efflux, reduce metabolism by gut Cytochrome P-450 enzymes, and circumnavigate the hepatic first-pass effect, facilitating absorption of drugs via intestinal lymphatic pathways. In the last two decades, the phenomenal success of SEDDS as a potential tool for oral delivery of drugs has extrapolated their applications to non-oral delivery also. Various innovative approaches and patented techniques have been reported on formulation of diverse oral and non-oral self-emulsifying (SE) systems not only of various synthetic and semisynthetic drugs, but also of several phytopharmaceuticals, nutraceuticals, and biological macromolecules. Of late, an escalating number of reports have been pouring in on special types of SE systems, mostly nanosized, employing functional excipients such as polar lipids, phospholipids, cellulosic polymer, diblock polymers, etc. This review paper provides an updated bird's-eye view account on the publications and patents of such novel SE approaches for use in both oral and non-oral therapeutics. Providing a relatively pithy overview, this paper thus endeavors to act as a repertoire of knowledge and know-how to guide the product development scientist in formulating variegated SE systems. PMID:24940626

Singh, Bhupinder; Beg, Sarwar; Khurana, Rajneet Kaur; Sandhu, Premjeet Singh; Kaur, Ravinder; Katare, Om Parkash



Intelligent drug delivery systems obtained by radiation  

NASA Astrophysics Data System (ADS)

Radiation-induced polymerization of acryloyl-L-proline methyl ester, an ?-aminoacid-containing monomer, in the presence of a crosslinking agent and a hydrophilic monomer gave rise to polymer hydrogels whose water content at equilibrium was found to decrease as the swelling temperature increased. Some hydrogel samples were obtained with entrapped acetaminophen, an analgesic and antipyretic drug. It was ascertained that the release of the drug was controlled by both the hydrophilicity of the polymer matrices and the environmental temperature.

Martellini, Flavia; Higa, Olga Z.; Takacs, Erzsebet; Safranj, Agneza; Yoshida, Masaru; Katakai, Ryoichi; Carenza, Mario



Potential and problems in ultrasound-responsive drug delivery systems  

PubMed Central

Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531

Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping



Self Emulsifying Drug Delivery System (SEDDS) for Phytoconstituents: a Review.  


The self emulsifying drug delivery system (SEDDS) is considered to be the novel technique for the delivery of lipophillic plant actives. The herbals as self emulsifying (SE) formulation significantly enhance the solubility and bioavailability of poorly aqueous soluble phytoconstituents. The self emulsifying drug delivery system (SEDDS) can be developed for such plant actives to enhance the oral bioavailability using different excipients (lipid, surfactant, co solvent etc.) and their concentration is selected on the basis of pre formulation studies like phase equilibrium studies, solvent capacity of oil for drug and mutual miscibility of excipients. The present review focuses mainly on the development of SEDDS and effect of excipients on oral bioavailability and aqueous solubility of poorly water soluble phytoconstituents/derived products. A recent list of patents issued for self emulsifying herbal formulation has also been included. The research data for various self emulsifying herbal formulation and patents issued was reviewed using different database such as PubMed, Google Scholar, Google patents, Scopus and Web of Science etc. In nutshell, we can say that SEDDS established as novel drug delivery system for herbals and with the advances in this technique, lots of patents on herbal SEDDS can be translated into the commercial products. PMID:25335929

Chouhan, Neeraj; Mittal, Vineet; Kaushik, Deepak; Khatkar, Anurag; Raina, Mitali



Transdermal drug delivery  

PubMed Central

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

Prausnitz, Mark R.; Langer, Robert



Microsponges: A novel strategy for drug delivery system.  


Microsponges are polymeric delivery systems composed of porous microspheres. They are tiny sponge-like spherical particles with a large porous surface. Moreover, they may enhance stability, reduce side effects and modify drug release favorably. Microsponge technology has many favorable characteristics, which make it a versatile drug delivery vehicle. Microsponge Systems are based on microscopic, polymer-based microspheres that can suspend or entrap a wide variety of substances, and can then be incorporated into a formulated product such as a gel, cream, liquid or powder. The outer surface is typically porous, allowing a sustained flow of substances out of the sphere. Microsponges are porous, polymeric microspheres that are used mostly for topical use and have recently been used for oral administration. Microsponges are designed to deliver a pharmaceutical active ingredient efficiently at the minimum dose and also to enhance stability, reduce side effects, and modify drug release. PMID:22247859

Kaity, Santanu; Maiti, Sabyasachi; Ghosh, Ashoke Kumar; Pal, Dilipkumar; Ghosh, Animesh; Banerjee, Subham



Packaged Au-PPy valves for drug delivery systems  

NASA Astrophysics Data System (ADS)

The most common methods for the drug delivery are swallowing pills or receiving injections. However, formulations that control the rate and period of medicine (i.e., time-release medications) are still problematic. The proposed implantable devices which include batteries, sensors, telemetry, valves, and drug storage reservoirs provide an alternative method for the responsive drug delivery system [1]. Using this device, drug concentration can be precisely controlled which enhances drug efficiency and decreases the side effects. In order to achieve responsive drug delivery, a reliable release valve has to be developed. Biocompatibility, low energy consumption, and minimized leakage are the main requirements for such release method. A bilayer structure composed of Au/PPy film is fabricated as a flap to control the release valve. Optimized potentiostatic control to synthesize polypyrrole (PPy) is presented. The release of miniaturize valve is tested and showed in this paper. A novel idea to simultaneously fabricate the device reservoirs as well as protective packaging is proposed in this paper. The solution of PDMS permeability problem is also mentioned in this article.

Tsai, Han-Kuan A.; Ma, Kuo-Sheng; Zoval, Jim; Kulinsky, Lawrence; Madou, Marc



Floating Drug Delivery of Nevirapine as a Gastroretentive System  

PubMed Central

A multiple-unit floating drug delivery system based on gas formation technique was developed, in order to prolong the gastric residence time and to increase the overall bioavailability of the dosage form. The floating bead formulations were prepared by dispersing nevirapine together with calcium carbonate in a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping the dispersion into an acidified solution of calcium chloride. Calcium alginate beads were formed, as the alginate underwent ionotropic gelation by calcium ions, and carbon dioxide developed from the reaction of carbonate salts with acid. The obtained beads were able to float due to CO2-gas formation and the gas entrapment by the polymeric membrane. The prepared beads were evaluated for percent drug loading, drug entrapment efficiency, morphology, surface topography, buoyancy, in-vitro release, and release kinetics. The formulations were optimized for different weight ratios of the gas-forming agent and sodium alginate. The beads containing higher amounts of calcium carbonate demonstrated an instantaneous, complete, and excellent floating ability over a period of 24 hours. The increased amount of the gas forming agent did not affect the time to float, but increased the drug release from the floating beads, while increasing the coating level of the gas-entrapped membrane, increased the time to float, and slightly retarded the drug release. Good floating properties and sustained drug release were achieved. Finally, these floating beads seemed to be a promising gastroretentive drug delivery system. PMID:21264092

Vedha, Hari BN; Brahma, Reddy A; Samyuktha, Rani B



Exosome mimetics: a novel class of drug delivery systems  

PubMed Central

The identification of extracellular phospholipid vesicles as conveyors of cellular information has created excitement in the field of drug delivery. Biological therapeutics, including short interfering RNA and recombinant proteins, are prone to degradation, have limited ability to cross biological membranes, and may elicit immune responses. Therefore, delivery systems for such drugs are under intensive investigation. Exploiting extracellular vesicles as carriers for biological therapeutics is a promising strategy to overcome these issues and to achieve efficient delivery to the cytosol of target cells. Exosomes are a well studied class of extracellular vesicles known to carry proteins and nucleic acids, making them especially suitable for such strategies. However, the considerable complexity and the related high chance of off-target effects of these carriers are major barriers for translation to the clinic. Given that it is well possible that not all components of exosomes are required for their proper functioning, an alternative strategy would be to mimic these vesicles synthetically. By assembly of liposomes harboring only crucial components of natural exosomes, functional exosome mimetics may be created. The low complexity and use of well characterized components strongly increase the pharmaceutical acceptability of such systems. However, exosomal components that would be required for the assembly of functional exosome mimetics remain to be identified. This review provides insights into the composition and functional properties of exosomes, and focuses on components which could be used to enhance the drug delivery properties of exosome mimetics. PMID:22619510

Kooijmans, Sander AA; Vader, Pieter; van Dommelen, Susan M; van Solinge, Wouter W; Schiffelers, Raymond M



In vivo Evaluation of Self Emulsifying Drug Delivery System for Oral Delivery of Nevirapine  

PubMed Central

Nevirapine is a highly lipophilic and water insoluble non-nucleoside reverse transcriptase inhibitor used for the treatment of HIV-1 infection. Lymphoid tissue constitutes the major reservoir of HIV virus and infected cells in HIV-infected patients. Self-emulsifying drug delivery system, using long chain triglycerides, is a popular carrier of drugs due to their ability to transport lipophilic drugs into the lymphatic circulation. However, HIV/AIDS patients experience a variety of functional and anatomical abnormalities in gastrointestinal tract that result in diarrhoea and nutrient malabsorption. Medium chain triglycerides are readily absorbed from the small bowel under conditions in which the absorption of long chain triglycerides is impaired. Therefore, nevirapine self-emulsifying drug delivery system containing medium chain fatty acid, caprylic acid and a solubilizer, Soluphor® P (2-pyrrolidone) was developed and found to be superior to the marketed conventional suspension with respect to in vitro diffusion and ex vivo intestinal permeability. This self-emulsifying drug delivery system has now been further investigated for in vivo absorption in an animal model. The contribution of caprylic acid and Soluphor® P on in vivo absorption of nevirapine was also studied in the present study. The bioavailability of nevirapine from self-emulsifying drug delivery system, after oral administration, was 2.69 times higher than that of the marketed suspension. The improved bioavailability could be due to absorption of nevirapine via both portal and intestinal lymphatic routes. The study indicates that medium chain or structured triglycerides can be a better option to develop self-emulsifying drug delivery system for lipophilic and extensively metabolised drugs like nevirapine for patients with AIDS-associated malabsorption. PMID:25035533

Chudasama, A. S.; Patel, V. V.; Nivsarkar, M.; Vasu, Kamala K.; Shishoo, C. J.



Kinetic limitations of cooperativity based drug delivery systems  

E-print Network

We study theoretically a novel drug delivery system that utilizes the overexpression of certain proteins in cancerous cells for cell specific chemotherapy. The system consists of dendrimers conjugated with "keys" (ex: folic acid) which "key-lock" bind to particular cell membrane proteins (ex: folate receptor). The increased concentration of "locks" on the surface leads to a longer residence time for the dendrimer and greater incorporation into the cell. Cooperative binding of the nanocomplexes leads to an enhancement of cell specificity. However, both our theory and detailed analysis of in-vitro experiments indicate that the degree of cooperativity is kinetically limited. We demonstrate that cooperativity and hence the specificity to particular cell type can be increased by making the strength of individual bonds weaker, and suggest a particular implementation of this idea. The implications of the work for optimizing the design of drug delivery vehicles are discussed.

Nicholas A. Licata; Alexei V. Tkachenko



Intrathecal Drug Delivery (ITDD) systems for cancer pain  

PubMed Central

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

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



Electrohydrodynamics: A facile technique to fabricate drug delivery systems  

Microsoft Academic Search

Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drug delivery systems (DDS) through a one-step process. The nanostructured 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

Syandan Chakraborty; I-Chien Liao; Andrew Adler; Kam W. Leong



Synthetic Microbes As Drug Delivery Systems.  


Synthetic cell therapy is a field that has broad potential for future applications in human disease treatment. Next generation therapies will consist of engineered bacterial strains capable of diagnosing disease, producing and delivering therapeutics, and controlling their numbers to meet containment and safety concerns. A thorough understanding of the microbial ecology of the human body and the interaction of the microbes with the immune system will benefit the choice of an appropriate chassis that engrafts stably and interacts productively with the resident community in specific body niches. PMID:25079685

Claesen, Jan; Fischbach, Michael A



Assemblage of novel release modules for the development of adaptable drug delivery systems  

E-print Network

Assemblage of novel release modules for the development of adaptable drug delivery systems Elena. The presence of the convex and concave bases in the swellable matrix slightly changed the overall drug delivery reserved. Keywords: Matrix; Release module; Swelling; Drug delivery system; Assemblage 1. Introduction

Peppas, Nicholas A.


Dynamic Feedback and the Design of Closed-loop Drug Delivery Systems  

E-print Network

Dynamic Feedback and the Design of Closed-loop Drug Delivery Systems John Milton1,2 , Sue Ann´eal, Montr´eal, Canada Abstract A closed-loop drug delivery system is constructed in which external negative. The advantage of this paradigm for drug delivery is that both the steady states and stability of the multiple

Campbell, Sue Ann


Molecular Analysis of Drug Delivery Systems Controlled by Dissolution of the Polymer Carrier  

E-print Network

Molecular Analysis of Drug Delivery Systems Controlled by Dissolution of the Polymer Carrier BALAJI NARASIMHAN AND NIKOLAOS A. PEPPASX Received September 4, 1996, from the Biomaterials and Drug Delivery-controlled drug delivery systems are characterized by a phase erosion of the polymer carrier that is associated

Peppas, Nicholas A.


Drug delivery systems based on sugar-macromolecule conjugates Benjamin G Davis* & Mark A Robinson  

E-print Network

Drug delivery systems based on sugar-macromolecule conjugates Benjamin G Davis* & Mark A Robinson-tuning of active drug delivery through their great ability to undergo site- specific modification], the potential of using carbohydrates to create a truly targeted (or actively-targeted) drug delivery system has

Davis, Ben G.


Application of Ultrasound Energy as a New Drug Delivery System  

NASA Astrophysics Data System (ADS)

Ultrasound has been in use for the last three decades as amodality for diagnostic imaging in medicine. Recently, there have beennumerous reports on the application of nonthermal ultrasound energyfor targeting or controlling drug release. This new concept oftherapeutic ultrasound combined with drugs has led to much excitementin various medical fields. Ultrasound energy can enhance the effectsof thrombolytic agents such as urokinase. Therapeutic ultrasoundcatheters are currently being developed for treatment ofcardiovascular diseases. Devices with ultrasound transducers implantedin transdermal drug patches are also being evaluated for possibledelivery of insulin through the skin. Chemical activation of drugs byultrasound energy for treatment of cancers is another new fieldrecently termed “Sonodynamic Therapy”. Various examples of ultrasoundapplication are under investigation which could lead to revolutionarydrug delivery systems in the future.

Tachibana, Katsuro; Tachibana, Shunro



Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems.  


For many drug candidates a modified in vivo drug release is desired to improve efficacy, sustain effect or minimise toxicity. Polymeric delivery systems, such as microspheres, nanospheres and polymeric films, have been extensively researched in an attempt to achieve modified drug release. Cyclodextrins offer an alternative approach. These cyclic oligosaccharides have the ability to form non-covalent complexes with a number of drugs and in so doing alter their physicochemical properties. In addition, the primary and secondary hydroxyl groups of the native (alpha, beta, gamma-) cyclodextrins are potential sites for chemical modification. It follows that the incorporation of these agents into polymeric drug delivery systems, as physical mixtures, covalently bound conjugates or cross-linking agents, frequently permits a greater degree of control of drug release. This paper reviews the incorporation of various cyclodextrins into polymeric formulations. The mechanisms by which cyclodextrin/polymer formulations act to modify drug release are considered. PMID:10704788

Bibby, D C; Davies, N M; Tucker, I G



Bionanocomposites containing magnetic graphite as potential systems for drug delivery.  


New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays. PMID:25455784

Ribeiro, Lígia N M; Alcântara, Ana C S; Darder, Margarita; Aranda, Pilar; Herrmann, Paulo S P; Araújo-Moreira, Fernando M; García-Hernández, Mar; Ruiz-Hitzky, Eduardo



Autonomous Rhythmic Drug Delivery Systems Based on Chemical and Biochemomechanical Oscillators  

Microsoft Academic Search

While many drug delivery systems target constant, or zero-order drug release, certain drugs and hormones must be delivered in rhythmic pulses in order to achieve their optimal effect. Here we describe studies with two model autonomous rhythmic delivery systems. The first system is driven by a pH oscillator that modulates the ionization state of a model drug, benzoic acid, which

Ronald A. Siegel



Small-scale systems for in vivo drug delivery  

Microsoft Academic Search

Recent developments in the application of micro- and nanosystems for drug administration include a diverse range of new materials and methods. New approaches include the on-demand activation of molecular interactions, novel diffusion-controlled delivery devices, nanostructured 'smart' surfaces and materials, and prospects for coupling drug delivery to sensors and implants. Micro- and nanotechnologies are enabling the design of novel methods such

David A LaVan; Terry McGuire; Robert Langer



Cyclodextrins in nasal drug delivery  

Microsoft Academic Search

Nasal drug delivery is an attractive approach for the systemic delivery of high potency drugs with a low oral bioavailability due to extensive gastrointestinal breakdown and high hepatic first-pass effect. For lipophilic drugs nasal delivery is possible if they can be dissolved in the dosage form. Peptide and protein drugs often have a low nasal bioavailability because of their large

F. W. H. M Merkus; J. C Verhoef; E Marttin; S. G Romeijn; P. H. M van der Kuy; W. A. J. J Hermens; N. G. M Schipper



JOURNAL OF MICROELECTROMECHANICAL SYSTEMS, VOL. 13, NO. 1, FEBRUARY 2004 75 A Water-Powered Micro Drug Delivery System  

E-print Network

Drug Delivery System Yu-Chuan Su and Liwei Lin, Member, IEEE, Member, ASME Abstract--A plastic micro drug delivery system has been suc- cessfully demonstrated by utilizing the principle of osmosis without, the prototype drug delivery system has a measured con- stant delivery rate at 0.2 L h for 10 h

Lin, Liwei


Utah-Inha Joint Research Center on Drug Delivery Systems & Advanced Therapeutics  

E-print Network

Utah-Inha Joint Research Center on Drug Delivery Systems & Advanced Therapeutics Inha University Hospital MISSION AND VISION: The Utah-Inha Joint Research Center on Drug Delivery therapeutics, controlled release, and targeted drug delivery from University of Utah's Department

Tipple, Brett


A novel liquefied gas based oral controlled release drug delivery system for liquid drug formulations.  


A novel liquefied gas based drug delivery system for the oral delivery of liquid and semi-solid drug formulations is presented. The capsule-shaped system is equipped with a capillary as an element controlling the release rate. The delivery mechanism is based on a constant vapor pressure produced by isopentane as a low-boiling liquefied gas. The liquid drug valproic acid (VA) was used as a model compound. The viscosity was increased by the addition of povidone (PVP). The VA-PVP gel exhibited pseudoplastic rheological properties, the shear rate was above 0.1s(-1), similar to a Newtonian liquid. The gels tested in the gas based delivery system provided near-zero-order release kinetics. The longest delivery time was up to ca. 8h. The system is characterized by high flexibility of the delivery rate, which can be achieved by adjusting system parameters such as the diameter and length of the capillary, the vapor pressure of the propellant and the viscosity of the drug formulation. PMID:22426133

Haznar-Garbacz, Dorota; Garbacz, Grzegorz; Eisenächer, Friederike; Klein, Sandra; Weitschies, Werner



Chitosan in nasal delivery systems for therapeutic drugs.  


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

Casettari, Luca; Illum, Lisbeth



A Pillararene-Based Ternary Drug-Delivery System with Photocontrolled Anticancer Drug Release.  


A novel ternary drug delivery system (DDS) is constructed using a photodegradable anticancer prodrug (Py-Cbl), a water-soluble pillararene supramolecular container (WP6), and the diblock copolymer methoxy-poly(ethylene glycol)114 -block-poly(L -lysine hydrochloride)200 . This DDS successfully addresses three important issues: enhancement of the water solubility of the anticancer prodrug; controlled release of the anticancer drug; accurate and quantitative measurement of the drug release. PMID:25318658

Yu, Guocan; Yu, Wei; Mao, Zhengwei; Gao, Changyou; Huang, Feihe



Progress in Psoriasis Therapy via Novel Drug Delivery Systems  

PubMed Central

Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient’s quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment. PMID:25386329

Vincent, Nitha; Ramya, Devi D; Vedha, Hari BN



Cubic and Hexagonal Liquid Crystals as Drug Delivery Systems  

PubMed Central

Lipids have been widely used as main constituents in various drug delivery systems, such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-based lyotropic liquid crystals. Among them, lipid-based lyotropic liquid crystals have highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix. The intricate nanostructures of the cubic phase and hexagonal phase have been shown to provide diffusion controlled release of active pharmaceutical ingredients with a wide range of molecular weights and polarities. In addition, the biodegradable and biocompatible nature of lipids demonstrates the minimum toxicity and thus they are used for various routes of administration. Therefore, the research on lipid-based lyotropic liquid crystalline phases has attracted a lot of attention in recent years. This review will provide an overview of the lipids used to prepare cubic phase and hexagonal phase at physiological temperature, as well as the influencing factors on the phase transition of liquid crystals. In particular, the most current research progresses on cubic and hexagonal phases as drug delivery systems will be discussed. PMID:24995330

Chen, Yulin; Ma, Ping; Gui, Shuangying



Gamma-sterilization-induced radicals in biodegradable drug delivery systems.  


Electron paramagnetic resonance (EPR) spectroscopy (1.2 and 9.25 GHz, 25 degrees C) was used to characterize free radicals in gamma-ray sterilized biodegradable polymers of the type which are in clinical use. Free radicals were detected in all irradiated polymer samples. The temperature of irradiation (25 degrees C vs dry ice temperature) had only a minor influence on the yield of radicals and the shape of the EPR spectra. In contrast, the composition of the polymers and the drugs incorporated in them did strongly influence the amount of radiation-induced free radicals and their reactivity. In general, polymers with high melting points and crystallinity had the highest yields of radicals observable at room temperature. We were able to use the free radicals induced by the usual sterilization procedures to follow the penetration of water and the degradation of the polymers in vitro and in vivo. The ability of in vivo EPR to follow drug delivery noninvasively and continuously in vivo, using the free radicals induced in the usual sterilization process indicates that this approach could be applied immediately for the characterization of these drug delivery systems in experimental animals and in the near future should be able to be used in human subjects. PMID:9022208

Mäder, K; Domb, A; Swartz, H M



Ionic liquids as ingredients in topical drug delivery systems.  


Because of their properties, ionic liquids (ILs) (Ranke et al.) offer many advantages in topical drug delivery systems. For example, ionic liquids can be used to increase the solubility of sparingly soluble drugs and to enhance their topical and transdermal delivery. Furthermore, ILs can be used either to synthesize active pharmaceutical ingredients or as antimicrobial ingredients. In the present work, the conventional oil-in-water (O/W) and water-in-oil (W/O) emulsions containing the hydrophilic IL [HMIM] [Cl] and the hydrophobic IL [BMIM] [PF6] were prepared, and the influence of the ILs on emulsion properties was evaluated. It was found that ILs could be successfully incorporated into the emulsion structure, resulting in stable formulations. The antimicrobial activity of ILs in the formulations was estimated, and their application as preservatives was confirmed by performing preservative efficacy tests. Evaluation of the in vitro cytotoxicity of the emulsions containing hydrophilic or hydrophobic ILs showed the low cytotoxicity of the carriers. Finally, penetration enhancement of a fluorescent dye as a model drug in the presence of ionic liquids was shown. PMID:23123180

Dobler, Dorota; Schmidts, Thomas; Klingenhöfer, Ines; Runkel, Frank



Bimodal gastroretentive drug delivery systems of lamotrigine: formulation and evaluation.  


Gastroretentive bimodal drug delivery systems of lamotrigine were developed using immediate release and extended release segments incorporated in a hydroxypropyl methylcellulose capsule and in vitro and in vivo evaluations were conducted. In vivo radiographic studies were carried out for the optimized formulation in healthy human volunteers with replacement of drug polymer complex by barium sulphate and the floating time was noted. Here the immediate release segment worked as loading dose and extended release segment as maintenance dose. The results of release studies of formulations with hydrophillic matrix to formulations with dual matrix hydroxypropyl methylcellulose acetate succinate shown that as the percentage of polymer increased, the release decreased. Selected formulation F2 having F-Melt has successfully released the drug within one hour and hydrophillic matrix composing polyethylene oxide with 5% hydroxypropyl methylcellulose acetate succinate showed a lag time of one hour and then extended its release up to 12th hour with 99.59% drug release following zero order kinetics with R(2) value of 0.989. The Korsmeyer-Peppas equation showed the R(2) value to be 0.941 and n value was 1.606 following non-Fickian diffusion pattern with supercase II relaxation mechanism. Here from extended release tablet the drug released slowly from the matrix while floating. PMID:25593380

Poonuru, R R; Gonugunta, C S R



Bimodal Gastroretentive Drug Delivery Systems of Lamotrigine: Formulation and Evaluation  

PubMed Central

Gastroretentive bimodal drug delivery systems of lamotrigine were developed using immediate release and extended release segments incorporated in a hydroxypropyl methylcellulose capsule and in vitro and in vivo evaluations were conducted. In vivo radiographic studies were carried out for the optimized formulation in healthy human volunteers with replacement of drug polymer complex by barium sulphate and the floating time was noted. Here the immediate release segment worked as loading dose and extended release segment as maintenance dose. The results of release studies of formulations with hydrophillic matrix to formulations with dual matrix hydroxypropyl methylcellulose acetate succinate shown that as the percentage of polymer increased, the release decreased. Selected formulation F2 having F-Melt has successfully released the drug within one hour and hydrophillic matrix composing polyethylene oxide with 5% hydroxypropyl methylcellulose acetate succinate showed a lag time of one hour and then extended its release up to 12th hour with 99.59% drug release following zero order kinetics with R2 value of 0.989. The Korsmeyer-Peppas equation showed the R2 value to be 0.941 and n value was 1.606 following non-Fickian diffusion pattern with supercase II relaxation mechanism. Here from extended release tablet the drug released slowly from the matrix while floating. PMID:25593380

Poonuru, R. R.; Gonugunta, C. S. R



Safe and efficient drug delivery system with liposomes for intrathecal application of an antivasospastic drug, fasudil.  


Pharmacological treatment for cerebral ischemia and cerebral vasospasm following subarachnoid hemorrhage (SAH) cannot attain sufficiently high concentrations of the drugs in the cerebrospinal fluid (CSF) without precipitating systemic side effects. We recently developed a liposomal drug delivery system for intrathecal application that can maintain effective concentrations of cerebral vasodilator, fasudil, in the CSF. A single intrathecal injection of liposomal fasudil could maintain a therapeutic drug concentration in the CSF over a period time due to their sustained-release property, significantly decreasing infarct size in a rat model of acute ischemia and reducing vasoconstriction of the rat and dog basilar artery in a model of SAH. In this review, we are introducing our new less-invasive intrathecal drug delivery system that provides an alternative and safe method to deliver therapeutic agents. PMID:16508135

Ishida, Tatsuhiro; Takanashi, Yoshihiro; Kiwada, Hiroshi



Development of ocular drug delivery systems using molecularly imprinted soft contact lenses.  


Abstract Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels. PMID:25113431

Tashakori-Sabzevar, Faezeh; Mohajeri, Seyed Ahmad



Bionanocomposites based on layered double hydroxides as drug delivery systems  

NASA Astrophysics Data System (ADS)

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.

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



Cubosomes as targeted drug delivery systems - a biopharmaceutical approach.  


Cubosomes are reversed bicontinuous cubic phases and possess unique physicochemical properties. These special systems are receiving much attention for the delivery of various hydrophilic, hydrophobic and amphiphilic drugs with enhanced bioavailability and high loading capacity. A wide variety of drugs are applicable for cubosome formulation for various routes of delivery. The lipids used in cubosome formulation are more stable and offer stability to the formulation during shelf-life. The article reviews about the back ground, techniques of cubosome preparation such as high pressure homogenization, probe ultrasonication and automated cubosome preparation; and also methods of cubosomes preparation such as top down, bottom up and other methods with pictorial presentation. This article emphasizes the phase transition and also targeted approaches of cubosomes. The characterization studies for cubosomes such as cryo transmission electron microscopy, differential scanning calorimetry and scanning electron microscopy followed by in-vitro and in-vivo evaluation studies of cubosomes were explained with appropriate examples. Recent applications of cubosomes were explained with reference to flurbiprofen, odorranalectin, diazepam and dexamethasone. The advantages, disadvantages and limitations of cubosomal technology were emphasized. PMID:24836404

Lakshmi, Naga M; Yalavarthi, Prasanna R; Vadlamudi, Harini C; Thanniru, Jyotsna; Yaga, Gowri; K, Haritha



The use of gelatin in a multiple drug delivery system  

NASA Astrophysics Data System (ADS)

The use of gelatin for growth factor delivery was investigated. Protein-gelatin interactions were characterized using the Biomolecular Interaction Detection (BIND) system. Acidic gelatin sheets and basic gelatin microspheres were fabricated and optimized for delivering transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-2. The two delivery vehicles were then combined to produce two distinct release sequences and the effect of sequence on bone healing was determined. Using the BIND system, TGF-beta1 was found to interact more strongly with acidic gelatin than basic gelatin whereas BMP-2 only slightly favors basic gelatin over acidic gelatin. Acidic gelatin sheets were fabricated by a casting technique. These sheets successfully delivered TGF-beta1 to a rabbit ulna defect to encourage new bone formation. Basic gelatin microspheres were fabricated by the precision particle fabrication (PPF) method. Uniform drug distribution within the microspheres lead to controlled release of BMP-2 that induced bone formation within the thigh muscle of mice. The sheets and microspheres were combined to deliver both drugs either simultaneously or with a four-day delay to a rabbit calvarial defect. Both sequences encouraged more bone regeneration than empty defects by 8 weeks. Protein-gelatin interactions improved protein stability and lead to release through enzymatic degradation of the gelatin. Growth factors released either singly or in a dual system from gelatin successfully produced bone in vivo. However, single release systems require higher dosages to achieve similar healing results as observed in the dual release systems. No difference was observed between the dual release systems investigated.

Morgan, Abby W.


Advanced Drug-Delivery Systems of Curcumin for Cancer Chemoprevention  

PubMed Central

From ancient times, chemopreventive agents have been used to treat/prevent several diseases, including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell-culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been demonstrated to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician’s armamentarium. PMID:21546540

Bansal, Shyam S.; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V.; Gupta, Ramesh C.



Advanced drug delivery systems of curcumin for cancer chemoprevention.  


Since ancient times, chemopreventive agents have been used to treat/prevent several diseases including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, antioxidant, antiproliferative, anticarcinogenic, and antiangiogenic activity in various cell cultures and some animal studies. Research over the past 4 decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been shown to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician's armamentarium. PMID:21546540

Bansal, Shyam S; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V; Gupta, Ramesh C



Autonomous Rhythmic Drug Delivery Systems Based on Chemical and Biochemomechanical Oscillators  

Microsoft Academic Search

While many drug delivery systems target constant, or zero-order drug release, certain drugs and hormones must be delivered\\u000a in rhythmic pulses in order to achieve their optimal effect. Here we describe studies with two model autonomous rhythmic delivery\\u000a systems. The first system is driven by a pH oscillator that modulates the ionization state of a model drug, benzoic acid,\\u000a which

Ronald A. Siegel


Synthesis and Characterization of a Magnetically Responsive Polymeric Drug Delivery System  

E-print Network

A magnetic target drug delivery system consisting of biodegradable polymeric microspheres (poly D, L-lactic acid) loaded with magnetite nanoparticles (10-100 nm) and anticancer drug (paclitaxel) was studied. The magnetite ...

Yu, Shi


Magnetic and fluorescent multifunctional chitosan nanoparticles as a smart drug delivery system  

Microsoft Academic Search

An innovative drug delivery system based on magnetic and fluorescent multifunctional chitosan nanoparticles was developed, which combined magnetic targeting, fluorescent imaging and stimulus-responsive drug release properties into one drug delivery system. Water-soluble superparamagnetic Fe3O4 nanoparticles, CdTe quantum dots (QDs) and pharmaceutical drugs were simultaneously incorporated into chitosan nanoparticles; cross-linking the composite particles with glutaraldehyde tailored their size, morphology, surface properties

Linlin Li; Dong Chen; Yanqi Zhang; Zhengtao Deng; Xiangling Ren; Xianwei Meng; Fangqiong Tang; Jun Ren; Lin Zhang



Microneedle-based drug delivery systems for transdermal route.  


Transdermal delivery offers an attractive, noninvasive administration route but it is limited by the skin's barrier to penetration. Minimally invasive techniques, such as the use of microneedles (MNs), bypass the stratum corneum (SC) barrier to permit the drug's direct access to the viable epidermis. These novel micro devices have been developed to puncture the skin for the transdermal delivery of hydrophilic drugs and macromolecules, including peptides, DNA and other molecules, that would otherwise have difficulty passing the outermost layer of the skin, the SC. Using the tools of the microelectronics industry, MNs have been fabricated with a range of sizes, shapes and materials. MNs have been shown to be robust enough to penetrate the skin and dramatically increase the skin permeability of several drugs. Moreover, MNs have reduced needle insertion pain and tissue trauma and provided controlled delivery across the skin. This review focuses on the current state of the art in the transdermal delivery of drugs using various types of MNs and developments in the field of microscale devices, as well as examples of their uses and clinical safety. PMID:24144208

Pierre, Maria Bernadete Riemma; Rossetti, Fabia Cristina



Recent progress in solid-state NMR studies of drugs confined within drug delivery systems.  


Recent progress in the application of solid-state NMR (SS NMR) spectroscopy in structural studies of active pharmaceutical ingredients (APIs) embedded in different drug carriers is detailed. This article is divided into sections. The first part reports short characterization of the nanoparticles and microparticles that can be used as drug delivery systems (DDSs). The second part shows the applicability of SS NMR to study non-steroidal anti-inflammatory drugs (NSAIDs). In this section, problems related to API-DDS interactions, morphology, local molecular dynamics, nature of inter- or intramolecular connections, and pore filling are reviewed for different drug carriers (e.g. mesoporous silica nanoparticles (MSNs), cyclodextrins, polymeric matrices and others). The third and fourth sections detail the recent applications of SS NMR for searching for antibiotics and anticancer drugs confined in zeolites, MSNs, amorphous calcium phosphate and other carriers. PMID:24398051

Skorupska, Ewa; Jeziorna, Agata; Kazmierski, Slawomir; Potrzebowski, Marek J



Natural products as potential drug permeation enhancer in transdermal drug delivery system.  


Permeation enhancers are defined as substances that are capable of promoting penetration of drugs into skin and transdermal therapeutic systems offers a more reliable mean of administering drug through the skin. Skin is a natural barrier so it is necessary to employ enhancement strategies to improve topical bioavailability. This review explores that natural products have got potential to enhance the permeation of the drug through skin by reversibly reducing the skin barrier resistance. The use of natural products is the most reliable means of permeation enhancement of transdermally administered drugs and permits the delivery of broader classes of drugs through the stratum corneum. They are safe, non-toxic, pharmacologically inert, non-irritating, and non-allergenic to use as permeation enhancers. The present review initially highlights the current status of natural products on the basis of SAR studies which have shown significant enhancer activities. PMID:24481830

Patil, Umesh K; Saraogi, Richa



Dedicated controllers for sensor embedded electrode architecture of noninvasive drug delivery system  

Microsoft Academic Search

This paper summarizes the author's endeavor in the recent past on the development of a Non-invasive Drug Delivery System (NIDDS) for applications in the area of dermatology. After investigating the basic requirements of a drug delivery system, a design has been formulated, which makes use of the power of a microcontroller to monitor and control some of the control applications

S. Ravichandran; Ng Weili; Lam Hwei Hwei; Yuan Ran Dong; Hong Ka Lic; Lee Chia Yin; Lim Shi Yi Darren; Wu Lie Quan



Gold nanoparticle platforms as drug and biomacromolecule delivery systems  

PubMed Central

Gold nanoparticles (AuNPs) are a suitable platform for development of efficient delivery systems. AuNPs can be easily synthesized, functionalized, and are biocompatible. The tunability of the AuNP monolayer allows for complete control of surface properties for targeting and stability/release using these nanocarriers. This review will discuss several delivery strategies utilizing AuNPs. PMID:20547192

Duncan, Bradley; Kim, Chaekyu; Rotello, Vincent M.



Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their  

E-print Network

Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours-invasively monitor drug delivery in vivo. We also visualize the targeting of the tumour microenvironment by the drug substantially reduced the size of the tumour compared with systemic delivery of the same drug. C ancer

Bogyo, Matthew


A patchless dissolving microneedle delivery system enabling rapid and efficient transdermal drug delivery  

PubMed Central

Dissolving microneedles (DMNs) are polymeric, microscopic needles that deliver encapsulated drugs in a minimally invasive manner. Currently, DMN arrays are superimposed onto patches that facilitate their insertion into skin. However, due to wide variations in skin elasticity and the amount of hair on the skin, the arrays fabricated on the patch are often not completely inserted and large amount of loaded materials are not delivered. Here, we report “Microlancer”, a novel micropillar based system by which patients can self-administer DMNs and which would also be capable of achieving 97 ± 2% delivery efficiency of the loaded drugs regardless of skin type or the amount of hair on the skin in less than a second. PMID:25604728

Lahiji, Shayan F.; Dangol, Manita; Jung, Hyungil



Osmotically regulated asymmetric capsular systems for simultaneous sustained delivery of anti-tubercular drugs  

Microsoft Academic Search

Sustained release asymmetric membrane capsular systems were developed for simultaneous oral delivery of rifampicin and isoniazid sodium in order to reduce the problems associated with the multi drug therapy of tuberculosis. Dense semipermeable membrane coating capsules were also prepared for the delivery of these drugs by adopting two different filling approaches. In vitro release studies were carried out for both

D. Prabakaran; Paramjit Singh; K. S. Jaganathan; Suresh P. Vyas



Design and development of a self-nanoemulsifying drug delivery system for telmisartan for oral drug delivery  

PubMed Central

Background and Aim: Telmisartan (TEL) is an angiotensin II receptor blocker (ARB) antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of poorly water soluble TEL. Materials and Methods: The solubility of TEL in various oils was determined to identify the oil phase of a SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. A SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size, zeta potential, pH, refractive index, and viscosity. Results: The developed SNEDDS formulation contained TEL (20 mg), Tween® 20 (43.33%w/w), Carbitol® (21.67%w/w), and Acrysol® EL 135 (32%w/w). The optimized formulation of the TEL-loaded SNEDDS exhibited a complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug suspension by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of TEL from the SNEDDS compared with the pure drug suspension. Conclusions: These results suggest the potential use of the SNEDDS to improve the dissolution and oral bioavailability of poorly water soluble TEL. PMID:23071930

Patel, Jaydeep; Kevin, Garala; Patel, Anjali; Raval, Mihir; Sheth, Navin



Magnetic and fluorescent multifunctional chitosan nanoparticles as a smart drug delivery system  

NASA Astrophysics Data System (ADS)

An innovative drug delivery system based on magnetic and fluorescent multifunctional chitosan nanoparticles was developed, which combined magnetic targeting, fluorescent imaging and stimulus-responsive drug release properties into one drug delivery system. Water-soluble superparamagnetic Fe3O4 nanoparticles, CdTe quantum dots (QDs) and pharmaceutical drugs were simultaneously incorporated into chitosan nanoparticles; cross-linking the composite particles with glutaraldehyde tailored their size, morphology, surface properties and drug release behaviors. The system showed superparamagnetic and strong fluorescent properties, and was used as a controlled drug release vehicle, which showed pH-sensitive drug release over a long time. The composite magnetic and fluorescent chitosan nanoparticles are potential candidates as a smart drug delivery system.

Li, Linlin; Chen, Dong; Zhang, Yanqi; Deng, Zhengtao; Ren, Xiangling; Meng, Xianwei; Tang, Fangqiong; Ren, Jun; Zhang, Lin



An overview of clinical and commercial impact of drug delivery systems.  


Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems. PMID:24747160

Anselmo, Aaron C; Mitragotri, Samir



An implantable drug-delivery system based on shape memory alloy micro-actuation  

Microsoft Academic Search

Shape memory alloy actuators feature an extremely high power-to-volume ratio. This property is a major advantage for miniature applications. This paper describes implantable drug-delivery systems based on shape memory alloy micro-actuation. A first type is designed for use with solid drugs while a second design enables delivery of liquid drugs. The operating principle of the latter system is based on

Dominiek Reynaerts; Jan Peirs; Hendrik Van Brussel



The Benefits and Challenges Associated with the Use of Drug Delivery Systems in Cancer Therapy  

PubMed Central

The use of Drug Delivery Systems as nanocarriers for chemotherapeutic agents can improve the pharmacological properties of drugs by altering drug pharmacokinetics and biodistribution. Among the many drug delivery systems available, both micelles and liposomes have gained the most attention in recent years due to their clinical success. There are several formulations of these nanocarrier systems in various stages of clinical trials, as well as currently clinically approved liposomal-based drugs. In this review, we discuss these drug carrier systems, as well as current efforts that are being made in order to further improve their delivery efficacy through the incorporation of targeting ligands. In addition, this review discusses aspects of drug resistance attributed to the remodeling of the extracellular matrix that occurs during tumor development and progression, as well as to the acidic, hypoxic, and glucose deprived tumor microenvironment. Finally, we address future prospective approaches to overcoming drug resistance by further modifications made to these drug delivery systems, as well as the possibility of coencapsulation/coadministration of various drugs aimed to surmount some of these microenvironmental-influenced obstacles for efficacious drug delivery in chemotherapy. PMID:20417189

Cukierman, Edna; Khan, David R.



Novel Drug Delivery System Shows Early Promise for Treating Lupus in Mice  


... System Shows Early Promise for Treating Lupus in Mice A drug delivery system using nanoparticle technology that ... administered the MPA-loaded nanogel to lupus-prone mice that had not yet developed symptoms of the ...


Concept for a gas-cell-driven drug delivery system for therapeutic applications.  


This paper presents a concept for an implantable micro-pump based on hydrogen-generating gas cells. The gas-generating cell is separated from the drug reservoir by an expandable latex membrane. The system offers linear drug delivery with flowrates ranging from 8 nl/s to 2 microl/s and a total delivery volume of up to 160 ml. Drugs can be dispensed over a wide backpressure range. The device is scalable based on the size of the gas-producing cell and requires no external energy source. Possible fields of application include in vivo local drug delivery for chemotherapy, diabetes, and pain management. PMID:22320059

Becker, S; Xu, T; Ilchmann, F; Eisler, J; Wolf, B



Nanocapsules: The Weapons for Novel Drug Delivery Systems  

PubMed Central

Introduction Nanocapsules, existing in miniscule size, range from 10 nm to 1000 nm. They consist of a liquid/solid core in which the drug is placed into a cavity, which is surrounded by a distinctive polymer membrane made up of natural or synthetic polymers. They have attracted great interest, because of the protective coating, which are usually pyrophoric and easily oxidized and delay the release of active ingredients. Methods Various technical approaches are utilized for obtaining the nanocapsules; however, the methods of interfacial polymerization for monomer and the nano-deposition for preformed polymer are chiefly preferred. Most important characteristics in their preparation is particle size and size distribution which can be evaluated by using various techniques like X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolu¬tion transmission electron microscopy, X-ray photoelectron spectroscopy, superconducting quantum interference device, multi angle laser light scattering and other spectroscopic techniques. Results Nanocapsules possessing extremely high reproducibility have a broad range of life science applications. They may be applied in agrochemicals, genetic engineering, cosmetics, cleansing products, wastewater treatments, adhesive component applications, strategic delivery of the drug in tumors, nanocapsule bandages to fight infec¬tion, in radiotherapy and as liposomal nanocapsules in food science and agriculture. In addition, they can act as self-healing materials. Conclusion The enhanced delivery of bio¬active molecules through the targeted delivery by means of a nanocapsule opens numerous challenges and opportunities for the research and future development of novel improved therapies. PMID:23678444

Kothamasu, Pavankumar; Kanumur, Hemanth; Ravur, Niranjan; Maddu, Chiranjeevi; Parasuramrajam, Radhika; Thangavel, Sivakumar



Cell-Mediated Drugs Delivery  

PubMed Central

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

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



Silver nanoscale antisense drug delivery system for photoactivated gene silencing.  


The unique photophysical properties of noble metal nanoparticles contribute to their potential as photoactivated drug delivery vectors. Here we demonstrate the synthesis and characterization of 60-80 nm silver nanoparticles (SNPs) decorated with thiol-terminated photolabile DNA oligonucleotides. In vitro assays and fluorescent confocal microscopy of treated cell cultures show efficient UV-wavelength photoactivation of surface-tethered caged ISIS2302 antisense oligonucleotides possessing internal photocleavable linkers. As a demonstration of the advantages of these novel nanocarriers, we investigate properties including: enhanced stability to nucleases, increased hybridization activity upon photorelease, and efficient cellular uptake as compared to commercial transfection vectors. Their potential as multicomponent delivery agents for oligonucleotide therapeutics is shown through regulation of ICAM-1 (Intracellular Adhesion Molecule-1) silencing. Our results suggest a means to achieve light-triggered, spatiotemporally controlled gene silencing via nontoxic silver nanocarriers, which hold promise as tailorable platforms for nanomedicine, gene expression studies, and genetic therapies. PMID:23473419

Brown, Paige K; Qureshi, Ammar T; Moll, Alyson N; Hayes, Daniel J; Monroe, W Todd



Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina  

NASA Astrophysics Data System (ADS)

In this study, two cholesterol derivatives, (4-cholesterocarbonyl-4?-(N,N,N-triethylamine butyloxyl bromide) azobenzene (CAB) and 4-cholesterocarbonyl-4?-(N,N-diethylamine butyloxyl) azobenzene (ACB), one of which is positively charged while the other is neutral, were synthesized and incorporated with phospholipids and cholesterol to form doxorubicin (DOX)-loaded liposomes. PEGylation was achieved by including 1,2-distearoyl-sn-glycero-3-phosphatiylethanol-amine-N-[methoxy-(polyethylene glycol)-2000 (DSPE-PEG2000). Our results showed that PEGylated liposomes displayed significantly improved stability and the drug leakage was decreased compared to the non-PEGylated ones in vitro. The in vivo study with rats also revealed that the pharmacokinetics and circulation half-life of DOX were significantly improved when liposomes were PEGylated (p < 0.05). In particular, the neutral cholesterol derivative ACB played some role in improving liposomes’ stability in systemic circulation compared to the conventional PC liposome and the positively charged CAB liposome, with or without PEGylation. In addition, in the case of local drug delivery, the positively charged PEG-liposome not only delivered much more of the drug into the rats’ retinas (p < 0.001), but also maintained much longer drug retention time compared to the neutral PEGylated liposomes.

Geng, Shengyong; Yang, Bin; Wang, Guowu; Qin, Geng; Wada, Satoshi; Wang, Jin-Ye



Preparation and drug release mechanism of CTS-TAX-NP-MSCs drug delivery system.  


Targeting delivery of anticancer agents is a promising field in anticancer therapy. Inherent tumor-tropic and migratory properties of mesenchymal stem cells (MSCs) make them potential vehicles for targeting drug delivery systems for tumors. Although, MSCs have been successfully studied and discussed as a vehicle for cancer gene therapy, they have not yet been studied adequately as a potential vehicle for traditional chemical anticancer drugs. In this study, we have engineered MSCs as a potential targeting delivery vehicle for paclitaxel (TAX)-loaded nanoparticles (NPs). The size, surface charge, starving time of MSCs, incubating time and concentration of NPs could influence the efficiency of NPs uptake. In vitro release of TAX from CTS (chitosan)-TAX-NP-MSCs and the expression of P-glycoprotein demonstrated that release of TAX from MSCs might involve both passive diffusion and active transport. In vitro migration assays indicated that MSCs at passage number 3 have the highest migrating ability. Although, the migration ability of CTS-TAX-NP-MSCs could be inhibited by uptake of CTS-TAX-NPs, this ability could recover 6 days after the internalization. PMID:23933442

Dai, Tian; Yang, Enyun; Sun, Yongjun; Zhang, Linan; Zhang, Li; Shen, Ning; Li, Shuo; Liu, Lei; Xie, Yinghua; Wu, Shaomei; Gao, Zibin



Development of Bioadhesive Chitosan Superporous Hydrogel Composite Particles Based Intestinal Drug Delivery System  

PubMed Central

Bioadhesive superporous hydrogel composite (SPHC) particles were developed for an intestinal delivery of metoprolol succinate and characterized for density, porosity, swelling, morphology, and bioadhesion studies. Chitosan and HPMC were used as bioadhesive and release retardant polymers, respectively. A 32 full factorial design was applied to optimize the concentration of chitosan and HPMC. The drug loaded bioadhesive SPHC particles were filled in capsule, and the capsule was coated with cellulose acetate phthalate and evaluated for drug content, in vitro drug release, and stability studies. To ascertain the drug release kinetics, the drug release profiles were fitted for mathematical models. The prepared system remains bioadhesive up to eight hours in intestine and showed Hixson-Crowell release with anomalous nonfickian type of drug transport. The application of SPHC polymer particles as a biomaterial carrier opens a new insight into bioadhesive drug delivery system and could be a future platform for other molecules for intestinal delivery. PMID:23984380

Modhia, Ishan; Mehta, Anant; Patel, Rupal; Patel, Chhagan




E-print Network

SMART DRUG DELIVERY AND BIONANOTECHNOLOGY Nicholas A Peppas Center forBiomaterials, Drug Delivery for nanoscale structures in drug delivery. Uses such as carriers for controlled and targeted drug delivery materials [1]. We report on major new developments of recognitive drug delivery systems. Novel drug delivery

Peppas, Nicholas A.


Naltrexone: a review of existing sustained drug delivery systems and emerging nano-based systems.  


Narcotic antagonists such as naltrexone (NTX) have shown some efficiency in the treatment of both opiate addiction and alcohol dependence. A few review articles have focused on clinical findings and pharmacogenetics of NTX, advantages and limitations of sustained release systems as well as pharmacological studies of NTX depot formulations for the treatment of alcohol and opioid dependency. To date, three NTX implant systems have been developed and tested in humans. In this review, we summarize the latest clinical data on commercially available injectable and implantable NTX-sustained release systems and discuss their safety and tolerability aspects. Emphasis is also laid on recent developments in the area of nanodrug delivery such as NTX-loaded micelles and nanogels as well as related research avenues. Due to their ability to increase the therapeutic index and to improve the selectivity of drugs (targeted delivery), nanodrug delivery systems are considered as promising sustainable drug carriers for NTX in addressing opiate and alcohol dependence. PMID:24704710

Goonoo, Nowsheen; Bhaw-Luximon, Archana; Ujoodha, Reetesh; Jhugroo, Anil; Hulse, Gary K; Jhurry, Dhanjay



Drug delivery to the ear.  


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. PMID:23323784

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



Osmotic Drug Delivery System as a Part of Modified Release Dosage Form  

PubMed Central

Conventional drug delivery systems are known to provide an immediate release of drug, in which one can not control the release of the drug and can not maintain effective concentration at the target site for longer time. Controlled drug delivery systems offer spatial control over the drug release. Osmotic pumps are most promising systems for controlled drug delivery. These systems are used for both oral administration and implantation. Osmotic pumps consist of an inner core containing drug and osmogens, coated with a semipermeable membrane. As the core absorbs water, it expands in volume, which pushes the drug solution out through the delivery ports. Osmotic pumps release drug at a rate that is independent of the pH and hydrodynamics of the dissolution medium. The historical development of osmotic systems includes development of the Rose-Nelson pump, the Higuchi-Leeper pumps, the Alzet and Osmet systems, the elementary osmotic pump, and the push-pull system. Recent advances include development of the controlled porosity osmotic pump, and systems based on asymmetric membranes. This paper highlights the principle of osmosis, materials used for fabrication of pumps, types of pumps, advantages, disadvantages, and marketed products of this system. PMID:22852100

Keraliya, Rajesh A.; Patel, Chirag; Patel, Pranav; Keraliya, Vipul; Soni, Tejal G.; Patel, Rajnikant C.; Patel, M. M.



Near-infrared-controlled, targeted hydrophobic drug-delivery system for synergistic cancer therapy.  


Hydrophobicity has been an obstacle that hinders the use of many anticancer drugs. A critical challenge for cancer therapy concerns the limited availability of effective biocompatible delivery systems for most hydrophobic therapeutic anticancer drugs. In this study, we have developed a targeted near-infrared (NIR)-regulated hydrophobic drug-delivery platform based on gold nanorods incorporated within a mesoporous silica framework (AuMPs). Upon application of NIR light, the photothermal effect of the gold nanorods leads to a rapid rise in the local temperature, thus resulting in the release of the entrapped drug molecules. By integrating chemotherapy and photothermotherapy into one system, we have studied the therapeutic effects of camptothecin-loaded AuMP-polyethylene glycol-folic acid nanocarrier. Results revealed a synergistic effect in vitro and in vivo, which would make it possible to enhance the therapeutic effect of hydrophobic drugs and decrease drug side effects. Studies have shown the feasibility of using this nanocarrier as a targeted and noninvasive remote-controlled hydrophobic drug-delivery system with high spatial/temperal resolution. Owing to these advantages, we envision that this NIR-controlled, targeted drug-delivery method would promote the development of high-performance hydrophobic anticancer drug-delivery system in future clinical applications. PMID:23765904

Yang, Xinjian; Liu, Zhen; Li, Zhenhua; Pu, Fang; Ren, Jinsong; Qu, Xiaogang



A polyvalent aptamer system for targeted drug delivery.  


Poor efficacy and off-target systemic toxicity are major problems associated with current chemotherapeutic approaches to treat cancer. We developed a new form of polyvalent therapeutics that is composed of multiple aptamer units synthesized by rolling circle amplification and physically intercalated chemotherapy agents (termed as "Poly-Aptamer-Drug"). Using a leukemia cell-binding aptamer and doxorubicin as a model system, we have successfully constructed Poly-Aptamer-Drug systems and demonstrated that the Poly-Aptamer-Drug is significantly more effective than its monovalent counterpart in targeting and killing leukemia cells due to enhanced binding affinity (? 40 fold greater) and cell internalization via multivalent effects. We anticipate that our Poly-Aptamer-Drug approach will yield new classes of tunable therapeutics that can be utilized to effectively target and treat cancers while minimizing the side effects of chemotherapy. PMID:24044994

Zhang, Zhiqing; Ali, M Monsur; Eckert, Mark A; Kang, Dong-Ku; Chen, Yih Yang; Sender, Leonard S; Fruman, David A; Zhao, Weian



Design and simulation of an implantable medical drug delivery system using microelectromechanical systems technology  

Microsoft Academic Search

A unique design of an implantable micropump for medical drug delivery systems was proposed. The peristaltic pumping principle was selected. Three pump chambers are individually actuated by each bulk PZT (lead zirconate titanate) disk in a peristaltic motion. It is this peristaltic motion that propels the fluid. The design of the micropump includes inlet, three pump chambers, three silicon membranes,

Li Cao; Susan Mantell; Dennis Polla



Classification of stimuli-responsive polymers as anticancer drug delivery systems.  


Abstract Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed. PMID:24547737

Taghizadeh, Bita; Taranejoo, Shahrouz; Monemian, Seyed Ali; Salehi Moghaddam, Zoha; Daliri, Karim; Derakhshankhah, Hossein; Derakhshani, Zaynab



Nanoparticles as Drug Delivery Systems in Cancer Medicine: Emphasis on RNAi-Containing Nanoliposomes  

PubMed Central

Nanomedicine is a growing research field dealing with the creation and manipulation of materials at a nanometer scale for the better treatment, diagnosis and imaging of diseases. In cancer medicine, the use of nanoparticles as drug delivery systems has advanced the bioavailability, in vivo stability, intestinal absorption, solubility, sustained and targeted delivery, and therapeutic effectiveness of several anticancer agents. The expansion of novel nanoparticles for drug delivery is an exciting and challenging research filed, in particular for the delivery of emerging cancer therapies, including small interference RNA (siRNA) and microRNA (miRNAs)-based molecules. In this review, we focus on the currently available drug delivery systems for anticancer agents. In addition, we will discuss the promising use of nanoparticles for novel cancer treatment strategies. PMID:24287462

Rivera Díaz, Mónica; Vivas-Mejia, Pablo E.



Responsive polymeric delivery systems  

Microsoft Academic Search

This paper discusses the state of the art in a relatively new approach in the field of controlled drug delivery–responsive polymeric drug delivery systems. Such systems are capable of adjusting drug release rates in response to a physiological need. The fundamental principles of externally and self-regulated delivery systems are examined. Special attention is paid to specific clinical settings such as

Joseph Kost; Robert Langer



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

PubMed Central

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

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



75 FR 45640 - Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...  

Federal Register 2010, 2011, 2012, 2013, 2014

...Drug Delivery Systems; Availability AGENCY: Food and announcing the availability of a draft guidance...and development--as well as during manufacturing...FDA is announcing the availability of a draft guidance...and development--as well as during...



Topical Delivery of Aceclofenac: Challenges and Promises of Novel Drug Delivery Systems  

PubMed Central

Osteoarthritis (OA), a common musculoskeletal disorder, is projected to affect about 60 million people of total world population by 2020. The associated pain and disability impair the quality of life and also pose economic burden to the patient. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in OA, while diclofenac is the most prescribed one. Oral NSAIDs are not very patient friendly, as they cause various gastrointestinal adverse effects like bleeding, ulceration, and perforation. To enhance the tolerability of diclofenac and decrease the common side effects, aceclofenac (ACE) was developed by its chemical modification. As expected, ACE is more well-tolerated than diclofenac and possesses superior efficacy but is not completely devoid of the NSAID-tagged side effects. A series of chemical modifications of already planned drug is unjustified as it consumes quanta of time, efforts, and money, and this approach will also pose stringent regulatory challenges. Therefore, it is justified to deliver ACE employing tools of drug delivery and nanotechnology to refine its safety profile. The present review highlights the constraints related to the topical delivery of ACE and the various attempts made so far for the safe and effective topical delivery employing the novel materials and methods. PMID:25045671

Kumar, Manish; Kumar, Pramod; Malik, Ruchi; Sharma, Gajanand; Kaur, Manmeet; Katare, O. P.



Topical delivery of aceclofenac: challenges and promises of novel drug delivery systems.  


Osteoarthritis (OA), a common musculoskeletal disorder, is projected to affect about 60 million people of total world population by 2020. The associated pain and disability impair the quality of life and also pose economic burden to the patient. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in OA, while diclofenac is the most prescribed one. Oral NSAIDs are not very patient friendly, as they cause various gastrointestinal adverse effects like bleeding, ulceration, and perforation. To enhance the tolerability of diclofenac and decrease the common side effects, aceclofenac (ACE) was developed by its chemical modification. As expected, ACE is more well-tolerated than diclofenac and possesses superior efficacy but is not completely devoid of the NSAID-tagged side effects. A series of chemical modifications of already planned drug is unjustified as it consumes quanta of time, efforts, and money, and this approach will also pose stringent regulatory challenges. Therefore, it is justified to deliver ACE employing tools of drug delivery and nanotechnology to refine its safety profile. The present review highlights the constraints related to the topical delivery of ACE and the various attempts made so far for the safe and effective topical delivery employing the novel materials and methods. PMID:25045671

Raza, Kaisar; Kumar, Manish; Kumar, Pramod; Malik, Ruchi; Sharma, Gajanand; Kaur, Manmeet; Katare, O P



Controlled Release System for Localized and Sustained Drug Delivery Applications  

NASA Astrophysics Data System (ADS)

Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is possible to prepare biodegradable microparticles with a uniform size distribution and high drug loading efficiency. However, this could only be achieved with a hybrid system consisting of chitosan matrix interior and then exterior coating of PLGA or PLA. A two layer coating of PLGA 50:50 was shown to be optimal with sustainable controlled drug release for almost 5 days and with 91% of degradation (weight loss) in 8 weeks.

Rodriguez, Lidia Betsabe


An Engineering Approach to Biomedical Sciences: Advanced Strategies in Drug Delivery Systems Production  

PubMed Central

Development and optimization of novel production techniques for drug delivery systems are fundamental steps in the “from the bench to the bedside” process which is the base of translational medicine. In particular, in the current scenery where the need for reducing energy consumption, emissions, wastes and risks drives the development of sustainable processes, new pharmaceutical manufacturing does not constitute an exception. In this paper, concepts of process intensification are presented and their transposition in drug delivery systems production is discussed. Moreover, some examples on intensified techniques, for drug microencapsulation and granules drying, are reported. PMID:23905058

Barba, Anna Angela; Dalmoro, Annalisa; d’Amore, Matteo



Bioresponsive matrices in drug delivery  

PubMed Central

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



Calculation of Droplet Size and Formation Time in Electrohydrodynamic Based Pulsatile Drug Delivery System  

E-print Network

Electrohydrodynamic (EHD) generation, a commonly used method in BioMEMS, plays a significant role in the pulsed-release drug delivery system for a decade. In this paper, an EHD based drug delivery system is well designed, which can be used to generate a single drug droplet as small as 2.83 nL in 8.5 ms with a total device of 2x2x3 mm^3, and an external supplied voltage of 1500 V. Theoretically, we derive the expressions for the size and the formation time of a droplet generated by EHD method, while taking into account the drug supply rate, properties of liquid, gap between electrodes, nozzle size, and charged droplet neutralization. This work proves a repeatable, stable and controllable droplet generation and delivery system based on EHD method.

Zheng, Yi; Hu, Junqiang; Lin, Qiao



Advanced drug delivery to the lymphatic system: lipid-based nanoformulations  

PubMed Central

The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects uptake of drug into the lymphatic system. Two lipid-based nanoformulations, ie, solid lipid nanoparticles and nanostructured lipid carriers, have been administered via multiple routes (subcutaneous, pulmonary, and intestinal) for targeting of the lymphatic system. This paper provides a detailed review of novel lipid-based nanoformulations and their lymphatic delivery via different routes, as well as the in vivo and in vitro models used to study drug transport in the lymphatic system. Physicochemical properties that influence lymphatic delivery as well as the advantages of lipid-based nanoformulations for lymphatic delivery are also discussed. PMID:23926431

Khan, Arshad Ali; Mudassir, Jahanzeb; Mohtar, Noratiqah; Darwis, Yusrida



The application of carbon nanotubes in target drug delivery systems for cancer therapies  

PubMed Central

Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies. PMID:21995320




PubMed Central

Tuberculosis has claimed its victims throughout much of known human history and is currently the most devastating human bacterial disease. The ability to infect human population on a global scale, combined with the widespread emergence of multi-drug resistant strains, has led to the placement of Mycobacterium tuberculosis on the National Institute of Allergy and Infectious Diseases (NIAID) list of Biodefence and Emerging Infectious Disease Threats Agents. The resurgence of interest in tuberculosis (TB) has stemmed because of increased evidences from developed countries. Contrary to expectations, no country has reached the phase of elimination and in no subsection of society TB has been completely eliminated. A deeper understanding of the process will assist in the identification of the host and mycobacterial efforts involved and provide targets for therapeutic strategies against tuberculosis. The article presents a view on pathogenesis of tuberculosis and its diverse manifestations, host defense evasion, mechanisms of microbial persistence, emergence of Multiple Drug Resistance and Extensive Drug Resistance, conventional therapy used and the possible novel systems which are under extensive investigation as drug carriers for improving the cytosolic concentration of the anti-tubercular agents. PMID:22247841

Kaur, Kirtipal; Gupta, Anuj; Narang, R.K.; Murthy, R.S.R.



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


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. PMID:22734868

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



Modular reservoir concept for MEMS-based transdermal drug delivery systems  

NASA Astrophysics Data System (ADS)

While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management.

Cantwell, Cara T.; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P.



Polymers and formulation strategies of nanofibrous systems for drug delivery application and tissue engineering.  


During the last decade, the formulation of nanofibrous materials loaded with different drugs for biomedical applications has evoked considerable interest. The large specific surface area, the special micro- and macrostructure of fiber mats, the possibility for gradual release and site-specific local delivery of the active compounds lead to cytotoxicity decrease and enhancement of the therapeutic effect of drugs and implants. The present review details the different spinning techniques applied for the design of micro- and nanofibrous drug delivery systems. It furthermore deals with the use of various polymers that are capable for the formation of fiber scaffolds of various biomedical applications. PMID:25386827

Sebe, I; Kallai-Szabo, B; Zelko, R; Szabo, D



Formulation Development and Bioavailability Evaluation of a Self-Nanoemulsified Drug Delivery System of Oleanolic Acid  

Microsoft Academic Search

This study aims to formulate and evaluate bioavailability of a self-nanoemulsified drug delivery system (SNEDDS) of a poorly\\u000a water-soluble herbal active component oleanolic acid (OA) for oral delivery. Solubility of OA under different systems was\\u000a determined for excipient selection purpose. Four formulations, where OA was fixed at the concentration of 20 mg\\/g, were prepared\\u000a utilizing Sefsol 218 as oil phase, Cremophor

Jia Xi; Qi Chang; Chak K. Chan; Zhao Yu Meng; Geng Nan Wang; Jia Bei Sun; Yi Tao Wang; Henry H. Y. Tong; Ying Zheng



A gastroretentive drug delivery system of lisinopril imbibed on isabgol-husk.  


The gastroretentive drug delivery system is site-specific and allows the drug to remain in the stomach for a prolonged period of time so that it can be released in a controlled manner in gastrointestinal tract. The present study was carried out to develop a gastroretentive drug delivery system using isabgol as an excipient to prolong the residence time of the model drug lisinopril in the stomach. The gastroretentive ability of isabgol was increased by addition of NaHCO3 as a gas-generating agent while its mucoadhesive property was enhanced by incorporation of HPMC-K4M. The drug, NaHCO3 and HPMC-K3M were imbibed on isabgol-husk as per entrapment efficiency of the isabgol-husk. After drying, the product was filled in a hard gelatin capsule and evaluated for its buoyancy, mucoadhesive properties, swelling index and in vitro drug release. The lisinopril released through isabgol was delayed by 12 hours when compared to a preparation available on the market which released the complete drug in 0.5 hours. The drug release study of lisinopril from the formulation follows first order kinetics using a diffusion controlled mechanism. The results from the present study revealed that isabgol can be used as a potential excipient for the formulation of gastroretentive drug delivery systems in the near future. PMID:24144200

Semwal, Ravindra; Semwal, Ruchi Badoni; Semwal, Deepak Kumar



Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review  

PubMed Central

Calcium phosphates (CaPs) are the most widely used bone substitutes in bone tissue engineering due to their compositional similarities to bone mineral and excellent biocompatibility. In recent years, CaPs, especially hydroxyapatite and tricalcium phosphate, have attracted significant interest in simultaneous use as bone substitute and drug delivery vehicle, adding a new dimension to their application. CaPs are more biocompatible than many other ceramic and inorganic nanoparticles. Their biocompatibility and variable stoichiometry, thus surface charge density, functionality, and dissolution properties, make them suitable for both drug and growth factor delivery. CaP matrices and scaffolds have been reported to act as delivery vehicles for growth factors and drugs in bone tissue engineering. Local drug delivery in musculoskeletal disorder treatments can address some of the critical issues more effectively and efficiently than the systemic delivery. CaPs are used as coatings on metallic implants, CaP cements, and custom designed scaffolds to treat musculoskeletal disorders. This review highlights some of the current drug and growth factor delivery approaches and critical issues using CaP particles, coatings, cements, and scaffolds towards orthopedic and dental applications. PMID:22127225

Bose, Susmita; Tarafder, Solaiman



Electrospun zein/eudragit nanofibers based dual drug delivery system for the simultaneous delivery of aceclofenac and pantoprazole.  


Electrospun composite zein/eudragit nanofibers were developed with an aim to deliver two different classes of drugs simultaneously that would restrict/compensate the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs). Co-administration of proton pump inhibitors is beneficial for patients consuming NSAIDs for treating chronic ailments like arthritis. In this study, aceclofenac/pantoprazole loaded zein/eudragit S 100 nanofibers were developed using a single nozzle electrospinning process. The morphological analysis revealed the uniform and smooth surface of the drug loaded nanofibers. The physico-thermal characterization of nanofibers depicted the molecular integration of the drugs with the polymers and also confirmed that the drugs were evenly distributed in the nanofibers in an amorphous state. In vitro release studies ensure the efficiency of the developed fibers in sustaining the release of both the drugs up to 8h. In vivo animal experiments further confirmed that the co-administration of pantoprazole along with aceclofenac reduced the gastro-intestinal toxicity induced by NSAIDs. The histological evaluation revealed the preserved mucosal architecture of rat gastric tissue treated with drug loaded composite nanofibers. Thus, dual drug delivery system comprising polymers with different release characteristics has been successfully developed and further, oral delivery of aceclofenac with reduced side effects was achieved. PMID:22960320

Karthikeyan, K; Guhathakarta, Soma; Rajaram, Rama; Korrapati, Purna Sai



Alginate drug delivery systems: application in context of pharmaceutical and biomedical research.  


Alginates are natural polymers widely used in the food industry because of their biocompatible, biodegradable character, nontoxicity and easy availability. The bioadhesive character of alginates makes them useful in the pharmaceutical industry as well. The application areas of sodium alginate-based drug delivery systems are many and these systems can be formulated as gels, matrices, membranes, nanospheres, microspheres, etc. Worldwide researchers are exploring possible applications of alginates as coating material, preparation of controlled-release drug delivery systems such as microspheres, beads, pellets, gels, fibers, membranes, etc. In the present review, such applications of alginates are discussed. PMID:25109399

Jain, Dharmendra; Bar-Shalom, Daniel



Implications of nanoscale based drug delivery systems in delivery and targeting tubulin binding agent, noscapine in cancer cells.  


Noscapine, a tubulin binding anticancer agent undergoing Phase I/II clinical trials, inhibits tumor growth in nude mice bearing human xenografts of breast, lung, ovarian, brain, and prostrate origin. The analogues of noscapine like 9-bromonoscapine (EM011) are 5 to 10-fold more active than parent compound, noscapine. Noscapinoids inhibit the proliferation of cancer cells that are resistant to paclitaxel and epothilone. Noscapine also potentiated the anticancer activity of doxorubicin in a synergistic manner against triple negative breast cancer (TNBC). However, physicochemical and pharmacokinetic (ED50˜300-600 mg/kg bodyweight) limitations of noscapine present hurdle in development of commercial anticancer formulations. Therefore, objectives of the present review are to summarize the chemotherapeutic potential of noscapine and implications of nanoscale based drug delivery systems in enhancing the therapeutic efficacy of noscapine in cancer cells. We have constructed noscapine-enveloped gelatin nanoparticles, NPs and poly (ethylene glycol) grafted gelatin NPs as well as inclusion complex of noscapine in ?-cyclodextrin (?-CD) and evaluated their physicochemical characteristics. The Fe3O4 NPs were also used to incorporate noscapine in its polymeric nanomatrix system where molecular weight of the polymer governed the encapsulation efficiency of drug. The enhanced noscapine delivery using ?PAR-targeted optical-MR imaging trackable NPs offer a great potential for image directed targeted delivery of noscapine. Human Serum Albumin NPs (150-300 nm) as efficient noscapine drug delivery systems have also been developed for potential use in breast cancer. PMID:22571485

Chandra, Ramesh; Madan, Jitender; Singh, Prashant; Chandra, Ankush; Kumar, Pradeep; Tomar, Vartika; Dass, Sujata K



Biodegradable polymers and their potential use in parenteral veterinary drug delivery systems.  


Biodegradable polymers have been extensively studied for numerous drug delivery systems for human health purposes. The ever-increasing value of animals to human society allows the application of pharmaceutical developments in the veterinary field from those developed in human medicine. Although many similarities between the human and animal health industries exist there are also notable differences. This paper provides an insight into the animal health market with regard to the challenges and special considerations associated with veterinary drug delivery. It also gives an overview of biodegradable polymers that are used or have been tested in the veterinary field. The purpose of this paper is to highlight some recent developments in this area and to investigate the directions in which veterinary pharmaceutics is heading. In particular, examples of existing biodegradable veterinary drug delivery systems are presented together with applications including intravaginal devices, injectables and implantable systems. PMID:15191792

Winzenburg, Gesine; Schmidt, Carsten; Fuchs, Stefan; Kissel, Thomas



Development of Mesophasic Microreservoir-Based Transdermal Drug Delivery System of Propranolol  

PubMed Central

The mesophasic microreservoir comprises lyotrophic liquid crystals. The liquid crystals were prepared of Brij-35, cetosteryl alcohol and propranolol and evaluated for parameters viz. anisotropy, size and size distribution and drug entrapment efficiency. Subsequent to this liquid crystals based transdermal drug delivery system (TDS) was prepared by incorporating liquid crystals in previously prepared matrix based transdermal patch and evaluated for stability studies like temperature, humidity and aging. The system was also studied for tensile strength, moisture content, water vapor transmission, drug content, anisotropy and In vitro drug release studies. PMID:21394252

Omray, L. K.; Kohli, S.; Khopade, A. J.; Patil, S.; Gajbhiye, Asmita; Agrawal, G. P.



Expansile Nanoparticles: Synthesis, Characterization, and in Vivo Efficacy of an Acid-Responsive Polymeric Drug Delivery System  

E-print Network

-Responsive Polymeric Drug Delivery System Aaron P. Griset, Joseph Walpole, Rong Liu, Ann Gaffey, Yolonda L. Colson are being employed for an increasing number of medical applications. In terms of drug delivery applica- tions, these particles are being investigated as a means to increase drug solubility, alter


Chitosan superporous hydrogel composite-based floating drug delivery system: A newer formulation approach  

PubMed Central

Objective: In this study efforts have been made to design a drug delivery system based on a superporous hydrogel composite, for floating and sustained delivery of Ranitidine hydrochloride. Materials and Methods: The characterization studies were performed by the measurement of apparent density, porosity, swelling studies, mechanical strength studies, and scanning electron microscopy studies. The prepared formulation was evaluated for buoyant behavior, in vitro drug release, kinetics of drug release, and stability. The release profile of Ranitidine hydrochloride was investigated by changing the release retardant polymer in the formulation. To ascertain the kinetics of drug release, the drug release profiles were fitted to mathematical models that included zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas, Weibull, and Hopfenberg models. Results: Scanning electron microscopy images clearly indicated the formation of interconnected pores and capillary channels, and cross-linked Chitosan molecules were observed around the peripheries of the pores. The prepared drug delivery system floated and delivered the Ranitidine hydrochloride for about 17 hours. The in vitro drug release from the proposed system was best explained by the Korsmeyer-Peppas model. The values of the diffusion exponent in the Korsmeyer-Peppas model ranged between 0.47 ± 0.02 and 0.66 ± 0.02, which appeared to indicate a coupling of the diffusion and erosion mechanisms, anomalous non-Fickian transport. Conclusion: It was concluded that the proposed floating drug delivery system, based on the superporous hydrogel composite containing Chitosan as a composite material, is promising for stomach-specific delivery of Ranitidine hydrochloride. PMID:21814446

Chavda, Hitesh; Patel, Chhaganbhai



Towards multifunctional, targeted drug delivery systems using mesoporous silica nanoparticles - opportunities & challenges  

NASA Astrophysics Data System (ADS)

One of the big challenges of medicine today is to deliver drugs specifically to defected cells. Nanoparticulate drug carriers have the potential to answer to this call, as nanoparticles can cross physiological barriers and access different tissues, and also be provided in a targetable form aimed at enhancing cell specificity of the carrier. Recent developments within material science and strong collaborative efforts crossing disciplinary borders have highlighted the potential of mesoporous silica nanoparticles (MSNs) for such targeted drug delivery. Here we outline recent advances which in this sense push MSNs to the forefront of drug delivery development. Relatively straightforward inside-out tuning of the vehicles, high flexibility, and potential for sophisticated release mechanisms make these nanostructures promising candidates for targeted drug delivery such as `smart' cancer therapies. Moreover, due to the large surface area and the controllable surface functionality of MSNs, they can be controllably loaded with large amounts of drugs and coupled to homing molecules to facilitate active targeting, simultaneously carrying traceable (fluorescent or magnetically active) modalities, also making them highly interesting as theragnostic agents. However, the increased relative surface area and small size, and flexible surface functionalization which is beneficially exploited in nanomedicine, consequently also includes potential risks in their interactions with biological systems. Therefore, we also discuss some safety issues regarding MSNs and highlight how different features of the drug delivery platform influence their behaviour in a biological setting. Addressing these burning questions will facilitate the application of MSNs in nanomedicine.

Rosenholm, Jessica M.; Sahlgren, Cecilia; Lindén, Mika



Formulation, Evaluation and Optimization of Pectin- Bora Rice Beads for Colon Targeted Drug Delivery System  

PubMed Central

Purpose: The purpose of this research was to established new polysaccharide for the colon targeted drug delivery system, its formulation and in vitro and in vivo evaluation. Methods: Microspheres containing pectin and bora rice were prepared by ionotropic gelation technique using zinc acetate as cross linking agent and model drug used was glipizide. A 32 full factorial design was employed to study the effect of independent variables, polymer to drug ratio (A), and concentration of cross linking agent (B) on dependent variables, particle size, swelling index, drug entrapment efficiency and percentage drug release. Results: Results of trial batches indicated that polymer to drug ratio and concentration of cross linking agent affects characteristics of beads. Beads were discrete, spherical and free flowing. Beads exhibited small particle size and showed higher percentage of drug entrapment efficiency. The optimized batch P2 exhibited satisfactory drug entrapment efficiency 68% and drug release was also controlled for more than 24 hours. The polymer to drug ratio had a more significant effect on the dependent variables. In vivo gamma scintigraphy study of optimized pectin-bora rice beads demonstrated degradation of beads whenever they reached to the colon. Conclusion: Bora rice is potential polysaccharide for colon targeted drug delivery system. PMID:24511481

Ramteke, Kuldeep Hemraj; Nath, Lilakant



Design and Evaluation of a Novel Matrix Type Multiple Units as Biphasic Gastroretentive Drug Delivery Systems  

Microsoft Academic Search

A biphasic gastroretentive floating drug delivery system with multiple-unit mini-tablets based on gas formation technique\\u000a was developed to maintain constant plasma level of a drug concentration within the therapeutic window. The system consists\\u000a of loading dose as uncoated core units, and prolonged-release core units are prepared by direct compression process; the latter\\u000a were coated with three successive layers, one of

Meka Lingam; Thadisetty Ashok; Vobalaboina Venkateswarlu; Yamsani Madhusudan Rao



Heterostructured layered aluminosilicate-itraconazole nanohybrid for drug delivery system.  


A nanohybrid, consisting of layered aluminosilicate as a host material and itraconazole as a guest molecule, was successfully synthesized through the interfacial intercalation reaction across the boundary between water and water-immiscible liquid at the various pH. According to the powder X-ray diffraction pattern, the basal spacing of the intraconazole-layered aluminosilicate nanohybrid increased from 14.7 to 22.7 A depending on the pH of the aqueous suspension. The total amounts of itraconazole in the hybrids were determined to be 2.3-25.4 wt% by HPLC analysis. The in vivo pharmacokinetics study was performed in rats in order to compare the absorptions of itraconazole for the itraconazole-layered aluminosilicate nanohybrid and a commercial product, Sporanox. The pharmacokinetic data for the nanohybrid and Sporanox showed that the mean area under the plasma concentration-time curve (AUC, 2477 +/- 898 ng x hr/mL and 2630 +/- 953 ng x hr/mL, respectively) and maximum concentration (Cmax, 225.4 +/- 77.4 ng x hr/mL and 223.6 +/- 51.9 ng x hr/mL, respectively), were within the bioequivalence (BE) range. Therefore, we concluded that this drug-layered aluminosilicate nanohybrid system has a great potential for its application in formulation of poorly soluble drugs. PMID:24245252

Yang, Jae-Hun; Jung, Hyun; Kim, Su Yeon; Yo, Chul Hyun; Choy, Jin-Ho



Bioactive electrospun fish sarcoplasmic proteins as a drug delivery system.  


Nano-microfibers were made from cod (Gadus morhua) sarcoplasmic proteins (FSP) (Mw<200kDa) using the electrospinning technique. The FSP fibers were studied by scanning electron microscopy, and the fiber morphology was found to be strongly dependent on FSP concentration. Interestingly, the FSP fibers were insoluble in water. However, when exposed to proteolytic enzymes, the fibers were degraded. The degradation products of the FSP fibers proved to be inhibitors of the diabetes-related enzyme DPP-IV. The FSP fibers may have biomedical applications, among others as a delivery system. To demonstrate this, a dipeptide (Ala-Trp) was encapsulated into the FSP fibers, and the release properties were investigated in gastric buffer and in intestinal buffer. The release profile showed an initial burst release, where 30% of the compound was released within the first minute, after which an additional 40% was released (still exponential) within the next 30min (gastric buffer) or 15min (intestinal buffer). The remaining 30% was not released in the timespan of the experiment. PMID:25033436

Stephansen, Karen; Chronakis, Ioannis S; Jessen, Flemming



Oleic acid based heterolipid synthesis, characterization and application in self-microemulsifying drug delivery system.  


There is increasing demand for lipids owing to their use in formulating lipid based drug delivery systems of poorly soluble drugs. The present work discusses the synthesis, characterization of oleic acid based heterolipid and its use as oil in the development of self-microemulsifying drug delivery system (SMEDDS) for parenteral delivery. Synthesis was carried out by Michael addition of tert-butyl acrylate to 3-amino-1-propanol to obtain di-tert-butyl aminopropanol derivative. Reaction of this di-tert-butyl aminopropanol derivative with oleoyl chloride using p-dimethylaminopyridine as a coupling agent gave the desired heterolipid. It was characterized by (1)H NMR, (13)C NMR and MS to confirm the structure. It did not exhibit any measurable cytotoxicity, even up to 80?g/ml concentration. Application in parenteral drug delivery was explored using furosemide (FUR), a BCS class IV drug, as a model. FUR showed three times greater solubility in the heterolipid as compared to oleic acid. SMEDDSs were developed using heterolipid as oily phase, Solutol HS 15(®) as surfactant and ethanol as a co-surfactant. Developed SMEDDS could form spontaneous microemulsion on addition to various aqueous phases with mean globule size <70nm without any phase separation or drug precipitation even after 24h, and exhibited negligible hemolytic potential. PMID:22266534

Kalhapure, Rahul S; Akamanchi, Krishnacharya G



An Implantable MEMS Micropump System for Drug Delivery in Small Animals  

PubMed Central

We present the first implantable drug delivery system for controlled dosing, timing, and location in small animals. Current implantable drug delivery devices do not provide control over these factors or are not feasible for implantation in research animals as small as mice. Our system utilizes an integrated electrolysis micropump, is refillable, has an inert drug reservoir for broad drug compatibility, and is capable of adjustment to the delivery regimen while implanted. Electrochemical impedance spectroscopy (EIS) was used for characterization of electrodes on glass substrate and a flexible Parylene substrate. Benchtop testing of the electrolysis actuator resulted in flow rates from 1 to 34 ?L/min on glass substrate and up to 6.8 ?L/min on Parylene substrate. The fully integrated system generated a flow rate of 4.72 ± 0.35 ?L/min under applied constant current of 1.0 mA while maintaining a power consumption of only ~3 mW. Finally, we demonstrated in vivo application of the system for anti-cancer drug delivery in mice. PMID:22273985

Gensler, Heidi; Sheybani, Roya; Li, Po-Ying; Lo, Ronalee; Meng, Ellis



Drug delivery Combinatorial Drug Conjugation Enables Nanoparticle  

E-print Network

Drug delivery Combinatorial Drug Conjugation Enables Nanoparticle Dual-Drug Delivery Santosh Aryal, Che-Ming Jack Hu, and Liangfang Zhang* A new approach to loading multiple drugs onto the same drug through hydrolyzable linkers to form drug conjugates, is reported. In contrast to loading individual types

Zhang, Liangfang


Reversal of multidrug resistance by stimuli-responsive drug delivery systems for therapy of tumor.  


Multidrug resistance (MDR) is a major obstacle to successful cancer therapy, especially for chemotherapy. The new drug delivery system (DDS) provides promising approaches to reverse MDR, for which the poor cellular uptake and insufficient intracellular drug release remain rate-limiting steps for reaching the drug concentration level within the therapeutic window. Stimulus-coupled drug delivery can control the drug-releasing pattern temporally and spatially, and improve the accumulation of chemotherapeutic agents at targeting sites. In this review, the applications of DDS which is responsive to different types of stimuli in MDR cancer therapy is introduced, and the design, construction, stimuli-sensitivity and the effect to reverse MDR of the stimuli-responsive DDS are discussed. PMID:23611952

Yin, Qi; Shen, Jianan; Zhang, Zhiwen; Yu, Haijun; Li, Yaping



Drug Formulation / Drug Delivery Raj Suryanarayanan (Sury)  

E-print Network

Drug Formulation / Drug Delivery Raj Suryanarayanan (Sury) Department of Pharmaceutics College)Physical Pharmaceutics (Materials Science) Suryanarayanan, Sun Drug Delivery K di ll P bh P Si l Wi dKandimalla, Prabha, Panyam, Siegel, Wiedmann 2 #12;#12;Center for Translational Drug Delivery Developing

Blanchette, Robert A.


Chitosan-alginate composites blended with cloisite 30B as a novel drug delivery system for anticancer drug paclitaxel  

Microsoft Academic Search

In the present research program, polymer composites have been used as the drug carrier for delivery system of anticancer drug\\u000a Paclitaxel. Chitosan (CS) and sodium alginate (ALG) with different ratios were blended with different wt% of montmorillonite\\u000a (MMT) (Cloisite 30B) solution by solvent evaporation method. MMT was incorporated in the formulation as a matrix material\\u000a component which also plays the

P. L. Nayak; Debasish Sahoo


Optimal periodic control of a drug delivery system Subbarao Varigonda 1  

E-print Network

, Ronald A. Siegel 3 , Prodromos Daoutidis 4 Abstract Administration of certain drugs at a steady rate on the spatiotemporal pattern of drug administration, or drug delivery. With proper design, dosage forms can is a function of present drug concentration in the blood. For such drugs constant rate, or zero-order delivery

Georgiou, Tryphon T.


Development of Drug Delivery Systems Based on Layered Hydroxides for Nanomedicine  

PubMed Central

Layered hydroxides (LHs) have recently fascinated researchers due to their wide application in various fields. These inorganic nanoparticles, with excellent features as nanocarriers in drug delivery systems, have the potential to play an important role in healthcare. Owing to their outstanding ion-exchange capacity, many organic pharmaceutical drugs have been intercalated into the interlayer galleries of LHs and, consequently, novel nanodrugs or smart drugs may revolutionize in the treatment of diseases. Layered hydroxides, as green nanoreservoirs with sustained drug release and cell targeting properties hold great promise of improving health and prolonging life. PMID:24802876

Barahuie, Farahnaz; Hussein, Mohd Zobir; Fakurazi, Sharida; Zainal, Zulkarnain



Pharmaceutically active ionic liquid self-assembled vesicles for the application as an efficient drug delivery system.  


Shuttle-drug: Self-assembled vesicles of a pharmaceutically active ionic liquid are shown to be an efficient drug delivery system, which realizes the controlled release of its pharmaceutically active component directly. PMID:24038920

Zhang, Longlong; Liu, Jing; Tian, Tingting; Gao, Ya; Ji, Xiaoqing; Li, Zhonghao; Luan, Yuxia



Development and evaluation of diclofenac sodium thermorevesible subcutaneous drug delivery system.  


The objective of current work was to develop and evaluate thermoreversible subcutaneous drug delivery system for diclofenac sodium. The poloxamer 407, methyl cellulose, hydroxypropyl methyl cellulose and polyethylene glycol were used alone and in combination in different ratios to design the delivery system. The physical properties like Tsol-gel, viscosity, clarity of solution and gel were evaluated. The in vitro release of the drug delivery system was evaluated using membrane less method and the drug release kinetics and mechanism was predicted by applying various mathematical models to the in vitro dissolution data. Rabbits were used as in vivo model following subcutaneous injection to predict various pharmacokinetics parameters by applying Pk-Summit software. The in vitro and in vivo data revealed that the system consisting of the poloxamer 407 in concentration of 20% (DP20) was the most capable formulation for extending the drug release and maintaining therapeutic blood level of DS for longer duration (144 h). The data obtained for drug content after autoclaving the solutions indicate that autoclaving results in 6% degradation of DS. The data also suggested that the studied polymers poloxamer, MC and PG are good candidate to extend the drug release possessing a unique thermoreversible property. PMID:23084951

Nasir, Fazli; Iqbal, Zafar; Khan, Jamshaid A; Khan, Abad; Khuda, Fazli; Ahmad, Lateef; Khan, Amirzada; Khan, Abbas; Dayoo, Abdullah; Roohullah



Intraarterial chemotherapy for head and neck cancer, Part 1: Theoretical considerations and drug delivery systems.  


The principal objective of regional chemotherapy is tumor cell kill. The rationale for regional delivery is based on the steep dose/response curve exhibited by most antineoplastic agents. Intraarterial (IA) chemotherapy has the potential advantage of increased drug concentration at the tumor site, decreased systemic drug levels, and continuous tumor cell exposure to an antineoplastic agent. Despite these advantages, the use of IA chemotherapy has not been universally accepted. This is in part due to the difficulties associated with establishing and maintaining arterial access. Considerable improvement in the techniques and efficacy of regional therapy for head and neck cancer will be necessary before there is widespread clinical acceptance. These improvements must be based on anatomic and pharmacologic factors that ensure success of regional therapy. In addition, the development of safe, reliable delivery systems will be necessary. Part 1 of this two-part article will review these factors and discuss delivery systems. PMID:6358134

Baker, S R; Wheeler, R



Design and in vitro evaluation of multiparticulate floating drug delivery system of zolpidem tartarate  

Microsoft Academic Search

Zolpidem tartarate is a non-benzodiazepine, sedative-hypnotic, which finds its major use in various types of insomnia. The present work relates to development of multiparticulate floating drug delivery system based on gas generation technique to prolong the gastric residence time and to increase the overall bioavailability. Modified release dosage form of zolpidem tartarate adapted to release over a predetermined time period,

P. P. Amrutkar; P. D. Chaudhari; S. B. Patil


Heparin drug delivery system for prevention of posterior capsular opacification in rabbit eyes  

Microsoft Academic Search

Background. The aim of this study was to investigate the safety and efficacy of a heparin drug delivery system (HEP DDS) for prevention of posterior capsular opacification (PCO) in rabbits. Methods. Fifty New Zealand albino rabbits (50 eyes) undergoing phacoemulsification were equally divided into five groups receiving normal saline eye drops (group A), a carrier DDS implanted into the posterior

Lixin Xie; Jie Sun; Zhan Yao



A luminescent nanoporous hybrid material based drug delivery system showing excellent theranostics potential for cancer.  


A novel hybrid nanoporous material (LNH-1) bearing a tris(propyliminomethyl)-phloroglucinol fluorescent moiety in the framework has been designed and administration of an LNH-1 based drug delivery system containing doxorubicin to cancer cells showed inhibition of proliferation, suggesting its future potential theranostics application in cancer. PMID:23872783

Modak, Arindam; Barui, Ayan Kumar; Patra, Chitta Ranjan; Bhaumik, Asim



Recent developments in drug delivery.  


Some recent innovative approaches to drug delivery have demonstrated that the administration of drugs can be more rigidly controlled with respect to the rate and amount of drug delivered to sites of action than from the conventional dosage forms. One category of controlled release referred to as programmed drug delivery primarily involves the application of polymers of defined specifications to release agents from either non-bioerodible membrane-controlled systems or bioerodible and non-bioerodible matrices. Also included here are the pro-drugs, inactive derivatives of drugs which are transformed into the active form in vivo but possess improved solubility, stability and disposition properties, yielding more efficient action and fewer side effects. Thus, exploitation of several routes of administration have resulted in products which are inserted ophtalmically, rectally or vaginally, implanted subcutaneously, taken orally or applied topically to achieve transdermal delivery of drugs to the systemic circulation. In several cases, release is designed to follow zero-order kinetics to achieve control of therapeutic plasma concentrations for prolonged time periods. Targeting of drugs by carrier is another form of controlled release technology. Normally administered intravenously, carriers such as liposomes, nanoparticles, microspheres, human cells and linear macromolecules are finding application in treating disease states with drugs which previously were unavailable to treatment. PMID:10262189

Rogers, J A



Influence of systemic administration of atelocollagen on mouse livers: an ideal biomaterial for systemic drug delivery.  


Atelocollagen (AC), a biomaterial with low antigenicity and high bioaffinity, has been widely used in implantable materials in clinical practice. Preclinical studies have demonstrated that AC is a potential drug carrier for local and systemic delivery of cytokines, growth factors, plasmid DNA, small interfering RNA, and microRNA. AC is also believed to have low systemic toxicity on the basis of the safety of implant usage; however, this is not enough determined. Therefore, we performed whole genome expression profiling in mouse liver after systemic administration of AC or the cationic liposome carrier DOTAP/cholesterol (LP) and compared the changes of gene expressions associated with hepatotoxicity. Microarray analysis revealed that systemic LP administration significantly increased expression of toxicity-related genes, i.e., those for lipocalin-2, cyclin-dependent kinase inhibitor 1A, serum amyloid A isoforms, chemokine ligands, and granzyme B. Alternatively, AC administration did not alter the expression of any of these genes. Further gene ontology (GO) enrichment analysis highlighted the characteristic annotations extracted from genes upregulated after LP administration, and most of them were related to toxicity annotations such as immune response, inflammatory response, and apoptosis induction. In contrast, GO enrichment analysis of genes induced after AC administration revealed that only three annotations, all of which were unrelated to toxicity. These findings indicate that AC is potentially far less hepatotoxic than LP after systemic administration, suggesting that AC may be an excellent biomaterial for nontoxic drug delivery system carriers. PMID:22129739

Ogawa, Shingo; Onodera, Jun; Honda, Rika; Fujimoto, Ichiro



Influence of lipid composition and drug load on the In Vitro performance of self-nanoemulsifying drug delivery systems.  


The influence of lipid composition and drug load on the in vitro performance of lipid-based drug delivery systems was investigated during dispersion and in vitro lipolysis of two self-nanoemulsifying drug delivery systems (SNEDDS). SNEDDS preconcentrates consisted of the same mass ratios of lipid, surfactant, and cosolvent but varied in the chain length of the lipid component. Utilization of the surfactant Cremophor EL resulted in pronounced changes in the droplet size of dispersed SNEDDS containing increasing drug loads of the poorly water-soluble compound simvastatin (SIM). In contrast, the droplet size of dispersed medium-chain (MC)-SNEDDS based on the surfactant Cremophor RH40 was not affected by increasing drug loads of SIM, whereas the droplet size of the corresponding long-chain (LC)-SNEDDS increased. During 60?min in vitro lipolysis, MC-SNEDDS maintained approximately 95% of SIM in solution, independent of the drug load. At the start of lipolysis of LC-SNEDDS, up to 34% of the drug precipitated. However, the initial precipitate dissolved in the lipolysis medium 30 min after start of in vitro lipolysis. The study suggests that drug load and lipid composition should be considered for the design of SNEDDS. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1721-1731, 2012. PMID:22294458

Thomas, Nicky; Müllertz, Anette; Graf, Anja; Rades, Thomas



Capillary Physiology and Drug Delivery in Central  

E-print Network

Capillary Physiology and Drug Delivery in Central Nervous System Lymphomas Peter C. Warnke, MD,1 drug delivery, we quantita- tively assessed pharmacokinetic factors in seven patients. The capillary the chemosensitivity of primary cen- tral nervous system lymphomas to water-soluble drugs could result from improved

Timmer, Jens


Advanced drug and gene delivery systems based on functional biodegradable polycarbonates and copolymers.  


Biodegradable polymeric nanocarriers are one of the most promising systems for targeted and controlled drug and gene delivery. They have shown several unique advantages such as excellent biocompatibility, prolonged circulation time, passive tumor targeting via the enhanced permeability and retention (EPR) effect, and degradation in vivo into nontoxic products after completing their tasks. The current biodegradable drug and gene delivery systems exhibit, however, typically low in vivo therapeutic efficacy, due to issues of low loading capacity, inadequate in vivo stability, premature cargo release, poor uptake by target cells, and slow release of therapeutics inside tumor cells. To overcome these problems, a variety of advanced drug and gene delivery systems has recently been designed and developed based on functional biodegradable polycarbonates and copolymers. Notably, polycarbonates and copolymers with diverse functionalities such as hydroxyl, carboxyl, amine, alkene, alkyne, halogen, azido, acryloyl, vinyl sulfone, pyridyldisulfide, and saccharide, could be readily obtained by controlled ring-opening polymerization. In this paper, we give an overview on design concepts and recent developments of functional polycarbonate-based nanocarriers including stimuli-sensitive, photo-crosslinkable, or active targeting polymeric micelles, polymersomes and polyplexes for enhanced drug and gene delivery in vitro and in vivo. These multifunctional biodegradable nanosystems might be eventually developed for safe and efficient cancer chemotherapy and gene therapy. PMID:24858708

Chen, Wei; Meng, Fenghua; Cheng, Ru; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan



The role of multiscale computational approaches for rational design of conventional and nanoparticle oral drug delivery systems  

PubMed Central

Multiscale computational modeling of drug delivery systems (DDS) is poised to provide predictive capabilities for the rational design of targeted drug delivery systems, including multi-functional nanoparticles. Realistic, mechanistic models can provide a framework for understanding the fundamental physico-chemical interactions between drug, delivery system, and patient. Multiscale computational modeling, however, is in its infancy even for conventional drug delivery. The wide range of emerging nanotechnology systems for targeted delivery further increases the need for reliable in silico predictions. This review will present existing computational approaches at different scales in the design of traditional oral drug delivery systems. Subsequently, a multiscale framework for integrating continuum, stochastic, and computational chemistry models will be proposed and a case study will be presented for conventional DDS. The extension of this framework to emerging nanotechnology delivery systems will be discussed along with future directions. While oral delivery is the focus of the review, the outlined computational approaches can be applied to other drug delivery systems as well. PMID:18019831

Haddish-Berhane, Nahor; Rickus, Jenna L; Haghighi, Kamyar



Recent advances in lymphatic targeted drug delivery system for tumor metastasis  

PubMed Central

The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers. PMID:25610710

Zhang, Xiao-Yu; Lu, Wei-Yue



Modified Titanium Implant as a Gateway to the Human Body: The Implant Mediated Drug Delivery System  

PubMed Central

The aim of this study was to investigate the efficacy of a proposed new implant mediated drug delivery system (IMDDS) in rabbits. The drug delivery system is applied through a modified titanium implant that is configured to be implanted into bone. The implant is hollow and has multiple microholes that can continuously deliver therapeutic agents into the systematic body. To examine the efficacy and feasibility of the IMDDS, we investigated the pharmacokinetic behavior of dexamethasone in plasma after a single dose was delivered via the modified implant placed in the rabbit tibia. After measuring the plasma concentration, the areas under the curve showed that the IMDDS provided a sustained release for a relatively long period. The result suggests that the IMDDS can deliver a sustained release of certain drug components with a high bioavailability. Accordingly, the IMDDS may provide the basis for a novel approach to treating patients with chronic diseases. PMID:25136624

Park, Young-Seok; Cho, Joo-Youn; Hwang, Chee Il



Recent advances in lymphatic targeted drug delivery system for tumor metastasis.  


The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers. PMID:25610710

Zhang, Xiao-Yu; Lu, Wei-Yue



[Mechanisms of hydroxypropyl methylcellulose for the precipitation inhibitor of supersaturatable self-emulsifying drug delivery systems].  


Hydroxypropyl methylcellulose (HPMC) propels self-emulsifying drug delivery systems (SEDDS) to achieve the supersaturated state in gastrointestinal tract, which possesses important significance to enhance oral absorption for poorly water-soluble drugs. This study investigated capacities and mechanisms of HPMC with different viscosities (K4M, K15M and K100M) to inhibit drug precipitation of SEDDS in the simulated gastrointestinal tract environment in vitro. The results showed that HPMC inhibited drug precipitation during the dispersion of SEDDS under gastric conditions by inhibiting the formation of crystal nucleus and the growth of crystals. HPMC had evident effects on the rate of SEDDS lipolysis and benefited the distribution of drug molecules across into the aqueous phase and the decrease of drug sediment. The mechanisms were related to the formed network of HPMC and its viscosities and molecular weight. These results offered a reference for selecting appropriate type of HPMC as the precipitation inhibitor of supersaturatable SEDDS. PMID:23888703

Xiao, Lu; Yi, Tao



Setting bioequivalence requirements for drug development based on preclinical data: optimizing oral drug delivery systems  

Microsoft Academic Search

The recently proposed Biopharmaceutics Classification System can be used to classify drugs and set standards for scale-up and post-approval changes as well as standards for in vitro\\/in vivo correlation for immediate and controlled release products. This classification scheme is based on determining the underlying process that is controlling the drug absorption rate and extent, namely, drug solubility and intestinal membrane

E. Lipka; G. L. Amidon



Use of microwave nondestructive testing (NDT) technique to characterize the film for applications in transdermal drug delivery system  

Microsoft Academic Search

The present study investigated the potential of microwave nondestructive testing (NDT) technique for use in characterization of film for the application in transdermal drug delivery system. Hydroxypropyl methylcellulose and loratadine were selected as model matrix material and drug, respectively. Both blank and drug-loaded films were prepared using the solvent-evaporation method. The films were subjected to dimensional analysis, drug content assay

NorKhaizan Anuar; Wong Tin Wui; D. K. Ghodgaonkar; M. N. Taib



A ceramic-based anticancer drug delivery system to treat breast cancer  

Microsoft Academic Search

Drug delivery systems offer the advantage of sustained targeted release with minimal side effect. In the present study, the\\u000a therapeutic efficacy of a porous silica–calcium phosphate nanocomposite (SCPC) as a new delivery system for 5-Fluorouracil\\u000a (5-FU) was evaluated in vitro and in vivo. In vitro studies showed that two formulations; SCPC50\\/5-FU and SCPC75\\/5-FU hybrids\\u000a were very cytotoxic for 4T1 mammary

Ahmed El-Ghannam; Krista Ricci; Ahmed Malkawi; Kiarash Jahed; Kumar Vedantham; Heather Wyan; Lauren D. Allen; Didier Dréau



Aptamers as drug delivery vehicles.  


The benefits of directed and selective therapy for systemic treatment are reasons for increased interest in exploiting aptamers for cell-specific drug delivery. Nucleic acid based pharmaceuticals represent an interesting and novel tool to counter human diseases. Combining inhibitory potential and cargo transfer upon internalization, nanocarriers as well as various therapeutics including siRNAs, chemotherapeutics, photosensitizers, or proteins can be imported via these synthetic nucleic acids. However, widespread clinical application is still hampered by obstacles that must be overcome. In this review, we give an overview of applications and recent advances in aptamer-mediated drug delivery. We also introduce prominent selection methods as well as useful approaches in choice of drug and conjugation method. We discuss the challenges that need to be considered and present strategies that have been applied to achieve intracellular delivery of effectors transported by readily internalized aptamers. PMID:25130604

Kruspe, Sven; Mittelberger, Florian; Szameit, Kristina; Hahn, Ulrich



Recent advances in stealth coating of nanoparticle drug delivery systems  

PubMed Central

Modifying surfaces of nanoparticles (NPs) with polyethylene glycol (PEG), the so called PEGylation, is the most commonly used method for reducing premature clearance of NPs from the circulation. However, several reports point out that PEGylation may negatively influence the performance of NPs as a drug carrier. Alternative surface modification strategies, including substitute polymers, conditional removal of PEG, and biomimetic surface modification, may provide solutions for the limitations of PEG. PMID:22231928

Amoozgar, Zohreh; Yeo, Yoon



Potential for Layered Double Hydroxides-Based, Innovative Drug Delivery Systems  

PubMed Central

Layered Double Hydroxides (LDHs)-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as excellent protection of loaded molecules from undesired degradation. Toxicological studies have also found LDHs to be biocompatible compared with other widely used nanoparticles, such as iron oxide, silica, and single-walled carbon nanotubes. A plethora of bio-molecules have been reported to either attach to the surface of or intercalate into LDH materials through co-precipitation or anion-exchange reaction, including amino acid and peptides, ATPs, vitamins, and even polysaccharides. Recently, LDHs have been used for gene delivery of small molecular nucleic acids, such as antisense, oligonucleotides, PCR fragments, siRNA molecules or sheared genomic DNA. These nano-medicines have been applied to target cells or organs in gene therapeutic approaches. This review summarizes current progress of the development of LDHs nanoparticle drug carriers for nucleotides, anti-inflammatory, anti-cancer drugs and recent LDH application in medical research. Ground breaking studies will be highlighted and an outlook of the possible future progress proposed. It is hoped that the layered inorganic material will open up new frontier of research, leading to new nano-drugs in clinical applications. PMID:24786098

Zhang, Kai; Xu, Zhi Ping; Lu, Ji; Tang, Zhi Yong; Zhao, Hui Jun; Good, David A.; Wei, Ming Qian



Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems  

PubMed Central

Detonation nanodiamonds (NDs) are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans. PMID:23326195

Kaur, Randeep; Badea, Ildiko



Skin Delivery of Kojic Acid-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging  

PubMed Central

The aging process causes a number of changes in the skin, including oxidative stress and dyschromia. The kojic acid (KA) is iron chelator employed in treatment of skin aging, and inhibits tyrosinase, promotes depigmentation. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation through the skin and improve the drug activity. This study is aimed at structurally developing and characterizing a kojic acid-loaded LCS, consists of water (W), cetostearyl isononanoate (oil—O) and PPG-5-CETETH-20 (surfactant-S) and evaluating its in vitro skin permeation and retention. Three regions of the diagram were selected for characterization: A (35% O, 50% S, 15% W), B (30% O, 50% S, 20% W) and C (20% O, 50% S, 30% W), to which 2% KA was added. The formulations were subjected to polarized light microscopy, which indicated the presence of a hexagonal mesophase. Texture and bioadhesion assay showed that formulation B is suitable for topical application. According to the results from the in vitro permeation and retention of KA, the formulations developed can modulate the permeation of KA in the skin. The in vitro cytotoxic assays showed that KA-unloaded LCS and KA-loaded LCS didn't present cytotoxicity. PPG-5-CETETH-20-based systems may be a promising platform for KA skin delivery. PMID:24369010

Gonçalez, M. L.; Corrêa, M. A.; Chorilli, M.



A vision for cyclodextrin nanoparticles in drug delivery systems and pharmaceutical applications.  


Cyclodextrins (CDs) have brought a revolution in the pharmaceutical field over the last decade. Natural and modified CDs (?-CD and ?-CD) have been studied and some have gained US FDA approval or achieved 'Generally Regarded as Safe' (GRAS) status. Another characteristic of CDs is the ease with which they can be induced to form supramolecular structures for its use in drug delivery. CDs, grafted or crosslinked with polymers, are now being developed into 'smart' systems for efficient targeted drug delivery, especially for hydrophobic drugs. Amphiphilic CDs have the ability to form nanospheres or nanocapsules via a simple nanoprecipitation technique. This review deals with different types of CDs, and their efficacy, physicochemical properties and transformation into nanoparticles with interesting in vitro and in vivo applications. PMID:24981652

Lakkakula, Jaya Raju; Maçedo Krause, Rui Werner



Developing micro-/nanoparticulate drug delivery systems using “design of experiments”  

PubMed Central

Of late, micro and nanoparticluate drug delivery systems have been gaining immense importance primarily attributed to their improved drug release controlling and targeting efficiencies. Also, the small particle size and desirable surface charge associated with these delivery systems render them suitable for specific applications like lymphatic uptake, pulmonary uptake, tumor targeting, brain targeting, etc. For decades, micro and nanoparticulate systems have been prepared by the conventional “trial and error” approach of changing One Variable at a Time (OVAT). Using this methodology, the solution of a specific problematic formulation characteristic can certainly be achieved, but attainment of the true optimal composition is never guaranteed. Thus, the present manuscript provides an updated account of the systematic approach “Design of Experiments (DoE)” as applicable to formulation development of microparticles and nanostructured systems. Besides providing a bird's eye view of the various experimental designs and optimization techniques employed for DoE optimization of such systems, the present manuscript also presents a copilation of the major micro/nano-structuctred systems optimized through DoE till date. In a nutshell, the article will act both as a ready reckoner of DoE optimization of micro/nano drug delivery systems and a catalyst in providing an impetus to young pharmaceutical “nano & micro” researchers to venture into the rewarding field of systematic DoE optimization. PMID:23071925

Singh, Bhupinder; Bhatowa, Rahul; Tripathi, Chandra Bhushan; Kapil, Rishi



Role of excipients and polymeric advancements in preparation of floating drug delivery systems  

PubMed Central

Since decade or two, the development of floating drug delivery systems becomes a significant and novel tool as having low density than gastric content. There are various advanced polymers including chitosan, eudragit, etc., and excipients such as; pore forming agent, surfactants, etc. All of them are discussed briefly, and results are concluded from various reputed researches. We have discussed all natural and synthetic systems with their effect on the release and other parameters which are essential for the floating formulation development. PMID:25599027

Kaushik, Avinash Y; Tiwari, Ajay K; Gaur, Ajay



A Transdermal Drug Delivery System Based on LIGA Technology and Soft Lithography  

NASA Astrophysics Data System (ADS)

This report presents a transdermal drug delivery system based on LIGA fabricated microparts. It is a portable device combining a magnetically actuated micro gear pump with a microneedle array. The fluidic behaviour of the system is analyzed in order to predict its performance according to the dimension of the microparts and then compared to experimental data. The manufacturing process of both micropump and microneedle array are described.

Matteucci, Marco; Perennes, Frederic; Marmiroli, Benedetta; Di Fabrizio, Enzo



Role of excipients and polymeric advancements in preparation of floating drug delivery systems.  


Since decade or two, the development of floating drug delivery systems becomes a significant and novel tool as having low density than gastric content. There are various advanced polymers including chitosan, eudragit, etc., and excipients such as; pore forming agent, surfactants, etc. All of them are discussed briefly, and results are concluded from various reputed researches. We have discussed all natural and synthetic systems with their effect on the release and other parameters which are essential for the floating formulation development. PMID:25599027

Kaushik, Avinash Y; Tiwari, Ajay K; Gaur, Ajay



Mesenchymal stromal cells loading curcumin-INVITE-micelles: A drug delivery system for neurodegenerative diseases.  


This work reports on the formation of a carrier-in-carrier device for the systemic delivery and targeting of hydrophobic drugs mediated by micelle-loaded mesenchymal stromal cells (MSCs) (carrier-in-carrier) to be administered by intravenous injection. The innate ability of MSCs to reach injured tissues such as the central nervous system or other damaged tissues, is the key for the second order delivery and first order targeting. Inulin-d-alfa-tocopherol succinate micelles (INVITE M) are able to incorporate highly hydrophobic drugs and, due to their dimensions (?7nm diameter), to penetrate the cell membrane easily and quickly. This study demonstrates that the curcumin loaded micelles (INVITE MC), sterilized by filtration, reached the maximum loading in MSCs in few minutes and that the loading was concentration-dependent. When "naked" curcumin was used, an evident cytotoxicity on MSCs was detected, while INVITE micelles protected them from this effect. Moreover, MSCs loaded with INVITE MC are able to release the entrapped drug. This study strongly supports the feasibility of the carrier-in-carrier approach for the therapy of selected diseases, i.e., this innovative drug delivery system will be proposed for the treatment of the amyotrophic lateral sclerosis (ALS). PMID:25524221

Tripodo, Giuseppe; Chlapanidas, Theodora; Perteghella, Sara; Vigani, Barbara; Mandracchia, Delia; Trapani, Adriana; Galuzzi, Marta; Tosca, Marta Cecilia; Antonioli, Barbara; Gaetani, Paolo; Marazzi, Mario; Torre, Maria Luisa



Formulation and in vitro characterization of a novel solid lipid-based drug delivery system.  


The liquid self-emulsifying drug delivery system (L-SEDDS), commonly used to deliver effective but poorly water-soluble oleanolic acid (OA), has many limitations such as high manufacturing costs, few choices of dosage forms, risk of leakage from hard gelatin capsules, low stability, limited portability, incompatibility with capsule materials, and relatively restricted storage conditions. Thus the main purpose of our study was to develop a promising solid lipid-based drug delivery system (S-SEDDS) for OA. The S-SEDDS, prepared from wet granulation with an optimized L-SEDDS formulation and mannitol, was characterized by particle size analysis, scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction. Finally, the solubility of the OA-loaded S-SEDDS was compared with that of OA powder in the dissolution assay. Our new S-SEDDS for OA was developed from the optimum L-SEDDS with ethyl oleate (oil phase), Labrasol (surfactant), and Transcutol P (cosurfactant) at a volume ratio of 15:71:14 with 1.5% w/v OA and mannitol. The dissolution of OA was improved by 60% compared with that of the pure OA powder. All the problems associated with the L-SEDDS were resolved. The methodologies we developed for OA delivery could also be utilized for the delivery of other drugs with the S-SEDDS. PMID:25450625

Ma, Hongxing; Chu, Mingjuan; Itagaki, Kiyoshi; Xin, Ping; Zhou, Xuegang; Zhang, Dawei; Wang, Youzhi; Fu, Jia; Sun, Shiqin



Design of a transdermal delivery system for aspirin as an antithrombotic drug.  


Aspirin has become the gold standard to which newer antiplatelet drugs are compared for reducing risks of cardiovascular diseases, while keeping low cost. Oral aspirin has a repertoire of gastrointestinal side effects even at low doses and requires high frequent dosing because it undergoes extensive presystemic metabolism. Transdermal delivery offers an alternative route that bypasses the gut and may be more convenient and safer for aspirin delivery especially during long-term use. This study comprised formulation of aspirin in different topical bases. Release studies revealed that hydrocarbon gel allowed highest drug release. In vitro permeation studies revealed high drug permeation from hydrocarbon gel. Several chemical penetration enhancers were monitored for augmenting the permeation from this base. Combination of propylene glycol and alcohol showed maximum enhancing effect and, hence, was selected for biological investigation. The biological performance of the selected formulation was assessed by measuring the inhibition of platelet aggregation relevant to different dosage regimens aiming to minimize both drug dose and frequency of application. The results demonstrated the feasibility of successfully influencing platelet function and revealed that the drug therapeutic efficacy in transdermal delivery system is dose independent. Biological performance was re-assessed after storage and the results revealed stability and persistent therapeutic efficacy. PMID:16949225

Ammar, H O; Ghorab, M; El-Nahhas, S A; Kamel, R



Emerging Research and Clinical Development Trends of Liposome and Lipid Nanoparticle Drug Delivery Systems  

PubMed Central

Liposomes are spherical-enclosed membrane vesicles mainly constructed with lipids. Lipid nanoparticles are loaded with therapeutics and may not contain an enclosed bilayer. The majority of those clinically approved have diameters of 50–300 nm. The growing interest in nanomedicine has fueled lipid–drug and lipid–protein studies, which provide a foundation for developing lipid particles that improve drug potency and reduce off-target effects. Integrating advances in lipid membrane research has enabled therapeutic development. At present, about 600 clinical trials involve lipid particle drug delivery systems. Greater understanding of pharmacokinetics, biodistribution, and disposition of lipid–drug particles facilitated particle surface hydration technology (with polyethylene glycol) to reduce rapid clearance and provide sufficient blood circulation time for drug to reach target tissues and cells. Surface hydration enabled the liposome-encapsulated cancer drug doxorubicin (Doxil) to gain clinical approval in 1995. Fifteen lipidic therapeutics are now clinically approved. Although much research involves attaching lipid particles to ligands selective for occult cells and tissues, preparation procedures are often complex and pose scale-up challenges. With emerging knowledge in drug target and lipid–drug distribution in the body, a systems approach that integrates knowledge to design and scale lipid–drug particles may further advance translation of these systems to improve therapeutic safety and efficacy. PMID:24338748




Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications  

PubMed Central

The focus on nanotechnology in cancer treatment and diagnosis has intensified due to the serious side effects caused by anticancer agents as a result of their cytotoxic actions on normal cells. This nonspecific action of chemotherapy has awakened a need for formulations capable of definitive targeting with enhanced tumor-killing. Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important area of nanomedicine. Currently several nanomaterial-based drug-delivery systems are in vogue and several others are in various stages of development. Tumor-targeted drug-delivery systems are envisioned as magic bullets for cancer therapy and several groups are working globally for development of robust systems. PMID:22403487

Ranganathan, Ramya; Madanmohan, Shruthilaya; Kesavan, Akila; Baskar, Ganga; Krishnamoorthy, Yoganathan Ramia; Santosham, Roy; Ponraju, D; Rayala, Suresh Kumar; Venkatraman, Ganesh



Treatment of intermediate stage hepatocellular carcinoma: a review of intrahepatic doxorubicin drug-delivery systems.  


The biopharmaceutical properties of doxorubicin delivered via two drug-delivery systems (DDSs) for the palliative treatment of unresectable hepatocellular carcinoma were reviewed with relation to the associated liver and tumor (patho)physiology. These two DDSs, doxorubicin emulsified with Lipiodol(®) and doxorubicin loaded into DC Bead(®) are different regarding tumor delivery, release rate, local bioavailability, if and how they can be given repeatedly, biodegradability, length of embolization and safety profile. There have been few direct head-to-head comparisons of these DDSs, and in-depth investigations into their in vitro and in vivo performance is warranted. PMID:24856170

Dubbelboer, Ilse R; Lilienberg, Elsa; Ahnfelt, Emelie; Sjögren, Erik; Axén, Niklas; Lennernäs, Hans



Cyclodextrins in drug delivery: An updated review  

Microsoft Academic Search

The purpose of this review is to discuss and summarize some of the interesting findings and applications of cyclodextrins\\u000a (CDs) and their derivatives in different areas of drug delivery, particularly in protein and peptide drug delivery and gene\\u000a delivery. The article highlights important CD applications in the design of various novel delivery systems like liposomes,\\u000a microspheres, microcapsules, and nanoparticles. In

Rajeswari Challa; Alka Ahuja; Javed Ali; R. K. Khar



An implantable device for localized drug delivery and sensing  

E-print Network

There are many potential clinical applications for localized drug delivery and sensing systems, such as cancer, vaccinations, pain management, and hormone therapy. Localized drug delivery systems reduce the amount of drug ...

Daniel, Karen D



Drug Release Kinetics and Transport Mechanisms of Non-degradable and Degradable Polymeric Delivery Systems  

PubMed Central

Importance of the field The advancement in material design and engineering has led to the rapid development of novel materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on drug release kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level. Areas covered in this review The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literatures published after 1990s. The release kinetics of selected drug compounds from various material systems will be discussed in case studies. Recent progresses in the mathematical models based on different transport mechanisms will be highlighted. What the reader will gain This article aims to provide an overview of structure-function relationships of selected non-degradable and degradable polymers as drug delivery matrices. Take home message Understanding the structure-function relationship of the material system is key to the successful design of a delivery system for a particular application. Moreover, developing complex polymeric matrices requires more robust mathematical models to elucidate the solute transport mechanisms. PMID:20331353

Fu, Yao; Kao, Weiyuan John



Hydroxyapatite-magnetite-MWCNT nanocomposite as a biocompatible multifunctional drug delivery system for bone tissue engineering  

NASA Astrophysics Data System (ADS)

New magnetic hydroxyapatite-based nanomaterials as bone-specific systems for controlled drug delivery have been synthesized. The synthesized hydroxyapatite, HA, decorated with magnetite nanoparticles by a deposition method (HA/Fe3O4) and the nanocomposite system obtained using magnetic multi-walled carbon nanotubes (HA/MWCNT/Fe3O4) as a filler for HA have been characterized by chemical and morphological analyses, and their biological behavior was investigated. The systems have also been doped with clodronate in order to combine the effect of bone biomineralization induced by hydroxyapatite-based composites with the decrease of osteoclast formation induced by the drug. An analysis of the preosteoclastic RAW264.7 cell proliferation by MTT assay confirmed the high biocompatibility of the three systems. TRAP staining of RAW 264.7 conditioned with sRAKL to induce osteoclastogenesis, cultured in the presence of the systems doped and undoped with clodronate, showed the inhibitory effect of clodronate after we counted the MNC TRAP+cells but only in the osteoclast formation; in particular, the system HA/Fe3O4-Clo exerted a high inhibitory effect compared to the drug alone. These results demonstrate that the synthesized nanocomposites are a biocompatible magnetic drug delivery system and can represent a useful multimodal platform for applications in bone tissue engineering.

Pistone, Alessandro; Iannazzo, Daniela; Panseri, Silvia; Montesi, Monica; Tampieri, Anna; Galvagno, Signorino



Nanomiemgel - A Novel Drug Delivery System for Topical Application - In Vitro and In Vivo Evaluation  

PubMed Central

Aim The objective of this study was to formulate and evaluate a unique matrix mixture (nanomiemgel) of nanomicelle and nanoemulsion containing aceclofenac and capsaicin using in vitro and in vivo analyses and to compare it to a marketed formulation (Aceproxyvon). Methods Nanomicelles were prepared using Vitamin E TPGS by solvent evaporation method and nanoemulsion was prepared by high-pressure homogenization method. In vitro drug release and human skin permeation studies were performed and analyzed using HPLC. The efficiency of nanomiemgel as a delivery system was investigated using an imiquimod-induced psoriatic like plaque model developed in C57BL/6 mice. Results Atomic Force Microscopy images of the samples exhibited a globular morphology with an average diameter of 200, 250 and 220 nm for NMI, NEM and NMG, respectively. Nanomiemgel demonstrated a controlled release drug pattern and induced 2.02 and 1.97-fold more permeation of aceclofenac and capsaicin, respectively than Aceproxyvon through dermatomed human skin. Nanomiemgel also showed 2.94 and 2.09-fold greater Cmax of aceclofenac and capsaicin, respectively than Aceproxyvon in skin microdialysis study in rats. The PASI score, ear thickness and spleen weight of the imiquimod-induced psoriatic-like plaque model were significantly (p<0.05) reduced in NMG treated mice compared to free drug, NEM, NMI & Aceproxyvon. Conclusion Using a new combination of two different drug delivery systems (NEM+NMI), the absorption of the combined system (NMG) was found to be better than either of the individual drug delivery systems due to the utilization of the maximum possible paths of absorption available for that particular drug. PMID:25546392

Somagoni, Jaganmohan; Boakye, Cedar H. A.; Godugu, Chandraiah; Patel, Apurva R.; Mendonca Faria, Henrique Antonio; Zucolotto, Valtencir; Singh, Mandip



In vivo imaging of drug delivery systems in the gastrointestinal tract.  


An essential basis for the understanding of the complex interplay between oral drug delivery systems and gastrointestinal physiology is the ability to relate deposition of the dosage form to the plasma concentration time profile. The pharmaceutical scientist requires an array of methods that provide information on formulation disposition without influencing the physiological process, commonly termed "non-invasive" imaging modalities. In this paper, a short historical view on the suitability of different imaging modalities for the investigation of the fate of drug delivery systems in the GI tract is given. The focus of the review is the presentation of currently mostly used methodologies scintigraphy, magnetic tracking techniques like magnetic marker monitoring (MMM), magnetic moment imaging (MMI), AC biosusceptometry (ACB) and magnetic resonance imaging and the discussion of their strengths and weaknesses. PMID:21820499

Weitschies, Werner; Wilson, Clive G



Coloring brain tumor with multi-potent micellar nanoscale drug delivery system  

NASA Astrophysics Data System (ADS)

Brain tumor, especially glioblastoma multiforme (GBM), is one of the most malignant tumors, which not only demands perplexing treatment approaches but also requires potent and effective treatment modality to deal with recurrence of the tumor. Photodynamic therapy (PDT) is a treatment which has been recommended as a third-level treatment. We are trying to investigate possibility of the PDT as an efficient adjuvant therapeutic modality for the treatment of brain tumor. Inhibition of tumor progression with photosensitizer was verified, in vitro. With micellar nanoscale drug delivery system, localization of the tumor was identified, in vivo, which is able to be referred as photodynamic diagnosis. With consequent results, we are suggesting photodynamic diagnosis and therapy is able to be performed simultaneously with our nanoscale drug delivery system.

Chong, Kyuha; Choi, Kyungsun; Kim, EunSoo; Han, Eun Chun; Lee, Jungsul; Cha, Junghwa; Ku, Taeyun; Yoon, Jonghee; Park, Ji Ho; Choi, Chulhee



Cyclodextrin-based supramolecular systems for drug delivery: Recent progress and future perspective  

PubMed Central

The excellent biocompatibility and unique inclusion capability as well as powerful functionalization capacity of cyclodextrins and their derivatives make them especially attractive for engineering novel functional materials for biomedical applications. There has been increasing interest recently to fabricate supramolecular systems for drug and gene delivery based on cyclodextrin materials. This review focuses on state of the art and recent advances in the construction of cyclodextrin-based assemblies and their applications for controlled drug delivery. First, we introduce cyclodextrin materials utilized for self-assembly. The fabrication technologies of supramolecular systems including nanoplatforms and hydrogels as well as their applications in nanomedicine and pharmaceutical sciences are then highlighted. At the end, the future directions of this field are discussed. PMID:23673149

Zhang, Jianxiang; Ma, Peter X



Nanotechnology-based drug delivery systems for treatment of oral cancer: a review  

PubMed Central

Oral cancer (oral cavity and oropharynx) is a common and aggressive cancer that invades local tissue, can cause metastasis, and has a high mortality rate. Conventional treatment strategies, such as surgery and chemoradiotherapy, have improved over the past few decades; however, they remain far from optimal. Currently, cancer research is focused on improving cancer diagnosis and treatment methods (oral cavity and oropharynx) nanotechnology, which involves the design, characterization, production, and application of nanoscale drug delivery systems. In medicine, nanotechnologies, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, gold nanoparticles, hydrogels, cyclodextrin complexes, and liquid crystals, are promising tools for diagnostic probes and therapeutic devices. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for oral cancers. PMID:25143724

Calixto, Giovana; Bernegossi, Jéssica; Fonseca-Santos, Bruno; Chorilli, Marlus



Polypyrrole Film as a Drug Delivery System for the Controlled Release of Risperidone  

NASA Astrophysics Data System (ADS)

Conducting polymers are finding applications in medicine including drug delivery systems, biosensors and templates for the regeneration of nervous pathways. We aim to develop a novel system where the drug release rate can be controlled by electrical stimulation. Polypyrrole (PPY) is being used as a drug delivery system due to its inherent electrical conductivity, ease of preparation and apparent biocompatibility. Risperidone is an atypical antipsychotic drug used in the treatment of psychosis and related disorders, including schizophrenia. PPY was synthesised using p-toluene sulfonic acid as a primary dopant, in the presence of risperidone. A validated high performance liquid chromatography (HPLC) analytical method was used to quantify risperidone release. It has been demonstrated that the release rate of risperidone can be altered through the application, or absence, of electrical stimulation. Technology such as this would find use in drug-delivering implants where the dose could be adjusted through application of external stimulus, optimising benefit to side effect ratio, while simultaneously ensuring patient adherence (which is a particular challenge in mental health conditions).

Svirskis, Darren; Travas-Sejdic, Jadranka; Rodgers, Anthony; Garg, Sanjay



Collagen as a delivery system for hydrophobic drugs: studies with cyclosporine.  


The time-honored approach to delivering drugs to the ocular surface is through the use of liquid drops and semisolid ointments. Such delivery systems, however, are not efficient at delivering therapeutic concentrations of drugs to the cornea and intraocularly. Over the past several years, we tested the biopolymer, collagen, as a means of delivering both hydrophilic and hydrophobic drugs to the ocular surface. This study summarizes results obtained using the hydrophobic drug, cyclosporine, incorporated into collagen shields and collagen particles. Corn oil drops containing cyclosporine were used as the control. Groups of anesthetized rabbits were fitted with collagen shields containing cyclosporine, treated topically with collagen particles containing cyclosporine suspended in an ocular surface lubricant, or given topical drops of corn oil containing cyclosporine. At intervals after a single treatment with one of the drug formulations, corneas, aqueous humor, and blood were collected for analysis of cyclosporine concentration. With either of the two collagen vehicles, peak concentrations of the drug were found in the cornea 4 hours after application. The corn oil vehicle yielded a significantly lower and earlier peak concentration (1 hour after application). By 8 hours, significant amounts of the drug were still present in the corneas of the collagen-treated animals, whereas drug levels in the corn oil treatment group had returned to baseline. Drug delivery profiles in the aqueous humor were similar, except that the amounts of drug were five times lower. No cyclosporine was detected in the blood from any of the treated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8590264

Gebhardt, B M; Kaufman, H E



Exemestane Loaded Self-Microemulsifying Drug Delivery System (SMEDDS): Development and Optimization  

Microsoft Academic Search

The purpose of this research work was to formulate and characterize self-micro emulsifying drug delivery system containing\\u000a exemestane. The solubility of exemestane was determined in various vehicles. Pseudo ternary phase diagram was used to evaluate\\u000a the micro-emulsification existence area. SMEDDS formulations were tested for micro-emulsifying properties, and the resultant\\u000a formulations loaded with exemestane (ME1, ME2, ME3, ME4 and ME5) were

Ajeet K. Singh; Akash Chaurasiya; Manish Singh; Satish C. Upadhyay; Rama Mukherjee; Roop K. Khar



Compressed matrix dual-component vaginal drug delivery system containing metoclopramide hydrochloride  

Microsoft Academic Search

The purpose of the present investigation was to produce a quick\\/slow biphasic delivery system for metocloprami- de hydrochloride using the superdisintegrant Ac-di-sol for the fast release layer and hydroxypropyl methylcellulose K100M and Ucarflock 302 to modulate the release of the drug. A dual component tablet made up of a sustained release and an immediate release layer was prepared by direct



ATTEMPTS: a heparin\\/protamine-based delivery system for enzyme drugs  

Microsoft Academic Search

A prodrug delivery system termed “Antibody Targeted, Triggered, Electrically Modified Prodrug-Type Strategy (ATTEMPTS)” has been developed to permit the antibody-directed administration of inactive enzyme drug including tissue-type plasminogen activator (tPA), and allow a subsequent triggered release of the active tPA at the target site. Cation-modified tPA (mtPA) was attached to a heparin–antifibrin complex via ionic interaction, and the active tPA

J. F Liang; Y. T Li; H Song; Y. J Park; S. S Naik; V. C Yang



Challenges in design and characterization of ligand-targeted drug delivery systems  

PubMed Central

Targeting of therapeutic agents to molecular markers expressed on the surface of cells requiring clinical intervention holds promise to improve specificity of delivery, enhancing therapeutic effects while decreasing potential damage to healthy tissues. Drug targeting to cellular receptors involved in endocytic transport facilitates intracellular delivery, a requirement for a number of therapeutic goals. However, after several decades of experimental design, there is still considerable controversy on the practical outcome of drug targeting strategies. The plethora of factors contributing to the relative efficacy of targeting makes the success of these approaches hardly predictable. Lack of fully specific targets, along with selection of targets with spatial and temporal expression well aligned to interventional requirements, pose difficulties to this process. Selection of adequate sub-molecular target epitopes determines accessibility for anchoring of drug conjugates and bulkier drug carriers, as well as proper signaling for uptake within the cell. Targeting design must adapt to physiological variables of blood flow, disease status, and tissue architecture by accommodating physicochemical parameters such as carrier composition, functionalization, geometry, and avidity. In many cases, opposite features need to meet a balance, e.g., sustained circulation versus efficient targeting, penetration through tissues versus uptake within cells, internalization within endocytic compartment to avoid efflux pumps versus accessibility to molecular targets within the cytosol, etc. Detailed characterization of these complex physiological factors and design parameters, along with a deep understanding of the mechanisms governing the interaction of targeted drugs and carriers with the biological environment, are necessary steps toward achieving efficient drug targeting systems. PMID:22709588

Muro, Silvia



Self-double-emulsifying drug delivery system (SDEDDS): a new way for oral delivery of drugs with high solubility and low permeability.  


Water-in-oil-in-water (w/o/w) double emulsions are potential for enhancing oral bioavailability of drugs with high solubility and low permeability, but their industrial application is limited due to the instability. Herein, we developed a novel formulation, self-double-emulsifying drug delivery systems (SDEDDS) by formulating mixtures of hydrophilic surfactants and water-in-oil (w/o) emulsions, which were easier to be stable through formulations optimization. SDEDDS can spontaneously emulsify to water-in-oil-in-water (w/o/w) double emulsions in the mixed aqueous gastrointestinal environment, with drugs encapsulated in the internal water phase of the double emulsions. We employed SDEDDS to improve the oral absorption of pidotimod, a peptide-like drug with high solubility and low permeability. The optimized pidotimod-SDEDDS were found to be stable up to 6 months under 25°C. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with SDEDDS showed 2.56-fold (p<0.05) increased absorption of pidotimod, compared to the pidotimod solution. Histopathologic studies confirmed that SDEDDS exerted absorption promoting effect without serious local damages. These studies demonstrate that SDEDDS may be a promising strategy for peroral delivery of peptide and peptidomimetic drugs. PMID:21356300

Qi, Xiaole; Wang, Lishuang; Zhu, Jiabi; Hu, Zhenyi; Zhang, Jie



The Biocompatibility of Nanodiamonds and Their Application in Drug Delivery Systems  

PubMed Central

Nanodiamonds (NDs), as a new member of the carbon nanoparticles family, have attracted more and more attention in biomedicine recently due to their excellent physical and chemical properties. This paper summarizes the main results from the in vitro and in vivo safety assessments of NDs and reports the application of NDs in the development of drug delivery systems. In view of the NDs' characteristics of easy formation of a porous cluster structure in solution, an adsorption model for a variety of functional molecules on the ND clusters is proposed, which provides new ideas for developing a novel smart drug with various features such as sustained-release, targeting, and fluorescence imaging. PMID:22509196

Zhu, Ying; Li, Jing; Li, Wenxin; Zhang, Yu; Yang, Xiafeng; Chen, Nan; Sun, Yanhong; Zhao, Yun; Fan, Chunhai; Huang, Qing



Osmotically regulated asymmetric capsular systems for simultaneous sustained delivery of anti-tubercular drugs.  


Sustained release asymmetric membrane capsular systems were developed for simultaneous oral delivery of rifampicin and isoniazid sodium in order to reduce the problems associated with the multi drug therapy of tuberculosis. Dense semipermeable membrane coating capsules were also prepared for the delivery of these drugs by adopting two different filling approaches. In vitro release studies were carried out for both types of systems and the results were compared. Asymmetric membrane capsules provided sustained release of rifampicin associated with initial burst release, where isoniazid release rates were comparatively high due to higher aqueous solubility. Dense semipermeable membrane systems provided controlled release of both drugs but were devoid of initial burst release of isoniazid. To overcome these drawbacks, a modified asymmetric system was developed by adding appropriate amount of hydrophilic polymer mixture with isoniazid. The system provided satisfactory sustained release of rifampicin and isoniazid with initial burst release may be sufficient to achieve minimum effective concentration in blood. In vitro dissolution kinetics of the systems followed first order kinetics and statistical analysis of release rate data proved that modified asymmetric system was better amongst the developed systems. PMID:14980772

Prabakaran, D; Singh, Paramjit; Jaganathan, K S; Vyas, Suresh P



Preparation and characterization of conjugated polyamidoamine-MPEG-methotrexate for potential drug delivery system  

NASA Astrophysics Data System (ADS)

Star polymers have unique characteristics due to their well-defined size and tailor ability which makes these polymers attractive candidates as carriers in drug delivery system applications. This work focuses on attaching a drug to the star polymer (polyamidoamine). The conjugation of polyamidoamine (PAMAM, generation 4) with methotrexate (MTX) (model drug) was studied in which monomethyl polyethylene glycol (MPEG) was used as a linker to reduce the toxicity of dendrimer. Conjugation starts with attaching the drug to the linker and followed by further conjugation with the polyamidoamine (PAMAM) dendrimer. The conjugation of PAMAM-PEG-MTX was confirmed through UV-Vis, FTIR, 1H NMR and DSC. The loading capacities and release profile of this conjugate were determined using 1H NMR and UV spectrometer.

Mohd Sabri, Siti Noorzidah bt; Abu, Norhidayah; Mastor, Azreena; Hisham, Siti Farhana; Noorsal, Kartini



Enhancement of oral bioavailability of cyclosporine A: comparison of various nanoscale drug-delivery systems  

PubMed Central

A variety of nanoscale delivery systems have been shown to enhance the oral absorption of poorly water-soluble and poorly permeable drugs. However, the performance of these systems has seldom been evaluated simultaneously. The aim of this study was to compare the bioavailability enhancement effect of lipid-based nanocarriers with poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to highlight the importance of the lipid composition, with cyclosporine A (CyA) as a model drug. CyA-loaded PLGA NPs, nanostructured lipid carriers (NLCs), and self-microemulsifying drug-delivery systems (SMEDDS) were prepared. The particle size of PLGA NPs (182.2±12.8 nm) was larger than that of NLCs (89.7±9.0 nm) and SMEDDS (26.9±1.9 nm). All vehicles are charged negatively. The entrapment efficiency of PLGA NPs and NLCs was 87.6%±1.6% and 80.3%±0.6%, respectively. In vitro release tests indicated that the cumulative release of CyA was lower than 4% from all vehicles, including Sandimmun Neoral®, according to the dialysis method. Both NLCs and SMEDDS showed high relative oral bioavailability, 111.8% and 73.6%, respectively, after oral gavage administration to beagle dogs, which was not statistically different from commercial Sandimmun Neoral®. However, PLGA NPs failed to achieve efficient absorption, with relative bioavailability of about 22.7%. It is concluded that lipid-based nanoscale drug-delivery systems are superior to polymeric NPs in enhancing oral bioavailability of poorly water-soluble and poorly permeable drugs. PMID:25378925

Wang, Kai; Qi, Jianping; Weng, Tengfei; Tian, Zhiqiang; Lu, Yi; Hu, Kaili; Yin, Zongning; Wu, Wei



Enhancement of oral bioavailability of cyclosporine A: comparison of various nanoscale drug-delivery systems.  


A variety of nanoscale delivery systems have been shown to enhance the oral absorption of poorly water-soluble and poorly permeable drugs. However, the performance of these systems has seldom been evaluated simultaneously. The aim of this study was to compare the bioavailability enhancement effect of lipid-based nanocarriers with poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to highlight the importance of the lipid composition, with cyclosporine A (CyA) as a model drug. CyA-loaded PLGA NPs, nanostructured lipid carriers (NLCs), and self-microemulsifying drug-delivery systems (SMEDDS) were prepared. The particle size of PLGA NPs (182.2 ± 12.8 nm) was larger than that of NLCs (89.7 ± 9.0 nm) and SMEDDS (26.9 ± 1.9 nm). All vehicles are charged negatively. The entrapment efficiency of PLGA NPs and NLCs was 87.6%± 1.6% and 80.3%± 0.6%, respectively. In vitro release tests indicated that the cumulative release of CyA was lower than 4% from all vehicles, including Sandimmun Neoral(®), according to the dialysis method. Both NLCs and SMEDDS showed high relative oral bioavailability, 111.8% and 73.6%, respectively, after oral gavage administration to beagle dogs, which was not statistically different from commercial Sandimmun Neoral(®). However, PLGA NPs failed to achieve efficient absorption, with relative bioavailability of about 22.7%. It is concluded that lipid-based nanoscale drug-delivery systems are superior to polymeric NPs in enhancing oral bioavailability of poorly water-soluble and poorly permeable drugs. PMID:25378925

Wang, Kai; Qi, Jianping; Weng, Tengfei; Tian, Zhiqiang; Lu, Yi; Hu, Kaili; Yin, Zongning; Wu, Wei



Mechanism-Based Tumor-Targeting Drug Delivery System. Validation of Efficient Vitamin Receptor-Mediated Endocytosis and Drug Release  

PubMed Central

An efficient mechanism-based tumor-targeting drug delivery system, based on tumor-specific vitamin-receptor mediated endocytosis, has been developed. The tumor-targeting drug delivery system is a conjugate of a tumor-targeting molecule (biotin: vitamin H or vitamin B-7), a mechanism-based self-immolative linker and a second-generation taxoid (SB-T-1214) as the cytotoxic agent. This conjugate (1) is designed to be (i) specific to the vitamin receptors overexpressed on tumor cell surface, (ii) internalized efficiently through receptor-mediated endocytosis, followed by smooth drug release via glutathione-triggered self-immolation of the linker. In order to monitor and validate the sequence of events hypothesized, i.e., receptor-mediated endocytosis of the conjugate, drug release, and drug-binding to the target protein (microtubules), three fluorescent/fluorogenic molecular probes (2, 3 and 4) were designed and synthesized. The actual occurrence of these processes was unambiguously confirmed by means of confocal fluorescence microscopy (CFM) and flow cytometry using L1210FR leukemia cells, overexpressing biotin receptors. The molecular probe 4, bearing the taxoid linked to fluorescein, was also used to examine the cell specificity (i.e., efficacy of receptor-based cell targeting) for three cell lines, L1210FR (biotin receptors overexpressed), L1210 (biotin receptors not overexpressed) and WI38 (normal human lung fibroblast, biotin receptor negative). As anticipated, the molecular probe 4 exhibited high specificity only to L1210FR. To confirm the direct correlation between the cell-specific drug delivery and anticancer activity of the probe 4, its cytotoxicity against these three cell lines was also examined. The results clearly showed a good correlation between the two methods. In the same manner, excellent cell-specific cytotoxicity of the conjugate 1 (without fluorescein attachment to the taxoid) against the same three cell lines was confirmed. This mechanism-based tumor-targeting drug delivery system will find a range of applications. PMID:20429547

Chen, Shuyi; Zhao, Xianrui; Chen, Jingyi; Chen, Jin; Kuznetsova, Larisa; Wong, Stanislaus S.; Ojima, Iwao



Polymersomes as an effective drug delivery system for glioma--a review.  


Glioma is one of the most commonly occurring malignant brain tumours which need proper treatment strategy. The current therapies for treating glioma like surgical resection, radiotherapy, and chemotherapy have failed in achieving satisfactory results and this forms a rationale for the development of novel drug delivery systems. Among them, polymersomes are superior novel carriers with diverse functions like enhanced stability, low permeability, tunable membrane properties, surface functionality, and long blood circulation time which make them suitable for cancer therapy. These are bilayered vesicles capable of encapsulating both hydrophilic and hydrophobic drugs used to target glioma effectively. In this review, we have discussed on general preparation, characterization, and targeting aspects of surface modified polymersomes for effective delivery of therapeutic agents to glioma. PMID:24830300

Krishnamoorthy, Balakumar; Karanam, Vamshikrishna; Chellan, Vijaya Raghavan; Siram, Karthik; Natarajan, Tamil Selvan; Gregory, Marslin



Recent advances in ocular drug delivery.  


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 conditions of use and prolonged action. PMID:23153114

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



Kinetic analysis of receptor-mediated endocytosis (RME) of proteins and peptides: use of RME as a drug delivery system  

Microsoft Academic Search

Receptor-mediated endocytosis (RME) which plays an important role in the elimination of biologically active polypeptide can be utilized as a target of the drug delivery system (DDS) which aims to deliver the drug with a limited membrane permeability into the cell. To estimate the efficiency of DDS, it is essential to quantify the cellular uptake of the drug and carriers.

Yukio Kato; Takeshi Seita; Takashi Kuwabara; Yuichi Sugiyama



Formulation and evaluation of niosomal nasal drug delivery system of folic acid for brain targeting.  


Nasal mucosa offers advantages to deliver drugs to brain via olfactory route thus provides rapid onset of drug action and hence faster therapeutic effect. Therefore, various strategies have been proposed to improve the delivery of different drugs to brain including liposomes, colloidal drug carriers, micelles, chimeric peptide technology and nanotechnology through nasal route. The low blood level of folates is the primary cause of depression in Alzheimer's disease. Folic acid is a water soluble vitamin showing difficulty in crossing the blood brain barrier and thus was formulated as niosomal nasal drug delivery systems to target the brain. In the present work, folic acid niosomes were prepared using different nonionic surfactants i.e., span 20, span 60, span 80, tween 20, tween 80 and cholesterol by using lipid layer hydration technique. These were evaluated for particle size, viscosity, osmotic shock, entrapment efficiency and in vitro drug release. The influence of different formulation variables such as surfactant type, surfactant concentration, and cholesterol concentration was optimized for required size distribution, viscosity, entrapment efficiency and in vitro release. The prepared niosomes were in the size range of 3.05-5.625 µm. Niosomes prepared with span 60 and cholesterol in the ratio of 1:1 (50 mg: 50 mg) shown higher entrapment efficiency of 69.42% and better in vitro drug release of 64.2% at the end of 12 hrs and therefore considered as optimized formulation. The stability studies were carried out by storing niosomes at 4±1°C and 25±1°C and showed good stability over the period of storage. The release of drug from niosomes followed anomalous diffusion and obeyed first order release kinetics. Ex-vivo perfusion studies were also performed by using rat model, about 48.15% of drug was found to be absorbed through nasal cavity at the end of 6 hrs. PMID:23863098

Ravouru, Nagaraju; Kondreddy, Pallavi; Korakanchi, Deepthy; Haritha, M



Current treatment options and drug delivery systems as potential therapeutic agents for ovarian cancer: a review.  


Ovarian cancer is one of the most common and deadliest gynecologic cancer with about 75% of the patients presenting in advanced stages. The introduction of intraperitoneal chemotherapy in 2006 had led to a 16 month improvement in the overall survival. However, catheter-related complication and the complexity of the procedure had deterred intraperitoneal route as the preferred route of treatment. Other alternative treatments had been developed by incorporating other FDA-approved agents or procedures such as pegylated liposomal doxorubicin (PLD), hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and the administration of bevacizumab. Various clinical trials were conducted on these alternatives as both the first-line treatment and second- or third-line therapy for the recurrent disease. The outcome of these studies were summarized and discussed. A prospective improvement in the treatment of ovarian cancer could be done through the use of a drug delivery system. Selected promising recent developments in ovarian cancer drug delivery systems using different delivery vehicles, surface modifications, materials and drugs were also reviewed. PMID:25491871

Ye, Hongye; Karim, Anis Abdul; Loh, Xian Jun



Sensor-integrated polymer actuators for closed-loop drug delivery system  

NASA Astrophysics Data System (ADS)

This work presents manufacturing and testing of a closed-loop drug delivery system where drug release is achieved by an electrochemical actuation of an array of polymeric valves on a set of drug reservoirs. The valves are based on bi-layer structures made of polypyrrole/gold in the shape of a flap that is hinged on one side of a valve seat. Drugs stored in the underlying chambers are released by bending the bi-layer flaps back with a small applied bias. These polymeric valves simultaneously function as both drug release components and biological/chemical sensors responding to a specific biological or environmental stimulus. The sensors may send signals to the control module to realize closed-loop control of the drug release. In this study a glucose sensor has been integrated with the polymeric actuators through immobilization of glucose oxidase(GOx) within polypyrrole(PPy) valves. Sensitivities per unit area of the integrated glucose sensor have been measured and compared before and after the actuation of the sensor/actuator PPy/DBS/GOx film. Other sensing parameters such as linear range and response time were discussed as well. Using an array of these sensor/actuator cells, the amount of released drug, e.g. insulin, can be precisely controlled according to the surrounding glucose concentration detected by the glucose sensor. Activation of these reservoirs can be triggered either by the signal from the sensor, or by the signal from the operator. This approach also serves as the initial step to use the proposed system as an implantable drug delivery platform in the future.

Xu, Han; Wang, Chunlei; Kulinsky, Lawrence; Zoval, Jim; Madou, Marc



Targeted Drug Delivery in Pancreatic Cancer  

PubMed Central

Effective drug delivery in pancreatic cancer treatment remains a major challenge. Because of the high resistance to chemo and radiation therapy, the overall survival rate for pancreatic cancer is extremely low. Recent advances in drug delivery systems hold great promise for improving cancer therapy. Using liposomes, nanoparticles, and carbon nanotubes to deliver cancer drugs and other therapeutic agents such as siRNA, suicide gene, oncolytic virus, small molecule inhibitor and antibody has been a success in recent pre-clinical trials. However, how to improve the specificity and stability of the delivered drug using ligand or antibody directed delivery represent a major problem. Therefore, developing novel, specific, tumor-targeted drug delivery systems is urgently needed for this terrible disease. This review summarizes the current progress on targeted drug delivery in pancreatic cancer, and provides important information on potential therapeutic targets for pancreatic cancer treatment. PMID:19853645

Yu, Xianjun; Zhang, Yuqing; Chen, Changyi; Yao, Qizhi; Li, Min



Fabrication methods and performance of low-permeability microfluidic components for a miniaturized wearable drug delivery system  

E-print Network

In this paper, we describe low-permeability components of a microfluidic drug delivery system fabricated with versatile micromilling and lamination techniques. The fabrication process uses laminate sheets which are machined ...

Mescher, Mark J.


Protease-mediated drug delivery  

NASA Astrophysics Data System (ADS)

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.

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



Thiolated poly(aspartic acid) as potential in situ gelling, ocular mucoadhesive drug delivery system.  


The ophthalmic formulations on the market suffer from poor bioavailability, and it would therefore be useful to design a new formulation which is able to prolong the residence time and reduce the administration frequency. Polymer matrices which exhibit strong mucoadhesion are promising platforms in ocular drug delivery from the aspect of improved bioavailability. In the present study, an in situ gelling, mucoadhesive drug delivery system was fabricated from thiolated poly(aspartic acid) (ThioPASP). The thiol groups of ThioPASP are able to form disulphide linkages with the mucin glycoproteins and prolong the residence time on the eye. The effects of the thiol groups on the structure, swelling behaviour and mucoadhesive character of the gel and on the drug release profile were determined. The gel structure was characterized by means of rheology. The ThioPASP gel was demonstrated by rheology, tensile test and 'wash away' measurements to display strong mucoadhesion. The drug release from the ThioPASP gel was studied on a vertical Franz diffusion cell: a burst release of sodium diclofenac occurred in the first hour, followed by sustained release of the encapsulated drug for up to 24h. The results proved the importance of the presence of the thiol groups and suggested that a ThioPASP formulation can be useful as an in situ gelling, ocular dosage form. PMID:25445832

Horvát, Gabriella; Gyarmati, Benjámin; Berkó, Szilvia; Szabó-Révész, Piroska; Szilágyi, Barnabás Áron; Szilágyi, András; Soós, Judit; Sandri, Giuseppina; Bonferoni, Maria Cristina; Rossi, Silvia; Ferrari, Franca; Caramella, Carla; Csányi, Erzsébet; Budai-Sz?cs, Mária



[Preparation and in vitro evaluation of self-assembled beads drug delivery system of berberine hydrochloride].  


The purpose of the present work was to investigate the innovative self-assembling system, "beads", prepared by continuously shaking alpha-cyclodextrin and soybean oil without the use of organic solvents and surfactants at room temperature. Berberine hydrochloride previously dissolved in soybean oil was chosen as a model drug to explore the shape, structure, drug loading and in vitro release of beads. The particle size and drug loading of berberine hydrochloride-loaded beads were (2.25 +/- 0.23) mm and (67.02 +/- 0.64) microg x g(-1), respectively. Confocal microscopy showed that the core-shell structure of beads could contain poorly water soluble drugs or lipophilic drugs in the lipid core. The drug release rate and cumulative releases of beads were both higher than those of raw medicine of berberine hydrochloride in simulated intestinal fluid. These results suggested that beads were the novel and potential lipid-based drug delivery system for lipophilic or poorly water soluble traditional Chinese medicine. PMID:24066585

Liu, Chuan; Xu, Yani; Ouyang, Hui; Yi, Tao



Anthracycline Nano-Delivery Systems to Overcome Multiple Drug Resistance: A Comprehensive Review  

PubMed Central

Anthracyclines (doxorubicin, daunorubicin, and idarubicin) are very effective chemotherapeutic drugs to treat many cancers; however, the development of multiple drug resistance (MDR) is one of the major limitations for their clinical applications. Nano-delivery systems have emerged as the novel cancer therapeutics to overcome MDR. Up until now, many anthracycline nano-delivery systems have been developed and reported to effectively circumvent MDR both in-vitro and in-vivo, and some of these systems have even advanced to clinical trials, such as the HPMA-doxorubicin (HPMA-DOX) conjugate. Doxil, a DOX PEGylated liposome formulation, was developed and approved by FDA in 1995. Unfortunately, this formulation does not address the MDR problem. In this comprehensive review, more than ten types of developed anthracycline nano-delivery systems to overcome MDR and their proposed mechanisms are covered and discussed, including liposomes; polymeric micelles, conjugate and nanoparticles; peptide/protein conjugates; solid-lipid, magnetic, gold, silica, and cyclodextrin nanoparticles; and carbon nanotubes. PMID:23888183

Ma, Ping; Mumper, Russell J.



pH-responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment  

PubMed Central

In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles (MSNs) with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanoparticles, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail. PMID:24738037

Yang, Ke-Ni; Zhang, Chun-Qiu; Wang, Wei; Wang, Paul C.; Zhou, Jian-Ping; Liang, Xing-Jie



Microprocessor controlled transdermal drug delivery.  


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. PMID:16713690

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



Microspheres of biodegradable polymers as a drug-delivery system in the vitreous.  


Microspheres of biodegradable polymers were evaluated as a potential controlled-release drug-delivery system in the vitreous. The microspheres were prepared with polymers of poly(lactic acid) or copolymers of glycolic acid and lactic acid. The release of 5-fluorouracil (5-FU) from the microspheres was studied in vitro. Poly(lactic acid) microspheres released 70-85% of total 5-FU over 7 days. Microspheres of polymers with a smaller molecular weight released the drug more rapidly. Copolymer microspheres released 98% of 5-FU over 2 days. The rate of drug release was controllable by changing the molecular weight of the polymers or using a matrix of copolymer. The intravitreal kinetics of the microspheres were studied in ten rabbits in vivo. A suspension of microspheres was injected into the vitreous cavity of five normal eyes and five vitrectomized eyes. By 48 +/- 5.2 days after injection, the microspheres disappeared from the vitreous cavity in the five normal eyes. Clearance from the vitreous cavity was accelerated in the five rabbits that underwent vitrectomy (14 +/- 2.4 days; P less than 0.001). No difference was found in the b waves of electroretinograms before and after injection of the microspheres. The histologic study showed no abnormal findings as a result of the injection. These results suggested that microspheres of biodegradable polymers may be a potential delivery system for the controlled release of drugs in the vitreous. PMID:2032801

Moritera, T; Ogura, Y; Honda, Y; Wada, R; Hyon, S H; Ikada, Y



Design and evaluation of transdermal drug delivery system for curcumin as an anti-inflammatory drug.  


The purpose of this research was to develop a matrix-type transdermal therapeutic system containing herbal drug, curcumin (CUR), with different ratios of hydrophilic (hydroxyl propyl methyl cellulose K4M [HPMC K4M]) and hydrophobic (ethyl cellulose [EC]) polymeric systems by the solvent evaporation technique. Different concentrations of oleic acid (OA) were used to enhance the transdermal permeation of CUR. The physicochemical compatibility of the drug and the polymers was also studied by differential scanning calorimetry (DSC) and infrared (IR) spectroscopy. The results suggested no physicochemical incompatibility between the drug and the polymers. Formulated transdermal films were physically evaluated with regard to drug content, tensile strength, folding endurance, thickness, and weight variation. All prepared formulations indicated good physical stability. In vitro permeation studies of formulations were performed by using Franz diffusion cells. The results followed Higuchi kinetics, and the mechanism of release was diffusion-mediated. Formulation prepared with hydrophilic polymer containing permeation enhancer showed best in vitro skin permeation through rat skin as compared with all other formulations. This formulation demonstrated good anti-inflammatory activity against carrageenan-induced oedema in Wistar albino rats similar to standard formulation. PMID:18785045

Patel, Nikunjana A; Patel, Natvar J; Patel, Rakesh P



In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery  

E-print Network

drug delivery Tanja Blagus a , Bostjan Markelc a , Maja Cemazar a,b , Tina Kosjek c , Veronique Preat d 39, SI-1000 Ljubljana, Slovenia d Louvain Drug Research Institute, Pharmaceutics and Drug Delivery online 7 October 2013 Keywords: Electroporation Transdermal drug delivery Topical drug delivery Multi

Ljubljana, University of


New Methods of Drug Delivery  

Microsoft Academic Search

Conventional forms of drug administration generally rely on pills, eye drops, ointments, and intravenous solutions. Recently, a number of novel drug delivery approaches have been developed. These approaches include drug modification by chemical means, drug entrapment in small vesicles that are injected into the bloodstream, and drug entrapment within pumps or polymeric materials that are placed in desired bodily compartments

Robert Langer



High-throughput in vitro drug release and pharmacokinetic simulation as a tool for drug delivery system development: Application to intravitreal ocular administration.  


In vitro estimation of release kinetics from drug delivery systems is needed in formulation development. Cost-effective methods of assessment for delivery systems are needed particularly in the case of biologicals and drug administration routes that are difficult to screen in vivo (e.g. intraocular drug delivery). As a proof-of-concept, we demonstrate here a practical high-throughput methodology to investigate in vitro drug release and predict resulting drug concentrations in the eye after intravitreal administration. 96-well plate based assay aided with robotic sampling was used to study release of eight model drugs of varying physicochemical properties (dexamethasone, vancomycin, alpha-lactalbumin, lysozyme, myoglobin, albumin, lactoferrin, human IgG) from twelve alginate microsphere formulations. The amount of drug released over a period of time was assessed by photometric and fluorescence methods. In vitro drug release rates obtained were used in pharmacokinetic simulations using one-compartment model of the vitreal cavity with anatomical volume of distribution and clearance estimates based on the literature precedence. An integrated approach of drug release screening and pharmacokinetic simulations can prove to be a useful methodology in guiding formulation development for ocular delivery in animal models. In general, the methodology has the potential to be a cost-effective tool for early stage drug delivery system discovery and development. PMID:25445526

Sarkhel, Sanjay; Ramsay, Eva; Kontturi, Leena-Stiina; Peltoniemi, Jonne; Urtti, Arto



Pectin-based systems for colon-specific drug delivery via oral route  

Microsoft Academic Search

Pectin-derived matrices are now being examined and tested for controlled drug delivery. Pectin is intact in the upper gastrointestinal tract and degraded by colonic microflora. The composition of this microflora remains relatively consistent across a diverse human population. Thus, pectin-derived drug carriers provide promising potential for colon-specific drug delivery. This paper reviews recent developments in pectin-derived formulations. Subjects reviewed include

LinShu Liu; Marshall L. Fishman; Joseph Kost; Kevin B. Hicks



Excipient effects on in vitro cytotoxicity of a novel paclitaxel self-emulsifying drug delivery system.  


Paclitaxel is a potent chemotherapeutic agent currently administered intravenously in polyoxyethylated castor oil (Cremophor EL) and dehydrated ethanol (1:1) for the treatment of solid tumors. The objective of this work was to develop a novel self-emulsifying drug delivery system (SEDDS) devoid of cremophor for the i.v./oral delivery of paclitaxel and to investigate the in vitro cytotoxicity of the combined excipients. The SEDDS formulations were characterized in terms of droplet size using a ternary phase diagram. The Caco-2 cell line was used to monitor the cytotoxicity of the excipients. Cell viability was determined colorimetrically at 570 nm utilizing the MTT assay. The distribution of the formulations on the phase diagram indicated the presence of macroemulsions ( approximately 1 microm), submicron emulsions (50-200 nm), and microemulsions (below 10 nm). An increase in the sodium deoxycholate excipient content led to an increase in physical stability but caused more chemical degradation of the drug and more cytotoxicity. The drug in the novel SEDDS was chemically stable for at least 1 year when kept as a two-part formulation. The drug loading was increased by approximately fivefold compared to the marketed i.v. formulation; the excipients presented a significantly reduced cytotoxicity and led to a stable microemulsion. PMID:14603486

Gursoy, Neslihan; Garrigue, Jean-Sebastien; Razafindratsita, Alain; Lambert, Gregory; Benita, Simon



Pioglitazone hydrochloride: chemopreventive potential and development of site-specific drug delivery systems.  


Abstract The aim of this study was to investigate the potential of pioglitazone hydrochloride as a promising anticancer agent and then to design and evaluate the colon-targeted delivery system. The role of pioglitazone hydrochloride as a promising anticancer agent was evaluated by in vitro cell line studies and in vivo 1,2-dimethylhydrazine-induced colon carcinogenesis in rats. In order to deliver the drug at site of action, i.e. colon, drug embedded in matrices containing a release retarding polymer (HPMC K4M) and a polysaccharide (locust bean gum) were prepared. These matrix systems were further enteric coated with Eudragit®S100 to minimize the premature drug release in the upper segments of the GIT. In vitro dissolution studies were performed in absence and presence of rat caecal contents on selected batches and samples were analyzed using a validated RP-HPLC method. Hence, the studies led to the conclusion that successful site-specific delivery systems of pioglitazone hydrochloride were developed to improve its therapeutic efficacy in the management of colorectal cancer. PMID:24547712

Sinha, Vivek Ranjan; Sethi, Shilpa



Self-assembly properties, aggregation behavior and prospective application for sustained drug delivery of a drug-participating catanionic system.  


In the present study, the self-assembly properties, aggregation behavior and potential application of mixed samples formed by an active drug (diclofenac sodium, DS) and conventional surfactant (didodecyldimethyl ammonium bromide, DDAB) are investigated with surface tension, transmission electron microscope (TEM), dynamic light scattering (DLS), zeta potential, conductivity, in vitro drug release and hemolytic toxicity measurements. The physicochemical parameters such as critical micelle concentration (CMC), the surface tension at CMC (?CMC), the maximum surface excess concentration (? max) and the minimum area per molecule headgroup at the air/water interface (A min) and degree of counterion binding (?) are obtained from the surface tension and electrical conductivity measurements. The results show that diclofenac sodium can decrease the surface tension of water and aggregate in the aqueous solution when its concentration is large enough. The CMC and ?CMC of the DS/DDAB mixed systems are found to have values between that of individual DS and DDAB solutions. TEM and DLS results demonstrate the formation of spherical vesicles in a wide range of the molar ratio of the two components. The amount of charge on the vesicles and their stability can be tuned by controlling the amount of drug and surfactant. To evaluate the potential use of the as-prepared DS/DDAB catanionic vesicles in drug delivery systems, the in vitro drug release and hemolytic toxicity are carried out. The results indicate that both the drug release behavior and the hemolytic toxicity are dependent on the composition of the samples, X1 (X1=nDS/n(DS+DDAB), decreasing with the decrease of X1. The results of this work suggested that the drug-participating catanionic vesicles can be used as a safe and an efficient vehicle for sustained drug release. PMID:23644346

Zhao, Lanxia; Liu, Jing; Zhang, Longlong; Gao, Ya; Zhang, Zhiqing; Luan, Yuxia



The Role of Oral Controlled Release Matrix Tablets in Drug Delivery Systems  

PubMed Central

Formulations that are able to control the release of drug have become an integral part of the pharmaceutical industry. In particular oral drug delivery has been the focus of pharmaceutical research for many years. This type of drug delivery has been at the centre of research due to its many benefits over conventional dosage. The focus of this review is on matrix tablets due to their widely use and simplicity of the formulation. This includes the discussion of various types of matrix tablets and factors affecting the drug release from these formulations. The mechanism of drug release from HPMC matrices is also discussed. PMID:23678458

Nokhodchi, Ali; Raja, Shaista; Patel, Pryia; Asare-Addo, Kofi



The Emerging Potential of Byproducts as Platforms for Drug Delivery Systems.  


Natural resources are widely used as raw materials by industries. In most cases, abundant byproducts with low economic interest are also generated from agro-industrial supply chains. There are several examples for the rational use of agro-industrial byproducts in nanobiotechnology field aiming for the development of novel products and processes with high value-added. Examples of these raw materials include carapaces, pelages, blood, bagasses, straws, and other byproducts. Molecules from such materials (e.g. chitosan, cellulose, and albumin) are used as scaffolds of unprecedented novel nanostructures. Research efforts comprising a combination of sustainability, nanobiotechnology, and nanomedicine have emerged. One major area of nanobiotechnological research of agro-industrial byproducts is the field of drug delivery systems (DDS). Among the main advantages of agro-industrial byproducts used as drug carriers are their abundance; low price; high biocompatibility; good biodegradability; moderate bioresorbability, associated with reduced systemic toxicity or even no toxicity; and often bioactivity. The goal of these efforts include not only the possibility to characterize and manipulate matter on nanoscale, but also to develop sustainable products and processes, including the development of platforms for drug carriers aiming for the treatment of pathologies such as cancer and diabetes. Indeed, there is great hope that the use of agro-industrial byproducts on nanobiotechnology will increase not only agricultural and livestock productivity, but will also contribute to other areas such as the development of DDS with new properties and low production costs; and sustainable environmental management due to the reuse of industrial discharged byproducts. This review will compile current findings on this perspective in drug delivery describing the challenges and applications of byproducts as building blocks for modern drug carrier systems. PMID:23746200

Joanitti, Graziella A; Silva, Luciano P



Novel application of Eudragit RL and cholesteryl oleyl carbonate to thermo-sensitive drug delivery system.  


The Eudragit RL 100 and propylene glycol (PG) membranes with and without cholesteryl oleyl carbonate (COC) were prepared by the solvent casting method to pioneer a novel application of a thermo-sensitive drug delivery system. After that, the properties of these membranes were investigated by thermal, scanning, and porosity studies. Drug permeation studies through all membranes were carried out using salbuthamol sulphate (SBS) at constant temperatures (25°C and 37°C), respectively. The permeability of SBS through the membranes with COC has been shown to be a discontinuous function of temperature, that is, their permeability increased steeply above the phase transition temperature (37°C) of the COC. The thermo-sensitive permeation mechanism for the membranes might be based on the structure change of the membranes caused by the phase transition, so that the membranes could absorb more water. Considering the high biological safety of Eudragit RL 100 and PG membranes with and without COC might be used to develop a novel thermo-sensitive drug delivery system. PMID:22397637

Cetin, Emel Oyku; Gundogdu, Evren; Baspinar, Yücel; Karasulu, Ercument; Kirilmaz, Levent



Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan  

PubMed Central

Irbesartan (IRB) is an angiotensin II receptor blocker antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of poorly water-soluble IRB. The solubility of IRB in various oils was determined to identify the oil phase of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. The optimized SNEDDS formulation contained IRB (75 mg), Cremophor® EL (43.33%), Carbitol® (21.67%) and Capryol® 90 (32%). SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size and zeta potential. The optimized formulation of IRB-loaded SNEDDS exhibited complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug solution by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of IRB from SNEDDS compared with the pure drug solution. These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability of poorly water-soluble IRB. PMID:22171286

Patel, Jaydeep; Patel, Anjali; Raval, Mihir; Sheth, Navin



Recent advances in ceramic implants as drug delivery systems for biomedical applications  

PubMed Central

Research in the development of new bioceramics with local drug delivery capability for bone regeneration technologies is receiving great interest by the scientific biomedical community. Among bioceramics, silica-based ordered mesoporous materials are excellent candidates as bone implants due to two main reasons: first, the bioactive behavior of such materials in contact with simulated body fluids, ie, a carbonate hydroxyapatite similar to the mineral phase of bone is formed onto the materials surfaces. Second, their capability of acting as delivery systems of a large variety of biologically active molecules, including drugs to treat bone infection, inflammation or diseases, and molecules that promote bone tissue regeneration, such as peptides, proteins, growth factors, and other osteogenic agents. The recent chemical and technological advances in the nanometer scale has allowed the design of mesoporous silicas with tailored structural and textural properties aimed at achieving a better control over molecule loading and release kinetics. Moreover organic modification of mesoporous silica walls has been revealed as a key strategy to modulate molecule adsorption and delivery rates. PMID:19337409

Colilla, Montserrat; Manzano, Miguel; Vallet-Regí, María



Preparation and characterization of 6-mercaptopurine-coated magnetite nanoparticles as a drug delivery system  

PubMed Central

Background Iron oxide nanoparticles are of considerable interest because of their use in magnetic recording tape, ferrofluid, magnetic resonance imaging, drug delivery, and treatment of cancer. The specific morphology of nanoparticles confers an ability to load, carry, and release different types of drugs. Methods and results We synthesized superparamagnetic nanoparticles containing pure iron oxide with a cubic inverse spinal structure. Fourier transform infrared spectra confirmed that these Fe3O4 nanoparticles could be successfully coated with active drug, and thermogravimetric and differential thermogravimetric analyses showed that the thermal stability of iron oxide nanoparticles coated with chitosan and 6-mercaptopurine (FCMP) was markedly enhanced. The synthesized Fe3O4 nanoparticles and the FCMP nanocomposite were generally spherical, with an average diameter of 9 nm and 19 nm, respectively. The release of 6-mercaptopurine from the FCMP nanocomposite was found to be sustained and governed by pseudo-second order kinetics. In order to improve drug loading and release behavior, we prepared a novel nanocomposite (FCMP-D), ie, Fe3O4 nanoparticles containing the same amounts of chitosan and 6-mercaptopurine but using a different solvent for the drug. The results for FCMP-D did not demonstrate “burst release” and the maximum percentage release of 6-mercaptopurine from the FCMP-D nanocomposite reached about 97.7% and 55.4% within approximately 2,500 and 6,300 minutes when exposed to pH 4.8 and pH 7.4 solutions, respectively. By MTT assay, the FCMP nanocomposite was shown not to be toxic to a normal mouse fibroblast cell line. Conclusion Iron oxide coated with chitosan containing 6-mercaptopurine prepared using a coprecipitation method has the potential to be used as a controlled-release formulation. These nanoparticles may serve as an alternative drug delivery system for the treatment of cancer, with the added advantage of sparing healthy surrounding cells and tissue. PMID:24106420

Dorniani, Dena; Hussein, Mohd Zobir bin; Kura, Aminu Umar; Fakurazi, Sharida; Shaari, Abdul Halim; Ahmad, Zalinah



Food, physiology and drug delivery.  


Gastrointestinal physiology is dynamic and complex at the best of times, and a multitude of known variables can affect the overall bioavailability of drugs delivered via the oral route. Yet while the influences of food and beverage intake as just two of these variables on oral drug delivery have been extensively documented in the wider literature, specific information on their effects remains sporadic, and is not so much contextually reviewed. Food co-ingestion with oral dosage forms can mediate several changes to drug bioavailability, yet the precise mechanisms underlying this have yet to be fully elucidated. Likewise, the often detrimental effects of alcohol (ethanol) on dosage form performance have been widely observed experimentally, but knowledge of which has only moderately impacted on clinical practice. Here, we attempt to piece together the available subject matter relating to the influences of both solid and liquid foodstuffs on the gastrointestinal milieu and the implications for oral drug delivery, with particular emphasis on the behaviour of modified-release dosage forms, formulation robustness and drug absorption. Providing better insight into these influences, and exemplifying cases where formulations have been developed or modified to circumvent their associated problems, can help to appropriately direct the design of future in vitro digestive modelling systems as well as oral dosage forms resilient to these effects. Moreover, this will help to better our understanding of the impact of food and alcohol intake on normal gut behaviour and function. PMID:23612358

Varum, F J O; Hatton, G B; Basit, A W



Skin Irritation in Transdermal Drug Delivery Systems: A Strategy for its Reduction  

Microsoft Academic Search

Purpose  Active pharmaceutical ingredients (API) in transdermal drug delivery systems (TDS) often causes skin irritation such as erythema\\u000a and edema. We have studied a possible approach for the reduction of skin irritation by patch formulations that control the\\u000a rates of skin permeation and elimination of API.\\u000a \\u000a \\u000a \\u000a Methods  Loxoprofen (LX-base) was used to induce the skin irritation. The redness value (?a) was evaluated

Koji Kawahara; Kakuji Tojo



Self nanoemulsifying drug delivery system (SNEDDS) of rosuvastatin calcium: design, formulation, bioavailability and pharmacokinetic evaluation.  


The aim of the present study is to improve solubility and bioavailability of Rosuvastatin calcium using self nanoemulsifying drug delivery system (SNEDDS). Self emulsifying property of various oils including essential oils was evaluated with suitable surfactants and co-surfactants. Ternary phase diagrams were constructed based on Rosuvastatin calcium solubility analysis for optimizing the system. The prepared formulations were evaluated for self emulsifying time, robustness to dilution, droplet size determination and zeta potential analysis. The system was found to be robust in different pH media and dilution volume. The globule size of the optimized system was less than 200nm which could be an acceptable nanoemulsion size range. The zeta potential of the selected CN 7 SNEDDS formulation (cinnamon oil 30%; labrasol 60%; Capmul MCM C8 10%) was -29.5±0.63 with an average particle size distribution of 122nm. In vitro drug release studies showed remarkable increase in dissolution of CN7 SNEDDS compared to marketed formulation. In house developed HPLC method for determination of Rosuvastatin calcium in rat plasma was used in the bioavailability and pharmacokinetic evaluation. The relative bioavailability of self nanoemulsified formulation showed an enhanced bioavailability of 2.45 times greater than that of drug in suspension. The obtained plasma drug concentration data was processed with PKSolver 2.0 and it was best fit into the one compartment model. PMID:24012665

Balakumar, Krishnamoorthy; Raghavan, Chellan Vijaya; selvan, Natarajan Tamil; prasad, Ranganathan Hari; Abdu, Siyad



Microneedles for transdermal drug delivery  

Microsoft Academic Search

The success of transdermal drug delivery has been severely limited by the inability of most drugs to enter the skin at therapeutically useful rates. Recently, the use of micron-scale needles in increasing skin permeability has been proposed and shown to dramatically increase transdermal delivery, especially for macromolecules. Using the tools of the microelectronics industry, microneedles have been fabricated with a

Mark R Prausnitz



Formulation and statistical optimization of a novel crosslinked polymeric anti-tuberculosis drug delivery system.  


The crux of this research was the pragmatic investigation into the formulation of a reconstitutable multiparticulate anti-tuberculosis drug delivery system for facilitated administration for the attainment of segregated gastrointestinal (GI) delivery of rifampicin (RIF) and isoniazid (INH) in order to address issues of unacceptable RIF bioavailability on coadministration with INH. Ionotropically crosslinked polymeric enterospheres for delivery of INH to the small intestine were developed via a response surface methodology for the design and optimization of the formulation and processing variables. A 3(4) Box-Behnken statistical design was constructed. The concentration of zinc sulfate salting-out and crosslinking electrolyte, the crosslinking reaction time, the drying temperature (DT), and the concentration of triethyl citrate plasticizer were varied for determination of their effect on the molar amount of zinc (n(Zn)) incorporated in the crosslinked enterosphere, drug entrapment efficiency (DEE), and mean dissolution time (MDT) at t(2h) in acidic media (0.1 M HCl). Complexometric determination of zinc cations (Zn(2+)) revealed that 23.70-287.89 mol of Zn(2+) per mole of polymer were implicated in crosslink formation. DEE of 27.92% to 99.77% were obtained. Drug release at t(2h) ranged from 1.67% to 73.04%. The salting-out and crosslinking agent significantly affected n(Zn) (p = 0.034) and the DEE (p = 0.000), as did the concentration of plasticizer employed (p = 0.000 and 0.002, respectively). High DTs (>42.5 degrees C) also significantly improved DEE (p = 0.029). ZnSO(4) had a significant effect on the MDT (p = 0.000). A dry dispersible multiparticulate system incorporating the optimally designed INH-loaded enterospheres and RIF was developed. Bivariate regression analysis of UV spectrophotometric absorbance data allowed in vitro resolution of RIF and INH release at simulated gastric pH. PMID:17879985

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



More good news about polymeric plant- and algae-derived biomaterials in drug delivery systems.  


Natural polymers are continuously investigated for use in pharmaceutical and tissue engineering applications due to the renewability of their supply. Besides the conventional use of natural materials in dosage form design such as fillers, they are progressively investigated as functional excipients in specialised dosage forms. The hydrophilic nature of natural polymers together with their non-toxic and biodegradable properties make them useful in the design of modified release dosage forms. Matrix type tablets and beads made from natural gums and mucilages often exhibit sustained drug release through erosion in combination with swelling. Natural polymers are used to reach different pharmaceutical objectives, for instance, inulin and pectin are plant derived polymers that have suitable properties to produce colon-specific drug delivery. Alginate is an example of a natural polymer that has been used in the formulation of gastro-retentive dosage forms. Different cellulose derived polymers have been investigated as coating materials for dosage forms. Natural polymers can be chemically modified to produce molecules with specific properties and formation of co-polymers or polymer mixtures provide new opportunities to develop innovative drug delivery systems. PMID:24597532

Scholtz, Jacques; Van der Colff, Jaco; Steenekamp, Jan; Stieger, Nicole; Hamman, Josias



Rutin-phospholipid complex: an innovative technique in novel drug delivery system- NDDS.  


Biopharmaceutical properties together with potency contribute critically towards clinical efficacy of the drugs by influencing the dissolution and bioavailability. The aim of this study was to develop an amphiphilic phyto-phospholipid complex in order to enhance the delivery of poorly soluble rutin. The rutin-phospholipid complex (Ru-PLc) was prepared and investigated for various physico-chemical parameters like drug loading, infrared absorption (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM), aqueous/ n-octanol solubility and dissolution study. The in vitro anti-oxidant activity was also studied. In the SEM, Ru-PLc was found fluffy and porous with rough surface morphology. FTIR, DSC and XRPD data confirmed the formation of phospholipid complex. The water/ noctanol solubility of rutin was improved from 2.88 to 45.71 ?g/ ml and 68.17 to 245.18 ?g/ ml, respectively in the complex. The improved dissolution was shown by the phospholipid complex at different pH buffers. The antioxidant activity indicated that, the bioactivity of rutin was maintained even after being complexed with the phospholipid. Based on the results, it can be concluded that the phospholipid complex may be considered as a promising drug delivery system for improving the overall absorption and bioavailability of the rutin molecule. PMID:22283645

Singh, Devendra; Rawat, M S M; Semalty, Ajay; Semalty, Mona



On-site management of investigational products and drug delivery systems in conformity with Good Clinical Practices (GCPs)  

Microsoft Academic Search

Background Investigators and research teams participating in clinical trials have to deal with complex investigational products, study designs, and research environments. The emergence of new drug delivery systems and investigational products combining more than one drug and the development of biodrugs such as monoclonal antibodies, peptides, siRNA, and gene therapy to treat orphan or common diseases constitute a new challenge

Julie Méthot; Diane Brisson; Daniel Gaudet



Design and Evaluation of Self-Emulsifying Drug Delivery System (SEDDS) Of Carvedilol to Improve the Oral Absorption  

PubMed Central

Background: Self-emulsifying drug delivery system is an isotropic mixture of natural or synthetic oils, non-ionic surfactants or, one or more hydrophilic solvent and co-solvents/surfactant and polymer that improve bioavailability and increase solubility of poorly-soluble drugs. Objectives: This study was aimed to prepare and develop a stable formulation for self-emulsifying drug delivery system to enhance the solubility, release rate, and oral absorption of the poorly-soluble drug, carvedilol. Materials and Methods: The prepared self-emulsifying drug delivery system formulations were evaluated regarding their particle size, refractory index (RI), emulsifying efficiency, drug release, and rat intestine permeability. Results: The results showed oleic acid as oil with Labrafil as surfactant and Labrafac PG (propylene glycol dicaprylocapraye) as co-surfactant with hydroxypropyl methylcellulose and Poloxamer as polymer prepared stable emulsions with a refractive index higher than acidic medium and water. The particle size of formulations was influenced by the type of polymer so that the mean particle size in the self-emulsifying drug delivery system formulations containing hydroxypropyl methylcellulose have a higher particle size compared to Poloxamer formulations. The percentage of drug release after 24 hours (R24) for Poloxamer and hydroxypropyl methylcellulose formulations were 61.24-70.61% and to 74.26-91.11%, respectively. The correlation between percentages of drug released after 24 hours with type of polymer was significant. In permeation studies, a significant and direct correlation existed between P4 and surfactant/co-surfactant ratio. The self-emulsifying drug delivery system formulations showed drug permeability through the rat intestine 2.76 times more, compared with the control. Conclusions: This study demonstrated that physicochemical properties, in vitro release and rat intestine permeability were dependent upon the contents of S/C, water and oil percentage in formulations. PMID:25237644

Salimi, Anayatollah; Sharif Makhmal Zadeh, Behzad; Hemati, Ali asghar; Akbari Birgani, Sanaz



Intravenous drug delivery in neonates: lessons learnt.  


Intravenous drug administration presents a series of challenges that relate to the pathophysiology of the neonate and intravenous infusion systems in neonates. These challenges arise from slow intravenous flow rates, small drug volume, dead space volume and limitations on the flush volume in neonates. While there is a reasonable understanding of newborn pharmacokinetics, an appreciation of the substantial delay and variability in the rate of drug delivery from the intravenous line is often lacking. This can lead to difficulties in accurately determining the pharmacokinetic and pharmacodynamic relationship of drugs in the smallest patients. The physical variables that affect the passage of drugs through neonatal lines need to be further explored in order to improve our understanding of their impact on the delivery of drugs by this route in neonates. Through careful investigation, the underlying causes of delayed drug delivery may be identified and administration protocols can then be modified to ensure predictable, appropriate drug input kinetics. PMID:24482352

Sherwin, Catherine M T; Medlicott, Natalie J; Reith, David M; Broadbent, Roland S



The emerging potential of by-products as platforms for drug delivery systems.  


Natural resources are widely used as raw materials by industries. In most cases, abundant byproducts with low economic interest are also generated from agro-industrial supply chains. There are several examples for the rational use of agro-industrial byproducts in the nanobiotechnology field aiming for the development of novel products and high value added processes. Such raw materials include carapaces, pelages, blood, bagasses, and straws. Molecules from such materials (e.g. chitosan, cellulose, and albumin) are used as scaffolds of unprecedented novel nanostructure. Research efforts comprising a combination of sustainability, nanobiotechnology, and nanomedicine have emerged. One major area in nano-biotechnological research of agro-industrial byproducts is represented by the field of drug delivery systems (DDS). Among the main advantages of agro-industrial byproducts used as drug carriers are their abundance; low price; high biocompatibility; good biodegradability; moderate bioresorbability, associated with reduced systemic toxicity or even no toxicity; and often bioactivity. The goal of these efforts includes not only the possibility to characterize and manipulate matter on the nanoscale, but also to develop sustainable products and processes, including the development of platforms for drug delivery aiming for the treatment of pathologies such as cancer and diabetes. Indeed, there is great hope that the use of agro-industrial byproducts in nanobiotechnology will increase not only agricultural and livestock productivity, but will also contribute to other areas such as the development of DDS with new properties and low production costs; and sustainable environmental management due to the reuse of industrial discharged byproducts. This review will compile current findings on the use of byproducts as building blocks for modern drug carrier systems, emphasizing the challenges and promising applications. PMID:24712518

Joanitti, Graziella A; Silva, Luciano P



A hematoporphyrin-based delivery system for drug resistance reversal and tumor ablation.  


Nanotechnology-based drug delivery systems have been intensively investigated, while only a few of them can be used for clinic application. Hematoporphyrin (HP), a major molecule in erythrocyte, has been widely used in photodynamic therapy (PDT). In the present study, polyethylene glycol (PEG) modified hematoporphyrin (HPP)-based nanoparticle system was designed to load doxorubicin (HPPD), in achieving a synergistic effect of chemotherapy and PDT. Herein we presented that HPPD formed narrowly dispersed nanoparticles at 35 ± 2 nm, yielding an enhanced drug release at pH5.8 along with laser radiation. This combined treatment with HPPD and radiation facilitated drug penetration to the nucleus thereby reducing 12-fold decrease in IC50 value and promoting apoptosis in drug-resistant breast cancer cells. Notably, little toxicity was detected with HPP at the cellular level and in animal models. Live animal imaging revealed that HPPD performed ultra high tumor uptake in both mice and marmoset models. Strikingly, intravenous administration of HPPD and radiation on the tumor achieved efficient tumor ablation, without inducing myocardial injury. We report here the development of a biomolecule, HP-based nanoparticle system, which can synergistically yield chemotherapy and PDT. PMID:24373420

Ren, Yu; Wang, Ruirui; Liu, Yang; Guo, Hua; Zhou, Xuan; Yuan, Xubo; Liu, Chaoyong; Tian, Jianguo; Yin, Haifang; Wang, Yinsong; Zhang, Ning



Developments on drug delivery systems for the treatment of mycobacterial infections.  


The clinical management of tuberculosis and other mycobacterial diseases with antimycobacterial chemotherapy remains a difficult task. The classical treatment protocols are long-lasting; the drugs reach mycobacteria-infected macrophages in low amounts and/or do not persist long enough to develop the desired antimycobacterial effect; and the available agents induce severe toxic effects. Nanotechnology has provided a huge improvement to pharmacology through the designing of drug delivery systems able to target phagocytic cells infected by intracellular pathogens, such as mycobacteria. Liposomes and nanoparticles of polymeric nature represent two of the most efficient drug carrier systems that after in vivo administration are endocytosed by phagocytic cells and then release the carried agents into these cells. This article reviews the relevant publications describing the effectiveness of the association of antimycobacterial agents with liposomes or nanoparticles for the treatment of mycobacterioses, particularly for Mycobacterium tuberculosis and M. avium infections. The increased therapeutic index of antimycobacterial drugs; the reduction of dosing frequency; and the improvement of solubility of hydrophobic agents, allowing the administration of higher doses, have been demonstrated in experimental infections. These advantages may lead to new therapeutic protocols that will improve patient compliance and, consequently, lead to a more successful control of mycobacterial infections. The potential therapeutic advantages resulting from the use of non-invasive administration routes for nanoparticulate systems are also discussed. PMID:18473884

Gaspar, M M; Cruz, A; Fraga, A G; Castro, A G; Cruz, M E M; Pedrosa, J



Nanowired drug delivery for neuroprotection in central nervous system injuries: modulation by environmental temperature, intoxication of nanoparticles, and comorbidity factors.  


Recent developments in nanomedicine resulted in targeted drug delivery of active compounds into the central nervous system (CNS) either through encapsulated material or attached to nanowires. Nanodrug delivery by any means is supposed to enhance neuroprotection due to rapid accumulation of drugs within the target area and a slow metabolism of the compound. These two factors enhance neuroprotection than the conventions drug delivery. However, this is still uncertain whether nanodrug delivery could alter the pharmacokinetics of compounds making it more effective or just longer exposure of the compound for extended period of time is primarily responsible for enhanced effects of the drugs. Our laboratory is engaged in understanding of the nanodrug delivery using TiO(2) nanowires in CNS injuries models, for example, spinal cord injury (SCI), hyperthermia and/or intoxication of nanoparticles with or without other comorbidity factors, that is, diabetes or hypertension in rat models. Our observations suggest that nanowired drug delivery is effective under normal situation of SCI and hyperthermia as evidenced by significant reduction in the blood-brain barrier (BBB) breakdown, brain edema formation, cognitive disturbances, neuronal damages, and brain pathologies. However, when the pathophysiology of these CNS injuries is aggravated by nanoparticles intoxication or comorbidity factors, adjustment in dosage of nanodrug delivery is needed. This indicates that further research in nanomedicine is needed to explore suitable strategies in achieving greater neuroprotection in CNS injury in combination with nanoparticles intoxication or other comorbidity factors for better clinical practices. PMID:22162425

Sharma, Hari Shanker; Sharma, Aruna



Pulsed Laser Processing of Functionalized Polysaccharides for Controlled Release Drug Delivery Systems  

NASA Astrophysics Data System (ADS)

We report on the deposition of triacetate-pullulan polysaccharide thin films on drug pellets (diclofenac sodium) by matrix assisted pulsed laser evaporation method. The radiation generated by a pulsed excimer KrF* laser source (? = 248 nm, ? = 20 ns) operated at 2 Hz repetition rate was used for ice targets evaporation. The timed - controlled drug delivery was proved by spectroscopic in vitro studies and in vivo anti-inflammatory investigations on rabbits. We showed that the coating of drug pellets with triacetate-pullulan thin films resulted in the delayed delivery of the drug for up to 30 min.

Cristescu, R.; Popescu, C.; Popescu, A. C.; Socol, G.; Mihailescu, I.; Caraene, G.; Albulescu, R.; Buruiana, T.; Chrisey, D.


Gastroretentive drug delivery system of Ranitidine hydrochloride based on osmotic technology: development and evaluation.  


Gastroretentive drug delivery systems (GRDDS) of Ranitidine hydrochloride (RHC) has been designed based on the osmotic technology, with the floating and swelling features in order to prolong the gastric retention time. The developed system consisted of osmotic core (containing drug, osmotic agent and hydrophilic polymers), coated with semipermeable membrane (SPM) which is then further coated with compression coating of gelling agent (HPMC K4M) containing gas generating agent (citric acid). All the developed formulations were evaluated for floating lag time, duration of floating, drug content and in-vitro drug release profile. Formulation variables like levels of hydrophilic polymer (0-18.26%w/w), type of plasticizer (PEG-400, Dibutyl phthalate), coat thickness of SPM (60-100 microm), were found to affect the drug release from the developed formulations. Drug release was directly proportional to hydrophilic nature of plasticizer but inversely proportional to the levels of hydrophilic polymer and coat thickness of SPM. Drug release from developed formulations was independent of level of gas generating agent in compression coat, pH and agitation intensities of release media but dependent on osmotic pressure of the release media. All the developed formulation showed floating lag time of less than 2 min (desired) and were floated for more than 12 hr. Floating lag time was inversely related to level of citric acid in compression coat and directly related to the density of the developed formulations. The manufacturing procedure was found to be reproducible and formulations were stable after 3 months accelerated stability study. Prediction of steady state levels showed the plasma concentrations of RHC to be within desired range. PMID:18855605

Kumar, P; Singh, S; Mishra, B



Biodegradable polymeric nanoparticles as drug delivery devices  

Microsoft Academic Search

This review presents the most outstanding contributions in the field of biodegradable polymeric nanoparticles used as drug delivery systems. Methods of preparation, drug loading and drug release are covered. The most important findings on surface modification methods as well as surface characterization are covered from 1990 through mid-2000.

Kumaresh S Soppimath; Tejraj M Aminabhavi; Anandrao R Kulkarni; Walter E Rudzinski



ATTEMPTS: a heparin/protamine-based delivery system for enzyme drugs.  


A prodrug delivery system termed "Antibody Targeted, Triggered, Electrically Modified Prodrug-Type Strategy (ATTEMPTS)" has been developed to permit the antibody-directed administration of inactive enzyme drug including tissue-type plasminogen activator (tPA), and allow a subsequent triggered release of the active tPA at the target site. Cation-modified tPA (mtPA) was attached to a heparin-antifibrin complex via ionic interaction, and the active tPA can subsequently be released by the addition of protamine, a competitive heparin inhibitor. Anti-fibrin IgG was conjugated to heparin via an end-point attachment to form the heparin-antifibrin complex which provides the targeting efficiency of the final heparin/mtPA complex. Cation modification was performed by either chemical conjugation by linking (Arg)7Cys to tPA with N-succinimidy-3-(2-pyridyldithio) propionate or by recombinant DNA methods. Results show that the modification process did not significantly alter the specific activity of tPA with regard to plasminogen activation, fibrin-binding ability, and response toward fibrinogen. The complexes of both modified tPA-heparin did not yield any intrinsic catalytic activity owing to the blockage of the active site of tPA by the attached heparin. On the other hand, heparin-induced inhibition of modified tPA activity was reversed by adding protamine, which is similar to that of a prodrug delivery system. These results suggest that heparin/protamine-based enzyme delivery systems may be a useful tool to improve current enzyme therapeutic status, as well as thrombolytic therapy, by both regulating the release of active enzyme and aborting the associated systemic toxic effect. Currently, modification of enzyme drugs has been optimized by recombinant DNA technology assisted by computer simulation. In addition, the original strategy has been revised to obtain enhanced therapeutic efficacy. PMID:11772450

Liang, J F; Li, Y T; Song, H; Park, Y J; Naik, S S; Yang, V C



Orally dissolving strips: A new approach to oral drug delivery system  

PubMed Central

Recently, fast dissolving films are gaining interest as an alternative of fast dissolving tablets. The films are designed to dissolve upon contact with a wet surface, such as the tongue, within a few seconds, meaning the consumer can take the product without need for additional liquid. This convenience provides both a marketing advantage and increased patient compliance. As the drug is directly absorbed into systemic circulation, degradation in gastrointestinal tract and first pass effect can be avoided. These points make this formulation most popular and acceptable among pediatric and geriatric patients and patients with fear of choking. Over-the-counter films for pain management and motion sickness are commercialized in the US markets. Many companies are utilizing transdermal drug delivery technology to develop thin film formats. In the present review, recent advancements regarding fast dissolving buccal film formulation and their evaluation parameters are compiled. PMID:24015378

Bala, Rajni; Pawar, Pravin; Khanna, Sushil; Arora, Sandeep



Development, Characterization, and Pharmacodynamic Evaluation of Hydrochlorothiazide Loaded Self-Nanoemulsifying Drug Delivery Systems  

PubMed Central

The objective of the current work was to develop optimized self-nanoemulsifying drug delivery systems (SNEDDS) and evaluate their in vitro and in vivo performance. The research comprised various studies which includes solubility studies in various vehicles, pseudoternary phase diagram construction, and preparation and characterization of SNEDDS along with in vitro dissolution and in vivo pharmacodynamic profiling. Based on dissolution profile, a remarkable increase in rate of dissolution was observed in comparison with plain drug and marketed formulation. Optimized SNEDDS formulation was composed of Capmul MCM (19.17% w/w), Tween 80 (57.5%?w/w), Transcutol P (12.7%?w/w), and HCT (4.17%?w/w). In vivo pharmacodynamic evaluation in Wistar rats showed considerable increase in pharmacological effect of HCT by SNEDDS formulation as compared with plain HCT. PMID:25580455

Yadav, Pankajkumar S.; Yadav, Ekta; Verma, Amita; Amin, Saima



Advances in ophthalmic drug delivery.  


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. PMID:25531930

Morrison, Peter Wj; Khutoryanskiy, Vitaliy V



Semifluorinated alkanes as a liquid drug carrier system for topical ocular drug delivery.  


Semifluorinated alkanes (SFA, e.g. perfluorobutylpentane F4H5, perfluorohexyloctane F6H8) are inert, non-toxic fluids capable of dissolving lipophilic drugs. The aim of this study to assess the bioavailability and safety of SFAs as drug solvents for the topical ocular application of Cyclosporin A (CsA). A commercially available CsA formulation (Restasis, 0.05% CsA in castor oil) was tested against two novel formulations of 0.05% CSA in (a) F4H5 containing Ethanol (0.5 w/w%) and (b) F6H8 containing Ethanol (0.5 w/w%) with 0.05% CsA. Formulations were tested on rabbit corneas cultured on an artificial anterior chamber with a constant flow of an aqueous humour supplement (Ex Vivo Eye Irritation Test (EVEIT) system). Anterior chamber fluids were sampled at multiple time points to analyse the CsA concentration following single and repeated application regimes by HPLC. Photographs of fluorescein sodium-stained corneas were recorded for corneal toxicity evaluation. The impact of the formulations on the integrity of the corneal barrier function was tested after drug application by fluorescein sodium corneal diffusion experiments. The influence on the corneal metabolism was evaluated by analysis of the metabolic markers glucose and lactate. Restasis did not pass the corneal barrier after short term application, CsA in ethanolic F4H6 reached a maximum of 152.95 ng/ml in anterior chamber fluid samples whilst CsA in ethanolic F6H8 reached a maximum of 15.12 ng/ml. After repeated applications for 8h, Restasis reached 21.07 ng/ml compared to 247.62 ng/ml and 174.5 ng/ml for F4H5 and F6H8, respectively. No corneal toxicity was observed in following application of any of the formulations. In contrast to the commercially available castor oil-based formulation, CsA dissolved in SFAs reached therapeutic inner ocular concentrations after topical administration, possibly leading to the replacement of systemic applications of CsA for inflammatory ocular disease. PMID:24844949

Dutescu, R M; Panfil, C; Merkel, O M; Schrage, N



PEGylated mesoporous silica as a redox-responsive drug delivery system for loading thiol-containing drugs.  


In this paper, we describe the development of a redox-responsive delivery system based on 6-mercaptopurine (6-MP)-conjugated colloidal mesoporous silica (CMS) via disulfide bonds. mPEG was modified on the surface of silica to improve the dispersibility and biocompatiblity of CMS by reducing hemolysis and protein adsorption. The CMS carriers with different amounts of thiol groups were prepared to evaluate the impact of modified thiol on the drug loading efficiency. In vitro release studies demonstrated that the CMS nanoparticles exhibited highly redox-responsive drug release. The cumulative release of 6-MP was less than 3% in absence of GSH, and reached more than 70% within 2h in the presence of 3mM GSH. In addition, by comparing the cumulative release profiles of CMS-SS-MP@mPEG with their counterparts without the grafting of hydrophilic PEG, it was found that mPEG chains did not hinder the drug release due to the cleavable disulfide bonds and the improved dispersibility. Overall, this work provides a new strategy to connect thiol-containing/thiolated drugs and hydrophilic polymers to the interior and exterior of silica via disulfide bonds to obtain redox-responsive release and improve the dispersibility and biocompatibility of silica. PMID:25445534

Zhao, Qinfu; Wang, Chen; Liu, Ying; Wang, Jiahong; Gao, Yikun; Zhang, Xiaojing; Jiang, Tongying; Wang, Siling



Elastin-like polypeptides and their applications in anticancer drug delivery systems: a review.  


Abstract Elastin-like polypeptides (ELPs) are large molecular weight biopolymers. They have been widely studied as macromolecular carriers for targeted delivery of drugs. The aim of the present article is to review the available information on ELPs (including our recent investigations), their properties, drug delivery applications to tumor sites and future perspectives. This review also provides information on the use of short synthetic ELPs for making ELP-drug conjugates, for targeted delivery of anticancer drugs. In the present review we also focus on the point that short ELPs can also be used for targeting anticancer drugs to tumor sites as they behave similar to long ELPs regarding their capacity to undergo inverse temperature transition (ITT) behavior. PMID:24215207

Saxena, Rubha; Nanjan, Moola Joghee



Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0-100 µM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.

Sun, Yun; Chen, Zhi-long; Yang, Xiao-xia; Huang, Peng; Zhou, Xin-ping; Du, Xiao-xia



Preformed albumin corona, a protective coating for nanoparticles based drug delivery system.  


The non-specific interaction between nanoparticles (NPs) and plasma proteins occurs immediately after NPs enter the blood, resulting in the formation of the protein corona that thereafter replaces the original NPs and becomes what the organs and cells really see. Consequently, the in vivo fate of NPs and the biological responses to the NPs are changed. This is one substantial reason for the two main problems of the NPs based drug delivery system, i.e. nanotoxicity and rapid clearance of NPs from the blood after intravenous injection. Here, we demonstrate the successful application of the preformed albumin corona in inhibiting the plasma proteins adsorption and decreasing the complement activation, and ultimately in prolonging the blood circulation time and reducing the toxicity of the polymeric PHBHHx NPs. Since the interaction of proteins with various nano-materials and/or -particles is ubiquitous, pre-forming albumin corona has a great potential to be a versatile strategy for optimizing the NPs based drug delivery system. PMID:23932500

Peng, Qiang; Zhang, Shu; Yang, Qin; Zhang, Ting; Wei, Xue-Qin; Jiang, Li; Zhang, Chao-Liang; Chen, Qian-Ming; Zhang, Zhi-Rong; Lin, Yun-Feng



Emerging Intra-Articular Drug Delivery Systems for the Temporomandibular Joint  

PubMed Central

Temporomandibular joint (TMJ) disorders are a heterogeneous group of diseases that cause progressive joint degeneration leading to chronic pain and reduced quality of life. Both effective pain reduction and restoration of TMJ function remain unmet challenges. Intra-articular injections of corticosteroids and hyaluronic acid are currently used to treat chronic pain, but these methods require multiple injections that increase the risk of iatrogenic joint damage and other complications. The small and emerging field of TMJ tissue engineering aims to reduce pain and disability through novel strategies that induce joint tissue regeneration. Development of methods for sustained, intra-articular release of growth factors and other pro-regenerative signals will be critical for the success of TMJ tissue engineering strategies. This review discusses methods of intra-articular drug delivery to the TMJ, as well as emerging injectable controlled release systems with potential to improve TMJ drug delivery, to encourage further research in the development of sustained release systems for both long-term pain management and to enhance tissue engineering strategies for TMJ regeneration. PMID:18835358

Mountziaris, Paschalia M.; Kramer, Phillip R.; Mikos, Antonios G.



Refillable and magnetically actuated drug delivery system using pear-shaped viscoelastic membrane.  


We report a refillable and valveless drug delivery device actuated by an external magnetic field for on-demand drug release to treat localized diseases. The device features a pear-shaped viscoelastic magnetic membrane inducing asymmetrical deflection and consecutive touchdown motion to the bottom of the dome-shaped drug reservoir in response to a magnetic field, thus achieving controlled discharge of the drug. Maximum drug release with 18?±?1.5??g per actuation was achieved under a 500?mT magnetic flux density, and various controlled drug doses were investigated with the combination of the number of accumulated actuations and the strength of the magnetic field. PMID:25379104

So, Hongyun; Seo, Young Ho; Pisano, Albert P



Recent advances in ophthalmic drug delivery  

PubMed Central

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

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



Magnetizable implants for targeted drug delivery  

NASA Astrophysics Data System (ADS)

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.

Forbes, Zachary Graham


Assessing the viability of microsponges as gastro retentive drug delivery system of curcumin: optimization and pharmacokinetics.  


The work was aimed to validate the gastroretentive potential of microsponges via optimization of targeted floating curcumin microsponges for improved site specific absorption for gastric cancer Modified quasi emulsion solvent diffusion method was used to formulate microsponges using 3(2) full factorial design. The effect of different levels of ethyl cellulose and polyvinyl alcohol concentration, selected as independent variables was determined on the % entrapment efficiency, % buoyancy and % cumulative drug release. Modified rosette rise apparatus was used for in vitro release and the release data best fitted Higuchi's model and mechanism of drug release was diffusion (n). The optimized formulation (MS5) demonstrated favourable % entrapment efficiency (90.7 ± 1.7), % buoyancy (82.0 ± 2.0) and % cumulative drug release (85.2 ± 1.07) with maximum desirability factor of 0.816. SEM revealed spherical and porous microsponges. DSC confirmed molecular dispersion of the drug in the microsponges polymeric matrix. DRIFT revealed no chemical interaction between the drug and polymer used. The in vitro permeation of curcumin through gastric mucin gel layer affirmed the capability of microsponges to deliver drug across mucin r and reach the target site to treat gastric cancer. Anticancer oral dose of microsponges was calculated as 50mg by cytotoxicity assay in human cancer cell line KB. The pharmacokinetic evaluation of MS5 in rabbits revealed 10-fold increase in bioavailability as compared to native curcumin, demonstrated the superiority of microsponges over native curcumin as gastro retentive drug delivery system. This study presents a new approach based on floating ability of microsponges for treatment of gastric cancer. PMID:24184218

Arya, Priyanka; Pathak, Kamla



The Cellular Engineering & Nano-Therapeutics Laboratory (CENT LAB) Our research program focuses on the development of bio-inspired drug delivery systems that enhance  

E-print Network

on the development of bio-inspired drug delivery systems that enhance the therapeutic activity of the incorporated molecules, macromolecules, and polymeric drug delivery systems across epithelial and endothelial barriers drug molecules while eliminating or minimizing their potential side effects. We follow two parallel

Kamat, Vineet R.


Microneedle delivery for improved efficacy of antiretroviral and antibiotic drugs  

E-print Network

Two classes of drugs, antiretrovirals and antibiotics, could benefit greatly from delivery through microneedles. Microneedles (MN) offer an increase in efficacy for these drugs by providing delivery to the lymphatic system ...

Stauber, Zachary Jason



The development and in vivo evaluation of a colon drug delivery system using human volunteers.  


The aim of this study was to develop a multiple-unit dosage system that released model drug into the colon, and also to evaluate the efficiency of the dosage form in human volunteers. The developed system combines pH-, time- and biodegradable polymer-based mechanisms for drug targeting to the colon. Pellet cores containing caffeine as model drug and chitosan and microcrystalline cellulose as excipients were prepared by the extrusion/spheronization method. The prepared pellets were film coated with a pH-dependent polymer, Eudragit FS 30 D. The coating total weight gain was 28.83% (w/w). Thanks to the application of an outer enteric film and the multiple unit design of the dosage form, the variability in gastric emptying was overcome, and a colon-specific targeting relied on the reproducibility of a small intestinal transit time, which was reported to be 3 ± 1 hours. A biodegradable polymer in the pellet core, chitosan, ensured the site-specific release of the model drug due to its solubility at the lower pH of the colonic region and by its biodegradability from the bacteria present. The efficiency of the system was confirmed by the in vivo testing of human saliva. The time of the first appearance of caffeine into the saliva, T(lag), was used as a parameter to estimate the disintegration time of the pellets into the gastrointestinal tract. The caffeine appeared in the saliva within 6.95 ± 1.12 hours (T(lag)) in 9 volunteers. A comparison of the reported colon arrival times indicates that the developed system is applicable to colonic drug delivery. PMID:22211714

Zimová, Lucie; Vetchý, David; Muselík, Jan; Štembírek, Jan



Novel Drug Delivery Systems: Potential in Improving Topical Delivery of Antiacne Agents  

Microsoft Academic Search

Acne is the most common cutaneous disorder of multifactorial origin with a prevalence of 70–85% in adolescents. The majority of the acne sufferers exhibit mild to moderate acne initially, which progresses to the severe form in certain cases. Topical therapy is employed as first-line treatment in mild acne, whereas for moderate and severe acne, systemic therapy is required in addition

A. A. Date; B. Naik; M. S. Nagarsenker



Preparation and pharmaceutical evaluation of new tacrolimus-loaded solid self-emulsifying drug delivery system.  


The purpose of this study was to develop a novel tacrolimus-loaded solid self-emulsifying drug delivery system (SEDDS) using Labrafac as an oil phase. The ternary phase diagram was plotted with Labrafac, Labrasol and Lauroglycol used as an oil, surfactant and co-surfactant, respectively. The liquid SEDDS formulated with Labrasol, Lauroglycol and Labrafac (70:15:15, volume ratio) furnished the smallest emulsion globule size. The solid SEDDS was obtained by spray-drying the liquid mixture containing the liquid SEDDS with 5 % tacrolimus and silicon dioxide. Furthermore, dissolution of tacrolimus from the solid SEDDS and pharmacokinetics in rats was studied compared to the commercial product. The solid SEDDS produced relatively larger emulsion globule size than that exhibited by the corresponding liquid SEDDS. However, this size variation was not significantly different. The solid SEDDS with approximately 280 nm emulsion droplet size improved the dissolution of the drug compared to drug power and the commercial product. It resulted in significantly higher plasma concentration, AUC and Cmax, and shorter Tmax values than did the commercial product (p < 0.05). The enormously enhanced oral bioavailability of tacrolimus in rats was attributed to relatively faster absorption due to accelerated dissolution of the drug from the solid SEDDS. Therefore, this novel solid SEDDS prepared with Labrafac as an oil phase is an excellent way to achieve better bioavailability of tacrolimus given via the oral route. PMID:25134927

Seo, Youn Gee; Kim, Dong-Wuk; Cho, Kwan Hyung; Yousaf, Abid Mehmood; Kim, Dong Shik; Kim, Jeong Hoon; Kim, Jong Oh; Yong, Chul Soon; Choi, Han-Gon



Protein encapsulated magnetic carriers for micro/nanoscale drug delivery systems.  

SciTech Connect

Novel methods for drug delivery may be based on nanotechnology using non-invasive magnetic guidance of drug loaded magnetic carriers to the targeted site and thereafter released by external ultrasound energy. The key building block of this system is to successfully synthesize biodegradable, magnetic drug carriers. Magnetic carriers using poly(D,L-lactide-co-glycolide) (PLGA) or poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) as matrix materials were loaded with bovine serum albumin (BSA) by a double-emulsion technique. BSA-loaded magnetic microspheres were characterized for size, morphology, surface charge, and magnetization. The BSA encapsulation efficiency was determined by recovering albumin from the microspheres using dimethyl sulfoxide and 0.05N NaOH/0.5% SDS then quantifying with the Micro-BCA protein assay. BSA release profiles were also determined by the Micro-BCA protein assay. The microspheres had drug encapsulation efficiencies up to 90% depending on synthesis parameters. Particles were spherical with a smooth or porous surface having a size range less than 5 {mu}m. The surface charge (expressed as zeta potential) was near neutral, optimal for prolonged intravascular survival. The magnetization of these BSA loaded magnetic carriers was 2 to 6 emu/g, depending on the specific magnetic materials used during synthesis.

Xie, Y.; Kaminski, M. D.; Mertz, C. J.; Finck, M. R.; Guy, S. G.; Chen, H.; Rosengart, A. J.; Chemical Engineering; Univ. of Chicago, Pritzker School of Medicine



Fluorination of electrospun hydrogel fibers for a controlled release drug delivery system.  


Electrospinning and fluorination were carried out in order to obtain a controlled release drug delivery system to solve the problem of both an initial burst of the drug and a limited release time. Poly(vinyl alcohol) was electrospun with Procion Blue as a model drug and heat treated in order to obtain cross-linked hydrogel fibers. Two different kinds of electrospun fibers of thin and thick diameters were obtained by controlling the electrospinning conditions. Thin fibers offer more available sites than thick fibers for surface modification during fluorination. Fluorination was conducted to control the release period by introducing hydrophobic functional groups on the surface of fibers. With an increase in the reaction pressure of the fluorine gas hydrophobic C-F and C-F(2) bonds were more effectively introduced. Over-fluorination of the fibers at higher reaction pressures of fluorine gas led to the introduction of C-F(2) bonds, which made the surface of the fibers hydrophobic and resulted in a decrease in their swelling potential. When C-F bonds were generated the initial drug burst decreased dramatically and total release time increased significantly, by a factor of approximately 6.7 times. PMID:19531386

Im, Ji Sun; Yun, Jumi; Lim, Youn-Mook; Kim, Hyung-Il; Lee, Young-Seak



Tumor-Targeted Drug Delivery with Aptamers  

PubMed Central

Cancer is one of the leading causes of death around the world. Tumor-targeted drug delivery is one of the major areas in cancer research. Aptamers exhibit many desirable properties for tumor-targeted drug delivery, such as ease of selection and synthesis, high binding affinity and specificity, low immunogenicity, and versatile synthetic accessibility. Over the last several years, aptamers have quickly become a new class of targeting ligands for drug delivery applications. In this review, we will discuss in detail about aptamer-based delivery of chemotherapy drugs (e.g. doxorubicin, docetaxel, daunorubicin, and cisplatin), toxins (e.g. gelonin and various photodynamic therapy agents), and a variety of small interfering RNAs. Although the results are promising which warrants enthusiasm for aptamer-based drug delivery, tumor homing of aptamer-based conjugates after systemic injection has only been achieved in one report. Much remains to be done before aptamer-based drug delivery can reach clinical trials and eventually the day-to-day management of cancer patients. Therefore, future directions and challenges in aptamer-based drug delivery are also discussed. PMID:21838687

Zhang, Yin; Hong, Hao; Cai, Weibo



A novel hybrid delivery system: polymer-oil nanostructured carrier for controlled delivery of highly lipophilic drug all-trans-retinoic acid (ATRA).  


Many recently developed drugs encounter delivery issues due to their high lipophilicity and poor aqueous solubility. This study reports the development of a novel hybrid nanocarrier known as polymer-oil nanostructured carrier (PONC), in which highly lipophilic drugs such as all-trans-retinoic acid (ATRA) and indomethacin pre-solubilized in oil phase were dispersed in a polymeric matrix of poly(D,L-lactic-co-glycolic acid) (PLGA). In comparison to the standard PLGA only nanoparticles, PONC substantially increased the encapsulation efficiency of ATRA and indomethacin by up to 259% and 124%, respectively. Differential scanning calorimetry analysis revealed that the inclusion of oil introduced nanostructure into the polymeric matrix of the carrier. This feature facilitated more uniform distribution of the drug molecules which subsequently led to improved drug release kinetics with significantly reduced burst release effects (p<0.05). PONC was lyophilizable, remained physically stable when stored at low temperatures, and demonstrated low non-specific carrier toxicity. Delivery of ATRA by PONC also significantly improved its anticancer activity over the standard PLGA only nanoparticles (p<0.05). Our findings have therefore validated a promising delivery system that integrates the advantages of lipid-based (e.g. efficient encapsulation of highly lipophilic drugs) and polymeric colloidal carriers (e.g. uniform size, good stability), plus potential therapeutic benefits for delivery of poorly water-soluble anticancer drugs like ATRA. PMID:22850294

Narvekar, Mayuri; Xue, Hui Yi; Wong, Ho Lun



Controlled release of oral tetrahydrocurcumin from a novel self-emulsifying floating drug delivery system (SEFDDS).  


The objectives of this study were to develop and evaluate a novel self-emulsifying floating drug delivery system (SEFDDS) that resulted in improved solubility, dissolution, and controlled release of the poorly water-soluble tetrahydrocurcumin (THC). The formulations of liquid self-emulsifying drug delivery system (SEDDS; mixtures of Labrasol, Cremophor EL, Capryol 90, Labrafac PG) were optimized by solubility assay and pseudo-ternary phase diagram analysis. The liquid SEDDS was mixed with adsorbent (silicon dioxide), glyceryl behenate, pregelatinized starch, sodium starch glycolate, and microcrystalline cellulose and transformed into pellets by the extrusion/spheronization technique. The resulting pellets with 22% liquid SEDDS had a uniform size and good self-emulsification property. The microemulsions in aqueous media of different self-emulsifying floating pellet formulations were in a particle size range of 25.9-32.5 nm. Use of different weight proportions of glyceryl behenate and sodium starch glycolate in pellet formulations had different effects on the floating abilities and in vitro drug release. The optimum formulation (F2) had a floating efficiency of 93% at 6 h and provided a controlled release of THC over an 8-h period. The release rate and extent of release of THC liquid SEDDS (80% within 2 h) and self-emulsifying floating pellet formulation (80% within 8 h) were significantly higher than that of unformulated THC (only 30% within 8 h). The pellet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. Controlled release from this novel SEFDDS can be a useful alternative for the strategic development of oral solid lipid-based formulations. PMID:21181511

Setthacheewakul, Saipin; Kedjinda, Wichan; Maneenuan, Duangkhae; Wiwattanapatapee, Ruedeekorn



Semi-solid Sucrose Stearate-Based Emulsions as Dermal Drug Delivery Systems  

PubMed Central

Mild non-ionic sucrose ester surfactants can be employed to produce lipid-based drug delivery systems for dermal application. Moreover, sucrose esters of intermediate lipophilicity such as sucrose stearate S-970 possess a peculiar rheological behavior which can be employed to create highly viscous semi-solid formulations without any further additives. Interestingly, it was possible to develop both viscous macroemulsions and fluid nanoemulsions with the same chemical composition merely by slight alteration of the production process. Optical light microscopy and cryo transmission electron microscopy (TEM) revealed that the sucrose ester led to the formation of an astonishing hydrophilic network at a concentration of only 5% w/w in the macroemulsion system. A small number of more finely structured aggregates composed of surplus surfactant were likewise detected in the nanoemulsions. These discoveries offer interesting possibilities to adapt the low viscosity of fluid O/W nanoemulsions for a more convenient application. Moreover, a simple and rapid production method for skin-friendly creamy O/W emulsions with excellent visual long-term stability is presented. It could be shown by franz-cell diffusion studies and in vitro tape stripping that the microviscosity within the semi-solid formulations was apparently not influenced by their increased macroviscosity: the release of three model drugs was not impaired by the complex network-like internal structure of the macroemulsions. These results indicate that the developed semi-solid emulsions with advantageous application properties are highly suitable for the unhindered delivery of lipophilic drugs despite their comparatively large particle size and high viscosity. PMID:24310496

Klang, Victoria; Schwarz, Julia C.; Matsko, Nadejda; Rezvani, Elham; El-Hagin, Nivine; Wirth, Michael; Valenta, Claudia



Multi-drug delivery system based on alginate/calcium carbonate hybrid nanoparticles for combination chemotherapy.  


A facile strategy to prepare nano-sized drug carriers for co-delivery of multiple types of drugs in combination chemotherapy was developed. Inorganic/organic hybrid alginate/CaCO3 nanoparticles were prepared by co-precipitation in an aqueous solution under very mild conditions. A hydrophilic drug (doxorubicin hydrochloride, DOX) and a hydrophobic drug (paclitaxel, PTX) were co-encapsulated in the hybrid nanoparticles. For comparison, PTX loaded nanoparticles and DOX loaded nanoparticles were also prepared. The measurement based on dynamic light scattering indicated all nanoparticles had a mean size less than 200 nm with a relatively narrow size distribution. The morphology of the nanoparticles was observed by TEM. The in vitro drug release study showed that the release of DOX and PTX from the dual drug loaded nanoparticles could be effectively sustained. The tumor cell inhibitory effect of the drug loaded nanoparticles was evaluated in HeLa cells and MCF-7/ADR cells. The dual drug loaded nanoparticles exhibited significantly enhanced cell uptake and nuclear localization as compared with the single drug loaded nanoparticles. As a result, the dual drug loaded nanoparticles had a significantly enhanced cell inhibitory effect, especially for drug resistant tumor cells. These results indicated that alginate/CaCO3 hybrid nanoparticles have promising applications for the co-delivery of drugs with different physicochemical properties in combination chemotherapy to overcome multidrug resistance. PMID:25315499

Wu, Jin-Long; Wang, Chao-Qun; Zhuo, Ren-Xi; Cheng, Si-Xue



Stereomicroscopic imaging technique for the quantification of cold flow in drug-in-adhesive type of transdermal drug delivery systems.  


Cold flow is a phenomenon occurring in drug-in-adhesive type of transdermal drug delivery systems (DIA-TDDS) because of the migration of DIA coat beyond the edge. Excessive cold flow can affect their therapeutic effectiveness, make removal of DIA-TDDS difficult from the pouch, and potentially decrease available dose if any drug remains adhered to pouch. There are no compendial or noncompendial methods available for quantification of this critical quality attribute. The objective was to develop a method for quantification of cold flow using stereomicroscopic imaging technique. Cold flow was induced by applying 1 kg force on punched-out samples of marketed estradiol DIA-TDDS (model product) stored at 25°C, 32°C, and 40°C/60% relative humidity (RH) for 1, 2, or 3 days. At the end of testing period, dimensional change in the area of DIA-TDDS samples was measured using image analysis software, and expressed as percent of cold flow. The percent of cold flow significantly decreased (p < 0.001) with increase in size of punched-out DIA-TDDS samples and increased (p < 0.001) with increase in cold flow induction temperature and time. This first ever report suggests that dimensional change in the area of punched-out samples stored at 32°C/60%RH for 2 days applied with 1 kg force could be used for quantification of cold flow in DIA-TDDS. PMID:24585397

Krishnaiah, Yellela S R; Katragadda, Usha; Khan, Mansoor A



Technological and biopharmaceutical optimization of nystatin release from a multiparticulate based bioadhesive drug delivery system.  


Formulation considerations of a new drug delivery system include controlling the site of release of the active ingredient, maintaining drug level for a suitable time and decreasing dosage frequency. In research and development practice, these therapeutic benefits can be attained by selecting suitable active ingredients and optimizing procedure parameters, determining the composition of the medicine, and dissolution properties. The aim of our study was to design a pharmaceutical preparation with increased local therapeutic effect in the therapy of gastrointestinal candidiasis. The polyene antibiotic nystatin may be an optimal choice for active agent, incorporated in a bioadhesive multiparticulate system. Choosing the proper excipients in the proper dosage form and ensuring prolonged residence time may further improve the optimal treatment. Using an experimental design, the micropellets were prepared with 5% nystatin content, taking the factors average pellet size (~200 to ~800 ?m) and the amount of applied carbomer and hydroxyethylcellulose (0-5%) into consideration. Dissolution of the active ingredient was detected by UV spectrophotometric and microbiological assay. The bioadhesive character of the multiparticulate dosage form was examined by ex vivo wash-off test. The only factor which significantly influenced the examined parameters was average pellet size. The proportion of applied bioadhesive excipients had significance mostly in interactions with average pellet size. Eventually, optimized drug release (5-10 min mean dissolution time, 50-55% bioadhesion retention) could be achieved with 550 ?m pellet size, containing carbomer and hydroxyethylcellulose in 85:15 ratio. PMID:23528741

Pál, Szilárd; Nagy, Sándor; Bozó, Tamás; Kocsis, Béla; Dévay, Attila



Preparation and in vitro evaluation of mebeverine HCl colon-targeted drug delivery system.  


Mebeverine HCl is a water soluble drug commonly used to treat irritable bowel syndrome by acting directly on the smooth muscles of the colon. This work was aimed at the formulation and in vitro evaluation of a colon-targeted drug delivery system containing mebeverine HCl. Matrix tablets were prepared using ethyl cellulose (EC), Eudragit RL 100 either solely or in combination by wet granulation technique. Dissolution was carried out in 0.1 N HCl for 2?h followed by pH 6.8 phosphate buffer for eight hours. Uncoated forms released more than 5% drug in 0.1 N HCl therefore, Eudragit L100 was used as a coat. The results indicated very slow release profile. As a result, single retardant was used to prepare the matrix and coated by Eudragit L 100. The matrix containing 7% Eudragit RL 100 and 6% of binder was subjected to further studies to assess the effect of different coats (Eudragit L 100-55 and cellulose acetate phthalate) and different binders (pectin and sodium alginate) on the release profile. Eudragit L 100 and pectin were the best coating agent and binder, respectively. The final formula was stable and it can be concluded that the prepared system has the potential to deliver mebeverine HCl in vivo to the colon. PMID:20429815

Abdullah, Ghassan Z; Abdulkarim, Muthanna F; Chitneni, Mallikarjun; Mutee, Ahmed F; Ameer, Omar Z; Salman, Ibrahim M; Noor, Azmin M



Asymmetric membrane capsules of phenylephrine hydrochloride: an osmotically controlled drug delivery system.  


The aim of the current study was to develop osmotically controlled release system of freely water soluble drug phenylephrine hydrochloride by use of asymmetric membrane capsules to reduce the dosing frequency and consequently improve the patient compliance. Ethyl cellulose asymmetric membrane capsules were developed by phase inversion process and solubility modulation was accomplished by common ion effect wherein sodium chloride was included in the formulation that also served as an osmogen. The effect of formulation variables namely level of polymer (ethyl cellulose), level of pore former (glycerol) and level of osmogen (sodium chloride) on the in vitro release of the drug was evaluated by 2(3) factorial design. Effects of environmental factors on the release rate of the drug from asymmetric membrane capsules were also evaluated. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and inner porous region for the prepared asymmetric membrane. The dimensional analysis of asymmetric membrane capsule documented the capsules to be of uniform cap and body size comparable to commercial hard gelatin capsules. In vitro release studies results showed that incorporation of higher amount of osmogen not only increased the osmotic pressure but also controlled the drug release for a period of 12 hr. The drug release was inversely proportional to the level of polymer in asymmetric membrane capsule but directly related to the level of pore former in the membrane. The optimized asymmetric membrane capsule (F5) was able to provide zero order release of phenylephrine hydrochloride independent of agitation rate, intentional defect in the membrane and pH of dissolution medium but was dependent on the osmotic pressure gradient between inside and outside of the delivery system. PMID:21696358

Kumar, Anil; Philip, Anil Kumar; Pathak, Kamla



Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a potential Anticancer Drug Delivery System  

NASA Astrophysics Data System (ADS)

Solid lipid nanoparticles (SLNs) consist of spherical solid lipid particles in the nanometer size range, which are dispersed in water or in an aqueous surfactant solution. SLN technology represents a promising new approach to deliver hydrophilic as well as lipophilic drugs. The commercialization of SLN technology remains limited despite numerous efforts from researchers. The purpose of this research was to advance SLN preparation methodology by investigating the feasibility of preparing glyceryl monostearate (GMS) nanoparticles by using three preparation methods namely microemulsion technique, magnetic stirring technique and temperature modulated solidification technique of which the latter two were developed in our laboratory. An anticancer drug 5-fluorouracil was incorporated in the SLNs prepared via the temperature modulated solidification process. Optimization of the magnetic stirring process was performed to evaluate how the physicochemical properties of the SLN was influenced by systematically varying process parameters including concentration of the lipid, concentration of the surfactant, type of surfactant, time of stirring and temperature of storage. The results demonstrated 1:2 GMS to tween 80 ratio, 150 ml dispersion medium and 45 min stirring at 4000 RPM speed provided an optimum formulation via the temperature modulated solidification process. SLN dispersions were lyophilized to stabilize the solid lipid nanoparticles and the lyophilizates exhibited good redispersibility. The SLNs were characterized by particle size analysis via dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), drug encapsulation efficiency and in vitro drug release studies. Particle size of SLN dispersion prepared via the three preparation techniques was approximately 66 nm and that of redispersed lyophilizates was below 500 nm. TEM images showed spherical to oval particles that were less dense in the core with a well-defined shell and the particle size was in agreement with the particle size analysis data obtained by DLS. DSC thermograms of the lyophilized SLNs indicate a reduction in the crystallinity order of GMS particles. The drug encapsulation efficiency was found to be approximately 30%. In vitro drug release studies from redispersed lyophilized SLNs showed that 17 % of the encapsulated drug was released within 2 h. The SLNs prepared in our lab demonstrated characteristics that can potentially be utilized in an anticancer drug delivery system. Future in vitro cell culture and in vivo animal model studies will delineate compatibility and utility of these formulations in biological systems.

Patel, Meghavi


Calcium phosphate ceramics in drug delivery  

NASA Astrophysics Data System (ADS)

Calcium phosphate (CaP) particulates, cements and scaffolds have attracted significant interest as drug delivery vehicles. CaP systems, including both hydroxyapaptite and tricalcium phosphates, possess variable stoichiometry, functionality and dissolution properties which make them suitable for cellular delivery. Their chemical similarity to bone and thus biocompatibility, as well as variable surface charge density contribute to their controlled release properties. Among specific research areas, nanoparticle size, morphology, surface area due to porosity, and chemistry controlled release kinetics are the most active. This article discusses CaP systems in their particulate, cements, and scaffold forms for drug, protein, and growth factor delivery toward orthopedic and dental applications.

Bose, Susmita; Tarafder, Solaiman; Edgington, Joe; Bandyopadhyay, Amit



Natural gums as sustained release carriers: development of gastroretentive drug delivery system of ziprasidone HCl  

PubMed Central

Background Objective of this study is to show the potential use of natural gums in the development of drug delivery systems. Therefore in this work gastro retentive tablet formulations of ziprasidone HCl were developed using simplex lattice design considering concentration of okra gum, locust bean gum and HPMC K4M as independent variables. A response surface plot and multiple regression equations were used to evaluate the effect of independent variables on hardness, flag time, floating time and drug release for 1 h, 2 h, and 8 h and for 24 h. A checkpoint batch was also prepared by considering the constraints and desirability of optimized formulation to improve its in vitro performance. Significance of result was analyzed using ANOVA and p < 0.05 was considered statistically significant. Results Formulation chiefly contains locust bean gum found to be favorable for hardness and floatability but combined effect of three variables was responsible for the sustained release of drug. The in vitro drug release data of check point batch (F8) was found to be sustained well compared to the most satisfactory formulation (F7) of 7 runs. The ‘n’ value was found to be between 0.5 and 1 suggesting that release of drug follows anomalous (non-fickian) diffusion mechanism indicating both diffusion and erosion mechanism from these natural gums. Predicted results were almost similar to the observed experimental values indicating the accuracy of the design. In vivo floatability test indicated non adherence to the gastric mucosa and tablets remain buoyant for more than 24 h. Conclusions Study showed these eco-friendly natural gums can be considered as promising SR polymers. PMID:23352292



DNA nanotechnology: from sensing and DNA machines to drug-delivery systems.  


DNA/nanoparticle hybrid systems combine the unique electronic and optical properties of nanomaterials with the recognition and catalytic properties of nucleic acids. These materials hold great promise for the development of new sensing platforms, the programmed organization of nanoparticles, the switchable control of plasmonic phenomena in the nanostructures, and the controlled delivery of drugs. In this Perspective, we summarize recent advances in the application of DNA/nanoparticle (NP) hybrids in these different disciplines. Nucleic acid-semiconductor quantum dot hybrids are implemented to develop multiplexed sensing platforms for targeted DNA. The chemiluminescence resonance energy transfer mechanism is introduced as a new transduction signal, and the amplified detection of DNA targets through the biocatalytic regeneration of analytes is demonstrated. DNA machines consisting of catenanes or tweezers, and modified with fluorophore/Au NP pairs are used as functional devices for the switchable "mechanical" control of the fluorescence properties of the fluorophore. Also, nucleic acid nanostructures act as stimuli-responsive caps for trapping drugs in the pores of mesoporous SiO2 nanoparticles. In the presence of appropriate biomarker triggers, the pores are unlocked, leading to the controlled release of anticancer drugs. Selective cancer-cell death is demonstrated with the stimuli-responsive SiO2 nanoparticles. PMID:24070191

Lu, Chun-Hua; Willner, Bilha; Willner, Itamar



Fast Disintegrating Quercetin-Loaded Drug Delivery Systems Fabricated Using Coaxial Electrospinning  

PubMed Central

The objective of this study is to develop a structural nanocomposite of multiple components in the form of core-sheath nanofibres using coaxial electrospinning for the fast dissolving of a poorly water-soluble drug quercetin. Under the selected conditions, core-sheath nanofibres with quercetin and sodium dodecyl sulphate (SDS) distributed in the core and sheath part of nanofibres, respectively, were successfully generated, and the drug content in the nanofibres was able to be controlled simply through manipulating the core fluid flow rates. Field emission scanning electron microscope (FESEM) images demonstrated that the nanofibres prepared from the single sheath fluid and double core/sheath fluids (with core-to-sheath flow rate ratios of 0.4 and 0.7) have linear morphology with a uniform structure and smooth surface. The TEM images clearly demonstrated the core-sheath structures of the produced nanocomposites. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results verified that quercetin and SDS were well distributed in the polyvinylpyrrolidone (PVP) matrix in an amorphous state, due to the favourite second-order interactions. In vitro dissolution studies showed that the core-sheath composite nanofibre mats could disintegrate rapidly to release quercetin within 1 min. The study reported here provides an example of the systematic design, preparation, characterization and application of a new type of structural nanocomposite as a fast-disintegrating drug delivery system. PMID:24185912

Li, Xiao-Yan; Li, Yan-Chun; Yu, Deng-Guang; Liao, Yao-Zu; Wang, Xia



Polymer hydrogel functionalized with biodegradable nanoparticles as composite system for controlled drug delivery  

NASA Astrophysics Data System (ADS)

The possibility to direct pharmacological treatments targeting specific cell lines using polymer nanoparticles is one of the main novelties and perspectives in nanomedicine. However, sometimes, the ability to maintain NPs localized at the site of the injection that work as a drug reservoir can represent a good and complementary option. In this direction we built a composite material made of polymeric hydrogel functionalized with polymer NPs. ?-caprolactone and polyethylene glycol have been copolymerized in a two-step synthesis of PEGylated NPs, while hydrogel was synthesized through polycondensation between NPs, agarose and branched polyacrylic acid. NP functionalization was verified with Fourier transform infrared spectroscopy (FTIR), high resolution magic angle spinning-nuclear magnetic resonance (HRMAS-NMR) spectroscopy and release kinetics from a hydrogel matrix and compared with NPs only physically entrapped into a hydrogel matrix. The characteristics of the resulting composite hydrogel-NPs system were studied both in terms of rheological properties and in its ability to sustain the release of To-Pro3, used as a drug mimetic compound to represent a promising drug delivery device.

Rossi, Filippo; Ferrari, Raffaele; Castiglione, Franca; Mele, Andrea; Perale, Giuseppe; Moscatelli, Davide



Synthesis of EF24-tripeptide chloromethyl ketone: a novel curcumin-related anticancer drug delivery system.  


The blood coagulation cascade includes a step in which the soluble protein, factor VIIa (fVIIa), complexes with its transmembrane receptor, tissue factor (TF). The fVIIa/TF protein-protein complex is subsequently drawn into the cell by endocytosis. The observation that TF is aberrantly and abundantly expressed on many cancer cells offers an opportunity to specifically target those cells with an effective anticancer drug. Thus, we propose a new drug delivery system, drug-linker-Phe-Phe-Arg-mk-fVIIa, which can associate with TF on the surface of cancer cells, but release the cytotoxic agent in the cytoplasm. Synthetic procedures have been developed for the preparation of phenylalanine-phenylalanine-arginine chloromethyl ketone, (FFRck) followed by coupling with the cytotoxin EF24 and subsequently fVIIa to give EF-24-FFRmk-fVIIa. When breast cancer cells (MDA-MB-231) and human melanoma cells (RPMI-7951) are treated with the complex, the cells are arrested to a greater extent than EF24 alone by comparison with controls. PMID:16722634

Sun, Aiming; Shoji, Mamoru; Lu, Yang J; Liotta, Dennis C; Snyder, James P



Formulation and in vivo evaluation of a self-microemulsifying drug delivery system of dutasteride.  


This study aimed to develop an effective formulation to improve the solubility and oral absorption of dutasteride by using a self-microemulsifying drug delivery system (SMEDDS). We used the d-optimal mixture design as a tool for developing an optimized SMEDDS formulation with excellent physicochemical characteristics such as mean particle size of <100 nm and percentage of drug dissolved at 15 min, >80%. An optimized dutasteride-loaded SMEDDS formulation consisted of 39.80% CapryolTM 90, 25.90% Cremophor® EL, and 34.30% Transcutol® HP and showed an emulsion droplet size of about 35.3 nm. Approximately 90% of dutasteride from the SMEDDS dissolved at 10 min in dissolution media of pH 1.2 and 6.8. Furthermore, pharmacokinetic studies in rats indicated that compared to the raw drug, the optimized SMEDDS formulation significantly improved the oral absorption of dutasteride. Therefore, preliminary results from our study suggest that the dutasteride-loaded self-microemulsifying formulation has a great potential for clinical application. PMID:23487399

Choo, G-H; Park, S-J; Hwang, S-J; Kim, M-S



Oxidized Porous Silicon Particles Covalently Grafted with Daunorubicin as a Sustained Intraocular Drug Delivery System  

PubMed Central

Purpose. To test the feasibility of covalent loading of daunorubicin into oxidized porous silicon (OPS) and to evaluate the ocular properties of sustained delivery of daunorubicin in this system. Methods. Porous silicon was heat oxidized and chemically functionalized so that the functional linker on the surface was covalently bonded with daunorubicin. The drug loading rate was determined by thermogravimetric analysis. Release of daunorubicin was confirmed in PBS and excised rabbit vitreous by mass spectrometry. Daunorubicin-loaded OPS particles (3 mg) were intravitreally injected into six rabbits, and ocular properties were evaluated through ophthalmic examinations and histology during a 3-month study. The same OPS was loaded with daunorubicin using physical adsorption and was evaluated similarly as a control for the covalent loading. Results. In the case of covalent loading, 67 ± 10 ?g daunorubicin was loaded into each milligram of the particles while 27 ± 10 ?g/mg particles were loaded by physical adsorption. Rapid release of daunorubicin was observed in both PBS and excised vitreous (?75% and ?18%) from the physical adsorption loading, while less than 1% was released from the covalently loaded particles. Following intravitreal injection, the covalently loaded particles demonstrated a sustained degradation of OPS with drug release for 3 months without evidence of toxicity; physical adsorption loading revealed a complete release within 2 weeks and localized retinal toxicity due to high daunorubicin concentration. Conclusions. OPS with covalently loaded daunorubicin demonstrated sustained intravitreal drug release without ocular toxicity, which may be useful to inhibit unwanted intraocular proliferation. PMID:23322571

Chhablani, Jay; Nieto, Alejandra; Hou, Huiyuan; Wu, Elizabeth C.; Freeman, William R.; Sailor, Michael J.; Cheng, Lingyun



Trojan particles: Large porous carriers of nanoparticles for drug delivery  

E-print Network

Trojan particles: Large porous carriers of nanoparticles for drug delivery N. Tsapis*, D. Bennett the drug release and delivery potential of nanoparticle (NP) systems with the ease of flow, processing drug delivery (12, 13). As a result of these limitations, NPs are not presently being explored


Effective drug delivery by PEGylated drug conjugates  

Microsoft Academic Search

The current review presents an update of drug delivery using poly(ethylene glycol) (PEG), that focuses on recent developments in both protein and organic drugs. Certainly the past 10 years has resulted in a renaissance of the field of PEG drug conjugates, initiated by the use of higher molecular weight PEGs (Mw>20,000), especially 40,000 which is estimated to have a plasma

Richard B. Greenwald; Yun H. Choe; Jeffrey McGuire; Charles D. Conover



Depot drug delivery system for 5-fluorouracil after filtration surgery in the rabbit.  


We investigated the potential value of 50:50 poly (DL glycolic acid-lactic acid) (PGLA) copolymer as a degradable depot delivery system for 5-fluorouracil (5-FU) after filtration surgery. Analysis of retrieved discs after implantation in 22 eyes of 22 pigmented rabbits showed a dual drug release profile and polymer mass loss characteristics. In a second group of pigmented rabbits implantation of PGLA discs impregnated with 5-FU (22 eyes) significantly lengthened the survival time of filtration fistulae compared with discs without 5-FU (18 eyes) or no disc (10 eyes) (p < 0.0001). Use of PGLA copolymer impregnated with 5-FU could prove valuable for patients undergoing glaucoma filtering surgery. PMID:7834564

Trope, G E; Cheng, Y L; Sheardown, H; Liu, G S; Menon, I A; Heathcote, J G; Rootman, D S; Chiu, W J; Gould, L



Targeted Drug Delivery to the Peripheral Nervous System using Gene Therapy  

PubMed Central

Gene transfer to target delivery of neurotrophic factors to the primary sensory afferent for treatment of polyneuropathy, or of inhibitory neurotransmitters for relief of chronic pain, offers the possibility of a highly selective targeted release of bioactive molecules within the nervous system. Preclinical studies with non-replicating herpes simplex virus (HSV)-based vectors injected into the skin to transduce neurons in the dorsal root ganglion have demonstrated efficacy in reducing-pain related behaviors in animal models of inflammatory pain, neuropathic pain, and pain caused by cancer, and in preventing progression of sensory neuropathy caused by toxins, chemotherapeutic drugs or resulting from diabetes. Successful completion of the first phase 1 clinical trial of HSV-mediated gene transfer in patients with intractable pain from cancer has set the stage for further clinical trials of this approach. PMID:22565023

Wolfe, Darren; Mata, Marina; Fink, David J.



Anticancer drug delivery system based on calcium carbonate particles loaded with a photosensitizer.  


In photodynamic therapy (PDT), photosensitizers are required to arrive in high concentrations at selective targets like cancer cells avoiding toxicity in healthy tissue. In this work, we propose the application of porous calcium carbonate carriers in the form of polycrystalline vaterite for this task. We investigated the loading efficiency for the photosensitizer Photosens in vaterite micro- and nanocarriers. A possible release mechanism depending on the surrounding pH was studied, showing a fast degradation of the carriers in buffers below pH7. These results hold out the prospect of a novel PDT drug delivery system. Variation of particle size or additional coatings allow custom-design of workload release curves. An intrinsic cancer-sensitivity can be expected from the pH-dependent release in the acidic microenvironment of cancer tissue. PMID:23932207

Svenskaya, Yulia; Parakhonskiy, Bogdan; Haase, Albrecht; Atkin, Vsevolod; Lukyanets, Evgeny; Gorin, Dmitry; Antolini, Renzo



Further characterization of theobroma oil-beeswax admixtures as lipid matrices for improved drug delivery systems.  


There is an increasing interest in lipid based drug delivery systems due to factors such as better characterization of lipidic excipients and formulation versatility and the choice of different drug delivery systems. It is important to know the thermal characteristics, crystal habit, texture, and appearance of a new lipid matrix when determining its suitability for use in certain pharmaceutical application. It is line with this that this research was embarked upon to characterize mixtures of beeswax and theobroma oil with a view to applying their admixtures in drug delivery systems such as solid lipid nanoparticles and nanostructured lipid carriers. Admixtures of theobroma oil and beeswax were prepared to contain 25% w/w, 50% w/w, and 75% w/w of theobroma oil. The admixtures were analyzed by differential scanning calorimetry (DSC), small angle X-ray diffraction (SAXD), wide angle X-ray diffraction (WAXD), and isothermal heat conduction microcalorimetry (IMC). The melting behavior and microstructures of the lipid admixtures were monitored by polarized light microscopy (PLM). Transmission electron microscopy (TEM) was used to study the internal structures of the lipid bases. DSC traces indicated that the higher melting peaks were roughly constant for the different admixtures, but lower melting peaks significantly increased (p < 0.05). The admixture containing 25% w/w of theobroma oil possessed highest crystallinity index of 95.6%. WAXD studies indicated different reflections for the different lipid matrices. However, new interferences were detected for all the lipid matrix admixtures between 2theta = 22.0 degrees and 2theta = 25.0 degrees. The lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed absence of the weak reflection characteristic of pure theobroma oil, while there was disappearance of the strong intensity reflection of beeswax in all the lipid matrix admixtures at all stages of the study. PLM micrographs revealed differences with regard to the thermal and optical behaviors depending on the composition of the matrix. The lipid matrix consisting of 75% w/w of theobroma oil showed a spherulite texture after 4 weeks of isothermal storage. Crystallization exotherms of lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed change in modification after 30 min with the latter having a greater time-dependent crystallization. Generally, low non-integral Avrami exponents and growth rate constants were obtained for all the lipid matrices, with the admixture containing 25% w/w theobroma oil having the lowest Avrami exponent and growth rate constant. Based on the results obtained, admixtures containing 50% w/w and 75% w/w of theobroma oil could be applied in the formulation of solid lipid nanoparticles and nanostructured lipid carriers as these lipid matrices possessed crystal characteristics that favour such drug delivery systems. PMID:16949805

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



In vitro evaluation of S-(+)-ibuprofen as drug candidate for intra-articular drug delivery system.  


Abstract Intra-articular drug delivery systems (DDSs) are envisaged as interesting alternative to locally release non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen to reduce pain in patients with osteoarthritis. The present study examines the efficacy of S-(+)-ibuprofen on cartilage degradation as drug candidate for DDS loading. Humeral cartilage and joint capsule explants were collected from healthy sheep shoulder joints and they were cultured in mono- or in co-culture for 13?days with LPS in combination with S-(+)-ibuprofen at 50?µM and 1?mM. S-(+)-ibuprofen (50?µM) blocked prostaglandins production in LPS-activated explants but did not reduce cartilage degradation. By contrast, 1?mM S-(+)-ibuprofen treatment of cartilage explants reduced nitric oxide synthesis by 51% (p?=?0.0072), proteoglycans degradation by 35% (p?=?0.0114) and expression of serum amyloid protein - the main protein induced upon LPS challenge - by 44% (p?drug candidate for the loading of intra-articular DDS. PMID:24168233

Bédouet, Laurent; Pascale, Florentina; Bonneau, Michel; Laurent, Alexandre



Multi-scale validation of a nanodiamond drug delivery system and multi-scale engineering education  

NASA Astrophysics Data System (ADS)

This dissertation has two primary concerns: (i) evaluating the uncertainty and prediction capabilities of a nanodiamond drug delivery model using Bayesian calibration and bias correction, and (ii) determining conceptual difficulties of multi-scale analysis from an engineering education perspective. A Bayesian uncertainty quantification scheme is used to analyze computational and experimental data for the localized cancer drug delivery system. Since this system is largely unknown, assessing the uncertainty at various developmental stages as well as on different physical scales is important to determine functioning of this system. Adsorption of DOX (a cancer fighting drug) to nanodiamonds is measured in two ways: (1) experimentally via UV Visible Spectroscopy and (2) numerically using stochastic molecular dynamics simulations. These two sets of data are used in a Bayesian calibration and bias correction analysis such that the pH is the input parameter, the percentage of carboxyl, the functional group on the surface of the nanodiamond, is the calibration parameter, and both modeling and experimental errors are accounted for in the uncertainty analysis. The acid dissociating constant pKa value of the nanodiamond is also used for system calibration. A Bayesian bias correction analysis is also performed to measure the impact of nanodiamond aggregation. From these analyses, an estimate of the uncertainty in the system is determined, the optimal pKa value and percentage of carboxyl is found, the impact of the experimental and modeling physical scale differences is examined, the impact of clustering is measured, and a research path to further reducing the system uncertainty is given. The second research issue covered in this dissertation addresses how to effectively teach this type of high-level, cross-disciplinary thinking, and multi-scale research to future engineers. The conceptual hurtles present in understanding multi-scale analysis were identified through one-on-one interviews with scientists and engineers spanning the experience spectrum (undergraduate students, graduate students, postdoctoral fellows, and professors). From these interviews, important issues involving understanding and teaching multi-scale analysis were documented. From there, a Northwestern course was modified and taught to specifically address many of these issues. Then a follow-up survey was conducted to rank these many issues in terms of importance. This is the first research to specifically address the role that multi-scale thinking has on conceptual understanding.

Schwalbe, Michelle Kristin


Modified PLA nano in situ gel: a potential ophthalmic drug delivery system.  


A novel nano in situ gel forming system of 5-Fluorouracil (5-FU) was investigated for its potential use for conjunctival/corneal squamous cell carcinoma (CCSC). The study was conducted in two steps, in the first step PLA nanoparticles were prepared and characterized; in the second step the drug loaded PLA nanoparticles were dispersed in sodium alginate solution yielding the modified nano in situ system, which were evaluated in rabbit eye. Size and morphology of prepared PLA particles were verified by using dynamic light scattering (DLS), atomic force microscope (AFM) and scanning electron microscope (SEM). In vitro and in vivo study of free 5-FU, PLA nanoparticles and modified nano in situ system were conducted in simulated tear fluid and in rabbit eye respectively. PLA nanoparticles were in size range of 128-194 nm with spherical shape and smooth surface with narrow size distribution. No polymer drug interaction was found as confirmed by FTIR, NMR and DSC. XRD of PLA nanoparticles confirmed that 5-FU was present in the crystalline state. In vitro experiments indicated a diffusion controlled release of 5-FU from both PLA nanoparticles and modified nano in situ system with high burst effect. Modified nano in situ gel system (MNS) significantly increased the Cmax and AUC0-8 in aqueous humor as compared to 5-FU solution and PLA nanoparticles. Higher 5-FU level in aqueous humor was possibly because of increased retention time of gel matrix-embedded drug loaded nanoparticles. Overall results showed the potential of MNS for ophthalmic delivery in the therapy of CCSC. PMID:21497491

Nagarwal, Ramesh C; Kumar, Rakesh; Dhanawat, M; Pandit, J K



Potential use of gelcasting hydroxyapatite porous ceramic as an implantable drug delivery system.  


Hydroxyapatite (HA) ceramic in a porous configuration is suggested as a drug release system. A new technique for the production of this material, based on the foaming of suspensions and in situ polymerization (gelcasting method), resulted in a material whose characteristics are likely to make it useful as an implantable drug delivery system. Three batches of HA ceramic with different porosities were characterized by X-ray diffraction and scanning electron microscopy (SEM). Pore size and shape as well as density were determined. In vitro experiments were performed in order to evaluate the dissolution behavior of cisplatin in the system. X-ray diffraction analysis showed that the final product consisted of a single phase, indicating that the sintering process had not affected the structure of the HA. Energy dispersive X-ray analysis (EDX) showed absence of impurities. Pore diameters were in the range 15--34 microm. SEM showed that the material presented a highly interconnected spheroidal porous network with open micropores and closed macropores. In vitro experiments showed significant differences in the release rate of cisplatin between three different porosities. PMID:11165099

Netz, D J; Sepulveda, P; Pandolfelli, V C; Spadaro, A C; Alencastre, J B; Bentley, M V; Marchetti, J M



Protein-Based Nanomedicine Platforms for Drug Delivery  

SciTech Connect

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 discussed for each type of protein based drug delivery system.

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



Molecularly imprinted polymers for drug delivery  

Microsoft Academic Search

Molecular imprinting technology has an enormous potential for creating satisfactory drug dosage forms. Although its application in this field is just at an incipient stage, the use of MIPs in the design of new drug delivery systems (DDS) and devices useful in closely related fields, such as diagnostic sensors, is receiving increasing attention. Examples of MIP-based DDS can be found

Carmen Alvarez-Lorenzo; Angel Concheiro



Novel insulin thiomer nanoparticles: in vivo evaluation of an oral drug delivery system.  


It was aim of the study to investigate the in vivo potential of a novel insulin-thiomer complex nanoparticulate delivery system. Insulin loaded nanoparticles were obtained by the formation of hydrogen bonds between poly(vinyl pyrrolidone) (PVP) and poly(acrylic acid)-cysteine (PAA-Cys) or poly(acrylic acid) (PAA), respectively, in the presence of insulin. Dissolution behavior of insulin from tablets as well as nanoparticulate suspensions was evaluated in vitro. Serum insulin concentrations and reduction of blood sugar values were determined after oral administration of nanoparticles formulated as enteric coated tablets and suspensions. Results displayed a low serum insulin concentration and pharmacological efficacy in terms of blood sugar reduction after oral administration of enteric coated tablets. On the contrary, nanoparticulate suspensions led to significant serum insulin concentrations. Furthermore a 2.3-fold improvement of the AUC of insulin could be achieved due to the use of thiolated PAA instead of unmodified PAA. In addition, a blood sugar reduction of 22% was observed. Results demonstrate that this novel complex nanoparticulate formulation is an encouraging new attempt toward the noninvasive delivery of peptide drugs. PMID:18159930

Deutel, Britta; Greindl, Melanie; Thaurer, Michael; Bernkop-Schnürch, Andreas



Polymeric conjugates for drug delivery  

PubMed Central

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

Larson, Nate; Ghandehari, Hamidreza



A new drug delivery system inhibits uveitis in an animal model after cataract surgery.  


Cataract surgery is a common ocular surgical procedure consisting in the implantation of an artificial intraocular lens (IOL) to replace the ageing, dystrophic or damaged natural one. The management of postoperative ocular inflammation is a major challenge especially in the context of pre-existing uveitis. The association of the implanted IOL with a drug delivery system (DDS) allows the prolonged intraocular release of anti-inflammatory agents after surgery. Thus IOL-DDS represents an "all in one" strategy that simultaneously addresses both cataract and inflammation issues. Polymeric DDS loaded with two model anti-inflammatory drugs (triamcinolone acetonide (TA) and cyclosporine A (CsA)) were manufactured in a novel way and tested regarding their efficiency for the management of intraocular inflammation during the 3 months following surgery. The study involved an experimentally induced uveitis in rabbits. Experimental results showed that medicated DDS efficiently reduced ocular inflammation (decrease of protein concentration in aqueous humour, inflammatory cells in aqueous humour and clinical score). Additionally, more than 60% of the loading dose remained in the DDS at the end of the experiment, suggesting that the system could potentially cover longer inflammatory episodes. Thus, IOL-DDS were demonstrated to inhibit intraocular inflammation for at least 3 months after cataract surgery, representing a potential novel approach to cataract surgery in eyes with pre-existing uveitis. PMID:23291445

Eperon, Simone; Rodriguez-Aller, Marta; Balaskas, Konstantinos; Gurny, Robert; Guex-Crosier, Yan



A lysosome-targeted drug delivery system based on sorbitol backbone towards efficient cancer therapy.  


A straightforward synthetic approach was adopted for the construction of a lysosome-targeted drug delivery system (TDDS) using sorbitol scaffold (Sor) linked to octa-guanidine and tetrapeptide GLPG, a peptide substrate of lysosomal cysteine protease, cathepsin B. The main objective was to efficiently deliver the potential anticancer drug, doxorubicin to the target sites, thereby minimizing dose-limiting toxicity. Three TDDS vectors were synthesized viz., DDS1: Sor-GLPG-Fl, DDS2: Sor-Fl (control) and DDS3: Sor-GLPGC-SMCC-Dox. Dox release from DDS3 in the presence of cathepsin B was studied by kinetics measurement based on the fluorescent property of Dox. The cytotoxicity of DDS1 was assessed and found to be non-toxic. Cellular internalization and colocalization studies of all the 3 systems were carried out by flow cytometry and confocal microscopy utilizing cathepsin B-expressing HeLa cells. DDS1 and DDS3 revealed significant localization within the lysosomes, in contrast to DDS2 (control). The doxorubicin-conjugated carrier, DDS3, demonstrated significant cytotoxic effect when compared to free Dox by MTT assay and also by flow cytometric analysis. The targeted approach with DDS3 is expected to be promising, because it is indicated to be advantageous over free Dox, which possesses dose-limiting toxicity, posing risk of injury to normal tissues. PMID:25062087

Maniganda, Santhi; Sankar, Vandana; Nair, Jyothi B; Raghu, K G; Maiti, Kaustabh K



Dendrimer-like assemblies based on organoclays as multi-host system for sustained drug delivery.  


Chemical modification of nanoclay will ensure further progress on these materials. In this work, we show that montmorillonite (MTM) nanosheets can be modified with ?-cyclodextrin (CD) via a nucleophilic substitution reaction between mono-6-(p-toluenesulfonyl)-6-deoxy-?-CD and an amino group of 3-aminopropyltriethoxysilane (APTES)-functionalized MTM. The resulting MTM-APTES-CD can be further self-assembled into dendrimer-like assemblies, exhibit a well-dispersed property even in Dulbecco's phosphate-buffered saline and do not aggregate for a period of at least 20days. The structure, morphology and assembly mechanism are systematically studied by (29)Si MAS NMR, FT-IR, (1)H NMR, SEM, FE-TEM, DLS and AFM, and the change in assemblies during the drug release is monitored using FE-TEM images. MTT assays indicate that the assemblies only have low cytotoxicity, while CLSM and TEM observations reveal that the assemblies can easily penetrate cultured human endothelial cells. When clopidogrel is used as a guest molecule, the assemblies show not only much higher loading capacities compared to MTM and other containing ?-CD assemblies or nanoparticles, but also a sustained release of clopidogrel up to 30days. This is attributed to the fact that the guest molecule is both supramolecularly complexed within the dendritic scaffold and intercalated into CD and MTM hosts. Host-guest systems between assemblies and various guests hold promising applications in drug delivery system and in the biomedical fields. PMID:25308929

Li, Wei; Sun, Lili; Pan, Lijun; Lan, Zuopin; Jiang, Tao; Yang, Xiaolan; Luo, Jianchun; Li, Ronghua; Tan, Liqing; Zhang, Shurong; Yu, Mingan



Spontaneous Emulsification of Nifedipine-Loaded Self-Nanoemulsifying Drug Delivery System.  


Self-nanoemulsifying drug delivery system (SNEDDS) can be used to improve dissolution of poorly water-soluble drugs. The objective of this study was to prepare SNEDDS by using ternary phase diagram and investigate their spontaneous emulsifying property, dissolution of nifedipine (NDP), as well as the pharmacokinetic profile of selected SNEDDS formulation. The results showed that the composition of the SNEDDS was a great importance for the spontaneous emulsification. Based on ternary phase diagram, the region giving the SNEDDS with emulsion droplet size of less than 300 nm after diluting in aqueous medium was selected for further formulation. The small-angle X-ray scattering curves showed no sharp peak after dilution at different percentages of water, suggesting non-ordered structure. The system was found to be robust in different dilution volumes; the droplet size was in nanometer range. In vitro dissolution study showed remarkable increase in dissolution of NDP from SNEDDS formulations compared with NDP powders. The pharmacokinetic study of selected SNEDDS formulation in male Wistar rats revealed the improved maximum concentration and area under the curve. Our results proposed that the developed SNEDDS formations could be promising to improve the dissolution and oral bioavailability of NDP. PMID:25367002

Weerapol, Yotsanan; Limmatvapirat, Sontaya; Kumpugdee-Vollrath, Mont; Sriamornsak, Pornsak



Expanding Alternative Delivery Systems.  

ERIC Educational Resources Information Center

Alternative educational delivery systems that might be useful to community colleges are considered. The following categories of delivery systems are covered: broadcast delivery systems; copy delivery systems, print delivery systems, computer delivery systems, telephone delivery systems, and satellites. Among the applications for broadcast…

Baltzer, Jan A.


Self micro-emulsifying drug delivery system of tacrolimus: Formulation, in vitro evaluation and stability studies  

PubMed Central

Background: Tacrolimus has poor solubility in water ranging from 4 to 12 ?g/mL. The oral bio availabilities of tacrolimus is poor and exhibits high intra and inter-subject variability (4-89%, average 25%) in the liver and the kidney transplant recipients and in patients with renal impairment. Aim: The present study deals with the development and characterization of self-micro-emulsifying drug delivery system to improve the oral bioavailability of poorly soluble drug tacrolimus. Materials and Methods: Solubility of the tacrolimus was estimated in various oils, surfactants, and co-surfactants. Various in vitro tests such as percentage transmittance, emulsification time, cloud point, precipitation, and thermodynamic stabilities were used to find out optimized formulations. Optimized liquid self micro-emulsifying (SMEDDS) were characterized by particle size analysis and converted in solid by using the Florite RE as an adsorbent, which is further characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and particle size analysis. Results: The optimized liquid SMEDDS formulation contained 10% Lauroglycol FCC as an oil, 60% Cremophor RH, and 30% PEG (polyethylene glycol) 400 as a surfactant and co-surfactant respectively. The optimized liquid and solid SMEDDS showed higher drug release than the marketed capsule and pure API (active pharmaceutical ingredient) powder. For optimized liquid SMEDDS and solid SMEDDS, the globule sizes were found 113 nm and 209 nm respectively. The solid state characterization of solid-SMEDDS by SEM, DSC, FTIR, and XRD revealed the absence of crystalline tacrolimus in the solid-SMEDDS. Shelf-lives for liquid SMEDDS and solid SMEDDS were found to be 1.84 and 2.25 year respectively. Conclusions: The results indicate that liquid SMEDDS and solid SMEDDS of tacrolimus, owing to nano-sized, have potential to enhance the absorption of the drug. PMID:24015381

Patel, Pranav V; Patel, Hitesh K; Panchal, Shital S; Mehta, Tejal A



Nanohybrid based on antibiotic encapsulated layered double hydroxide as a drug delivery system.  


Nanohybrid of cefuroxime (CFO) with layered double hydroxide (LDH) has been prepared, and the rate of dissolution and bioavailability of CFO using nanohybrid as a drug delivery system has been broadly studied. The intercalation process was confirmed by X-ray diffraction, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The CFO contents were found to be 19.0 wt% in the nanohybrid. The release mechanism of CFO was investigated with respect to anion and pH of the dissolution media such as gastric, intestinal and blood simulated media. The effect of pH was evaluated on the release of CFO from nanohybrid, and the dissolution of CFO from the nanohybrid was found to be a slow process at pH 4.0, 6.8, and 7.4. Further the addition of Cl ion and PAM in release media did not affect the release rate of drug at pH 4.0 and 6.8, while at pH 7.4, Cl ion and PAM have significant role on the drug release. At pH 1.2, the release study shows that LDH dissolved in the acidic medium and CFO released in its molecular form. The release behavior suggests two mechanisms that are responsible for the release of CFO from nanohybrid: weathering (dependent on the pH) and ion exchange (highly dependent on the anions). Surface reactions mediated by solid weathering ruled the release in gastric fluid, whereas anion exchange determined CFO release in lysosomal, intestinal, and blood medium. In order to evaluate the drug release mechanism, the released data were fitted by mathematical models describing various kinetic. PMID:25399066

Khan, Sher Bahadar; Alamry, Khalid A; Alyahyawi, Nedaa A; Asiri, Abdullah M; Arshad, Muhammad Nadeem; Marwani, Hadi M



Macromolecules in drug delivery Macromolecular targeting agents, carriers, and drugs  

E-print Network

Macromolecules in drug delivery Macromolecular targeting agents, carriers, and drugs #12;Why macromolecules in drug delivery? Classic chemotherapy Drug delivery? Targeting A carrier for small drugs A release mechanism (if necessary) Protection of drug cargo #12;How? 3

Barthelat, Francois


Development of phyllanthin-loaded self-microemulsifying drug delivery system for oral bioavailability enhancement.  


Abstract Phyllanthin, a poorly water-soluble herbal active component from Phyllanthus amarus, exhibited a low oral bioavailability. This study aims at formulating self-microemulsifying drug delivery systems (SMEDDS) containing phyllanthin and evaluating their in-vitro and in-vivo performances. Excipient screening was carried out to select oil, surfactant and co-surfactant. Formulation development was based on pseudo-ternary phase diagrams and characteristics of resultant microemulsions. Influences of dilution, pH of media and phyllanthin content on droplet size of the resultant emulsions were studied. The optimized phyllanthin-loaded SMEDDS formulation (phy-SMEDDS) and the resultant microemulsions were characterized by viscosity, self-emulsification performance, stability, morphology, droplet size, polydispersity index and zeta potential. In-vitro dissolution and oral bioavailability in rats of phy-SMEDDS were studied and compared with those of plain phyllanthin. Phy-SMEDDS consisted of phyllanthin/Capryol 90/Cremophor RH 40/Transcutol P (1.38:39.45:44.38:14.79) in % w/w. Phy-SMEDDS could be emulsified completely within 6?min and formed fine microemulsions, with average droplet range of 27-42?nm. Phy-SMEDDS was robust to dilution and pH of dilution media while the resultant emulsion showed no phase separation or drug precipitation after 8?h dilution. The release of phyllanthin from phy-SMEDDS capsule was significantly faster than that of plain phyllanthin capsule irrespective of pH of dissolution media. Phy-SMEDDS was found to be stable for at least 6 months under accelerated condition. Oral absorption of phyllanthin in rats was significantly enhanced by SMEDDS as compared with plain phyllanthin. Our study indicated that SMEDDS for oral delivery of phyllanthin could be an option to enhance its bioavailability. PMID:24237327

Duc Hanh, Nguyen; Mitrevej, Ampol; Sathirakul, Korbtham; Peungvicha, Penchom; Sinchaipanid, Nuttanan



Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system  

PubMed Central

Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS) is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood–brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretroviral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood–brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS. PMID:24741312

Gomes, Maria João; Neves, José das; Sarmento, Bruno



Molecular imprinted polymers as drug delivery vehicles.  


Abstract This review is aimed to discuss the molecular imprinted polymer (MIP)-based drug delivery systems (DDS). Molecular imprinted polymers have proved to possess the potential and also as a suitable material in several areas over a long period of time. However, only recently it has been employed for pharmaceuticals and biomedical applications, particularly as drug delivery vehicles due to properties including selective recognition generated from imprinting the desired analyte, favorable in harsh experimental conditions, and feedback-controlled recognitive drug release. Hence, this review will discuss their synthesis, the reason they are selected as drug delivery vehicles and for their applications in several drug administration routes (i.e. transdermal, ocular and gastrointestinal or stimuli-reactive routes). PMID:25317753

Zaidi, Shabi Abbas



Solid Lipid Nanoparticles: A Modern Formulation Approach in Drug Delivery System  

PubMed Central

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

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



A Targeted Liposome Delivery System for Combretastatin A4: Formulation Optimization through Drug Loading and In Vitro Release Studies  

Microsoft Academic Search

Efficient liposomal therapeutics require high drug loading and low leakage. The objective of this study is to develop a targeted liposome delivery system for combretastatin A4 (CA4), a novel antivascular agent, with high loading and stable drug encapsulation. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, and distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) were prepared by the lipid film hydration and extrusion



In Vitro and In Vivo Evaluation of a Hydrogel Reservoir as a Continuous Drug Delivery System for Inner Ear Treatment  

PubMed Central

Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear. PMID:25105670

Hessler, Roland; Stöver, Timo; Esser, Karl-Heinz; Möller, Martin; Lenarz, Thomas; Jolly, Claude; Groll, Jürgen; Scheper, Verena



Multi-Scale Validation of a Nanodiamond Drug Delivery System and Multi-Scale Engineering Education  

ERIC Educational Resources Information Center

This dissertation has two primary concerns: (i) evaluating the uncertainty and prediction capabilities of a nanodiamond drug delivery model using Bayesian calibration and bias correction, and (ii) determining conceptual difficulties of multi-scale analysis from an engineering education perspective. A Bayesian uncertainty quantification scheme…

Schwalbe, Michelle Kristin



The Use of Multi-Walled Carbon Nanotubes as Possible Carrier in Drug Delivery System for Aspirin  

Microsoft Academic Search

Carbon nanotubes (CNTs) have raised great interest in a number of applications, including field emission, energy storage, molecular electronics, sensors, biochips and drug delivery systems. This is due to their remarkable mechanical properties, chemical stability and biofunctionalizability. This nanomaterial is low in weight, has high strength and a high aspect ratio (long length compared to a small diameter). This paper

Alias Mohd. Yusof; Nor Aziah Buang; Lee Sze Yean; Mohd. Lokman Ibrahim



Chitosan Based Polyelectrolyte Complexes as Potential Carrier Materials in Drug Delivery Systems  

PubMed Central

Chitosan has been the subject of interest for its use as a polymeric drug carrier material in dosage form design due to its appealing properties such as biocompatibility, biodegradability, low toxicity and relatively low production cost from abundant natural sources. However, one drawback of using this natural polysaccharide in modified release dosage forms for oral administration is its fast dissolution rate in the stomach. Since chitosan is positively charged at low pH values (below its pKa value), it spontaneously associates with negatively charged polyions in solution to form polyelectrolyte complexes. These chitosan based polyelectrolyte complexes exhibit favourable physicochemical properties with preservation of chitosan’s biocompatible characteristics. These complexes are therefore good candidate excipient materials for the design of different types of dosage forms. It is the aim of this review to describe complexation of chitosan with selected natural and synthetic polyanions and to indicate some of the factors that influence the formation and stability of these polyelectrolyte complexes. Furthermore, recent investigations into the use of these complexes as excipients in drug delivery systems such as nano- and microparticles, beads, fibers, sponges and matrix type tablets are briefly described. PMID:20479980

Hamman, Josias H.



Peptide hydrogel as an intraocular drug delivery system for inhibition of postoperative scarring formation.  


A biocompatible hydrogel self-assembled from a peptide comprised of a peptide backbone containing Arg-Gly-Asp (RGD) sequence and a hydrophobic N-fluorenyl-9-methoxycarbonyl (FMOC) tail was designed and prepared to load antiproliferative model drug (5-fluorouracil, 5-Fu). After administering this 5-Fu-loaded peptide hydrogel in the filtering surgery of rabbit eyes, because of the sustained release of 5-Fu from the hydrogel to inhibit the scleral flap fibrosis efficiently, the pathology and immunohistochemistry demonstrate that the filtration fistula is patent without postoperative scarring formation, resulting in the significantly low intraocular pressure (IOP) of the rabbit eyes within postoperative 28 days. In a comparison with the conventional 5-Fu exposure, the strategy demonstrated here presents several advantages including providing convenience and preventing the toxicity of 5-Fu to the surrounding ocular tissues efficiently, suggesting a feasibility of this peptide hydrogel as a potential implanted drug delivery system for the inhibition of postoperative scarring formation. PMID:20707334

Xu, Xiao-Ding; Liang, Liang; Chen, Chang-Sheng; Lu, Bo; Wang, Na-ling; Jiang, Fa-Gang; Zhang, Xian-Zheng; Zhuo, Ren-Xi



Drug delivery system based on cyclodextrin-naproxen inclusion complex incorporated in electrospun polycaprolactone nanofibers.  


In this study, we select naproxen (NAP) as a reference drug and electrospun poly (?-caprolactone) (PCL) nanofibers as a fibrous matrix for our drug-delivery system. NAP was complexed with beta-cyclodextrin (?CD) to form inclusion complex (NAP-?CD-IC) and then NAP-?CD-IC was incorporated into PCL nanofibers via electrospinning. The incorporation of NAP without CD-IC into electrospun PCL was also carried out for a comparative study. Our aim is to analyze the release profiles of NAP from PCL/NAP and PCL/NAP-?CD-IC nanofibers and we investigate the effect of CD-IC on the release behavior of NAP from the nanofibrous PCL matrix. The characterization of NAP-?CD-IC and the presence of CD-IC in PCL/NAP-?CD-IC nanofibers were studied by FTIR, XRD, TGA, NMR and SEM. The SEM imaging of the electrospun PCL/NAP and PCL/NAP-?CD-IC nanofibers reveal that the average fiber diameter of these nanofibers is around 300nm, in addition, the aggregates of CD-IC in PCL/NAP-?CD-IC nanofibers is observed. The release study of NAP in buffer solution elucidate that the PCL/NAP-?CD-IC nanofibers have higher release amount of NAP than the PCL/NAP nanofibers due to the solubility enhancement of NAP by CD-IC. PMID:24316584

Canbolat, M Fatih; Celebioglu, Asli; Uyar, Tamer



Formulation and evaluation of gastroretentive microballoons containing baclofen for a floating oral controlled drug delivery system.  


The objective of the present study was to fabricate and evaluate a multiparticulate oral gastroretentive dosage form of baclofen characterized by a central large cavity (hollow core) promoting unmitigated floatation with practical applications to alleviate the signs and symptoms of spasticity and muscular rigidity. Solvent diffusion and evaporation procedure were applied to prepare floating microspheres with a central large cavity using various combinations of ethylcellulose (release retardant) and HPMC K4M (release modifier) dissolved in a mixture of dichloromethane and methanol (2:1). The obtained microspheres (700-1000 µm) exhibit excellent floating ability (86±2.00%) and release characteristics with entrapment efficiency of 95.2±0.32%. Microspheres fabricated with ethylcellulose to HPMC K4M in the ratio 8.5:1.5 released 98.67% of the entrapped drug in 12 h. Muscle relaxation caused by baclofen microspheres impairs the rotarod performance for more than 12 h. Abdominal X-ray images showed that the gastroretention period of the floating barium sulfate- labeled microspheres was no less than 10 h. The buoyant baclofen microspheres provide a promising gastroretentive drug delivery system to deliver baclofen in spastic patients with a sustained release rate. PMID:24730440

Dube, T S; Ranpise, N S; Ranade, A N



Liposomes interiorly thickened with thermosensitive nanogels as novel drug delivery systems.  


The fundamental structure of liposomes suffers from drawbacks of physical instability. To overcome this problem, the hypothesis of this study was to thicken the liposomal interior by incorporating thermosensitive in situ gel. The so called gelliposomes (GLs) were prepared by a thin-film method using poloxamer solutions as interior aqueous phase. Interior thermosensitive gelation was proved by observation of sustained dissolving of the poloxamer gel after destroying the lipid bilayers with Triton X-100; structural transformation as observed under optical microscopy in a heating-cooling circle also proved the fact of interior gelling. The sol-gel transition temperatures of GLs were in good correlation with those of the bulk poloxamer solution counterparts, which could be easily tailored by adjusting the concentration and ratio of poloxamer 407 (P407) to poloxamer 188 (P188). Membrane anisotropy measurement indicated increased membrane rigidity. In vitro release of the model drug cytosine arabinoside from GLs showed sustained release characteristics for at least one week with typical biphasic kinetics. Study on storage stability and protection against the destroying effect by membrane destroyers indicated improved physical stability in comparison with conventional liposomes. In situ evading of phagocytic uptake by macrophages was observed for GLs, which however should be attributed to the effect of exteriorly adsorbed poloxamers. In conclusion, GLs present distinct characteristics to be used as potential drug delivery systems. PMID:23872301

Zhang, Bei; Chen, Jian; Lu, Yi; Qi, Jianping; Wu, Wei



Progress in antiretroviral drug delivery using nanotechnology  

PubMed Central

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

Mallipeddi, Rama; Rohan, Lisa Cencia



Nanothermodynamics mediates drug delivery.  


The efficiency of penetration of nanodrugs through cell membranes imposes further complexity due to nanothermodynamic and entropic potentials at interfaces. Action of nanodrugs is effective after cell membrane penetration. Contrary to diffusion of water diluted common molecular drugs, nanosize imposes an increasing transport complexity at boundaries and interfaces (e.g., cell membrane). Indeed, tiny dimensional systems brought the concept of "nanothermodynamic potential," which is proportional to the number of nanoentities in a macroscopic system, from either the presence of surface and edge effects at the boundaries of nanoentities or the restriction of the translational and rotational degrees of freedom of molecules within them. The core element of nanothermodynamic theory is based on the assumption that the contribution of a nanosize ensemble to the free energy of a macroscopic system has its origin at the excess interaction energy between the nanostructured entities. As the size of a system is increasing, the contribution of the nanothermodynamic potential to the free energy of the system becomes negligible. Furthermore, concentration gradients at boundaries, morphological distribution of nanoentities, and restriction of the translational motion from trapping sites are the source of strong entropic potentials at the interfaces. It is evident therefore that nanothermodynamic and entropic potentials either prevent or allow enhanced concentration very close to interfaces and thus strongly modulate nanoparticle penetration within the intracellular region. In this work, it is shown that nano-sized polynuclear iron (III)-hydroxide in sucrose nanoparticles have a nonuniform concentration around the cell membrane of macrophages in vivo, compared to uniform concentration at hydrophobic prototype surfaces. The difference is attributed to the presence of entropic and nanothermodynamic potentials at interfaces. PMID:25416996

Stefi, Aikaterina L; Sarantopoulou, Evangelia; Kollia, Zoe; Spyropoulos-Antonakakis, Nikolaos; Bourkoula, Athanasia; Petrou, Panagiota S; Kakabakos, Sotirios; Soras, Georgios; Trohopoulos, Panagiotis N; Nizamutdinov, Alexey S; Semashko, Vadim V; Cefalas, Alkiviadis Constantinos



[Local and systemic delivery of high-molecular weight drugs by powder inhalation].  


The pulmonary route has recently attracted attention as a noninvasive administration route for peptide and protein drugs, and an insulin powder for inhalation was approved by authorities in Europe and the USA. The present study examined usefulness of insulin and gene powders for systemic and local inhalation therapy. We prepared several dry insulin powders by spray drying to examine the effect of additives on insulin absorption. Citric acid appears to be a safe and potent absorption enhancer for insulin in dry powder. However, in the powder with citric acid (MIC0.2 SD) insulin was unstable compared with the other powders examined. To improve insulin stability, a combination of insulin powder and citric acid powder was prepared (MIC Mix). MIC Mix showed hypoglycemic activity comparable to MIC0.2 SD while the insulin stability was much better than that of MIC SD. Next, dry insulin powders with mannitol were prepared with supercritical carbon dioxide (SCF); the powder thus prepared reduced blood glucose level rapidly and was more effective than that prepared by spray drying. Chitosan-pDNA complex powders as a pulmonary gene delivery system were also prepared with SCF and their in vivo activity was evaluated. The addition of chitosan suppressed the degradation of pCMV-Luc during preparation and increased the storage stability. The luciferase activity in mouse lung was evaluated after pulmonary administration of the powders. The chitosan-pDNA powder with an N/P ratio=5 increased the luciferase activity to 27 times that of the pCMV-Luc solution. These results suggest that gene powder with chitosan is a useful pulmonary gene delivery system. PMID:17409693

Okamoto, Hirokazu; Danjo, Kazumi



[Formulation and characetization of self-microemulsifying drug delivery systems according to their cytotoxic attributes].  


The aim of this study was to develop and examine novel drug delivery systems upon the cytotoxic behaviour of their tenside components. Different self-emulsifying combinations have been formulated by water dilution and oil dilution method with various previously tested tensides and co-tensides. The visual properties registered against the increment of the applied tenside component in Ternary triangular diagrams. Cartesian coordinate calculation was applied to select the adequate compositions. Self-emulsifying drug delivery systems are wildly used for enhanced bioavailabilty of oraly administrated pharmacons. Full particulars of topical application of these systems have not been evaluated yet. In our study the cellular effects of the applied amphiphilic tensides on human Caco-2 and HeLa cell monolayers as dependent upon their chemical structures and physicochemical properties have been evaluated. Cytotoxicity investigation was performed on Caco-2 and HeLa cells by MTT method. HeLa cells as in vitro model of cervix and Caco-2 cell monolayers as convenient and reliable in vitro models of the gastrointestinal tract have been chosen. According to the results of the formulation procedures it can be determined that each developed SMEDD mixtures belong to type IIIa or IIIb in the lipid formulation classification system (LFCS) proposed by Pouton. All of the formulated systems were immediately emulsified within the first second of contact with distilled water as dispersion medium and no evidence of phase separation or any instability problem have been observed for at least 72 h. The droplet diameter of dispersed self emulsifying compositions has been evaluated by Dynamic Light Scattering device. We concluded that the increased Transcutol HP concentrations lead to an obvious improvement in the optical clarity, which correlates with the determined particle size of the corresponding dispersion. In cytotoxicity test the toxic properties of the applied tensides have not been found as additive parameter. The most toxic component determined the cytotoxicitxy of the SMEDDS. Our results might ensure useful data for formulation of suitable SMEDDS with lower active ingredient necessity. Developed SMEDDS might be advantageous in terms of increased bioavailability, minimized side effect, and hence the patient compliance. PMID:25167702

Ujhelyi, Zoltán; Vecsernyés, Miklós; Bácskay, Ildikó



Self-nanoemulsifying drug-delivery system for improved oral bioavailability of rosuvastatin using natural oil antihyperlipdemic.  


Abstract Aim: The aim is improving the antihyperlipidemic activity of Rosuvastatin Calcium (Rs) through improving its solubility using self-nanoemulsifying drug delivery system (SNEDDS) containing natural oil full of unsaturated fatty acid and omega 3. Methods: A 7?×?3(2) full factorial design was adopted for optimization of oil ratio, Surfactant: Co-surfactant (S:CoS) ratio and oil:S/CoS ratio. Ternary phase diagrams were constructed for optimizing the system with drug loading (10 and 20%). The optimized SNEDD systems were evaluated according to their physical evaluation and drug release. Furthermore, the anti-hyperlipidemia efficacy was compared with commercially marketed product on rates followed by clinical study. Results: The system containing Tween 80:PEG 400 (3:1) and olive oil:garlic oil (1:1) as an oily phase has droplet size less than 100?nm, ZP (+23.43?±?2.58?mV), PDI (<0.02) and cloud point (>90?°C). In vitro drug release studies showed remarkable enhancement of the Rs release from Rs-SNEDDS. The antihyperlipidemic effect of Rs-SNEDDS is greater than that of the commercial tablets and the pure drug on rates and in hyperlipidemic patients. Conclusion: Rs-SNEDDS is a promising drug delivery system for improving the drug solubility and antihyperlipidemic effect using natural oils as (olive oil and garlic oil). PMID:25404208

Abo Enin, Hadel A



Nano and Microparticles as Controlled Drug Delivery Devices  

Microsoft Academic Search

Although, the drug delivery system (DDS) concept is not new, great progress has recently been made in the treatment of a variety of diseases. Targeting delivery of drugs to the diseased lesions is one of the most important aspects of DDS. To convey a sufficient dose of drug to the lesion, suitable carriers of drugs are needed. Nano and microparticle

Majeti N. V. Ravi



Polymethacrylate Microparticles Gel for Topical Drug Delivery  

Microsoft Academic Search

Purpose  Evaluating the potentials of particulate delivery systems in topical drug delivery.\\u000a \\u000a \\u000a \\u000a Methods  Polymethacrylate microparticles (MPs) incorporating verapamil hydrochloride (VRP) as a model hydrophilic drug with potential\\u000a topical clinical uses, using Eudragit RS100 and Eudragit L100 were prepared for the formulation of a composite topical gel.\\u000a The effect of initial drug loading, polymer composition, particularly the proportion of Eudragit L100 as an

Hagar Ibrahim Labouta; Labiba K. El-Khordagui



Transmucosal macromolecular drug delivery  

Microsoft Academic Search

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

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



Iontophoretic drug delivery  

Microsoft Academic Search

The composition and architecture of the stratum corneum render it a formidable barrier to the topical and transdermal administration of therapeutic agents. The physicochemical constraints severely limit the number of molecules that can be considered as realistic candidates for transdermal delivery. Iontophoresis provides a mechanism to enhance the penetration of hydrophilic and charged molecules across the skin. The principal distinguishing

Yogeshvar N. Kalia; Aarti Naik; James Garrison; Richard H. Guy



Layer-by-layer assembly of liposomal nanoparticles with PEGylated polyelectrolytes enhances systemic delivery of multiple anticancer drugs.  


Layer-by-layer (LbL)-engineered nanoparticles (NPs) are a promising group of therapeutic carriers used in an increasing number of biomedical applications. The present study uses a controlled LbL process to create a multidrug-loaded nanoplatform capable of promoting blood circulation time, biodistribution profile and controlling drug release in the dynamic systemic environment. LbL assembly is achieved by sequential deposition of poly-l-lysine (PLL) and poly(ethylene glycol)-block-poly(l-aspartic acid) (PEG-b-PLD) on liposomal nanoparticles (LbL-LNPs). This generates spherical and stable multilayered NPs ?240nm in size, enabling effective systemic administration. The numerous functional groups and compartments in the polyelectrolyte shell and core facilitate loading with doxorubicin and mitoxantrone. The nanoarchitecture effectively controls burst release, providing different release kinetics for each drug. LbL-LNPs are pH-sensitive, indicating that intracellular drug release can be increased by the acidic milieu of cancer cells. We further demonstrate that the LbL nanoarchitecture significantly reduces the elimination rates of both drugs tested and markedly extends their systemic circulation times, paving the way for efficacious tumor drug delivery. Because this delivery system accommodates multiple drugs, improves drug half-life and diminishes burst release, it provides an exciting platform with remarkable potential for combination therapeutics in cancer therapy. PMID:25169256

Ramasamy, Thiruganesh; Haidar, Ziyad S; Tran, Tuan Hiep; Choi, Ju Yeon; Jeong, Jee-Heon; Shin, Beom Soo; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh



Development of a protective dermal drug delivery system for therapeutic DNAzymes.  


RNA-cleaving DNAzymes are a potential novel class of nucleic acid-based active pharmaceutical ingredients (API). However, developing an appropriate drug delivery system (DDS) that achieves high bioavailability is challenging. Especially in a dermal application, DNAzymes have to overcome physiological barriers composed of penetration barriers and degrading enzymes. The focus of the present study was the development of a protective and penetration-enhanced dermal DDS that was tailor made for DNAzymes. DNAzyme Dz13 was used as a potential API for topical therapy against actinic keratosis. In the progress of development and selection, different preservatives, submicron emulsions (SMEs) and the physiological pH range were validated with respect to the API's integrity. A physicochemical stable SME of a pharmaceutical grade along with a high API integrity was achieved. Additionally, two developed protective systems, consisting of a liposomal formulation or chitosan-polyplexes, reduced the degradation of Dz13 in vitro. A combination of SME and polyplexes was finally validated at the skin and cellular level by in vitro model systems. Properties of penetration, degradation and distribution were determined. The result was enhanced skin penetration efficiency and increased cellular uptake with a high protective efficiency for DNAzymes due to the developed protective DDS. PMID:25541146

Marquardt, Kay; Eicher, Anna-Carola; Dobler, Dorota; Mäder, Ulf; Schmidts, Thomas; Renz, Harald; Runkel, Frank



Local Delivery System of Immune Modulating Drug for Unresectable Adenocarcinoma: In Vitro Experimental Study and In Vivo Animal Study  

SciTech Connect

The purpose of the study was to evaluate the efficacy and safety of a developed drug delivery system containing OK-432 through in vitro and animal study. An OK-432-impregnated polycarbonate/polyurethane stent membrane was used to develop a drug delivery system (DDS) enabling the locoregional release of OK-432. Polyethyleneglycol was used as a detergent and porosity generator. The stability of OK-432 in solvent, releasing kinetics of drug, and cytotoxicity of the DDS were evaluated. OK-432-impregnated DDS was implanted in mice in which a human adenocarcinoma cell line was injected and grown in their back. Flow cytometry and enzyme-linked immunosorbent assay were used for quantifying the amount of drug. OK-432 exposed to phosphate-buffered saline and OK-432 exposed to N,N-dimethylacetamide showed similar results on dot graphs and histograms. However, OK-432 exposed to tetrahydrofurane showed different dot graphs and histograms, which means that the antigenicity of the drug was changed. The release rate of OK-432 was maintained at a constant level for 6 weeks. The local delivery of OK-432 was found to have an antitumor effect on a human adenocarcinoma cell line in an animal study, but no effect on this cell line in in vitro cell culture. Histologic examination showed minimal inflammatory reaction in surrounding tissue. Our study shows that local treatment using this OK-432 release system is safe and effective in reducing adenocarcinoma in a mouse model.

Lee, Don Haeng [Inha University, College of Medicine, Department of Internal Medicine (Korea, Republic of); Kang, Sung-Gwon [Seoul National University Bundang Hospital, Department of Diagnostic Radiology (Korea, Republic of)], E-mail:; Jeong, Seok [Inha University, College of Medicine, Department of Internal Medicine (Korea, Republic of); Yoon, Chang Jin; Choi, Jung-Ah [Seoul National University Bundang Hospital, Department of Diagnostic Radiology (Korea, Republic of); Byun, Ju Nam [Chosun University, College of Medicine, Department of Radiology (Korea, Republic of); Park, Jae Hyung [Seoul National University Bundang Hospital, Department of Diagnostic Radiology (Korea, Republic of); Lee, Kyu Back [Korea University, College of Medicine, Department of Biomedical Engineering (Korea, Republic of)



A cell-targeted, size-photocontrollable, nuclear-uptake nanodrug delivery system for drug-resistant cancer therapy.  


The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy. The cell-membrane overexpression of P-glycoprotein (P-gp), which can actively efflux various anticancer drugs from the cell, is a major mechanism of MDR. Nuclear-uptake nanodrug delivery systems, which enable intranuclear release of anticancer drugs, are expected to address this challenge by bypassing P-gp. However, before entering the nucleus, the nanocarrier must pass through the cell membrane, necessitating coordination between intracellular and intranuclear delivery. To accommodate this requirement, we have used DNA self-assembly to develop a nuclear-uptake nanodrug system carried by a cell-targeted near-infrared (NIR)-responsive nanotruck for drug-resistant cancer therapy. Via DNA hybridization, small drug-loaded gold nanoparticles (termed nanodrugs) can self-assemble onto the side face of a silver-gold nanorod (NR, termed nanotruck) whose end faces were modified with a cell type-specific internalizing aptamer. By using this size-photocontrollable nanodrug delivery system, anticancer drugs can be efficiently accumulated in the nuclei to effectively kill the cancer cells. PMID:25479133

Qiu, Liping; Chen, Tao; Öçsoy, Ismail; Yasun, Emir; Wu, Cuichen; Zhu, Guizhi; You, Mingxu; Han, Da; Jiang, Jianhui; Yu, Ruqin; Tan, Weihong



In vitro and in vivo evaluation of oral systems for time and site specific delivery of drugs (Chronotopic technology).  


This paper reports the in vivo and in vitro evaluation of an oral system for time and/or site specific drug delivery prepared according to Chronotopic technology. The proposed device consists of a drug containing core coated by a hydrophilic polymeric layer, which determines the delay in release onset. By applying an outer gastroresistant film, and by properly modulating the delay duration, a colon-specific release can be achieved. The obtained results show that the proposed delivery system is capable of releasing drug after a programmed time (time-specific release) and of targeting the colon (site-specific release) when an external gastroresistant film is applied on units coated with an appropriate amount of a hydrophilic retarding polymer. PMID:10394705

Sangalli, M E; Maroni, A; Busetti, C; Zema, L; Giordano, F; Gazzaniga, A



A magnetic mesoporous silica nanoparticle-based drug delivery system for photosensitive cooperative treatment of cancer with a mesopore-capping agent and mesopore-loaded drug  

NASA Astrophysics Data System (ADS)

Lately, there has been a growing interest in anticancer therapy with a combination of different drugs that work by different mechanisms of action, which decreases the possibility that resistant cancer cells will develop. Herein we report on the development of a drug delivery system for photosensitive delivery of a known anticancer drug camptothecin along with cytotoxic cadmium sulfide nanoparticles from a magnetic drug nanocarrier. Core-shell nanoparticles consisting of magnetic iron-oxide-cores and mesoporous silica shells are synthesized with a high surface area (859 m2 g-1) and hexagonal packing of mesopores, which are 2.6 nm in diameter. The mesopores are loaded with anticancer drug camptothecin while entrances of the mesopores are blocked with 2-nitro-5-mercaptobenzyl alcohol functionalized CdS nanoparticles through a photocleavable carbamate linkage. Camptothecin release from this magnetic drug delivery system is successfully triggered upon irradiation with UV light, as measured by fluorescence spectroscopy. Photosensitive anticancer activity of the drug delivery system is monitored by viability studies on Chinese hamster ovarian cells. The treatment of cancer cells with drug loaded magnetic material leads to a decrease in viability of the cells due to the activity of capping CdS nanoparticles. Upon exposure to low power UV light (365 nm) the loaded camptothecin is released which induces additional decrease in viability of CHO cells. Hence, the capping CdS nanoparticles and loaded camptothecin exert a cooperative anticancer activity. Responsiveness to light irradiation and magnetic activity of the nanocarrier enable its potential application for selective targeted treatment of cancer.

Kneževi?, Nikola Ž.; Lin, Victor S.-Y.



Three Dimensional Transient Multifield Analysis of a Piezoelectric Micropump for Drug Delivery System for Treatment of Hemodynamic Dysfunctions  

Microsoft Academic Search

In this paper, we present design of a transdermal drug delivery system for treatment of cardiovascular or hemodynamic disorders\\u000a such as hypertension. The system comprises of integrated control electronics and microelectromechanical system devices such\\u000a as micropump, micro blood pressure sensor and microneedle array. The objective is to overcome the limitations of oral therapy\\u000a such as variable absorption profile and the

Asim Nisar; Nitin Afzulpurkar; Adisorn Tuantranont; Banchong Mahaisavariya



Hybrid liposomal PEGylated calix[4]arene systems as drug delivery platforms for curcumin.  


The tremendous therapeutic potential of curcumin as a chemopreventive, antineoplastic and chemosensitizing agent has failed to progress towards clinical development and commercialization due to its unfavorable physicochemical properties, low aqueous solubility, chemical instability, and pharmacokinetics. The present contribution is focused on the feasibility of using PEGylated calixarene, in particular polyoxyethylene-derivatized tert-butylcalix[4]arene, to prepare various platforms for delivery of curcumin such as inclusion complex, supramolecular aggregates, and hybrid liposomal systems. The inclusion complex is characterized by UV-vis and FT-IR spectroscopy as well as thermal gravimetrical analysis and differential scanning calorimetry. At concentrations exceeding the critical micellization concentration of PEGylated calixarene, the tremendous solubility enhancement of curcumin is attributed to additional solubilization and hydrophobic non-covalent interactions of the drug with supramolecular aggregates. A hybrid liposomal system is created via encapsulation of the inclusion complex in dipalmitoylphosphatidylcholine:cholesterol liposomes. Bare and liposomal curcumin:BEC-X inclusion complexes, as well as free curcumin were additionally investigated for cytotoxicity and apoptogenic activity against human tumor cell lines. PMID:24954662

Drakalska, Elena; Momekova, Denitsa; Manolova, Yana; Budurova, Dessislava; Momekov, Georgi; Genova, Margarita; Antonov, Liudmil; Lambov, Nikolay; Rangelov, Stanislav



Application of hot-melt coating process for designing a lipid based controlled release drug delivery system for highly aqueous soluble drugs.  


Hot-melt coating process (HMCP) was applied to develop a lipid based oral controlled release matrix system (tablet) to deliver highly aqueous soluble drugs using paracetamol as a model drug. Granules prepared from paracetamol and particular filler were coated with different levels of lipid and then compressed into tablets to get controlled/sustained delivery of the drug over an optimum period. Process parameters were optimized with particular focus on fluidization pattern during HMCP proposing a 'design space' with 'Quality by Design' (QbD) concept in mind. The results demonstrated that the granule composition influenced the drug release pattern, and the rate of release could be manipulated by varying the amount of lipid in the formulation. The in vitro release profile of the drug was pH-independent and the most promising release profile was obtained from tablets prepared from granules with the water-soluble filler, lactose, and coated at 9% (w/w) level with a lipid, glyceryl behanate. In vivo plasma profiles of the drug were predicted from the in vitro release profile data by convolution analysis which confirmed that the lactose based formulation with 9% (w/w) lipid coating on the granules would be suitable for controlled delivery of the drug over a period of 12 h making the formulation suitable for highly water soluble drug candidates like paracetamol with twice daily dose regimen. Moreover, the dissolution data adequately fitted into Higuchi model suggesting that the drug release occurred predominantly by diffusion. PMID:19420776

Knezevic, Zdravka; Gosak, Darko; Hraste, Marin; Rausl, Dragica; Khan, M Zahirul I



Fluorescent Microscope System to Monitor Real-Time Interactions between Focused Ultrasound, Echogenic Drug Delivery Vehicles, and Live Cell Membranes  

PubMed Central

Rapid development in the field of ultrasound triggered drug delivery has made it essential to study the real-time interaction between the membranes of live cells and the membranes of echogenic delivery vehicles under exposure to focused ultrasound. The objective of this work was to design an analysis system that combined fluorescent imagining, high speed videography, and definable pulse sequences of focused ultrasound to allow for real time observations of both cell and vehicle membranes. Documenting the behavior of the membranes themselves has not previously been possible due to limitations with existing optical systems used to understand the basic physics of microbubble/ultrasound interaction and the basic interaction between microbubbles and cells. The performance of this new system to monitor membrane behavior was demonstrated by documenting the modes of vehicle fragmentation at different ultrasound intensity levels. At 1.5 MPa the membranes were shown to completely fragment while at intensities below 1 MPa there is a popping and slow unfolding. The interaction between these vehicles and cell membranes was also documented by the removal of fluorescent particles from the surfaces of live cells out to 20 ?m from the microbubble location. The fluid flow created by microstreaming around ensonated microbubbles was documented at video recording speeds from 60 to 18,000 frames per second. This information about membrane behavior allows the chemical and physical properties of the drug delivery vehicle to be designed along with the ultrasound pulse sequence to cause the most efficient drug delivery. PMID:22749476

Ibsen, Stuart; Benchimol, Michael; Esener, Sadik



Compact, power-efficient architectures using microvalves and microsensors, for intrathecal, insulin, and other drug delivery systems.  


This paper describes a valve-regulated architecture, for intrathecal, insulin and other drug delivery systems, that offers high performance and volume efficiency through the use of micromachined components. Multi-drug protocols can be accommodated by using a valve manifold to modulate and mix drug flows from individual reservoirs. A piezoelectrically-actuated silicon microvalve with embedded pressure sensors is used to regulate dosing by throttling flow from a mechanically-pressurized reservoir. A preliminary prototype system is demonstrated with two reservoirs, pressure sensors, and a control circuit board within a 130cm(3) metal casing. Different control modes of the programmable system have been evaluated to mimic clinical applications. Bolus and continuous flow deliveries have been demonstrated. A wide range of delivery rates can be achieved by adjusting the parameters of the manifold valves or reservoir springs. The capability to compensate for changes in delivery pressure has been experimentally verified. The pressure profiles can also be used to detect catheter occlusions and disconnects. The benefits of this architecture compared with alternative options are reviewed. PMID:22580183

Li, Tao; Evans, Allan T; Chiravuri, Srinivas; Gianchandani, Roma Y; Gianchandani, Yogesh B



Disulfide cross-linked polyurethane micelles as a reduction-triggered drug delivery system for cancer therapy.  


Nanoscale carriers that stably load drugs in blood circulation and release the payloads in desirable sites in response to a specific trigger are of great interest for smart drug delivery systems. For this purpose, a novel type of disulfide core cross-linked micelles, which are facilely fabricated by cross-linking of poly(ethylene glycol)/polyurethane block copolymers containing cyclic disulfide moieties via a thiol-disulfide exchange reaction, are developed. A broad-spectrum anti-cancer drug, doxorubicin (DOX), is loaded into the micelles as a model drug. The drug release from the core cross-linked polyurethane micelles (CCL-PUMs) loaded with DOX is suppressed in normal phosphate buffer saline (PBS), whereas it is markedly accelerated with addition of an intracellular reducing agent, glutathione (GSH). Notably, although DOX-loaded CCL-PUMs display lower cytotoxicity in vitro compared to either free DOX or DOX-loaded uncross-linked polyurethane micelles, the drug-loaded CCL-PUMs show the highest anti-tumor efficacy with reduced toxicity in vivo. Since enhanced anti-tumor efficacy and reduced toxic side effects are key aspects of efficient cancer therapy, the novel reduction-responsive CCL-PUMs may hold great potential as a bio-triggered drug delivery system for cancer therapy. PMID:24574261

Yu, Shuangjiang; Ding, Jianxun; He, Chaoliang; Cao, Yue; Xu, Weiguo; Chen, Xuesi



The new insight into oral drug delivery system based on metal drugs in colon cancer therapy through ?-lactoglobulin/oxali-palladium nanocapsules.  


Many efforts have been made to improve the targeting and potential applications of oral drug delivery systems. In this paper, we have demonstrated and investigated how biopolymer nanocapsules can be used as a novel oral drug delivery system for metal-based drug delivery in colon cancer therapy. In this work, ?-lactoglobulin nanocapsules containing oxali-palladium were chosen to be synthesized and investigated for the use in colon cancer therapy. These nanocapsules were fabricated in three different pHs (3, 4.5 and 7) and investigated both in the presence and absence of low methoxyl pectin. The results obtained from these experiments indicated that the soluble and stable ?-lactoglobulin nanocapsules which contained oxali-palladium had the ability to be formed at a size smaller than 200 nm when in the presence of low methoxyl pectin and at pH 4.5. The in vitro release data indicated that the maximum release occurs at pH 7.0 and 7.5. There lease mechanism demonstrated an anomalous diffusion with a predominant contribution from erosion. Finally, it can be concluded that the ?-LG nanocapsules containing oxali-palladium complexed with low methoxyl pectin can be a very promising candidate for the use in oral drug delivery for colon cancer treatment. PMID:25190224

Ghalandari, Behafarid; Divsalar, Adeleh; Saboury, Ali Akbar; Parivar, Kazem



Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole.  


It was the purpose of this study to design and evaluate a new bioadhesive vaginal drug delivery system for clotrimazole. Chitosan, a cationic biopolymer derived by deacetylation of chitin, was modified by the introduction of thioglycolic acid (TGA). The modification was achieved by utilising a carbodiimide to link the carboxylic acid moieties of TGA covalently to the primary amino groups of chitosan. The amount of added carbodiimide was thereby varied, resulting in chitosan-TGA conjugates A and B with 160 microM (=micromol) and 280 microM thiol groups per gram polymer, respectively. In order to characterise the new polymers the water uptake, the disintegration behaviour, the bioadhesive properties utilising the rotating cylinder method, as well as the release of clotrimazole from tablets based on these derivatives were studied. The water uptake and cohesive properties of vaginal tablets consisting of these new conjugates could be significantly (p<0.05) improved. By adding clotrimazole the disintegration time of the conjugates was prolonged 1.6-fold for conjugate A and even 100-fold for conjugate B. Furthermore, the adhesion on vaginal mucosal tissue could be significantly improved. The addition of clotrimazole had also an impact on the adhesion time of chitosan-TGA conjugate B, which remained 26-times longer on vaginal mucosa than the corresponding unmodified polymer. The immobilisation of thiol groups guarantees a controlled drug release. Results of this study demonstrate that these new chitosan-TGA conjugates are very promising vehicles for the vaginal application of clotrimazole in treatment of mycotic infections. PMID:12044573

Kast, Constantia E; Valenta, Claudia; Leopold, Martina; Bernkop-Schnürch, Andreas



Formulation development and pharmacokinetics of puerarin self-emulsifying drug delivery systems.  


The main purpose of this work was to prepare a self-emulsifying drug delivery system (SEDDS) for a poorly water-soluble drug, puerarin. The solubility of puerarin was determined in various oils and surfactants. Oleic acid and Tween 80 provided relatively higher solubility. The addition of propylene glycol as a cosurfactant improved the solubility of puerarin and the spontaneity of self-emulsification. A series of mixtures composed of oleic acid, propylene glycol, and Tween 80 were prepared and their self-emulsifying properties were studied. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region, and the particle sizes of the resultant emulsions were determined using a laser diffraction sizer. The pharmacokinetic behaviors of three different SEDDS formulations were investigated in beagle dogs. The bioavailability of puerarin was compared using the pharmacokinetic parameters, peak plasma concentration (C(max)), time to reach peak plasma concentration (T(max)), and total area under the plasma concentration-time curve (AUC(0-infinity)). The analysis of the data showed a statistically significant difference between F2 and F4 (P < 0.01) as well as F3 and F4 (P < 0.01) with regard to the values of AUC(0-infinity) and C(max) but not between those of F2 and F3 (P > 0.05). In the case of parameter T(max), ke, no statistically significant difference (P > 0.05) among the values were observed. From these studies, a SEDDS containing oleic acid (17.5%), Tween 80 (34.5%), and propylene glycol (34.5%) (w/w) was selected as an optimized SEDDS formulation for puerarin. The data suggest the potential use of SEDDS to improve the oral absorption of puerarin. PMID:17390702

Dong-Qin, Quan; Gui-Xia, Xu; Xiang-Gen, Wu



A novel trans-lymphatic drug delivery system: Implantable gelatin sponge impregnated with PLGA–paclitaxel microspheres  

Microsoft Academic Search

A translymphatic drug delivery system which incorporates poly-lactide-co-glycolide–paclitaxel (PLGA–PTX) or PLGA–rhodamine microspheres into gelatin sponge matrix is described. The system combines the sustained release properties of PLGA–PTX with the structural advantages of gelatin matrix that can be implanted directly to the lymphatic site for both therapeutic and prophylactic purposes. The PLGA microspheres were prepared using spray drying technique. The particles

Jiang Liu; Dale Meisner; Elizabeth Kwong; Xiao Y. Wu; Michael R. Johnston



pH-responsive drug delivery system based on hollow silicon dioxide micropillars coated with polyelectrolyte multilayers  

PubMed Central

We report on the fabrication of polyelectrolyte multilayer-coated hollow silicon dioxide micropillars as pH-responsive drug delivery systems. Silicon dioxide micropillars are based on macroporous silicon formed by electrochemical etching. Due to their hollow core capable of being loaded with chemically active agents, silicon dioxide micropillars provide additional function such as drug delivery system. The polyelectrolyte multilayer was assembled by the layer-by-layer technique based on the alternative deposition of cationic and anionic polyelectrolytes. The polyelectrolyte pair poly(allylamine hydrochloride) and sodium poly(styrene sulfonate) exhibited pH-responsive properties for the loading and release of a positively charged drug doxorubicin. The drug release rate was observed to be higher at pH 5.2 compared to that at pH 7.4. Furthermore, we assessed the effect of the number of polyelectrolyte bilayers on the drug release loading and release rate. Thus, this hybrid composite could be potentially applicable as a pH-controlled system for localized drug release. PMID:25221455



pH-responsive drug delivery system based on hollow silicon dioxide micropillars coated with polyelectrolyte multilayers  

NASA Astrophysics Data System (ADS)

We report on the fabrication of polyelectrolyte multilayer-coated hollow silicon dioxide micropillars as pH-responsive drug delivery systems. Silicon dioxide micropillars are based on macroporous silicon formed by electrochemical etching. Due to their hollow core capable of being loaded with chemically active agents, silicon dioxide micropillars provide additional function such as drug delivery system. The polyelectrolyte multilayer was assembled by the layer-by-layer technique based on the alternative deposition of cationic and anionic polyelectrolytes. The polyelectrolyte pair poly(allylamine hydrochloride) and sodium poly(styrene sulfonate) exhibited pH-responsive properties for the loading and release of a positively charged drug doxorubicin. The drug release rate was observed to be higher at pH 5.2 compared to that at pH 7.4. Furthermore, we assessed the effect of the number of polyelectrolyte bilayers on the drug release loading and release rate. Thus, this hybrid composite could be potentially applicable as a pH-controlled system for localized drug release.

Alba, María; Formentín, Pilar; Ferré-Borrull, Josep; Pallarès, Josep; Marsal, Lluís F.



pH-responsive drug delivery system based on hollow silicon dioxide micropillars coated with polyelectrolyte multilayers.  


We report on the fabrication of polyelectrolyte multilayer-coated hollow silicon dioxide micropillars as pH-responsive drug delivery systems. Silicon dioxide micropillars are based on macroporous silicon formed by electrochemical etching. Due to their hollow core capable of being loaded with chemically active agents, silicon dioxide micropillars provide additional function such as drug delivery system. The polyelectrolyte multilayer was assembled by the layer-by-layer technique based on the alternative deposition of cationic and anionic polyelectrolytes. The polyelectrolyte pair poly(allylamine hydrochloride) and sodium poly(styrene sulfonate) exhibited pH-responsive properties for the loading and release of a positively charged drug doxorubicin. The drug release rate was observed to be higher at pH 5.2 compared to that at pH 7.4. Furthermore, we assessed the effect of the number of polyelectrolyte bilayers on the drug release loading and release rate. Thus, this hybrid composite could be potentially applicable as a pH-controlled system for localized drug release. PMID:25221455

Alba, María; Formentín, Pilar; Ferré-Borrull, Josep; Pallarès, Josep; Marsal, Lluís F



Amphiphilic linear-dendritic block copolymers for drug delivery  

E-print Network

Polymeric drug delivery systems have been widely used in the pharmaceutical industry. Such systems can solubilize and sequester hydrophobic drugs from degradation, thereby increasing circulation half-life and efficacy. ...

Nguyen, Phuong, Ph. D. Massachusetts Institute of Technology



Nanocarriers and Drug Delivery  

Microsoft Academic Search

Nanoparticles may serve, among other techniques, as a useful tool for achieving the main objective of regional cancer therapy:\\u000a they can deliver a higher concentration of the agent to the tumor and expose the tumor to active drug for longer periods than\\u000a safely possible with conventional formulations. These carriers combine many advantages, such as a potential for selective\\u000a targeting and

Svetlana Gelperina


Functional Cyclodextrin Polyrotaxanes for Drug Delivery  

NASA Astrophysics Data System (ADS)

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.

Yui, Nobuhiko; Katoono, Ryo; Yamashita, Atsushi


The significance of transferrin receptors in oncology: the development of functional nano-based drug delivery systems.  


Anticancer therapeutic research aims to improve clinical management of the disease through the development of strategies that involve currently-relevant treatment options and targeted delivery. Tumour-specific and -targeted delivery of compounds to the site of malignancy allows for enhanced cellular uptake, increased therapeutic benefit with high intratumoural drug concentrations, and decreased systemic exposure. Due to the upregulation of transferrin receptor expression in a wide variety of cancers, its function and its highly efficient recycling pathway, strategies involving the selective targeting of the receptor are well documented. Direct conjugation and immunotoxin studies using the transferrin peptide or anti-transferrin receptor antibodies as the targeting moiety have established the capacity to enhance cellular uptake, cross the blood brain barrier, limit systemic toxicity and reverse multi-drug resistance. Limitations in direct conjugation, including the difficulty in linking an adequate amount of therapeutic compound to the ligand or antibody have identified the requirement to develop novel delivery methods. The application of nanoparticulate theory in the development of functional drug delivery systems has proven to be most promising, with the ability to selectively modify size-dependent properties and surface chemistry. The transferrin modification on a range of nanoparticle formulations enhances selective cellular uptake through transferrin-mediated processes, and increases therapeutic benefit through the ability to encapsulate high concentrations of relevant drug to the tumour site. Although ineffective in crossing the blood brain barrier in its free form, chemotherapeutic compounds including doxorubicin, may be loaded into transferrin-conjugated nanocarriers and impart cytotoxic effects in glioma cells in vitro and in vivo. Additionally, transferrin-targeted nanoparticles may be used in selective diagnostic applications with enhanced selectivity and sensitivity. Four transferrin-modified nano-based drug delivery systems are currently in early phases of human clinical trials. Despite the collective promise, inconsistencies in some studies have exposed some limitations in current formulations and the difficulty in translating preliminary studies into clinically-relevant therapeutic options. The main objective of this review is to investigate the development of transferrin targeted nano-based drug delivery systems in order to establish the use of transferrin as a cancer-targeted moiety, and to ultimately evaluate the progression of cancer therapeutic strategies for future research. PMID:24387131

Tortorella, Stephanie; Karagiannis, Tom C



CCMR: Drug Delivery Using Nanoparticles  

NSDL National Science Digital Library

Safe and nontoxic drug delivery is an ongoing area of research. Some current methods of drug delivery include the use of nanoparticles, hydrogels, dendrimers, and micelles. Nanoparticles can be used as vehicles in which to transport certain drugs to cancerous cells. A certain class of nanoparticles called clays is especially useful in synthesizing these drug delivery vehicles. Layered Double Hydroxides (LDHs) are a type of hydrotalcite clay with a structure similar to smectite clays. They have a general structure that consists of layers of metal hydroxides connected to a layer of another metal hydroxide by hydrogen bonding. LDHs are made up of layers of a trivalent and a divalently charged cation coordinated by six oxygen atoms. The resulting structure consists of two-dimensional sheets with positively charged faces and negatively charged edges that are stacked together via hydrogen bonding between hydroxyl groups on adjacent sheets. These sheets generally have a very high aspect ratio, resulting in a large surface area. The positively charged layers are balanced by the presence of anions between them. A wide variety of LDHs can be synthesized depending on the various cations and interlayer anions used. Characterization of the LDHs themselves as well as LDHs intercalated with the drugs was performed using X-ray diffraction and TEM and SEM microscopy.

Lin, Joyce



Lipoidal Soft Hybrid Biocarriers of Supramolecular Construction for Drug Delivery  

PubMed Central

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

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



Barriers to drug delivery in solid tumors  

PubMed Central

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

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



Efficient delivery of anticancer drug MTX through MTX-LDH nanohybrid system  

NASA Astrophysics Data System (ADS)

We have been successful to intercalate anticancer drug, methotrexate (MTX), into layered double hydroxides (LDHs), Mg2Al(OH)6(NO3)·0.1H2O, through conventional co-precipitation method. Layered double hydroxides (LDHs) are endowed with great potential for delivery vector, since their cationic layers lead to safe reservation of biofunctional molecules such as drug molecules or genes. And their ion exchangeability and solubility in acidic media (pH<4) give rise to the controlled release of drug molecules. Moreover, it has been partly confirmed that LDH itself is non-toxic and facilitate the cellular permeation. To check the toxicity of LDHs, the osteosarcoma cell culture lines (Saos-2 and MG-63) and the normal one (human fibroblast) were used for in vitro test. The anticancer efficacy of MTX intercalated LDHs (MTX-LDH nanohybrids) was also estimated in vitro by the bioassay such as MTT and BrdU (5-bromo-2-deoxyuridine) with the bone cancer cell culture lines (Saos-2 and MG-63). According to the toxicity test results, LDHs do not harm to both the normal and cancer cells upto the concentration of 500 ug/mL. The anticancer efficacy test for the MTX-LDH nanohybrids turn out to be much more effective in cell suppression compared to the MTX itself. According to the cell-line tests, the MTX-LDH shows same drug efficacy to the MTX itself in spite of the low concentration by ˜5000 times. Such a high cancer suppression effect of MTX-LDH hybrid is surely due to the excellent delivery efficiency of inorganic delivery vector, LDHs.

Oh, Jae-Min; Park, Man; Kim, Sang-Tae; Jung, Jin-Young; Kang, Yong-Gu; Choy, Jin-Ho



Emergency delivery of Vasopressin from an implantable MEMS rapid drug delivery device  

E-print Network

An implantable rapid drug delivery device based on micro-electro-mechanical systems (MEMS) technology was designed, fabricated and validated for the in vivo rapid delivery of vasopressin in a rabbit model. In vitro ...

Ho Duc, Hong Linh, 1978-



Hydroxy fatty acid based polyanhydride as drug delivery system: synthesis, characterization, in vitro degradation, drug release, and biocompatibility.  


Low molecular weight hydroxy fatty acid based polyanhydrides were synthesized by one pot method, a variable of typical melt-condensation and characterized by FTIR, NMR, DSC, and GPC. Polymer degrades by both surface and bulk erosion as trailed by weight loss, anhydride loss and surface morphology. Control over drug release was accessed with drugs featuring different aqueous solubility, that is, methotrexate (hydrophobic) and 5-fluorouracil (hydrophilic). Effect of loading, at 5, 10, and 20% w/w of methotrexate on release profiles was also studied and negligible effect was discovered. Biocompatibility of polymers was evaluated in SD rats after SC injection of the polymer. Histopathology revealed initial inflammation of the tissues near the injection site however healed with time. Overall, these polymers were found good to control the release of the entrapped drug and were found biocompatible in preliminary in vivo study. Due to their low melting temperatures they can be injected locally (SC or intratumorally) to from regional in situ depot and have a great potential as a drug carrier for localized delivery of anticancer drugs. PMID:17635032

Jain, Jay Prakash; Modi, Sweta; Kumar, Neeraj



Tuning Pharmacokinetics and Biodistribution of a Targeted Drug Delivery System Through Incorporation of a Passive Targeting Component  

PubMed Central

Major challenges in the development of drug delivery systems (DDSs) have been the short half-life, poor bioavailability, insufficient accumulation and penetration of the DDSs into the tumor tissue. Understanding the pharmacokinetic (PK) parameters of the DDS is essential to overcome these challenges. Herein we investigate how surface chemistry affects the PK profile and organ distribution of a gold nanoparticle-based DDS containing both a passive and active targeting moiety via two common routes of administration: intravenous and intraperitoneal injections. Using LC/MS/MS, ELISA and INAA we report the half-life, peak plasma concentrations, area under the curve, ability to cross the peritoneal barrier and biodistribution of the nanoconjugates. The results highlight the design criteria for fine-tuning the PK parameters of a targeted drug delivery system that exploits the benefits of both active and passive targeting. PMID:25011609

Kudgus, Rachel A.; Walden, Chad A.; McGovern, Renee M.; Reid, Joel M.; Robertson, J. David; Mukherjee, Priyabrata



Drug delivery Preparation of Monodisperse Biodegradable Polymer  

E-print Network

Drug delivery Preparation of Monodisperse Biodegradable Polymer Microparticles Using a Microfluidic Flow-Focusing Device for Controlled Drug Delivery Qiaobing Xu, Michinao Hashimoto, Tram T. Dang, Todd microparticles have broad utility as vehicles for drug delivery and form the basis of several therapies approved

Prentiss, Mara


Drug delivery and nanoparticles: Applications and hazards  

PubMed Central

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, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed. PMID:18686775

De Jong, Wim H; Borm, Paul JA



A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery  

E-print Network

A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery Hong Chen1 the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within

Konofagou, Elisa E.


Development and characterization of polymeric nanoparticulate delivery system for hydrophillic drug: Gemcitabine  

NASA Astrophysics Data System (ADS)

Gemcitabine is a nucleoside analogue, used in various carcinomas such as non small cell lung cancer, pancreatic cancer, ovarian cancer and breast cancer. The major setbacks to the conventional therapy with gemcitabine include its short half-life and highly hydrophilic nature. The objectives of this investigation were to develop and evaluate the physiochemical properties, drug loading and entrapment efficiency, in vitro release, cytotoxicity, and cellular uptake of polymeric nano-particulate formulations containing gemcitabine hydrochloride. The study also entailed development and validation of a high performance liquid chromatography (HPLC) method for the analysis of gemcitabine hydrochloride. A reverse phase HPLC method using a C18 Luna column was developed and validated. Alginate and Poly lactide co glycolide/Poly-epsilon-caprolactone (PLGA:PCL 80:20) nanoparticles were prepared by multiple emulsion-solvent evaporation methodology. An aqueous solution of low viscosity alginate containing gemcitabine was emulsified into 10% solution of dioctyl-sulfosuccinate in dichloro methane (DCM) by sonication. The primary emulsion was then emulsified in 0.5% (w/v) aqueous solutio