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1

Intracochlear Drug Delivery Systems  

PubMed Central

Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

Borenstein, Jeffrey T.

2011-01-01

2

COLON TARGETED DRUG DELIVERY SYSTEMS  

Microsoft Academic Search

Colon targeted drug delivery systems have the potential to deliver drugs for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. In recent years, various pharmaceutical approaches have been developed for targeting the drugs to the colon include, formation of prodrugs, coating of pH-sensitive polymers, use of colon

Ceyda Tuba

3

Microfabricated injectable drug delivery system  

DOEpatents

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)

2002-01-01

4

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-

2005-01-01

5

Peptide and protein delivery using new drug delivery systems.  

PubMed

Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery. PMID:23662604

Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

2013-01-01

6

Physically facilitating drug-delivery systems  

PubMed Central

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

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

2012-01-01

7

Development of controlled release drug delivery systems  

Microsoft Academic Search

The newly emerged biotechnology of liposome-based drug delivery has drawn great interest in research and pharmaceuticals. ^ My research on developing controlled release drug delivery systems started with the synthesis of a highly reliable anchor for water-soluble polymers, which will serve as an anchor with a high affinity towards lipid bilayers and can be monitored by fluorescence. A new family

Ming Li

2002-01-01

8

Formulating Drug Delivery Systems by Spray Drying  

Microsoft Academic Search

The knowledge of the potential use of the spray-drying technology to prepare microparticulate drug delivery systems—microspheres and microcapsules—has been strongly improved over the last years. Various microparticulate spray drying systems used as vehicles for drug encapsulation and delivery that have been investigated for different purposes are presented here, including spray-dried powders formulated with hydrophilic polymers allowing controlled drug release, biodegradable

Maria-Inês Ré

2006-01-01

9

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

2011-01-01

10

Vaginal Drug Delivery Systems for HIV Prevention  

Microsoft Academic Search

Microbicides have become a principal focus for HIV prevention strategies. The successful design of drug delivery systems for\\u000a vaginal microbicide drug candidates brings with it a multitude of challenges. It is imperative that the chemical and physical\\u000a characteristics of the drug candidate and its mechanism of action be clearly understood and considered to successfully deliver\\u000a and target drug candidates efficiently.

Lisa Cencia Rohan; Alexandra B. Sassi

2009-01-01

11

Drug delivery systems for intraperitoneal therapy.  

PubMed

Disorders associated with the peritoneal cavity include peritoneal adhesions and intraperitoneal (IP) malignancies. To prevent peritoneal adhesions, physical barrier devices are used to prevent organs from contacting other structures in the abdomen and forming adhesions, or pharmacological agents that interfere with adhesion formation are administered intraperitoneally. IP malignancies are other disorders confined to the peritoneal cavity, which are treated by combination of surgical removal and chemotherapy of the residual tumor. IP drug delivery helps in the regional therapy of these disorders by providing relatively high concentration and longer half-life of a drug in the peritoneal cavity. Various studies suggest that IP delivery of anti-neoplastic agents is a promising approach for malignancies in the peritoneal cavity compared to the systemic administration. However, IP drug delivery faces several challenges, such as premature clearance of a small molecular weight drug from the peritoneal cavity, lack of target specificity, and poor drug penetration into the target tissues. Previous studies have proposed the use of micro/nanoparticles and/or hydrogel-based systems for prolonging the drug residence time in the peritoneal cavity. This commentary discusses the currently used IP drug delivery systems either clinically or experimentally and the remaining challenges in IP drug delivery for future development. PMID:20198409

Bajaj, Gaurav; Yeo, Yoon

2010-05-01

12

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

2011-01-01

13

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.

2004-03-01

14

Advances in Biodegradable Ocular Drug Delivery Systems  

Microsoft Academic Search

\\u000a The limitations of existing medical therapies for ocular disorders include low drug bioavailability, nonspecificity, side\\u000a effects, and poor treatment adherence to therapy. These limitations may be overcome through the use of sustained-release intraocular\\u000a drug delivery systems. Critical to the development of such systems has been the introduction of biocompatible polymers (biodegradable\\u000a and nonbiodegradable) that allow for drug release kinetics to

Susan S. Lee; Patrick Hughes; Aron D. Ross; Michael R. Robinson

15

Liposomes as delivery systems for antineoplastic drugs  

NASA Astrophysics Data System (ADS)

Liposome drug formulations are defined as pharmaceutical products containing active drug substances encapsulated within the lipid bilayer or in the interior aqueous space of the liposomes. The main importance of this drug delivery system is based on its drastic reduction in systemic dose and concomitant systemic toxicity that in comparison with the free drug, results in an improvement of patient compliance and in a more effective treatment. There are several therapeutic drugs that are potential candidates to be encapsulated into liposomes; particular interest has been focused in therapeutic and antineoplastic drugs, which are characterized for its low therapeutic index and high systemic toxicity. The use of liposomes as drug carriers has been extensively justified and the importance of the development of different formulations or techniques to encapsulate therapeutic drugs has an enormous value in benefit of patients affected by neoplastic diseases.

Medina, Luis Alberto

2014-11-01

16

Brain drug delivery systems for neurodegenerative disorders.  

PubMed

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

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

2012-09-01

17

A wireless actuating drug delivery system  

NASA Astrophysics Data System (ADS)

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

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

2015-04-01

18

Intelligent, self-powered, drug delivery systems  

NASA Astrophysics Data System (ADS)

Self-propelled nano/micromotors and pumps are considered to be next generation drug delivery systems since the carriers can either propel themselves (``motor''-based drug delivery) or be delivered (``pump''-based drug delivery) to the target in response to specific biomarkers. Recently, there has been significant advancement towards developing nano/microtransporters into proof-of-concept tools for biomedical applications. This review encompasses the progress made to date on the design of synthetic nano/micromotors and pumps with respect to transportation and delivery of cargo at specific locations. Looking ahead, it is possible to imagine a day when intelligent machines navigate through the human body and perform challenging tasks.

Patra, Debabrata; Sengupta, Samudra; Duan, Wentao; Zhang, Hua; Pavlick, Ryan; Sen, Ayusman

2013-01-01

19

Self-Emulsifying Drug Delivery Systems: Strategy for Improving Oral Delivery of Poorly Soluble Drugs  

Microsoft Academic Search

Drugs are most often administered by the oral route. However, more than 40% of new chemical entities exhibit poor aqueous solubility, resulting in unsatisfactory oral drug delivery. Recently, much attention has been focused on self- emulsifying drug delivery systems (SEDDS) to improve the oral bioavailability of poorly aqueous soluble drugs. SEDDS are isotropic mixtures of oil, surfactants, solvents and co-solvents\\/surfactants.

Jing-ling Tang; Jin Sun; Zhong-Gui He

2007-01-01

20

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

2011-01-01

21

Microsealed drug delivery systems: fabrications and performance.  

PubMed

The Microsealed Drug Delivery (MDD) system was developed to achieve several objectives: to maximize the bioavailability of a therapeutic agent in a target tissue; to minimize the adverse side effects of a therapeutic agent or its metabolites; to optimize the onset, rate, and duration of drug delivery; to maintain the steady-state plasma drug level within a therapeutic range for as long as required for effective treatment; and to improve the patient compliance to a therapeutic regimen. This drug delivery system is fabricated from a biocompatible elastomer by microdispersion of the drug reservoir, as immobilized microscopic spheres, in the cross-linked polymer matrix. The release of drugs is controlled at a programmed rate for a prolonged time period. Several physical shapes and sizes of controlled-release drug delivery devices can be fabricated from this MDD system for various biomedical applications. For subcutaneous controlled drug administration, a cylinder-shaped subdermal implant was fabricated from the MDD system for easy subcutaneous implantation and the controlled release of deoxycorticosterone acetate in rats at zero-order rates for a duration of up to 129 days for cardiovascular pharmacology studies. This is 1 example of the many controlled-release drug delivery devices that can be fabricated from the patented MDD system. A bandage-type transdermal MDD device was developed to release an androgen, testosterone, at a constant rate. Topical application of this testosterone-releasing transdermal patch over the skin in the umbilical area of monkeys was observed to achieve a relatively constant plasma level of testosterone for a duration of up to 31 days. The encouraging results laid the foundation for the recent development and marketing of Nitrodisc system. A donut-shaped vaginal device can be fabricated from the MDD system for the intravaginal controlled administration of an orally active contraceptive progestin, such as norethindrone, or of a combination of 1 progestin with 1 estrogen. A 7-shaped IUD can be fabricated from the MDD system for intrauterine controlled administration of an estrogen, such as estriol, or a progestin to achieve a localized contraceptive action. PMID:3930920

Chien, Y W

1985-01-01

22

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

2014-01-01

23

Bharatbook.com - Drug Delivery Systems forecasts for 2012 & 2017  

Microsoft Academic Search

Oral drug delivery systems will remain the largest method used for drug delivery. Orally disintegrating tablets and transmucosal drugs will generate strong growth opportunities in the delivery of pain control and other critical care medication. Ease of administration advantages will promote the widening use of chewable tablet dosages for nutritional, respiratory and central nervous system agents, especially pediatric preparations. Better

2008-01-01

24

Microemulsions based transdermal drug delivery systems.  

PubMed

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

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

2014-01-01

25

Provesicles as novel drug delivery systems.  

PubMed

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

Bayindir, Zerrin S; Yuksel, Nilufer

2015-01-01

26

Liposomes and Niosomes as Topical Drug Delivery Systems  

Microsoft Academic Search

The skin acts as a major target as well as a principle barrier for topical\\/transdermal (TT) drug delivery. The stratum corneum plays a crucial role in barrier function for TT drug delivery. Despite major research and development efforts in TT systems and the advantages of these routes, low stratum corneum permeability limits the usefulness of topical drug delivery. To overcome

M. J. Choi; H. I. Maibach

2005-01-01

27

Development of Controlled Release Drug Delivery Systems  

Microsoft Academic Search

The newly emerged biotechnology of liposome-based drug delivery has drawn great interest in research and pharmaceuticals. Lipsomes are potential candidates to carry highly toxic drugs to target cells in order to minimize the damage to normal cells and side effects. In the past two decades, extensive work has improved the stability of phospholipid lipsomes in physiological fluids as drug carriers.

Ming Li

2002-01-01

28

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

2008-01-01

29

Micro- and nano-fabricated implantable drug-delivery systems  

PubMed Central

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

Meng, Ellis; Hoang, Tuan

2013-01-01

30

Importance of novel drug delivery systems in herbal medicines  

PubMed Central

Novel drug delivery system is a novel approach to drug delivery that addresses the limitations of the traditional drug delivery systems. Our country has a vast knowledge base of Ayurveda whose potential is only being realized in the recent years. However, the drug delivery system used for administering the herbal medicine to the patient is traditional and out-of-date, resulting in reduced efficacy of the drug. If the novel drug delivery technology is applied in herbal medicine, it may help in increasing the efficacy and reducing the side effects of various herbal compounds and herbs. This is the basic idea behind incorporating novel method of drug delivery in herbal medicines. Thus it is important to integrate novel drug delivery system and Indian Ayurvedic medicines to combat more serious diseases. For a long time herbal medicines were not considered for development as novel formulations owing to lack of scientific justification and processing difficulties, such as standardization, extraction and identification of individual drug components in complex polyherbal systems. However, modern phytopharmaceutical research can solve the scientific needs (such as determination of pharmacokinetics, mechanism of action, site of action, accurate dose required etc.) of herbal medicines to be incorporated in novel drug delivery system, such as nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles and so on. This article summarizes various drug delivery technologies, which can be used for herbal actives together with some examples. PMID:22228938

Devi, V. Kusum; Jain, Nimisha; Valli, Kusum S.

2010-01-01

31

Targeted Drug Delivery Systems for Cancer Therapy  

Microsoft Academic Search

The role of cyclodextrin’s (CD) in drug delivery has advanced in recent years and this may be attributed to its biocompatibility and well established synthesis. Chemical modification of CDs has shown to extend the physicochemical properties and the host capacity for a variety of drugs. ?-CD has been widely used in the early stages of pharmaceutical applications because of its

Antonio Clementi; Christine OConnor; Mary McNamara; A. Mazzaglia; M. C. Aversa; A. Giuffrida

2008-01-01

32

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.

2011-11-01

33

Herbal Excipients in Novel Drug Delivery Systems  

PubMed Central

The use of natural excipients to deliver the bioactive agents has been hampered by the synthetic materials. However advantages offered by these natural excipients are their being non-toxic, less expensive and freely available. The performance of the excipients partly determines the quality of the medicines. The traditional concept of the excipients as any component other than the active substance has undergone a substantial evolution from an inert and cheap vehicle to an essential constituent of the formulation. Excipients are any component other than the active substance(s) intentionally added to formulation of a dosage form. This article gives an overview of herbal excipients which are used in conventional dosage forms as well as novel drug delivery systems. PMID:20046764

Shirwaikar, A.; Shirwaikar, Annie; Prabu, S. Lakshmana; Kumar, G. Aravind

2008-01-01

34

Controlled drug delivery systems: past forward and future back.  

PubMed

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

2014-09-28

35

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

2012-01-01

36

Novel Drug Delivery Systems for Posterior Segment Ocular Disease  

Microsoft Academic Search

Delivery of drugs to the eye, particularly for the treatment of posterior segment diseases, is a challenging task that requires\\u000a drug transport across barriers in the eye, which are present for the purpose of limiting the entry of drugs and xenobiotics.\\u000a The common methods of drug delivery to the eye—eyedrops, direct injection, and systemic administration—all have problems that\\u000a limit their

Heather Sheardown; W. Mark Saltzman

37

A Molecular Communication System Model for Particulate Drug Delivery Systems.  

PubMed

The goal of a Drug Delivery System (DDS) is to convey a drug where the medication is needed, while, at the same time, preventing the drug from affecting other healthy parts of the body. Drugs composed of micro or nano-sized particles (particulate DDS) that are able to cross barriers which prevent large particles from escaping the bloodstream are used in the most advanced solutions.Molecular Communication (MC) is used as an abstraction of the propagation of drug particles in the body. MC is a new paradigm in communication research where the exchange of information is achieved through the propagation of molecules. Here, the transmitter is the drug injection, the receiver is the drug delivery and the channel is realized by the transport of drug particles, thus enabling the analysis and design of a particulate DDS using communication tools. This is achieved by modeling the MC channel as two separate contributions, namely, the cardiovascular network model and the drug propagation network. The cardiovascular network model allows to analytically compute the blood velocity profile in every location of the cardiovascular system given the flow input by the heart. The drug propagation network model allows the analytical expression of the drug delivery rate at the targeted site given the drug injection rate. Numerical results are also presented to assess the flexibility and accuracy of the developed model. The study of novel optimization techniques for a more effective and less invasive drug delivery will be aided by this model, while paving the way for novel communication techniques for Intra-Body communication Networks (IBN). PMID:23807425

Chahibi, Youssef; Pierobon, Massimiliano; Song, Sang Ok; Akyildiz, Ian

2013-06-27

38

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

2012-01-01

39

Iontophoretic drug delivery system: focus on fentanyl.  

PubMed

Fentanyl iontophoretic transdermal system (ITS) is a novel, patient-activated drug delivery device used for the management of acute postoperative pain in the hospital setting. This credit-card-sized device uses an imperceptible current of 170 milliampere to actively deliver a fentanyl hydrochloride 40-microg dose into the vasculature over a 10-minute interval. The unit is programmed to lock out further doses after either 80 doses or 24 hours, whichever is reached first. When comparing fentanyl ITS with intravenously administered fentanyl, serum concentrations differ significantly at 10 minutes after the initial dose is administered: 0.1 ng/ml for fentanyl ITS versus 0.7 ng/ml for intravenous fentanyl. Fentanyl ITS absorption increases in a time-dependent fashion over the first 10 hours of dosing. Other pharmacokinetic parameters of fentanyl ITS are comparable to those of intravenous fentanyl after 24 hours (maximum concentration 1.37 and 1.82 microg/ml, time to maximum concentration 0.65 and 0.58 hr, and area under the concentration-time curve at 23-24 hrs 1.23 and 1.34 microg x hr/ml for fentanyl ITS and intravenous fentanyl, respectively,). This new technology exhibited superior analgesia compared with placebo in two placebo-controlled studies that used time to exit as a primary end point. In addition, fentanyl ITS proved equivalent to patient-controlled analgesia with intravenous morphine. Although adverse effects were congruent with those expected from pure-agonist opioids, subjects assigned to the ITS group did experience a higher rate of mild, clinically nonsignificant erythema at the system placement site. Judicious monitoring for opioid-induced respiratory depression is recommended for fentanyl ITS, although this adverse effect has not been observed in clinical trials. Fentanyl ITS may provide another useful alternative in the management of acute postoperative pain. PMID:17461710

Herndon, Chris M

2007-05-01

40

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.

2013-01-01

41

Recent trends in drug delivery system using protein nanoparticles.  

PubMed

Engineered nanoparticles that can facilitate drug formulation and passively target tumours have been under extensive research in recent years. These successes have driven a new wave of significant innovation in the generation of advanced particles. The fate and transport of diagnostic nanoparticles would significantly depend on nonselective drug delivery, and hence the use of high drug dosage is implemented. In this perspective, nanocarrier-based drug targeting strategies can be used which improve the selective delivery of drugs to the site of action, i.e. drug targeting. Pharmaceutical industries majorly focus on reducing the toxicity and side effects of drugs but only recently it has been realised that carrier systems themselves may pose risks to the patient. Proteins are compatible with biological systems and they are biodegradable. They offer a multitude of moieties for modifications to tailor drug binding, imaging or targeting entities. Thus, protein nanoparticles provide outstanding contributions as a carrier for drug delivery systems. This review summarises recent progress in particle-based therapeutic delivery and discusses important concepts in particle design and biological barriers for developing the next generation of particles drug delivery systems. PMID:24668188

Sripriyalakshmi, S; Jose, Pinkybel; Ravindran, Aswathy; Anjali, C H

2014-09-01

42

Development of colon targeted drug delivery systems for mebendazole  

Microsoft Academic Search

The objective of the present study is to develop colon targeted drug delivery systems for mebendazole using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for drug content uniformity, and were subjected to in vitro drug release studies. The

Y. S. R Krishnaiah; P Veer Raju; B Dinesh Kumar; P Bhaskar; V Satyanarayana

2001-01-01

43

A water-powered micro drug delivery system  

Microsoft Academic Search

A plastic micro drug delivery system has been successfully demonstrated by utilizing the principle of osmosis without any electrical power consumption. The system has an osmotic microactuator (see Su, Lin, and Pisano, J. Microelectromech., vol. 11, pp. 736-7462, Dec. 2002) and a polydimethylsiloxane (PDMS) microfluidic cover compartment consisting of a reservoir, a microfluidic channel and a delivery port. The typical

Yu-Chuan Su; Liwei Lin

2004-01-01

44

Gastroretentive drug delivery systems for the treatment of Helicobacter pylori  

PubMed Central

Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections. PMID:25071326

Zhao, Shan; Lv, Yan; Zhang, Jian-Bin; Wang, Bing; Lv, Guo-Jun; Ma, Xiao-Jun

2014-01-01

45

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

PubMed Central

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

2013-01-01

46

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

47

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

2013-01-01

48

Biomedical materials, devices and drug delivery systems by radiation techniques  

NASA Astrophysics Data System (ADS)

The study of radiation polymerization in a super-cooled state started in 1966 and has been applied to the immobilization of biofunctional materials since 1973. In the last twenty years, application has been concentrated to the immobilization of drugs and hormones for the purpose of drug delivery systems. Very recently, the author has proposed a concept of environmental signal responsive chemical delivery system, as a new generation of controlled release and delivery systems. The study and development of materials, devices and systems is described. The signal responsive delivery system consists of a sensor part and a controlled delivery part. Therefore, the use of immobilization techniques for the biochip sensor and the hydrogel actuator has been investigated. As a future goal, systems for the brain research are to be designed and studied.

Kaetsu, Isao

1996-03-01

49

Targeted electrohydrodynamic printing for micro-reservoir drug delivery systems  

NASA Astrophysics Data System (ADS)

Microfluidic drug delivery systems consisting of a drug reservoir and microfluidic channels have shown the possibility of simple and robust modulation of drug release rate. However, the difficulty of loading a small quantity of drug into drug reservoirs at a micro-scale limited further development of such systems. Electrohydrodynamic (EHD) printing was employed to fill micro-reservoirs with controlled amount of drugs in the range of a few hundreds of picograms to tens of micrograms with spatial resolution of as small as 20 µm. Unlike most EHD systems, this system was configured in combination with an inverted microscope that allows in situ targeting of drug loading at micrometer scale accuracy. Methylene blue and rhodamine B were used as model drugs in distilled water, isopropanol and a polymer solution of a biodegradable polymer and dimethyl sulfoxide (DMSO). Also tetracycline-HCl/DI water was used as actual drug ink. The optimal parameters of EHD printing to load an extremely small quantity of drug into microscale drug reservoirs were investigated by changing pumping rates, the strength of an electric field and drug concentration. This targeted EHD technique was used to load drugs into the microreservoirs of PDMS microfluidic drug delivery devices and their drug release performance was demonstrated in vitro.

Hwang, Tae Heon; Kim, Jin Bum; Som Yang, Da; Park, Yong-il; Ryu, WonHyoung

2013-03-01

50

pH-responsive drug-delivery systems.  

PubMed

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

2015-02-01

51

Coacervate delivery systems for proteins and small molecule drugs.  

PubMed

Coacervates represent an exciting new class of drug delivery vehicles, developed in the past decade as carriers of small molecule drugs and proteins. This review summarizes several well-described coacervate systems, including: i) elastin-like peptides for delivery of anticancer therapeutics; ii) heparin-based coacervates with synthetic polycations for controlled growth factor delivery; iii) carboxymethyl chitosan aggregates for oral drug delivery; iv) Mussel adhesive protein and hyaluronic acid coacervates. Coacervates present advantages in their simple assembly and easy incorporation into tissue engineering scaffolds or as adjuncts to cell therapies. They are also amenable to functionalization such as for targeting or for enhancing the bioactivity of their cargo. These new drug carriers are anticipated to have broad applications and noteworthy impact in the near future. PMID:25138695

Johnson, Noah R; Wang, Yadong

2014-12-01

52

Transdermal drug delivery  

Microsoft Academic Search

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, noncavitational ultrasound and iontophoresis have also resulted

Mark R Prausnitz; Robert Langer

2008-01-01

53

Processing of polymer nanofibers through electrospinning as drug delivery systems  

Microsoft Academic Search

The use of electrospun fibers as drug carriers could be promising in the future for biomedical applications, especially postoperative local chemotherapy. In this research work, electrospun fibers were developed as a new system for the delivery of ketoprofen as non-steroidal anti-inflammatory drug (NSAID). The fibers were made either from polycaprolactone (PCL) as a biodegradable polymer or polyurethane (PU) as a

El-Refaie Kenawy; Fouad I. Abdel-Hay; Mohamed H. El-Newehy; Gary E. Wnek

2009-01-01

54

Transdermal Absorption of Nitroglycerin from Microseal Drug Delivery (MDD) System  

Microsoft Academic Search

A recent important advance in biopharmaceutics has been the utilization of controlled delivery of drugs to the systemic circulation through the intact skin. With the conventional tablet and capsule dosage forms, the amount of drug absorbed through the gastrointestinal (GI) tract varies depending on the quan tity and types of food in the stomach, on the GI motility and transit

Aziz Karim

1983-01-01

55

Chronopharmaceutics based modern colon specific drug delivery systems.  

PubMed

Colon-targeted delivery of bioactives has recently gained importance in addressing specific needs in the therapy of colon based diseases. Many approaches have been attempted for the development of colon-specific delivery systems, with not much success in the past. With the advancement in the field of chronobiology, modern drug delivery approaches have elevated to a new concept of chronopharmacology i.e. the ability to deliver the therapeutic agent to a patient in a staggered profile. The increasing research interest surrounding this delivery system has widened the areas of pharmaceutics in particular with many more sub-disciplines expected to coexist in the near future. Chronopharmaceutics based technology has eliminated the drawbacks associated with the conventional colon specific delivery systems. This review on chronopharmaceutics based delivery lays emphasis on the existing technologies and future development. PMID:22564168

Tiwari, Akanksha; Shukla, Raj Kumar; Tiwari, Suresh; Naazneen, Surti

2012-12-01

56

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

PubMed

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

2014-11-10

57

Novel prospective in colon specific drug delivery system.  

PubMed

This review deals with the targeting of drugs to the lower gastrointestinal tract i.e. colon. Colonic drug delivery becomes important for localized action as well as for improved systemic availability of peptide and proteins. Drugs which have absorption window in the colonic region have been targeted using different novel technologies. pH sensitive polymers and prodrug based formulation have been used for the delivery of drugs into the colon. Different natural polymers have been used successfully for the delivery of drugs into the colon. Natural polymers are less toxic, biodegradable and easily available with a wide range of molecular weight and varying chemical compositions. One of the supporting properties associated with these polymers is that natural polymers can be used as approved pharmaceutical excipient. PMID:24967782

Bansal, Vipin; Malviya, Rishabha; Malaviya, Tanya; Sharma, Pramod Kumar

2014-01-01

58

Drug delivery systems, CNS protection, and the blood brain barrier.  

PubMed

Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID:25136634

Upadhyay, Ravi Kant

2014-01-01

59

Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier  

PubMed Central

Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID:25136634

Upadhyay, Ravi Kant

2014-01-01

60

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

1997-01-01

61

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

2014-01-01

62

A clinical perspective on mucoadhesive buccal drug delivery systems  

PubMed Central

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

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

2014-01-01

63

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

2013-03-01

64

Microparticulate drug delivery systems as an adjunct to cancer treatment.  

PubMed

In an attempt to improve the therapeutic ratio of cytotoxic drugs, which have steep dose-response curves, microparticulate drug delivery systems (MDDS) have been designed for regional administration. Introduction of antineoplastic drug containing microspheres, of appropriate size, into the arterial system of an organ harboring primary or metastatic tumor, will cause tumor infarction by an embolic effect and provide a slow release source of drug trapped within the tumor microvasculature. This review describes recent innovations in synthesis of MDDS and their potential clinical application. PMID:3300944

Kerr, D J

1987-01-01

65

Programmable nanomedicine: synergistic and sequential drug delivery systems  

NASA Astrophysics Data System (ADS)

Recent developments in nanomedicine for the cancer therapy have enabled programmable delivery of therapeutics by exploiting the stimuli-responsive properties of nanocarriers. These therapeutic systems were designed with the relevant chemical and physical properties that respond to different triggers for enhanced anticancer efficacy, including the reduced development of drug-resistance, lower therapeutic dose, site-specific transport, and spatiotemporally controlled release. This minireview discusses the current advances in programmable nanocarriers for cancer therapy with particular emphasis on synergistic and sequential drug delivery systems.

Pacardo, Dennis B.; Ligler, Frances S.; Gu, Zhen

2015-02-01

66

Interpenetrating Polymer Networks as Innovative Drug Delivery Systems  

PubMed Central

Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs) have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs. PMID:24949205

Lohani, Alka; Singh, Garima; Bhattacharya, Shiv Sankar; Verma, Anurag

2014-01-01

67

Inhaled formulations and pulmonary drug delivery systems for respiratory infections.  

PubMed

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

2014-10-24

68

Nanoengineered drug delivery systems for enhancing antibiotic therapy.  

PubMed

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

2015-03-01

69

Fundamentals, Design and Applications of Drug Delivery Systems  

Microsoft Academic Search

Chemical Engineers play an important and expanding role in the exciting field of drug delivery, yet undergraduate chemical engineering students are rarely exposed to drug delivery through their coursework. Chemical Engineering faculty at Rowan University are engaged in an effort to develop and integrate applied drug delivery coursework and experiments throughout the Rowan Engineering curriculum. This paper describes a senior\\/graduate

Stephanie Farrell; Robert P. Hesketh; Mariano J. Savelski; C. Stewart Slater

70

Iontophoretic transdermal drug delivery system using a conducting polymeric membrane  

Microsoft Academic Search

This work investigated the application of a porous polyaniline (PANi) membrane as a conducting polymeric membrane as well as an electrode in an iontophoretic transdermal drug delivery (TDD) system. Model drugs studied were: caffeine (MW: 194.2), lidocaine HCl (MW: 270.8) and doxycycline HCl (MW: 480.1). The PANi membrane was first tested as a simple membrane between the donor and receptor

Qiuxi Fan; Kamalesh K. Sirkar; Bozena Michniak

2008-01-01

71

Processing of Polymer Nanofibers Through Electrospinning as Drug Delivery Systems  

Microsoft Academic Search

The use of electrospun fibers as drug carriers could be promising in the future for biomedical applications, especially postoperative\\u000a local chemotherapy. In this research, electrospun fibers were developed as a new system for the delivery of ketoprofen as\\u000a non-steroidal anti-inflammatory drug (NSAID). The fibers were made either from polycaprolactone (PCL) as a biodegradable polymer\\u000a or polyurethane (PU) as a non-biodegradable

E. Kenawy; F. I. Abdel-Hay; M. H. El-Newehy; G. E. Wnek

72

Processing of Polymer Nanofibers Through Electrospinning as Drug Delivery Systems  

Microsoft Academic Search

The use of electrospun fibers as drug carriers could be promising in the future for biomedical applications, especially postoperative local chemotherapy. In this research, electrospun fibers were developed as a new system for the delivery of ketoprofen as non-steroidal anti-inflammatory drug (NSAID). The fibers were made either from polycaprolactone (PCL) as a biodegradable polymer or polyurethane (PU) as a non-biodegradable

E. Kenawy; F. I. Abdel-Hay; M. H. El-Newehy; G. E. Wnek

2009-01-01

73

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

2010-01-01

74

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

2014-01-01

75

Perspectives on: Chitosan Drug Delivery Systems Based on their Geometries  

Microsoft Academic Search

Chitosan is a natural polymer that has many physicochemical (polycationic, reactive OH and NH2 groups) and biological (bioactive, biocompatible, biodegradable) properties. These unique properties make chitosan an excellent material for the development of new biomedical applications. One of the most well known biomedical chitosan applications is in drug delivery systems. Chitosans have been used in the design of many different

Emir Baki Denkbas; Raphael M. Ottenbrite

2006-01-01

76

Acute Myeloid Leukemia: Nanomedicine drug delivery system could improve chemotherapy  

E-print Network

Acute Myeloid Leukemia: Nanomedicine drug delivery system could improve chemotherapy Chemotherapy), a disease which is responsive to intense chemotherapy based treatment regimens, which are at least curative) and Prof. Dr. Christian Buske (Comprehensive Cancer Center Ulm, Institute of Experimental Cancer Research

Pfeifer, Holger

77

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

2013-01-01

78

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

2009-01-01

79

Magnetic nanoparticle drug delivery systems for targeting tumor  

NASA Astrophysics Data System (ADS)

Tumor hypoxia, or low oxygen concentration, is a result of disordered vasculature that lead to distinctive hypoxic microenvironments not found in normal tissues. Many traditional anti-cancer agents are not able to penetrate into these hypoxic zones, whereas, conventional cancer therapies that work by blocking cell division are not effective to treat tumors within hypoxic zones. Under these circumstances the use of magnetic nanoparticles as a drug delivering agent system under the influence of external magnetic field has received much attention, based on their simplicity, ease of preparation, and ability to tailor their properties for specific biological applications. Hence in this review article we have reviewed current magnetic drug delivery systems, along with their application and clinical status in the field of magnetic drug delivery.

Mody, Vicky V.; Cox, Arthur; Shah, Samit; Singh, Ajay; Bevins, Wesley; Parihar, Harish

2014-04-01

80

Intelligent drug delivery system using UML diagrams analysis  

Microsoft Academic Search

A novel intelligent drug delivery system potential for the more effective therapy of the diabetics was proposed, and the composition\\u000a of system was analyzed. Based on the design of micro-electro-mechanical systems (MEMS), an iterative modeling process was\\u000a introduced. Unified modeling language (UML) was employed to describe the function requirement, and different diagrams were\\u000a built up to explore the static model,

Qi-feng Cui; Cheng-liang Liu; Xuan F. Zha

2008-01-01

81

Cyclodextrin based novel drug delivery systems  

Microsoft Academic Search

The versatile pharmaceutical material cyclodextrin’s (CDs) are classified into hydrophilic, hydrophobic, and ionic derivatives.\\u000a By the early 1950s the basic physicochemical characteristics of cyclodextrins had been discovered, since than their use is\\u000a a practical and economical way to improve the physicochemical and pharmaceutical properties such as solubility, stability,\\u000a and bioavailability of administered drug molecules. These CDs can serve as multi-functional

Amber Vyas; Shailendra Saraf; Swarnlata Saraf

2008-01-01

82

POROUS NANOPARTICLES IN DRUG DELIVERY SYSTEMS  

Microsoft Academic Search

This article concentrates mainly on fabrication of porous nanoparticles, its characterisation and its use for controlled release of drug. It also encompasses the strategies that have been used to translate and fabricate a wide range of particulate carriers e.g., nanospheres, liposomes, micelles, oil-in-water emulsions, with prolonged circulation and\\/or target specificity. Sol-gel technique is one of the most widely used techniques

Murray RK; Granner DK; Rodwell VW

83

PECTIN IN CONTROLLED DRUG DELIVERY  

Technology Transfer Automated Retrieval System (TEKTRAN)

Controlled drug delivery remains a research focus for public health to enhance patient compliance, drug efficiency and to reduce the side effects of drugs. Pectin, an edible plant polysaccharide, has shown potential for the construction of drug delivery systems for site-specific drug delivery. Sev...

84

Exosome mimetics: a novel class of drug delivery systems.  

PubMed

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 A A; Vader, Pieter; van Dommelen, Susan M; van Solinge, Wouter W; Schiffelers, Raymond M

2012-01-01

85

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

2012-01-01

86

Surgical Testing of a Microelectromechanical Systems (MEMS) Ocular Drug Delivery , S. Saloomeh2  

E-print Network

Surgical Testing of a Microelectromechanical Systems (MEMS) Ocular Drug Delivery System P.-Y. Li1 delivery of drugs for treating chronic ocular diseases. Both devices feature a refillable reservoir the cannula and into the eye. Both continuous and bolus drug delivery modes were possible in this system

Meng, Ellis

87

Pressure-sensitive adhesives for transdermal drug delivery systems  

Microsoft Academic Search

Adhesives are a critical component in transdermal drug delivery (TDD) devices. In addition to the usual requirements of functional adhesive properties, adhesives for TDD applications must have good biocompatibility with the skin, chemical compatibility with the drug, various components of the formulation, and provide consistent, effective delivery of the drug. This review discusses the three most commonly used adhesives (polyisobutylenes,

Hock S Tan; William R Pfister

1999-01-01

88

An implantable thermoresponsive drug delivery system based on Peltier device.  

PubMed

Locally dropping the temperature in vivo is the main obstacle to the clinical use of a thermoresponsive drug delivery system. In this paper, a Peltier electronic element is incorporated with a thermoresponsive thin film based drug delivery system to form a new drug delivery device which can regulate the release of rhodamine B in a water environment at 37 °C. Various current signals are used to control the temperature of the cold side of the Peltier device and the volume of water on top of the Peltier device affects the change in temperature. The pulsatile on-demand release profile of the model drug is obtained by turning the current signal on and off. The work has shown that the 2600 mAh power source is enough to power this device for 1.3 h. Furthermore, the excessive heat will not cause thermal damage in the body as it will be dissipated by the thermoregulation of the human body. Therefore, this simple novel device can be implanted and should work well in vivo. PMID:23467083

Yang, Rongbing; Gorelov, Alexander V; Aldabbagh, Fawaz; Carroll, William M; Rochev, Yury

2013-04-15

89

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.

2014-01-01

90

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

2014-01-01

91

CNS Drug Delivery Systems: Novel Approaches  

Microsoft Academic Search

The brain is a delicate organ, and nature has very efficiently protected it. The brain is shielded against potentially toxic substances by the presence of two barrier systems: the blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB). Unfortunately, the same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Despite aggressive research, patients suffering

Shadab A. Pathan; Zeenat Iqbal; Syed M. A. Zaidi; Sushma Talegaonkar; Divya Vohra; Gaurav K. Jain; Adnan Azeem; Nitin Jain; Jigar R. Lalani; Roop K. Khar; Farhan J. Ahmad

2009-01-01

92

Colon Targeted Drug Delivery Systems: A Review on Primary and Novel Approaches  

Microsoft Academic Search

The colon is a site where both local and systemic delivery of drugs can take place. Local delivery allows topical treatment of inflammatory bowel disease. However, treatment can be made effective if the drugs can be targeted directly into the colon, thereby reducing the systemic side effects. This review, mainly compares the primary approaches for CDDS (Colon Specific Drug Delivery)

Anil K. Philip; Betty Philip

2010-01-01

93

Design of a Multiple Drug Delivery System Directed at Periodontitis  

PubMed Central

Periodontal disease is highly prevalent, with 90% of the world population affected by either periodontitis or its preceding condition, gingivitis. These conditions are caused by bacterial biofilms on teeth, which stimulate a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The present research sought to demonstrate development of a multiple drug delivery system for stepwise treatment of different stages of periodontal disease. More specifically, multilayered films were fabricated from an association polymer comprising cellulose acetate phthalate and Pluronic F-127 to achieve sequential release of drugs. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. Different erosion times and adjustable sequential release profiles were achieved by modifying the number of layers or by inclusion of a slower-eroding polymer layer. Analysis of antibiotic and anti-inflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. The multilayered CAPP delivery system offers a versatile approach for releasing different drugs based on the pathogenesis of periodontitis and other conditions. PMID:23948165

Sundararaj, Sharath C.; Thomas, Mark V.; Peyyala, Rebecca; Dziubla, Thomas D.; Puleo, David A.

2013-01-01

94

Synthetic microbes as drug delivery systems.  

PubMed

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

2015-04-17

95

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

1999-05-01

96

Fundamental study for development magnetic drug delivery system  

NASA Astrophysics Data System (ADS)

Side-effects and lowering effects by diffusion of drugs such as anticancer agents is one of the serious issues in medication. To solve this problem, it is necessary to control the drugs quantitatively, spatially and temporally within the human body. Magnetic drug delivery system (MDDS) is one of the technologies to make it possible, in which the ferromagnetic drug injected into the blood vessel is conducted to diseased part by external magnetic force. As a fundamental experiment, the accumulation experiment using ferromagnetic particles were performed with simulated capillary vessels composed of glass beads channels in this work. Additionally, accumulation calculation of ferromagnetic particles was conducted to check the validity of accumulation experiment. From these result, the 2D distribution of particle accumulation in the experiment corresponded with that of particle accumulation in the calculation. It was suggested that the proper position of magnet should be changed according to the depth of diseased part.

Hirota, Y.; Akiyama, Y.; Izumi, Y.; Nishijima, S.

2009-10-01

97

Extended-release oral drug delivery technologies: monolithic matrix systems.  

PubMed

Oral drug delivery is the largest and the oldest segment of the total drug delivery market. It is the fastest growing and most preferred route for drug administration. Use of hydrophilic matrices for oral extended release of drugs is a common practice in the pharmaceutical industry. This chapter presents different polymer choices for fabrication of monolithic hydrophilic matrices and discusses formulation and manufacturing variables affecting the design and performance of the extended-release product by using selected practical examples. PMID:18369971

Tiwari, Sandip B; Rajabi-Siahboomi, Ali R

2008-01-01

98

Chemical delivery systems and soft drugs: Retrometabolic approaches of drug design  

PubMed Central

Inclusion of metabolic considerations in the drug design process leads to significant development in the field of chemical drug targeting and the design of safer drugs during past few years which is a part of an approach now designated as Retro metabolic drug design (RMDD). This approach represents systematic methodologies that integrate structure–activity and structure–metabolism relationships and are aimed to design safe, locally active compounds with an improved therapeutic index. It embraces two distinct methods, chemical delivery systems and a soft drug approach. Present review recapitulates an impression of RMDD giving reflections on the chemical delivery system and the soft drug approach and provides a variety of examples to embody its concepts. Successful application of such design principles has already been applied to a number of marketed drugs like esmolol; loteprednol etc., and many other candidates like beta blockers, ACE inhibitors, alkylating agents, antimicrobials etc., are also under investigation. PMID:25161372

Bhardwaj, Yashumati Ratan; Pareek, Ashutosh; Jain, Vivek; Kishore, Dharma

2013-01-01

99

A multi-scale stochastic drug release model for polymer-coated targeted drug delivery systems  

Microsoft Academic Search

A multi-scale mathematical model for drug release of oral targeted drug delivery systems was developed and applied to a commercially available delayed release tablet (Asacol®) that delivers 5-aminosalicyclic acid (5-ASA) to the colon. Underlying physical and biochemical principles governing the involved processes (diffusion and dissolution) were employed to develop the mathematical description. Finite element formulation was used to numerically solve

Nahor Haddish-Berhane; Chell Nyquist; Kamyar Haghighi; Carlos Corvalan; Ali Keshavarzian; Osvaldo Campanella; Jenna Rickus; Ashkan Farhadi

2006-01-01

100

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

2003-01-01

101

Synthetic tumor networks for screening drug delivery systems.  

PubMed

Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle's physico-chemical properties. A key factor is tumor microvasculature with complex effects including convective transport, high interstitial pressure and enhanced vascular permeability due to the presence of "leaky vessels". Current in vitro models of the tumor microenvironment for evaluating drug delivery are oversimplified and, as a result, show poor correlation with in vivo performance. In this study, we report on the development of a novel microfluidic platform that models the tumor microenvironment more accurately, with physiologically and morphologically realistic microvasculature including endothelial cell lined leaky capillary vessels along with 3D solid tumors. Endothelial cells and 3D spheroids of cervical tumor cells were co-cultured in the networks. Drug vehicle screening was demonstrated using GFP gene delivery by different formulations of nanopolymers. The synthetic tumor network was successful in predicting in vivo delivery efficiencies of the drug vehicles. The developed assay will have critical applications both in basic research, where it can be used to develop next generation delivery vehicles, and in drug discovery where it can be used to study drug transport and delivery efficacy in realistic tumor microenvironment, thereby enabling drug compound and/or delivery vehicle screening. PMID:25599856

Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Nichols, Joseph B; Garson, Charles J; Mills, Ivy R; Matar, Majed M; Fewell, Jason G; Pant, Kapil

2015-03-10

102

Application of In Situ Polymerization for Design and Development of Oral Drug Delivery Systems  

Microsoft Academic Search

Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to\\u000a light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides

Ndidi Ngwuluka; Joseph Reo; Linda Felton; Stephen Howard

2010-01-01

103

Design and Optimization of Floating Drug Delivery System of Acyclovir  

PubMed Central

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 32 full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t50%) and 70% (t70%) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t50% and t70% indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix. PMID:21694992

Kharia, A. A.; Hiremath, S. N.; Singhai, A. K.; Omray, L. K.; Jain, S. K.

2010-01-01

104

Development of magnetic drug delivery system using HTS bulk magnet  

NASA Astrophysics Data System (ADS)

Magnetic drug delivery system (MDDS) is the method which the magnetic seeded drug is injected into a blood vessel and then controlled and accumulated by a magnet located outside of the human body. A high accumulation efficiency of the drug to a local diseased part and reduction in side-effects to normal organs are expected by using MDDS. The most important element in MDDS is a magnetic field generator. The high temperature superconducting (HTS) bulk magnet which can generate high magnetic field and magnetic field gradient extending to a point distant from the magnet in several ten millimeters is necessary to achieve the MDDS. In this study, the computer simulation and model experiment were conducted in order to confirm the applicability of MDDS to ovary of the cow body.

Terada, T.; Fukui, S.; Mishima, F.; Akiyama, Y.; Izumi, Y.; Nishijima, S.

2008-09-01

105

Chitosan in nasal delivery systems for therapeutic drugs.  

PubMed

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

2014-09-28

106

From Drug Delivery Systems to Drug Release, Dissolution, IVIVC, BCS, BDDCS, Bioequivalence and Biowaivers  

Microsoft Academic Search

This is a summary report of the conference on drug absorption and bioequivalence issues held in Titania Hotel in Athens (Greece)\\u000a from the 28th to the 30th of May 2009. The conference included presentations which were mainly divided into three sections. The first section focused\\u000a on modern drug delivery systems such as polymer nanotechnology, cell immobilization techniques to deliver drugs

Vangelis Karalis; Eleni Magklara; Vinod P. Shah; Panos Macheras

2010-01-01

107

Physical blends of starch graft copolymers as matrices for colon targeting drug delivery systems  

Microsoft Academic Search

Colon targeting drug delivery systems have attracted many researchers due to the distinct advantages they present such as near neutral pH, longer transit time and reduced enzymatic activity. Moreover, in recent studies, colon specific drug delivery systems are gaining importance for use in the treatment of local pathologies of the colon and also for the systemic delivery of protein and

I. Silva; M. Gurruchaga; I. Goñi

2009-01-01

108

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

2014-01-01

109

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

2014-01-01

110

Applications of novel drug delivery system for herbal formulations.  

PubMed

Over the past several years, great advances have been made on development of novel drug delivery systems (NDDS) for plant actives and extracts. The variety of novel herbal formulations like polymeric nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions, microsphere, transferosomes, and ethosomes has been reported using bioactive and plant extracts. The novel formulations are reported to have remarkable advantages over conventional formulations of plant actives and extracts which include enhancement of solubility, bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, improved tissue macrophages distribution, sustained delivery, and protection from physical and chemical degradation. The present review highlights the current status of the development of novel herbal formulations and summarizes their method of preparation, type of active ingredients, size, entrapment efficiency, route of administration, biological activity and applications of novel formulations. PMID:20471457

Ajazuddin; Saraf, S

2010-10-01

111

Azithromycin novel drug delivery system for ocular application  

PubMed Central

Background: Azithromycin (AZT) is a macrolide antibiotic derived from and similar in structure to erythromycin. Oral administration of AZT is effective for the treatment of trachoma; however, topical formulations are difficult to develop because of the drug's hydrophobicity. The aim of this study is to formulate a novel topical ophthalmic delivery system of AZT. Materials and Methods: In the present study, ocular inserts of AZT are prepared using alginate, carbopol, and hydroxypropyl methylcellulose (HPMC) to solve the said formulation problem of drug and to facilitate ocular bioavailability. Ocular inserts were prepared by film casting method and the prepared films were subjected to investigations for their physical and mechanical properties, swelling behaviors, ex vivo bioadhesion, and in vitro drug release. Ocular irritation of the developed formulation was also checked by hen's egg chorioallantoic membrane test for ocular irritation potential. Results: The physicochemical, bioadhesive, and swelling properties of films were found to vary significantly depending on the type of polymers used and their combinations. The alginate films exhibited greater bioadhesion and showed higher tensile strength and elasticity than the carbopol films. HPMC addition to the films significantly affected the properties of ocular inserts. Carbopol:HPMC (30:70)-based ocular inserts sustained drug release for longest span of 6 h. The release profile of AZT showed that drug release was by both diffusion and swelling. The formulation was found to be practically nonirritant in ocular irritation studies. Conclusion: AZT can therefore be developed as an ocular insert delivery system for the treatment of ocular surface infections. PMID:23071916

Gilhotra, Ritu Mehra; Nagpal, Kalpana; Mishra, Dina Nath

2011-01-01

112

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

2014-01-01

113

A review of drug delivery systems for capsule endoscopy.  

PubMed

The development of a highly controllable drug delivery system (DDS) for capsule endoscopy has become an important field of research due to its promising applications in therapeutic treatment of diseases in the gastrointestinal (GI) tract and drug absorption studies. Several factors need to be considered to establish the minimum requirements for a functional DDS. Environmental factors of the GI tract and also pharmaceutical factors can help determine the requirements to be met by a DDS in an endoscopic capsule. In order to minimize the influence of such factors on the performance of an effective DDS, at least two mechanisms should be incorporated into a capsule endoscope: an anchoring mechanism to control the capsule position and a drug release mechanism to control variables such as the drug release rate, number of doses and amount of drug released. The implementation of such remotely actuated mechanisms is challenging due to several constraints, including the limited space available in a swallowable capsule endoscope and the delicate and complex environment within the GI tract. This paper presents a comprehensive overview of existing DDS. A comparison of such DDS for capsule endoscopy based on the minimum DDS requirements is presented and future work is also discussed. PMID:24384373

Munoz, Fredy; Alici, Gursel; Li, Weihua

2014-05-01

114

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

PubMed

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

2014-01-01

115

Evaluation of metal nanoparticles for drug delivery systems  

PubMed Central

Abstract Diminazene aceturate is a trypanocide with unwanted toxicity and limited efficacy. It was reasoned that conjugating diminazene aceturate to functionalized nanoparticle would lower untoward toxicity while improving selectivity and therapeutic efficacy. Silver and gold nanoparticles were evaluated for their capacities to serve as carriers for diminazene aceturate. The silver and gold nanoparticles were synthesized, functionalized and coupled to diminazene aceturate following established protocols. The nanoparticle conjugates were characterized. The free diminazene aceturate and drug conjugated nanoparticles were subsequently evaluated for cytotoxicity in vitro. The characterizations by transmission electron microscopy or UV/Vis spectroscopy revealed that conjugation of diminazene aceturate to silver or gold nanoparticles was successful. Evaluation for cytotoxic actions in vitro demonstrated no significance difference between free diminazene aceturate and the conjugates. Our data suggest that surface modified metal nanoparticles could be optimized for drug delivery systems.

Adeyemi, Oluyomi S; Sulaiman, Faoziyat A

2015-01-01

116

Novel nano drug delivery systems for hepatic tumor  

NASA Astrophysics Data System (ADS)

The adriamycin and galactose was grafted to dextran. The novel nanopartcile drug delivery system (DDS) was prepared from the chemical modified polysaccharide by the dialysis. The content of the ADR moiety in the polymeric-drug conjugate was about 2 mol%. The size and morphology of prepared nanoparticles were characterized using dynamic light scattering and transmission electron microscope. The results showed that the nanoparticles were spherical and their size was less than 200 nm. In vitro cytotoxicity of the nanoparticles was tested by the MTT assay. The nano DDS has similar cytotoxicity as free adriamycin for incubation with HepG2 cells. In contrast, for the incubation with Hela cells of the DDS, there was no signicant cytotoxicity change.

Cao, Yu; Liu, Jing; Ma, Hong; Bai, Jing; Qi, Chao

2009-08-01

117

Evaluation of metal nanoparticles for drug delivery systems.  

PubMed

Diminazene aceturate is a trypanocide with unwanted toxicity and limited efficacy. It was reasoned that conjugating diminazene aceturate to functionalized nanoparticle would lower untoward toxicity while improving selectivity and therapeutic efficacy. Silver and gold nanoparticles were evaluated for their capacities to serve as carriers for diminazene aceturate. The silver and gold nanoparticles were synthesized, functionalized and coupled to diminazene aceturate following established protocols. The nanoparticle conjugates were characterized. The free diminazene aceturate and drug conjugated nanoparticles were subsequently evaluated for cytotoxicity in vitro. The characterizations by transmission electron microscopy or UV/Vis spectroscopy revealed that conjugation of diminazene aceturate to silver or gold nanoparticles was successful. Evaluation for cytotoxic actions in vitro demonstrated no significance difference between free diminazene aceturate and the conjugates. Our data suggest that surface modified metal nanoparticles could be optimized for drug delivery systems. PMID:25859270

Adeyemi, Oluyomi S; Sulaiman, Faoziyat A

2015-04-01

118

Processing of Polymer Nanofibers Through Electrospinning as Drug Delivery Systems  

NASA Astrophysics Data System (ADS)

The use of electrospun fibers as drug carriers could be promising in the future for biomedical applications, especially postoperative local chemotherapy. In this research, electrospun fibers were developed as a new system for the delivery of ketoprofen as non-steroidal anti-inflammatory drug (NSAID). The fibers were made either from polycaprolactone (PCL) as a biodegradable polymer or polyurethane (PU) as a non-biodegradable polymer, or from the blends of the two. The release of the ketoprofen was followed by UV—VIS spectroscopy in phosphate buffer of pH 7.4 at 37°C and 20°C. The results showed that the release rates from the polycaprolactone, polyurethane and their blend were similar. However, the blend of the polycaprolactone with polyurethane improved its visual mechanical properties. Release profiles from the electrospun mats were compared to cast films of the various formulations.

Kenawy, E.; Abdel-Hay, F. I.; El-Newehy, M. H.; Wnek, G. E.

119

pH-sensitive nano-systems for drug delivery in cancer therapy.  

PubMed

Nanotechnology has been widely used in the development of new strategies for drug delivery and cancer therapy. Compared to traditional drug delivery systems, nano-based drug delivery system have greater potential in a variety of areas, such as multiple targeting functionalization, in vivo imaging, combined drug delivery, extended circulation time, and systemic control release. Nano-systems incorporating stimulus-responsive materials have remarkable properties which allow them to bypass biological barriers and achieve targeted intracellular drug delivery. As a result of the active metabolism of tumor cells, the tumor microenvironment (TME) is highly acidic compared to normal tissues. pH-Sensitive nano-systems have now been developed in which drug release is specifically triggered by the acidic tumor environment. Studies have demonstrated that novel pH-sensitive drug delivery systems are capable of improving the efficiency of cancer treatment. A number of these have been translated from bench to clinical application and have been approved by the Food and Drug Administration (FDA) for treatment of various cancerous diseases. Herein, this review mainly focuses on pH-sensitive nano-systems, including advances in drug delivery, mechanisms of drug release, and possible improvements in drug absorption, with the emphasis on recent research in this field. With deeper understanding of the difference between normal and tumor tissues, it might be possible to design ever more promising pH-responsive nano-systems for drug delivery and cancer therapy in the near future. PMID:24309541

Liu, Juan; Huang, Yuran; Kumar, Anil; Tan, Aaron; Jin, Shubin; Mozhi, Anbu; Liang, Xing-Jie

2014-01-01

120

Development of self-microemulsifying drug delivery system and solid-self-microemulsifying drug delivery system of telmisartan  

PubMed Central

Objective: Self-microemulsifying drug delivery system (SMEDDS) and solid-SMEDDS of telmisartan was aimed at overcoming the problems of poor solubility and bioavailability. Methodology: The formulation strategy included selection of oil phase based on saturated solubility studies and surfactant and co-surfactant screening on the basis of their emulsification ability. Ternary phase diagrams were constructed to identify the self-emulsifying region using a dilution method. The prepared formulations of SMEDDS were evaluated for their drug content, loading efficiency, morphology, globule size determination. Solid-SMEDDS were prepared by adsorption technique using microcrystalline cellulose (1% w/w) and were evaluated for micromeritic properties, scanning electron microscopy, differential scanning calorimetry, X-ray diffraction. Results: The formulation containing telmisartan (20 mg), castor oil (30% w/w), tween 20 (55% w/w), propylene glycol (15% w/w) was concluded to be optimized. The optimized SMEDDS and solid-SMEDDS exhibited 100% in vitro drug release up to 120 min, which was significantly higher (P < 0.05, t-test) than that of the pure drug. Solid-SMEDDS may be considered as a better solid dosage form as solidified formulations are more ideal than liquid ones in terms of its stability. Conclusion: These results suggest the potential use of SMEDDS and solid-SMEDDS to improve the dissolution and hence oral bioavailability of poorly water-soluble drugs like telmisartan through oral route. PMID:25426441

Jaiswal, Parul; Aggarwal, Geeta; Harikumar, Sasidharan Leelakumari; Singh, Kashmir

2014-01-01

121

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

2012-10-01

122

Cubosomes as targeted drug delivery systems - a biopharmaceutical approach.  

PubMed

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

2014-01-01

123

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.

124

Microfabricated drug delivery systems: from particles to pores  

Microsoft Academic Search

Microfabrication techniques which permit the creation of therapeutic delivery systems that possess a combination of structural, mechanical, and perhaps electronic features may surmount challenges associated with conventional delivery of therapy. In this review, delivery concepts are presented which capitalize on the strengths of microfabrication. Possible applications include micromachined silicon membranes to create implantable biocapsules for the immunoisolation of pancreatic islet

Sarah L. Tao; Tejal A. Desai

2003-01-01

125

Precise control of the drug kinetics by means of non-invasive magnetic drug delivery system  

NASA Astrophysics Data System (ADS)

In order to solve the problems of the side effects and medical lowering, has been advanced a study on the drug delivery system (DDS) to accumulate the drugs locally in the body with minimum dosage. The DDS is a system that controls the drug kinetics in the body precisely and accumulates the drug locally at the target part, keeping the drugs at high density. Among the DDS, the magnetic drug delivery system (MDDS) is the one that we studied. This is a technique to accumulate drugs by using the magnetic force as the physical driving force. Our previous researches showed the possibility of the technique of MDDS to accumulate the drugs with higher accumulation rate and locality than the traditional methods. It is necessary to apply a strong external magnetic field and a high magnetic gradient to accumulate the ferromagnetic drugs at a deep diseased part non-invasively. However, by applying a static magnetic field from one direction, the drug accumulates only at the surface of the body locates near the magnet. In this study, we tried to change the magnetic field applied by a superconducting bulk magnet with time, in order to make a constant and strong magnetic field applied in the center of the body and to accumulate the ferromagnetic drugs at the deep target part in the body. First of all, the effect of the surface treatment of the ferromagnetic drugs to prevent its absorption in the normal tissue was examined. Then, to increase the accumulation rate of the ferromagnetic drugs at the target part, the distribution of magnetic field was changed, and the optimum spatial and temporal conditions of magnetic field were examined.

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

2013-01-01

126

Single compartment drug delivery.  

PubMed

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

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

2014-09-28

127

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.

2011-01-01

128

Design of magnetic nanoparticles-assisted drug delivery system.  

PubMed

Magnetic nanoparticles (MNPs) have been designed for multifaceted applications such as contrast agents in magnetic resonance imaging (MRI) diagnosis, drug/gene carriers for different kinds of therapeutic agents, tissue repair, hyperthermia, immunoassay, and cell separation/sensing. This review highlights synthesis methods, stabilizers used for surface coating on MNPs, and target ligands for ferrying payloads to an interested disease area. Some of the recent biomedical applications of MNPs in the field of drug and DNA targeting delivery are extensively reviewed. PMID:21736546

Chen, Guo-Jing; Wang, Li-Fang

2011-01-01

129

Progress toward a Colon Targeting Nanoparticle Based Drug Delivery System  

E-print Network

......................................................... 11 2.2.1 Colon targeting oral drug delivery ....................................................... 11 2.2.2 Polysaccharide based pH sensitive and biodegradable hydrogels ....... 12 2.3 In vitro drug release models... of particles? size and surface charges .................... 20 3.3.1.2 Encapsulation efficiency and stability of PAX NPs in different pH of the aqueous solutions ........................................................ 22 3.3.2 LbL self...

Yu, Xiao

2012-07-16

130

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

E-print Network

. An important treatment modality is hormone replacement: insulin is given to patients with diabetes, thyroid restore as closely as possible the normal dynamics of hormonal regulation. Open loop drug delivery systems. However, when a closed-loop drug delivery system was used to administer insulin to diabetic patients [12

Campbell, Sue Ann

131

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

2003-01-01

132

Drug-Induced Morphology Switch in Drug Delivery Systems Based on Poly(2-oxazoline)s  

PubMed Central

Defined aggregates of polymers such as polymeric micelles are of great importance in the development of pharmaceutical formulations. The amount of drug that can be formulated by a drug delivery system is an important issue, and most drug delivery systems suffer from their relatively low drug-loading capacity. However, as the loading capacities increase, i.e., promoted by good drug–polymer interactions, the drug may affect the morphology and stability of the micellar system. We investigated this effect in a prominent system with very high capacity for hydrophobic drugs and found extraordinary stability as well as a profound morphology change upon incorporation of paclitaxel into micelles of amphiphilic ABA poly(2-oxazoline) triblock copolymers. The hydrophilic blocks A comprised poly(2-methyl-2-oxazoline), while the middle blocks B were either just barely hydrophobic poly(2-n-butyl-2-oxazoline) or highly hydrophobic poly(2-n-nonyl-2-oxazoline). The aggregation behavior of both polymers and their formulations with varying paclitaxel contents were investigated by means of dynamic light scattering, atomic force microscopy, (cryogenic) transmission electron microscopy, and small-angle neutron scattering. While without drug, wormlike micelles were present, after incorporation of small amounts of drugs only spherical morphologies remained. Furthermore, the much more hydrophobic poly(2-n-nonyl-2-oxazoline)-containing triblock copolymer exhibited only half the capacity for paclitaxel than the poly(2-n-butyl-2-oxazoline)-containing copolymer along with a lower stability. In the latter, contents of paclitaxel of 8 wt % or higher resulted in a raspberry-like micellar core. PMID:24548260

2015-01-01

133

Drug development in Parkinson's disease: from emerging molecules to innovative drug delivery systems.  

PubMed

Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like ?-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients. PMID:23827471

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

2013-11-01

134

Chemical Penetration Enhancers for Transdermal Drug Delivery Systems  

Microsoft Academic Search

Skin as an important site of drug application for both local and systemic effects. However in skin, the stratum corneum is the main barrier for drug penetration. Penetration enhancement technology is a challenging development that would increase the number of drugs available for transdermal administration. The permeation of drug through skin can be enhanced by both chemical penetration enhancement and

Inayat Bashir Pathan; C Mallikarjuna Setty

135

Influence of Drug Lipophilicity on Drug Release from Sclera After Iontophoretic Delivery of Mixed Micellar Carrier System to Human Sclera  

PubMed Central

Mixed micelles prepared using sodium taurocholate (TA) and egg lecithin (LE) were previously found to be an effective carrier for sustained release of a poorly water-soluble drug in transscleral iontophoretic delivery. The objectives of the present study were to investigate the effects of drug lipophilicity upon micellar carrier solubilization potential and drug release profiles from the sclera after iontophoretic delivery of model lipophilic drugs dexamethasone (DEX), triamcinolone acetonide (TRIAM), and ?-estradiol (E2?) with a mixed micellar carrier system of TA–LE (1:1 mole ratio). In this study, the micellar carrier system was characterized for drug solubilization. The micelles encapsulating these drugs were evaluated for transscleral passive and 2-mA iontophoretic delivery (both cathodal and anodal) and drug release from excised human sclera in vitro. The results show that drug solubility enhancement of the micellar carrier system increased with increasing drug lipophilicity. The more lipophilic drugs E2? and TRIAM displayed slower drug release from the sclera compared with the less lipophilic drug DEX after iontophoretic drug delivery with the mixed micelles. These results suggest that the combination of transscleral iontophoresis and micellar carriers is more effective in sustaining transscleral delivery of the more lipophilic drugs studied in this investigation. PMID:23150488

Chopra, Poonam; Hao, Jinsong; Li, S. Kevin

2013-01-01

136

Thermosensitive liposomal drug delivery systems: state of the art review  

PubMed Central

Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine. PMID:25258529

Kneidl, Barbara; Peller, Michael; Winter, Gerhard; Lindner, Lars H; Hossann, Martin

2014-01-01

137

Thermosensitive liposomal drug delivery systems: state of the art review.  

PubMed

Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine. PMID:25258529

Kneidl, Barbara; Peller, Michael; Winter, Gerhard; Lindner, Lars H; Hossann, Martin

2014-01-01

138

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.

2010-01-01

139

Recent developments of collagen-based materials for medical applications and drug delivery systems  

Microsoft Academic Search

In this review, an attempt was made to summarize some of the recent developments in the application of collagen as a biomaterial and in drug delivery systems. The main applications covered include: collagen for burn\\/wound cover dressings; osteogenic and bone filling materials; antithrombogenic surfaces; and immobilization of therapeutic enzymes. Recently, collagen used as a carrier for drug delivery has attracted

K. Panduranga Rao

1996-01-01

140

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

E-print Network

treatment and trials center, and preclinical research facilities at Inha University Hospital, Incheon, KoreaUtah-Inha Joint Research Center on Drug Delivery Systems & Advanced Therapeutics Inha University Hospital http://www.unidds.com MISSION AND VISION: The Utah-Inha Joint Research Center on Drug Delivery

Tipple, Brett

141

A survey on the applications of implantable micropump systems in drug delivery.  

PubMed

Systemic drug delivery is the most prevalent form of the drug administration; but it is not possible to extend this approach to all of diseases. In the traditional approaches of drug delivery, the drug spreads through whole of body and this could cause severe side effects in the healthy parts. In addition, in some parts of our body like the eye, ear and brain, there are biological barriers against drug penetration which made drug delivery to these organs as a challenging work. Micropumps are one of the MEMS based devices with great capabilities in controlled drug administration. The most prevalent application of micropumps in drug delivery is known as continuous subcutaneous insulin infusion (CSII) for diabetic patients; but our study showed that there are some other ongoing investigations to extend application of micropumps in new treatment methods for some incurred diseases. PMID:24533725

Mahnama, Ali; Nourbakhsh, Ahmad; Ghorbaniasl, Ghader

2014-01-01

142

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

2015-01-01

143

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

PubMed

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

2015-01-01

144

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

2011-01-01

145

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

PubMed

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

2014-09-28

146

[Proceedings of new drug delivery systems and their applications in the traditional Chinese drugs].  

PubMed

By referred to a lot of data, some new drug delivery systems(DDSs) including the Sustained and Controlled DDS, the Targeted DDS, the Transdermal DDS, the Bioadhensive DDS, the PowderJect DDS and the Self-Emulsifying DDS and their applications in TCD since 2000, will be summarized and some latest DDSs in the world including drug-eluting stents, gene therapy carrier system, biological chip, biomolecular motor-powered nanodevice and nanotrap will be also introduced in this paper. The objective of this paper is to introduce the new DDSs proceedings of and their applications in the Traditional Chinese Drugs(TCDs) and to provide some references for the pharmaceutics of TCD. For several recent years, the great success have been achieved in studying the new DDS application in the change of preparation of TCD by the investigators at home, but there is a large difference between at home and at board. So it is necessary to make a greater advance. During the modernization of TCD, there is an effective way that the new drug delivery systems(DDSs) will be applied in the change of the preparation of TCD. PMID:15139097

Zhou, Shao-hua; Xiao, Xiao-he; Yuan, Hai-long; Zhao, Yan-ling; Shan, Li-mei; Cai, Guang-ming

2003-07-01

147

Colon Targeted Drug Delivery Systems: A Review on Primary and Novel Approaches  

PubMed Central

The colon is a site where both local and systemic delivery of drugs can take place. Local delivery allows topical treatment of inflammatory bowel disease. However, treatment can be made effective if the drugs can be targeted directly into the colon, thereby reducing the systemic side effects. This review, mainly compares the primary approaches for CDDS (Colon Specific Drug Delivery) namely prodrugs, pH and time dependent systems, and microbially triggered systems, which achieved limited success and had limitations as compared with newer CDDS namely pressure controlled colonic delivery capsules, CODESTM, and osmotic controlled drug delivery which are unique in terms of achieving in vivo site specificity, and feasibility of manufacturing process. PMID:22125706

Philip, Anil K.; Philip, Betty

2010-01-01

148

Formulation and Evaluation of Galantamine Gel as Drug Reservoir in Transdermal Patch Delivery System  

PubMed Central

Galantamine hydrobromide is formulated in tablets and capsules prescribed through oral delivery for the treatment of Alzheimer's disease. However, oral delivery of drugs can cause severe side effects such as nausea, vomiting, and gastrointestinal disturbance. Transdermal delivery of galantamine hydrobromide could avoid these unwanted side effects. In this work, galantamine hydrobromide was formulated in gel drug reservoir which was then fabricated in the transdermal patch. The in vitro drug release studies revealed that the drug release from the donor chamber to receptor chamber of Franz diffusion cell was affected by the amount of polymer, amount of neutralizer, amount of drug, types of permeation enhancer, and amount of permeation enhancer. Visual observations of the gels showed that all formulated gels are translucent, homogeneous, smooth, and stable. These gels have pH in the suitable range for skin. The gel also showed high drug content uniformity. Hence, this formulation can be further used in the preparation of transdermal patch drug delivery system.

Fong Yen, Woo; Basri, Mahiran; Ahmad, Mansor; Ismail, Maznah

2015-01-01

149

Systemic drug delivery systems for bone tissue regeneration- a mini review.  

PubMed

Musculoskeletal metabolic diseases such as osteoporosis have become the major public health problems worldwide in our aging society. Pharmaceutical therapy is one of the approaches to prevent and treat related medical conditions. Most of the clinically used anti-osteoporotic drugs are administered systemically and have demonstrated some side effects in non-skeletal tissues. One of the innovative approaches to prevent potential adverse effects is the development of bone-targeting drug delivery technologies that not only minimizes the systemic toxicity but also improves the pharmacokinetic profile and therapeutic efficacy of chemical drugs. This paper reviews the currently available bone targeting drug delivery systems with emphasis as bone-targeting moieties, including the bonesurface- site-specific (bone formation dominant or bone resorption dominant) and cell-specific moieties. In addition, the connections of drug-bone-targeting moieties-carrier are also summarized, and the newly developed liposomes and nanoparticles are discussed for their potential use and main challenges in delivering therapeutic agents to bone tissue. As a rapid-developing biotechnology, systemic bonetargeting delivery system is promising but still in its infancy where challenges are ahead of us, including the stability and the toxicity issues, especially to fulfill the regulatory requirement to realize bench-to-bedside translation. Newly developed biomaterials and technologies with potential for safer and more effective drug delivery require multidisciplinary collaborations with preclinical and clinical scientists that are essential to facilitate their clinical applications. PMID:25594406

Xinluan, Wang; Yuxiao, Lai; Helena, Ng HueiLeng; Zhijun, Yang; Ling, Qin

2015-01-01

150

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

MedlinePLUS

... 2003 2002 2001 2000 1999 Spotlight on Research 2013 August 2013 Novel Drug Delivery System Shows Early Promise for ... systemic lupus erythematosus in mice. J Clin Invest. 2013;123(4):1741-1749. PMID: 23454752. The mission ...

151

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

2012-01-01

152

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

2014-07-01

153

ANALYSIS OF NIFEDIPINE CONTENT IN TRANSDERMAL DRUG DELIVERY SYSTEM USING NON-DESTRUCTIVE VISIBLE SPECTROPHOTOMETRY TECHNIQUE  

Microsoft Academic Search

The applicability of visible spectrophotometry technique as a tool to determine the drug content of polymeric film for use as a transdermal drug delivery system was investigated. Hydroxypropylmethycellulose (HPMC) was selected as the matrix polymer and nifedipine as the model drug. Blank and nifedipine-loaded HPMC films were prepared using the solvent evaporation method. The absorbance spectra of these films under

Normaizira Hamidi; Mohd Nasir Taib; Wong Tin Wui

2008-01-01

154

Transgenic probiotica as drug delivery systems: the golden bullet?  

PubMed

Functional human proteins are constitutively produced in genetically modified bacteria that survive on human mucosal surfaces, to the benefit of the host. The successful Phase I clinical trial with IL-10-producing Lactococcus lactis for Crohn's disease has opened new avenues for the use of transgenic bacteria as delivery vehicles. The major advantage of this novel strategy is the avoidance of systemic side effects associated with conventional therapies. This methodology opens up an alternative method for local delivery of therapeutic proteins to various mucosal tissues. PMID:17184157

Yuvaraj, Saravanan; Peppelenbosch, Maikel P; Bos, Nicolaas A

2007-01-01

155

Investigation of Drug Release from Biodegradable Polymeric Delivery System by Infrared Spectrometry  

Microsoft Academic Search

This study investigates some effective parameters in betamethasone release from in situ forming biodegradable drug delivery systems. The drug delivery systems are based on two biodegradable polymers of poly(D,L-lactide-co-glycolide) (PLGA), which are commercially called RG504h and RG756. Temperature, polymer type, and ?-irradiation are the parameters investigated by attenuated total reflectance Fourier transform-infrared (ATR-FTIR) spectrometry in the 1891–1324 cm spectral region. Obtained

Mohammadreza Khanmohammadi; Hossien Nemati; Mohammad Rafienia; Ahmad Jamshidi; Amir Bagheri Garmarudi

2008-01-01

156

Mathematical models in drug delivery: how modeling has shaped the way we design new drug delivery systems.  

PubMed

In this review we present some of the seminal contributions that have established the mathematical foundations of controlled drug delivery and led to the modern models. Mathematical modeling is no longer just a dry exercise in generating more and more complex models or a parametric fitting process, but rather an advanced analysis that can lead to a priori examination of a release/delivery process or a series of design equations that help the practitioner achieve a better formulation. PMID:24998939

Peppas, Nicholas A; Narasimhan, Balaji

2014-09-28

157

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.

2013-01-01

158

Cutting-edge technologies in colon-targeted drug delivery systems.  

PubMed

Oral colon-targeted drug delivery systems have gained enormous attention among researchers in the last two decades. The significance of this site-specific drug delivery system can be measured by its usefulness for delivering a variety of therapeutic agents, both for the treatment of local diseases or for systemic therapies. With the arrival of newer innovations, a large number of breakthrough technologies have emerged for targeting a drug molecule to the colon. Researchers have attempted various approaches in the development of these formulation technologies, such as pH-dependent, time-dependent and microflora-activated systems. Recently, a number of approaches have been proposed that utilize a novel concept of di-dependent drug delivery systems, that is, the systems in which the drug release is controlled by two factors: pH and time, and pH and microflora of the colon. This Editorial article is not intended to offer a comprehensive review on drug delivery, but shall familiarize the readers with the formulation technologies that have been developed for attaining colon-specific drug delivery. PMID:21933030

Patel, Mayur M

2011-10-01

159

Novel transdermal drug delivery system with polyhydroxyalkanoate and starburst polyamidoamine dendrimer  

Microsoft Academic Search

In search of an efficient transdermal drug delivery system (TDDS), a polyhydroxyalkanoate (PHA)-based system with a polyamidoamine dendrimer was examined. Tamsulosin was used as the model drug. The dendrimer was found to act as the weak enhancer. By adding the dendrimer, the dendrimer-containing PHA matrix achieved the clinically required amount of tamsulosin permeating through the skin model. This is also

Zhioxiong Wang; Yoshiaki Itoh; Yoshifumi Hosaka; Ichiro Kobayashi; Yoshihisa Nakano; Isamu Maeda; Fusako Umeda; Junji Yamakawa; Masaya Kawase; Kiyohito Yag

2003-01-01

160

Bacillus-shape design of polymer based drug delivery systems with janus-faced function for synergistic targeted drug delivery and more effective cancer therapy.  

PubMed

The particle shape of the drug delivery systems had a strong impact on their in vitro and in vivo performance, but there was limited availability of techniques to produce the specific shaped drug carriers. In this article, the novel methotrexate (MTX) decorated MPEG-PLA nanobacillus (MPEG-PLA-MTX NB) was prepared by the self-assembly technique followed by the extrusion through SPG membrane with high N2 pressure for targeted drug delivery, in which Janus-like MTX was not only used as a specific anticancer drug but could also be served as a tumor-targeting ligand. The MPEG-PLA-MTX NBs demonstrated much higher in vitro and in vivo targeting efficiency compared to the MPEG-PLA-MTX nanospheres (MPEG-PLA-MTX NSs) and MPEG-PLA nanospheres (MPEG-PLA NSs). In addition, the MPEG-PLA-MTX NBs also displayed much more excellent in vitro and in vivo antitumor activity than the MPEG-PLA-MTX NSs and free MTX injection. To our knowledge, this work provided the first example of the integration of the shape design (which mediated an early phase tumor accumulation and a late-phase cell internalization) and Janus-faced function (which mediated an early phase active targeting effect and a late-phase anticancer effect) on the basis of nanoscaled drug delivery systems. The highly convergent and cooperative drug delivery strategy opens the door to more drug delivery systems with new shapes and functions for cancer therapy. PMID:25710590

Cui, Fei; Lin, Jinyan; Li, Yang; Li, Yanxiu; Wu, Hongjie; Yu, Fei; Jia, Mengmeng; Yang, Xiangrui; Wu, Shichao; Xie, Liya; Ye, Shefang; Luo, Fanghong; Hou, Zhenqing

2015-04-01

161

Gene and Drug Delivery System with Soluble Inorganic Carriers  

Microsoft Academic Search

Inorganic-based delivery systems are attracting increased attention partially because their inertness gives rise to safety\\u000a and stability in biosystems and partially because their frameworks can be readily and exactly manipulated. Among the diverse\\u000a inorganic candidates, such as nanoparticles and clays, we have focused our attention on layered double hydroxides (LDH) with\\u000a anion-exchange capacity. Diverse anionic molecules can be loaded into

Jin-Ho Choy; Man Park; Jae-Min Oh

162

Alginate based hydrogel as a potential biopolymeric carrier for drug delivery and cell delivery systems: present status and applications.  

PubMed

Alginate is a non-toxic, biocompatible and biodegradable natural polymer with a number of peculiar physicochemical properties for which it has wide applications in drug delivery and cell delivery systems. Hydrogel formation can be obtained by interactions of anionic alginates with multivalent inorganic cations by simple ionotropic gelation method. Hydrophilic polymeric network of three dimensional cross linked structures of hydrogels absorb substantial amount of water or biological fluids. Among the numerous biomaterials used for hydrogel formation alginate has been and will continue to be one of the most important biomaterial. Therefore, in view of the vast literature support, we focus in this review on alginate - based hydrogel as drug delivery and cell delivery carriers for biomedical applications. Various properties of alginates, their hydrogels and also various techniques used for preparing alginate hydrogels have been reviewed. PMID:22998675

Giri, Tapan Kumar; Thakur, Deepa; Alexander, Amit; Ajazuddin; Badwaik, Hemant; Tripathi, Dulal Krishna

2012-11-01

163

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.

2011-01-01

164

Fast disintegrating tablets: Opportunity in drug delivery system  

PubMed Central

Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Oral drug delivery remains the preferred route for administration of various drugs. Recent developments in the technology have prompted scientists to develop FDTs with improved patient compliance and convenience. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. FDTs are solid unit dosage forms, which disintegrate or dissolve rapidly in the mouth without chewing and water. FDTs or orally disintegrating tablets provide an advantage particularly for pediatric and geriatric populations who have difficulty in swallowing conventional tablets and capsules. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray drying and use of disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and dissolution are also discussed. PMID:22247889

Parkash, Ved; Maan, Saurabh; Deepika; Yadav, Shiv Kumar; Hemlata; Jogpal, Vikas

2011-01-01

165

One-step fabrication of biocompatible carboxymethyl cellulose polymeric particles for drug delivery systems  

Microsoft Academic Search

Carboxymethyl cellulose (CMC) particles were synthesized in one step employing inverse micelle microemulsion polymerization using divinyl sulfone as crosslinking agent. These synthesized particles were further modified and demonstrated as drug delivery system. Acyclovir was chosen as the model drug. The synthesized CMC particles were made magnetic responsive by encasing independently prepared magnetic ferrite particles (Fe3O4) in CMC polymeric particles during

Sultan Butun; Fatma Gul Ince; Huseyin Erdugan; Nurettin Sahiner

2011-01-01

166

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

2012-01-01

167

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.

2014-01-01

168

Robust and versatile pectin-based drug delivery systems.  

PubMed

Pectin-based resistant, interactive and versatile hydrogel vehicles for oral administration have been prepared. These systems are thought to be versatile enough to allow the inclusion of substances (such as the surfactants tested: Pluronic, Tween, Na Lauryl sulphate) that may contribute to tailor the drug release patterns. Tolbutamide, that shows a discrete and pH-dependent solubility in water, has been employed as a model drug to test the capability of these matrices to overcome such drug-imposed restraints. The incorporation of different surfactants produced pectin-based hydrogels of difficult manipulation. In order to improve this drawback, two different strategies have been developed: blending with agarose or freeze-drying. The presence of agarose yields robust systems that can be handled and tested as prepared, in the fresh state. Freeze-drying not only allows to shape pure pectin and blend systems, but also generates a porous structure whose microstructure, determined by the different components included, influences on the drug release behavior. Tolbutamide release kinetics from freshly prepared matrices can be fitted to the Higuchi model while the freeze-dried ones adjust to the Korsmeyer-Peppas model; hence the hydrogel chains rearrangement processes rule the release during the rehydration process. PMID:25542990

Marras-Marquez, T; Peña, J; Veiga-Ochoa, M D

2015-02-20

169

PEG - a versatile conjugating ligand for drugs and drug delivery systems.  

PubMed

Polyethylene glycol (PEG) conjugation is a rapidly evolving strategy to solve hurdles in therapeutic delivery and is being used as an add-on tool to the traditional drug delivery methods. Chemically, PEGylation is a term used to denote modification of therapeutic molecules by conjugation with PEG. Efforts are constantly being made to develop novel strategies for conjugation of PEG with these molecules in order to increase its current applications. These strategies are specific to the therapeutic system used and also depend on the availability of activated PEGylating agents. Therefore, a prior knowledge is essential in selecting appropriate method for PEGylation. Once achieved, a successful PEGylation can amend the pharmacokinetic and pharmacodynamic outcomes of therapeutics. Specifically, the primary interest is in their ability to decrease uptake by reticuloendothelial system, prolong blood residence, decrease degradation by metabolic enzymes and reduce protein immunogenicity. The extensive research in this field has resulted into many clinical studies. The knowledge of outcome of these studies gave a good feedback and lessons which helped researchers to redesign PEG conjugates with improved features which can increase the chance of hitting the market. In light of this, the current paper highlights the approaches, novel strategies and the utilization of modern concept for PEG conjugation with respect to various bioactive components of clinical relevance. Moreover, this review also discusses potential clinical outcomes of the PEG conjugation, regulatory approved PEGylated product, clinical trials for newer formulations, and also provides future prospects of this technology. PMID:24997275

Kolate, Atul; Baradia, Dipesh; Patil, Sushilkumar; Vhora, Imran; Kore, Girish; Misra, Ambikanandan

2014-10-28

170

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

2013-01-01

171

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

2011-01-01

172

Pharmacokinetics of a degradable drug delivery system in bone.  

PubMed

Local delivery of antibiotics via a degradable carrier has the potential for high local antibiotic levels and avoids systemic toxicity. Intravenous access, renal function monitoring, and later surgical removal may not be required when degradable local delivery modalities are used. This study examined the in vivo elution of gentamicin from processed bovine collagen (Type I). Gentamicin impregnated collagen (3 mg/kg) was implanted into the femoral medullary canal of 45 adult white rabbits. The gentamicin was released into the bone and averaged greater than 600 micrograms/ml during the initial 48 hours. Local bone levels fell to 144.40 +/- 229.84 micrograms/ml at 5 days and were subsequently greater than or equal to 10.30 +/- 5.02 micrograms/ml through Day 28. Serum levels reached an average peak of 1.25 +/- 0.29 micrograms/ml 5 hours after implantation and fell below 1.0 microgram/ml at 12 hours after implantation. Serum levels subsequently averaged less than or equal to 0.63 +/- 0.09 microgram/ml through Day 28. Collagen impregnated with gentamicin proved to be an effective degradable carrier of gentamicin in the healthy rabbit; it provided local bone concentrations above the minimum inhibitory concentration of gentamicin and serum concentrations below levels associated with systemic toxicity as long as 28 days after implantation. PMID:9584386

Humphrey, J S; Mehta, S; Seaber, A V; Vail, T P

1998-04-01

173

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

PubMed Central

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

Ling, Peixue; Zhang, Tianmin

2013-01-01

174

A novel drug delivery system of gold nanorods with doxorubicin and study of drug release by single molecule spectroscopy.  

PubMed

The work presented here describes the fabrication of a novel drug delivery system, which consists of gold nanorods and doxorubicin, with the attachment of thioctic acid and folic acid, for the targeted release of drug to cancer cells. Doxorubicin, the potent anticancer drug, is widely used to treat various cancers. Gold nanorods were functionalized chemically to generate active groups for the attachment of drug molecules and subsequently attached to folic acid. The resulting nanostructure was characterized by UV-visible-NIR spectrophotometry, TEM techniques, zeta potential measurement and subsequently used to target folate receptor-expressing cancers cells for the delivery of doxorubicin. We generated a release profile for the release of doxorubicin from the nanostructures in KB cells using single-molecule fluorescence intensity images and fluorescence lifetime images. The results indicated that the nanorods were able to enter the target cells because of the attachment of folic acid and used as a carriers for the targeted delivery of doxorubicin. PMID:25148611

Mirza, Agha Zeeshan

2015-01-01

175

A smart drug delivery system from charge-conversion polymer-drug conjugate for enhancing tumor therapy and tunable drug release.  

PubMed

A smart drug delivery system is prepared by citraconylated polyaspartic acid (PASP) derivate-drug conjugate. The conjugate contains two pH-sensitive groups: citraconic amide and hydrazone linker. Citraconic amide group can enhance tumor therapy efficiency by the extracellular pH-sensitive charge-conversion property. Hydrazone linker between polymer and drug can cleave efficiently in the intracellular pH environment. The resulting conjugate shows dual-pH sensitive properties: extracellular pH-triggered enhanced tumor targeting and intracellular pH-triggered drug release. The results of physicochemical properties, intracellular location, and cytotoxicity of conjugate micelles demonstrate that this novel smart drug delivery system can enhance intracellular delivery of drug at a low pH and then release drug rapidly. PMID:24733784

Huang, Hailong; Li, Yapeng; Sa, Zongpeng; Sun, Yuan; Wang, Yuzhen; Wang, Jingyuan

2014-04-01

176

Application of Artificial Neural Networks in Controlled Drug Delivery Systems  

Microsoft Academic Search

Estimation of release profiles of drugs normally requires time-consuming trial-and-error experiments. Feed-forward neural networks including multilayer perceptron (MLP), radial basis function network (RBFN), and generalized regression neural network (GRNN) are used to predict the release profile of betamethasone (BTM) and betamethasone acetate (BTMA) where in situ forming systems consist of poly (lactide-co-glycolide), N-methyl-1-2-pyrolidon, and ethyl heptanoat as a polymer, solvent,

Mohammad Rafienia; Mahmood Amiri; Mohsen Janmaleki; Alireza Sadeghian

2010-01-01

177

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

Microsoft Academic Search

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

Y. Xie; M. D. Kaminski; C. J. Mertz; M. R. Finck; S. G. Guy; H. Chen; A. J. Rosengart

2005-01-01

178

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.

2014-11-01

179

Liposomal Formulations of Inflammatory Bowel Disease Drugs: Local versus Systemic Drug Delivery in a Rat Model  

Microsoft Academic Search

Purpose. Based on adherence to intestinal mucosa, intralumenally administered liposomal formulations of 5-aminosalicylate (5-ASA) and 6-mercaptopurine (6-MP) were studied for their potential to enhance local drug delivery to intestinal tissue for the treatment of inflammatory bowel disease. Methods. 5-ASA was encapsulated in standard phospholipid liposomes while 6-MP required encapsulation in nonphospholipid liposomes to obtain equivalent drug loading. Encapsulation efficiency was

Filippos Kesisoglou; Simon Yuji Zhou; Susan Niemiec; Jordan Wing Lee; Ellen M. Zimmermann; David Fleisher

2005-01-01

180

A review on mucoadhesive polymer used in nasal drug delivery system  

PubMed Central

This update review is on mucoadhesive polymers used in nasal dosage forms. The nasal mucosa provides a potentially good route for systemic drug delivery. One of the most important features of the nasal route is that it avoids first-pass hepatic metabolism, thereby reducing metabolism. The application of mucoadhesive polymers in nasal drug delivery systems has gained to promote dosage form residence time in the nasal cavity as well as improving intimacy of contact with absorptive membranes of the biological system. The various new technology uses in development of nasal drug delivery dosage forms are discussed. The various dosage forms are vesicular carriers (liposome, noisome), nanostructured particles, prodrugs, in situ gelling system with special attention to in vivo studies. PMID:22247888

Chaturvedi, Mayank; Kumar, Manish; Pathak, Kamla

2011-01-01

181

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

PubMed

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

2014-01-01

182

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

2012-01-01

183

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

PubMed

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

2014-12-01

184

Development of pulsatile systems for targeted drug delivery of celecoxib for prophylaxis of colorectal cancer.  

PubMed

The aim of the present study was to formulate fast release enteric-coated tablets for drug delivery to the colon. Two different approaches were used for the preparation of these tablets. The first included making use of superdisintegrant (SD) in the tablet. The amount of super disintegrant (cross-linked PVP) in the tablet and the coat weight were varied to formulate a suitable time-controlled release system, that would provide colon-specific drug delivery. The second approach consisted of development of osmogen-based tablets for drug delivery into the tracts of the colon. Two different osmogens, sodium chloride and potassium chloride, were used. These also were coated at different coat levels. Celecoxib was used as a model drug. In vitro drug release studies showed that superdisintegrants were more effective in showing burst effect in the tablets and therefore showed a rapid drug release as compared with osmogens, which would show a sustained drug release all through the colon. Osmotic tablets were formulated making use of a high concentration of osmogen sodium chloride (OM-SC) and potassium chloride (OM-KC) were further enteric-coated. These also were found to be useful in providing a sustained delivery of nearly 80-90% of the drug into the colonic region. The coat weight required in these tablets for protection in the upper gastrointestinal conditions varied from 9.69% in OM-KC tablets to 4.65% in OM-SC tablets. PMID:16556575

Sinha, V R; Bhinge, J R; Kumria, Rachna; Kumar, Manoj

2006-01-01

185

Pathogen-inspired drug delivery to the central nervous system.  

PubMed

For as long as the human blood-brain barrier (BBB) has been evolving to exclude bloodborne agents from the central nervous system (CNS), pathogens have adopted a multitude of strategies to bypass it. Some pathogens, notably viruses and certain bacteria, enter the CNS in whole form, achieving direct physical passage through endothelial or neuronal cells to infect the brain. Other pathogens, including bacteria and multicellular eukaryotic organisms, secrete toxins that preferentially interact with specific cell types to exert a broad range of biological effects on peripheral and central neurons. In this review, we will discuss the directed mechanisms that viruses, bacteria, and the toxins secreted by higher order organisms use to enter the CNS. Our goal is to identify ligand-mediated strategies that could be used to improve the brain-specific delivery of engineered nanocarriers, including polymers, lipids, biologically sourced materials, and imaging agents. PMID:25610755

McCall, Rebecca L; Cacaccio, Joseph; Wrabel, Eileen; Schwartz, Mary E; Coleman, Timothy P; Sirianni, Rachael W

2014-01-01

186

Amino Acid Transporter ATB0,+ as a delivery system for drugs and prodrugs.  

PubMed

ATB(0,+) is a unique amino acid transporter because of its broad substrate specificity and concentrative ability. This transporter recognizes neutral as well as cationic amino acids. It is energized by Na(+) and Cl(-) gradients and membrane potential. Many of the amino acids and amino acid derivatives that are substrates for ATB(0,+) serve as therapeutic agents (e.g., D-serine, carnitine, and nitric oxide synthase inhibitors). Recent studies have shown that the potential of ATB(0,+) as a drug delivery system may be greater than previously envisaged. ATB(0,+) can transport antiviral drugs such as acyclovir and ganciclovir when they are covalently coupled to the side chain of anionic amino acids. Chemical modification of the carboxyl groups in the side chain of aspartate and glutamate with drugs converts these anionic amino acids into neutral amino acid derivatives. Therefore, the modified drugs are recognized by ATB(0,+). Interestingly, even when acyclovir and ganciclovir are coupled as esters with alpha-carboxyl group of neutral amino acids, the modified drugs are transported via ATB(0,+). Similarly, the hydroxyl group in the side chains of serine and threonine can also be used to covalently couple drugs for delivery into cells via ATB(0,+). This increases the potential for designing a wide variety of amino acid-based prodrugs that can utilize ATB(0,+) as drug delivery system. Furthermore, the transporter is expressed in the colon, lung, and eye, the tissues easily amenable for drug delivery. These findings argue strongly in support of ATB(0,+) as a potential delivery system for a wide variety of drugs and prodrugs. PMID:16375689

Ganapathy, M E; Ganapathy, V

2005-12-01

187

Drug delivery system design and development for boron neutron capture therapy on cancer treatment.  

PubMed

We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,l-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content. PMID:24447933

Sherlock Huang, Lin-Chiang; Hsieh, Wen-Yuan; Chen, Jiun-Yu; Huang, Su-Chin; Chen, Jen-Kun; Hsu, Ming-Hua

2014-06-01

188

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

2010-01-01

189

Transducer design for a portable ultrasound enhanced transdermal drug-delivery system  

Microsoft Academic Search

For application in a portable transdermal drug-delivery system, novel transducers have been designed to enhance insulin transmission across skin using ultrasound. Previous research has shown transdermal delivery of insulin across skin using commercial sonicators operating at 20 kHz with intensities ranging from 12.5 to 225 mW\\/cm2. The goal of this research was to design and construct a small, lightweight transducer

Emiliano Maione; K. Kirk Shung; Richard J. Meyer; Jack W. Hughes; Robcrt E. Newnham; Nadine Barrie Smith

2002-01-01

190

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

2014-01-01

191

Distinctive features of "chronotherapeutic" and "pulsatile" drug delivery systems negating the practice of their interchangeable terminology.  

PubMed

The term pulsatile drug delivery has often been used as a synonym to chronotherapeutic drug delivery. This needs to be given a thought as both the drug delivery systems are entirely addressing different needs of the patients as well as the intentions of the formulators being different. Chronotherapeutic systems are based completely on circadian needs and response of the body and the need of the drug to be in its maximum concentrations at a particular time of the day, the fact being supported by endless list of ailments which elicit the related symptoms at a particular time of the day. Considering the formulation approach, one does not find major differences among site-specific chronotherapeutic systems and the basic and more conventional intestinal or colon targeted systems due to the mechanism and the site of landing of drug of both being almost similar even though the intention of the formulator being different. An ideal pulsatile system is the one delivering drug in different pulses with multiple troughs in release profile. The article explores the major differences in between the two systems and highlights the need of using appropriate terminology for these individual and distinct systems catering different needs. PMID:20132094

Ali, Javed; Baboota, Sanjula; Ahuja, Alka; Saigal, Nitin

2010-07-01

192

Computational modeling of environmentally responsive hydrogels (ERH) for drug delivery system.  

PubMed

The present work aims at computational analysis of environmentally responsive hydrogels with enormous prospective in the formulation aspect of drug delivery systems. The drug delivery potential of hydrogels to the targets is owing to the specific stimuli responsive nature of the hydrogels. The environmental factors looked upon in the study are changes in pH, alteration of temperature and glucose concentration rise originated in the body as a result of various disease conditions. Polymers, synthetic polypeptides and dendrimers have been used in the present work to study the feasibility of drug delivery. The computational methods have been used to formulate polymer properties, pharmacokinetics and toxicity studies. Diverse interactions approximating electrostatic, hydrophobic and hydrogen bond interactions acquire place during incorporation of drugs within the polymer and dendrimers. The covalent and electrostatic interactions between a drug and the surface of polymer and dendrimer have been analyzed. The docking interaction studies have been performed and the best polymer and dendrimer complex have been selected based on the docking score, binding energy and interaction energy with the drugs. G5 generation of poly amidoamine dendrimers and poly N-Ndiethyl acrylamide (PDEAAM) have been identified as most suitable stimuli-responsive effective drug carriers for anti diabetic drugs and diuretics. Favorable results have been obtained while using poly acrylic acid (PAA) for corticosteroids and polylysine for diabetic drugs. ConA protein along with poly aspartic acid also showed good results. PMID:23106779

Namboori, P K Krishnan; Ranjini, U P; Manakadan, Asha A; Jose, Anila; Silvipriya, K S; Belzik, N; Deepak, O M

2013-03-01

193

Microfabricated Engineered Particle Systems for Respiratory Drug Delivery and Other Pharmaceutical Applications  

PubMed Central

Particle Replication in Non-Wetting Templates (PRINT®) is a platform particle drug delivery technology that coopts the precision and nanoscale spatial resolution inherently afforded by lithographic techniques derived from the microelectronics industry to produce precisely engineered particles. We describe the utility of PRINT technology as a strategy for formulation and delivery of small molecule and biologic therapeutics, highlighting previous studies where particle size, shape, and chemistry have been used to enhance systemic particle distribution properties. In addition, we introduce the application of PRINT technology towards respiratory drug delivery, a particular interest due to the pharmaceutical need for increased control over dry powder characteristics to improve drug delivery and therapeutic indices. To this end, we have produced dry powder particles with micro- and nanoscale geometric features and composed of small molecule and protein therapeutics. Aerosols generated from these particles show attractive properties for efficient pulmonary delivery and differential respiratory deposition characteristics based on particle geometry. This work highlights the advantages of adopting proven microfabrication techniques in achieving unprecedented control over particle geometric design for drug delivery. PMID:22518316

Garcia, Andres; Mack, Peter; Williams, Stuart; Fromen, Catherine; Shen, Tammy; Tully, Janet; Pillai, Jonathan; Kuehl, Philip; Napier, Mary; DeSimone, Joseph M.; Maynor, Benjamin W.

2012-01-01

194

COMPUTATIONAL STUDIES OF CONTROLLED NANOPARTICLE AGGLOMERATIONS FOR MRI-GUIDED NANOROBOTIC DRUG-DELIVERY SYSTEMS  

E-print Network

(MRI) scanners have been proposed for localized drug delivery in the human body. The expectation systems that could perform diagnostic, curative and reconstructive treatments in the human body-guided nanorobotic system is based on the use of a MRI scanner to induce the required external driving forces

Mavroidis, Constantinos

195

Mirena ® (Levonorgestrel intrauterine system): A successful novel drug delivery option in contraception  

Microsoft Academic Search

This manuscript serves as a review of Mirena®, the levonorgestrel intrauterine system (LNG IUS) as a very successful drug delivery system. The LNG IUS has a very high contraceptive efficacy rate, and low rates of patient discontinuation. In addition to its contraceptive benefits, most users experience a decrease in menstrual bleeding over the 5 years of use. LNG IUS has also

Susan Rose; Angela Chaudhari; C. Matthew Peterson

2009-01-01

196

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

197

In Vitro Dissolution Testing Strategies for Nanoparticulate Drug Delivery Systems: Recent Developments and Challenges  

PubMed Central

Nanoparticulate systems have emerged as prevalent drug delivery systems over the past few decades. These delivery systems (such as liposomes, emulsions, nanocrystals, and polymeric nanocarriers) have been extensively used to improve bioavailability, prolong pharmacological effects, achieve targeted drug delivery, as well as reduce side effects. Considering that any unanticipated change in product performance of such systems may result in toxicity and/or change in vivo efficacy, it is essential to develop suitable in vitro dissolution/release testing methods to ensure product quality and performance, and to assist in product development. The present review provides an overview of the current in vitro dissolution/release testing methods such as dialysis, sample and separate, as well as continuous flow methods. Challenges and future directions in the development of standardized and biorelevant in vitro dissolution/release testing methods for novel nanoparticulate systems are discussed. PMID:24069580

Shen, Jie; Burgess, Diane J.

2013-01-01

198

76 FR 51038 - Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...  

Federal Register 2010, 2011, 2012, 2013, 2014

...been taken to minimize the amount of residual drug in a system after use to the lowest possible...It is expected that the amount of residual drug in a newly developed system (including new generic drug products) will not exceed that of...

2011-08-17

199

An implantable MEMS micropump system for drug delivery in small animals.  

PubMed

We present the first implantable drug delivery system for controlled timing and location of dosing in small animals. Current implantable drug delivery devices do not provide control over these factors nor are they 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 ?L/min 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; Mann, Ronalee Lo; Meng, Ellis

2012-06-01

200

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

2012-01-01

201

Bioactive electrospun fish sarcoplasmic proteins as a drug delivery system.  

PubMed

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

2014-10-01

202

A Microparticle/Hydrogel Combination Drug-Delivery System for Sustained Release of Retinoids  

PubMed Central

Purpose. To design and develop a drug-delivery system containing a combination of poly(d,l-lactide-co-glycolide) (PLGA) microparticles and alginate hydrogel for sustained release of retinoids to treat retinal blinding diseases that result from an inadequate supply of retinol and generation of 11-cis-retinal. Methods. To study drug release in vivo, either the drug-loaded microparticle–hydrogel combination was injected subcutaneously or drug-loaded microparticles were injected intravitreally into Lrat?/? mice. Orally administered 9-cis-retinoids were used for comparison and drug concentrations in plasma were determined by HPLC. Electroretinography (ERG) and both chemical and histologic analyses were used to evaluate drug effects on visual function and morphology. Results. Lrat?/? mice demonstrated sustained drug release from the microparticle/hydrogel combination that lasted 4 weeks after subcutaneous injection. Drug concentrations in plasma of the control group treated with the same oral dose rose to higher levels for 6?7 hours but then dropped markedly by 24 hours. Significantly increased ERG responses and a markedly improved retinal pigmented epithelium (RPE)–rod outer segment (ROS) interface were observed after subcutaneous injection of the drug-loaded delivery combination. Intravitreal injection of just 2% of the systemic dose of drug-loaded microparticles provided comparable therapeutic efficacy. Conclusions. Sustained release of therapeutic levels of 9-cis-retinoids was achieved in Lrat?/? mice by subcutaneous injection in a microparticle/hydrogel drug-delivery system. Both subcutaneous and intravitreal injections of drug-loaded microparticles into Lrat?/? mice improved visual function and retinal structure. PMID:22918645

Gao, Song-Qi; Maeda, Tadao; Okano, Kiichiro; Palczewski, Krzysztof

2012-01-01

203

In vitro and in vivo consideration of novel environmentally responsive ophthalmic drug delivery system.  

PubMed

In the present study, novel environmentally responsive ophthalmic drug delivery system composed of two gelling polymers with different phase transition mechanisms was developed in order to obtain sustained drug release in ocular cavity. Combination of polyacrylic acid (carbopol 934P) and xanthan gum was investigated as ophthalmic vehicle and assessed for its in vitro and in vivo performance. Different ratios of these polymers were used to prepare environmentally responsive ophthalmic drug delivery system by simple mixing procedure. Developed formulation was assessed for physical tests such as appearance/clarity, pH, gelation; and performance characteristics such as drug content, rheological measurement, in vitro release, antimicrobial efficiency, in vivo studies for eye irritation, residence time estimation. Prepared formulation showed agreeable appearance/clarity, acceptable pH and good gelation property. In vitro and in vivo studies demonstrated adequate drug content, desired rheological behavior and reasonable in vitro and in vivo drug release property. In conclusion, the optimum concentration of polymers results in increased residence time and sustained drug release. On the basis of these findings, environmentally responsive system based on combination of carbopol and xanthan gum may be considered as a promising tool for ophthalmic delivery. PMID:22200332

Deshmukh, Prashant K; Gattani, Surendra G

2013-01-01

204

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

2014-01-01

205

Novel gel-niosomes formulations as multicomponent systems for transdermal drug delivery.  

PubMed

The percutaneous permeation profiles of sulfadiazine sodium salt, propranolol hydrochloride and tyrosol from novel liquid crystal-niosomes formulations as multicomponent systems, were investigated. The new carriers were prepared from mixture of water/surfactant, AOT or Pluronic L64 as anionic and nonionic surfactants, respectively, in order to obtain lamellar LLC phases. The same surfactants were used to prepare also the vesicular systems (niosomes) that were added to the corresponding gel. The obtained multicomponent drug carrier was characterized by deuterium nuclear magnetic resonance spectroscopy, in order to understand if the introduction of the drug or drug-loaded niosomal suspension, as third component in the formulations, could influence the microstructure of the system and then the drug delivery across the skin. Simple AOT and L64-based niosomal formulations and LLCs phases were then prepared and used as control. Different drugs percutaneous availability was achieved, and the results revealed that the obtained gel-niosomes carriers were affected by the chemical structure of the drugs and by their affinity for the components. As a consequence these systems could be proposed as novel transdermal drug delivery systems, since they were found able to control the percutaneous permeation of small drugs across the skin. PMID:23732806

Tavano, Lorena; Gentile, Luigi; Oliviero Rossi, Cesare; Muzzalupo, Rita

2013-10-01

206

IMPLANTABLE MEMS DRUG DELIVERY SYSTEMS FOR ADMINISTRATION OF UNALTERED THERAPEUTIC AGENTS  

E-print Network

delivery vehicle for treating difficult-to-reach diseases affecting the posterior segment of the eye. Drug designed, fabricated, and tested (benchtop, ex vivo, and in vivo). Both systems share a common layout subconjunctivally, while the cannula is inserted through an incision into either the anterior or posterior segment

Meng, Ellis

207

Experimental characterization of a robotic drug delivery system based on magnetic propulsion  

Microsoft Academic Search

This paper reports on the experimental characterization of a robotic drug delivery system based on an endoscopic capsule propelled in water and silicone oil using electromagnetic actuation. Silicon oil is specifically chosen to mimic the viscous environment in the gastrointestinal (GI) tract within the human body. A permanent magnet is embedded inside the capsule to make it responsive to the

Hao Zhou; Gursel Alici; Weihua Li; Shaya Ghanbar

2011-01-01

208

Effective and well-tolerated drug delivery and restraint systems are essential for  

E-print Network

-Darken PhD, National Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715Effective and well-tolerated drug delivery and restraint systems are essential for studies and are increasingly being used in biomedical research (Scott 1994, Owen et al. 1997, Abbott et al. 2003, Mansfield

Saltzman, Wendy

209

Application of Ultrasound Energy as a New Drug Delivery System  

Microsoft Academic Search

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

Katsuro Tachibana; Shunro Tachibana

1999-01-01

210

A review of integrating electroactive polymers as responsive systems for specialized drug delivery applications.  

PubMed

Electroactive polymers (EAPs) are promising candidate materials for the design of drug delivery technologies, especially in conditions where an "on-off" drug release mechanism is required. To achieve this, EAPs such as polyaniline, polypyrrole, polythiophene, ethylene vinyl acetate, and polyethylene may be blended into responsive hydrogels in conjunction with the desired drug to obtain a patient-controlled drug release system. The "on-off" drug release mechanism can be achieved through the environmental-responsive nature of the interpenetrating hydrogel-EAP complex via (i) charged ions initiated diffusion of drug molecules; (ii) conformational changes that occur during redox switching of EAPs; or (iii) electroerosion. These release mechanisms are not exhaustive and new release mechanisms are still under investigation. Therefore, this review seeks to provide a concise incursion and critical overview of EAPs and responsive hydrogels as a strategy for advanced drug delivery, for example, controlled release of neurotransmitters, sulfosalicyclic acid from cross-linked hydrogel, and vaccine delivery. The review further discusses techniques such as linear sweep voltammetry, cyclic voltammetry, impedance spectroscopy, and chronoamperometry for the determination of the redox capability of EAPs. The future implications of the hydrogel-EAP composites include, but not limited to, application toward biosensors, DNA hybridizations, microsurgical tools, and miniature bioreactors and may be utilized to their full potential in the form of injectable devices as nanorobots or nanobiosensors. PMID:23852673

Pillay, Viness; Tsai, Tong-Sheng; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Modi, Girish; Naidoo, Dinesh; Tomar, Lomas K; Tyagi, Charu; Ndesendo, Valence M K

2014-06-01

211

Microbially triggered drug delivery to the colon  

Microsoft Academic Search

Increasing acceptance of protein- and peptide-based drugs necessitates an investigation into the suitability of various sites for their administration. Colon is being investigated for delivery of such molecules. Colon-specific drug delivery is designed to target drug molecules specifically to this area. Development of site-specific delivery systems may exploit a specific property of the target site for drug activation\\/release. The gastrointestinal

V. R Sinha; Rachna Kumria

2003-01-01

212

Drug-loaded nano-microcapsules delivery system mediated by ultrasound-targeted microbubble destruction: A promising therapy method  

PubMed Central

The nano-microcapsules drug delivery system is currently a promising method for the treatment of many types of diseases, particularly tumors. However, the drug delivery efficiency does not reach a satisfactory level to meet treatment demands. Therefore, the effectiveness of delivery needs to be improved. Based on the alterations in the structure and modification of nano-microcapsules, ultrasound-targeted microbubble destruction (UTMD), a safe physical targeted method, may increase tissue penetration and cell membrane permeability, aiding the drug-loaded nano-microcapsules ingress the interior of targeted tissues and cells. The effectiveness and exact mechanism of action of the drug-loaded nano-microcapsules delivery system mediated by UTMD have yet to be fully elucidated. In this study, the latest advancement in UTMD-mediated drug loaded nano-microcapsules system technology was reviewed and the hindrances of UTMD-mediated drug delivery were assessed, in combination with a prospective study. The findings suggested that the drug delivery efficiency of nano-microcapsules mediated by UTMD was distinctly improved. Thus, the UTMD-mediated drug-loaded nano-microcapsules delivery system may significantly improve the efficiency of drug delivery, which may be a promising new therapeutic method. PMID:24648976

MA, JING; DU, LIAN FANG; CHEN, MING; WANG, HANG HUI; XING, LING XI; JING, LI FANG; LI, YUN HUA

2013-01-01

213

Paclitaxel and Gemcitabine Combinational Drug-loaded Mucoadhesive Delivery System in the Treatment of Colon Cancers.  

PubMed

The combination of two different types of chemo-therapeutic drugs via nanocarriers is emerged as a promising strategy for treating multiple cancers. Such a co-delivery system will synchronize the drug exposure and synergize the therapeutic effects. Herein, we prepared a paclitaxel (PTX) and gemcitabine (GEM)-loaded N-succinyl chitosan nanoparticles (NSC NP) to target colon cancer. NSC NP showed a pH sensitive swelling at colonic pH and exhibited a sequential release pattern for both the drugs. Binary drug combination exhibited a synergistic cytotoxicity against HT-29 colon cancer cells with a remarkable G2/M phase arrest. Specifically, in vivo antitumor efficacy study showed that NSC NP prolonged the survival time of tumor-bearing mice up to 45 days wherein 50% of mice were still alive. Therefore, these results suggest that co-delivery of drugs with a suitable delivery system could potentially improve the therapeutic efficacy in colon cancers. The study can be further continued by using different types of chemotherapeutic drugs that targets different molecular targets using pH-sensitive nanocarriers. PMID:24941086

Guo, X-Y; Wang, P; Du, Q-G; Han, S; Zhu, S-M; Lv, Y-F; Liu, G-S; Hao, Z-M

2015-04-01

214

The biopolymer bacterial nanocellulose as drug delivery system: investigation of drug loading and release using the model protein albumin.  

PubMed

Although bacterial nanocellulose (BNC) has reached enormous interest for biomedical applications because of its outstanding material properties, investigations about its potential as drug delivery system are very rare. In the present study, for the first time, the applicability of BNC as drug delivery system for proteins using serum albumin as model drug was systematically investigated. Additionally, never-dried BNC was compared with freeze-dried BNC. For both types of BNC, a dependency of concentration, temperature, time, and preswelling for albumin loading and release could be demonstrated. These findings indicated an overlay of diffusion- and swelling-controlled processes, which could be confirmed by Ritger-Peppas equation. Freeze-dried samples showed a lower uptake capacity for albumin than native BNC, which was found to be related to changes of the fiber network during the freeze drying process as demonstrated by electron microscopy and protein staining experiments. The integrity and biological activity of proteins could be retained during the loading and release processes, which was demonstrated by gel electrophoresis and the use of luciferase as biologically active molecule. In conclusion, hydrophilicity, high biocompatibility, and controllable drug loading and release render BNC an innovative and attractive biopolymer for controlled drug delivery. PMID:23192666

Müller, Astrid; Ni, Zhixu; Hessler, Nadine; Wesarg, Falko; Müller, Frank A; Kralisch, Dana; Fischer, Dagmar

2013-02-01

215

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

2007-01-01

216

Development of oral drug delivery system using floating microspheres.  

PubMed

Floating acrylic resin microspheres with an internal hollow structure were prepared by a solvent diffusion and evaporation method. The yield of microspheres depended on the diffusion rate of ethanol and/or isopropanol in the organic phase. They were successfully produced when a mixture of ethanol and isopropanol was used instead of ethanol alone. The mixing ratio of components in the organic phase affected the size and the yield of microspheres and the best results were obtained at the volume ratio of ethanol:isopropanol:dichloromethane (8:2:5). Direct introduction of the organic phase into the aqueous phase through a glass tube also significantly improved the yield by avoiding the contact of organic phase with the surface of water. The optimum rotation speed and temperature were 250 rpm and 25 degrees C, respectively. Several different drugs with various physico-chemical properties were used as model drugs for encapsulation and release tests. When a drug had low solubility in dichloromethane and high solubility in both water and a mixture of ethanol/isopropanol, the loading efficiency was the lowest. The release profiles were significantly different depending on the solubility of a drug in the release medium and the physico-chemical properties of an encapsulated drug. PMID:10575624

Lee, J H; Park, T G; Choi, H K

1999-01-01

217

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

E-print Network

-array electrodes Monitoring system Controlled delivery Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non

Ljubljana, University of

218

Mesoporous bioactive glass as a drug delivery system: fabrication, bactericidal properties and biocompatibility.  

PubMed

Implant-associated infection remains a difficult medical problem in orthopaedic surgery. Here, we report on the fabrication of gentamicin-loaded mesoporous bioactive glass (Gent-MBG) for use as a controlled antibiotic delivery system to achieve the sustained release of antibiotics in the local sites of bone defects. The high surface area and mesoporous structure of MBG enable higher drug loading efficiency (79-83 %) than non-mesoporous biological glass (NBG) (18-19 %). Gent-MBG exhibits sustained drug release for more than 6 days, and this controlled release of gentamicin significantly inhibits bacterial adhesion and prevents biofilm formation by S. aureus (ATCC25923) and S. epidermidis (ATCC35984). Biocompatibility tests with human bone marrow stromal cells (hBMSCs) indicate that MBG has better biocompatibility than NBG. Therefore, Gent-MBG can be used as a controlled drug delivery system to prevent and/or treat orthopedic peri-implant infections. PMID:23695360

Li, Yang; Liu, Yi-Zhuo; Long, Teng; Yu, Xi-Bin; Tang, Ting-Ting; Dai, Ke-Rong; Tian, Bo; Guo, Ya-Ping; Zhu, Zhen-An

2013-08-01

219

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

2014-01-01

220

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

2005-01-01

221

Pectin/zein microspheres as a sustained drug delivery system  

Technology Transfer Automated Retrieval System (TEKTRAN)

A series of microspheres were prepared from pectins and corn proteins from various sources in the presence of the divalent ions calcium or zinc. The results showed that the yield of microsphere and the efficiency of drug incorporation were dependent on the type and ratio of biopolymers, the size of ...

222

CCMR: Controlled Drug Delivery From New Biomaterials  

NSDL National Science Digital Library

The development of controlled release systems for drug delivery is an area that has generated considerable research interest over the past decade. Biodegradable polymers, which degrade naturally via hydrolysis or enzymatic digestion, have demonstrated great potential for use in the preparation of controlled drug delivery systems. Biodegradable polymeric drug delivery systems hold several distinct advantages over more conventional oral and inhalation routes, including enhanced site specificity of drug delivery, reduced side effects, improved patient compliance, and greater overall efficacy. The primary objective of this work was to synthesize biodegradable polyesters based on a locked dimer of dihydroxyacetone (DHA).

Rhodes, Steven D.

2005-08-17

223

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

2014-01-01

224

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

2013-01-01

225

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

2011-01-01

226

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.

2013-01-01

227

15 years of ATTEMPTS: A macromolecular drug delivery system based on the CPP-mediated intracellular drug delivery and antibody targeting.  

PubMed

Traditionally, any drug intended for combating the tumor would distribute profoundly to other organs and tissues as lack of targeting specificity, thus resulting in limited therapeutic effects toward the tumor but severe drug-induced toxic side effects. To prevail over this obstacle of drug-induced systemic toxicity, a novel approach termed "ATTEMPTS" (antibody targeted triggered electrically modified prodrug type strategy) was designed, which directly introduces both of the targeting and prodrug features onto the protein drugs. The ATTEMPTS system is composed of the antibody targeting component consisting of antibodies linked with heparin, and the cell penetrating peptide (CPP) modified drug component. The two components mentioned above self-assembled into a tight complex via the charge to charge interaction between the anionic heparin and cationic CPP. Once accumulated at the targeting site, the CPP modified drug is released from the blockage by a second triggering agent, while remaining inactive in the circulation during tumor targeting thus aborting its effect on normal tissues. We utilized the heparin-induced inhibition on the cell-penetrating activity of CPP to create the prodrug feature, and subsequently the protamine-induced reversal of heparin inhibition to resume cell transduction of the protein drug via the CPP function. Our approach is the first known system to overcome this selectivity issue, enabling CPP-mediated cellular drug delivery to be practically applicable clinically. In this review, we thoroughly discussed the historical and novel progress of the "ATTEMPTS" system. PMID:25483423

Ye, Junxiao; Shin, Meong Cheol; Liang, Qiuling; He, Huining; Yang, Victor C

2015-05-10

228

Preparation and in vitro characterization of a non-effervescent floating drug delivery system for poorly soluble drug, glipizide.  

PubMed

The aim of the present study was to formulate a non-effervescent floating drug delivery system of glipizide, a poorly water soluble drug. The solubility of glipizide was initially enhanced using a solid dispersion (SD) strategy with the help of hydrophilic carriers such as poloxamer, cyclodextrin, and povidone. The optimized core material/SD was further formulated into non-effervescent floating tablets (NEFT) by using matrix ballooning inducers, such as crospovidone and release retarding agents including HPMC and PEO. Poloxamer-based solid dispersions prepared by a solvent evaporation technique showed the highest dissolution rate (1 : 10 drug to carrier ratio) compared with all other dispersions. NEFT were evaluated for all physico-chemical properties including in vitro buoyancy, dissolution, and release rate. All of the tablets were found to be within pharmacopoeial limits and all of the formulations exhibited good floating behavior. The formulations (F2 and F3) were optimized based on their 12 h drug retardation with continuous buoyancy. The optimized formulations were characterized using FTIR and DSC and no drug and excipient interaction was found. In-vitro buoyancy and dissolution studies showed that non-effervescent floating drug delivery systems provide a promising method of achieving prolonged gastric retention time and improved bioavailability of glipizide. PMID:25850215

Meka, Venkata Srikanth; Pillai, Shreeni; Dharmalingham, Senthil Rajan; Sheshala, Ravi; Gorajana, Adinarayana

2015-01-01

229

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

PubMed

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

2014-05-01

230

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

2011-01-01

231

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

2015-01-01

232

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

PubMed

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

2015-01-01

233

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

2009-01-01

234

Soluplus(®) micelles as a potential drug delivery system for reversal of resistant tumor.  

PubMed

Inhibiting or circumventing drug resistance by using drug delivery systems (DDSs) such as micelles has attracted significant attention recently. In this present study, a polyvinyl caprolactam-polyvinyl acetate-polyethylene (Soluplus(®)) micelle was developed as the delivery system for doxorubicin (DOX) and evaluated both in vitro and in vivo. In vitro, Soluplus(®) micelles could significantly enhance the cellular accumulation of DOX in MCF-7/DOX cells, meanwhile, P-glycoprotein (P-gp)-mediated drug efflux was inhibited which was also verified in the membrane fluidity study. And MCF-7/DOX cells were found to be more susceptible to the cytotoxic effects of DOX-M. In vivo, both the P-gp inhibitors verapamil and Soluplus(®) could improve the cytotoxicity of DOX·HCl in MCF-7/DOX tumor-bearing mice, which were further certified by the effect of Soluplus(®) on P-gp inhibition. Furthermore, the excellent antitumor efficacy of DOX-M by intravenous injection was also observed, which indicated that the P-gp inhibition effect of Soluplus(®) could enhance the susceptibility of resistant tumor to DOX in vivo. In conclusion, our study suggested that Soluplus(®) micelles might be an applicable drug delivery system for enhancing the antitumor efficacy of P-gp substrates. PMID:25661387

Jin, Xiang; Zhou, Bo; Xue, Lezhen; San, Weiguang

2015-02-01

235

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

PubMed

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

2014-01-01

236

Development and characterization of self emulsifying drug delivery system of a poorly water soluble drug using natural oil.  

PubMed

Objective of present study involves preparation and evaluation of self emulsifying drug delivery system (SEDDS) of ibuprofen using peanut oil. SEDDS were composed of varying concentrations of peanut oil (solvent), tween 80 (surfactant) and span 20 (co-surfactant). Influence of concentration of surfactant/co-surfactant and globule size on dissolution rate was investigated. Dissolution rate was studied in phosphate buffer pH 6.8 using dissolution apparatus II. The dissolution rate of self emulsifying capsule was found to be significantly faster than that from conventional tablet. The optimized SEDDS released approximately above 85% of ibuprofen within 30 min, while conventional ibuprofen tablet could released only 36% in 30 min. Therefore, these SEDDS could be a better alternative to conventional drug delivery system of ibuprofen. PMID:22876615

Sharma, Shivani; Bajaj, Himani; Bhardwaj, Piyush; Sharma, Anshul Dutt; Singh, Ranjeet

2012-01-01

237

Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design.  

PubMed

Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1-0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics. PMID:20553104

Dabhi, Mahesh R; Nagori, Stavan A; Gohel, Mukesh C; Parikh, Rajesh K; Sheth, Navin R

2010-01-01

238

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

PubMed

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

2006-12-11

239

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

KRAFT, JOHN C.; FREELING, JENNIFER P.; WANG, ZIYAO; HO, RODNEY J. Y.

2014-01-01

240

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

2012-01-01

241

In vitro drug release studies on guar gum-based colon targeted oral drug delivery systems of 5-fluorouracil  

Microsoft Academic Search

Intravenous administration of 5-fluorouracil for colon cancer therapy produces severe systemic side-effects due to its cytotoxic effect on normal cells. The broad objective of the present study was to develop novel tablet formulations for site-specific delivery of 5-fluorouracil to the colon without the drug being released in the stomach or small intestine using guar gum as a carrier. Fast-disintegrating 5-fluorouracil

Y. S. R Krishnaiah; V Satyanarayana; B Dinesh Kumar; R. S Karthikeyan

2002-01-01

242

Soluble gentamicin ophthalmic inserts as a drug delivery system.  

PubMed

A comparison was made of soluble 14C-gentamicin ophthalmic inserts with drop, ointment, and the subconjunctival routes of administration. The insert is a solid, solubilizable collagen polymer containing 14C-gentamicin. We compared the levels of 14C-gentamicin in the rabbit tear film and in multiple corneal and scleral biopsies to determine which route of administration gave the best results. The wafer route of administration gave the highest tear film and tissue concentration of drug. The tear film concentration by subconjunctival injection was surprisingly low. Soluble collagen inserts offer a new method of delivering high doses of gentamicin in infected corneal tissue in a convenient and atraumatic fashion. PMID:655927

Bloomfield, S E; Miyata, T; Dunn, M W; Bueser, N; Stenzel, K H; Rubin, A L

1978-05-01

243

Development of a multilayered association polymer system for sequential drug delivery  

NASA Astrophysics Data System (ADS)

As all the physiological processes in our body are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the primary objective of this research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. This particular device was designed aimed at the treatment of periodontitis, a highly prevalent oral inflammatory disease that affects 90% of the world population. This condition is caused by bacterial biofilm on the teeth, resulting in a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The polymers used for the fabrication of this multilayered device consists of cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion property of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. After the initial characterization of the CAPP system, the device was specifically modified to achieve sequential release of drugs aimed at the treatment of periodontitis. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. To obtain different erosion times and achieve appropriate release profiles specific to the disease condition, the device was modified by increasing the number of layers or by inclusion of a slower eroding polymer layer. In all the cases, the device was able to release the four different drugs in the designed temporal sequence. Analysis of antibiotic and antiinflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. Following extensive studies on the in vitro sequential drug release from these devices, the in vivo drug release profiles were investigated. The CAPP devices with different release rates and dosage formulations were implanted in a rat calvarial onlay model, and the in vivo drug release and erosion was compared with in vitro results. In vivo studies showed sequential release of drugs comparable to those measured in vitro, with some difference in drug release rates observed. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule. KEYWORDS: Multiple drug delivery, Periodontitis, Cellulose acetate phthalate, Pluronic F-127, Sequential drug release, in vitro drug release, in vivo drug release.

Chinnakavanam Sundararaj, Sharath kumar

244

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

2010-01-01

245

Hydrogel drug delivery system with predictable and tunable drug release and degradation rates  

PubMed Central

Many drugs and drug candidates are suboptimal because of short duration of action. For example, peptides and proteins often have serum half-lives of only minutes to hours. One solution to this problem involves conjugation to circulating carriers, such as PEG, that retard kidney filtration and hence increase plasma half-life of the attached drug. We recently reported an approach to half-life extension that uses sets of self-cleaving linkers to attach drugs to macromolecular carriers. The linkers undergo ?-eliminative cleavage to release the native drug with predictable half-lives ranging from a few hours to over 1 y; however, half-life extension becomes limited by the renal elimination rate of the circulating carrier. An approach to overcoming this constraint is to use noncirculating, biodegradable s.c. implants as drug carriers that are stable throughout the duration of drug release. Here, we use ?-eliminative linkers to both tether drugs to and cross-link PEG hydrogels, and demonstrate tunable drug release and hydrogel erosion rates over a very wide range. By using one ?-eliminative linker to tether a drug to the hydrogel, and another ?-eliminative linker with a longer half-life to control polymer degradation, the system can be coordinated to release the drug before the gel undergoes complete erosion. The practical utility is illustrated by a PEG hydrogel–exenatide conjugate that should allow once-a-month administration, and results indicate that the technology may serve as a generic platform for tunable ultralong half-life extension of potent therapeutics. PMID:23345437

Ashley, Gary W.; Henise, Jeff; Reid, Ralph; Santi, Daniel V.

2013-01-01

246

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

PubMed

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. PMID:25265364

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

2014-10-24

247

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

2014-10-01

248

Logical enzyme triggered (LET) layer-by-layer nanocapsules for drug delivery system  

NASA Astrophysics Data System (ADS)

Breast cancer is the second leading cause of morbidity and mortality among women in the United States. Early detection and treatment methods have resulted in 100% 5-year survival rates for stage 0-I breast cancer. Unfortunately, the 5-year survival rate of metastatic breast cancer (stage IV) is reduced fivefold. The most challenging issues of metastatic breast cancer treatment are the ability to selectively target the adenoma and adenocarcinoma cells both in their location of origin and as they metastasize following initial treatment. Multilayer/Layer-by-Layer (LbL) nanocapsules have garnered vast interest as anticancer drug delivery systems due to their ability to be easily modified, their capacity to encapsulate a wide range of chemicals and proteins, and their improved pharmacokinetics. Multilayer nanocapsule formation requires the layering of opposing charged polyelectrolytic polymers over a removable core nanoparticle. Our goal is to have a programmable nanocapsules degrade only after receiving and validating specific breast cancer biomarkers. The overall objective is to fabricate a novel programmable LbL nanocapsule with a specific logical system that will enhance functions pertinent to drug delivery systems. Our central hypothesis is that LbL technology coupled with extracellular matrix (ECM) protein substrates will result in a logical enzyme triggered LbL nanocapsule drug delivery system. This platform represents a novel approach toward a logically regulated nano-encapsulated cancer therapy that can selectively follow and deliver chemotherapeutics to cancer cells. The rationale for this project is to overcome a crucial limitation of existing drug delivery systems where chemotherapeutic can be erroneously delivered to non-carcinogenic cells.

Kelley, Marie-Michelle

249

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

2014-01-01

250

Issues and challenges in developing ruminal drug delivery systems  

Microsoft Academic Search

Ruminants have a specialised digestive system that contains anaerobic bacteria and protozoa capable of digesting the cellulosic materials that are so common in plant materials. In addition, their distinct digestive system can change the metabolism and mode of action of some nutrients, medicines or other bioactive materials when delivered orally or may provide opportunities for alternative oral dosing strategies. In

Th. F Vandamme; K. J Ellis

2004-01-01

251

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

2014-01-01

252

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

2013-01-01

253

Hydrogel-Based Colloidal Polymeric System for Protein and Drug Delivery: Physical and Chemical Characterization, Permeability Control and Applications  

Microsoft Academic Search

The use of polymeric nanoparticles as drug carriers is receiving an increasing amount of attention both in academia and industry.\\u000a The development of suitable delivery systems for protein drugs with high molecular weights and short half-lives is of current\\u000a interest. In addition, nanoparticles have a number of potential applications in drug and vaccine delivery as well as gene\\u000a therapy applications.

Ales Prokop; Evgenii Kozlov; Gianluca Carlesso; Jeffrey M. Davidson

254

Konjac glucomannan and konjac glucomannan/xanthan gum mixtures as excipients for controlled drug delivery systems. Diffusion of small drugs.  

PubMed

Konjac glucomannan (KGM), alone or in combination with xanthan gum (XG), was evaluated as main component of systems capable of controlling the diffusion of small molecules with a view of their use in drug delivery. To provide the study with enough general character, KGM batches were obtained from the three main areas of excipient harmonization (Europe, USA and Japan). The rheological evaluation at physiological temperature of KGM (0.5%, w/v) aqueous dispersions, with or without XG at different ratios, showed significant variability among the three KGMs owing to differences in the acetylation degree. The Japanese and European varieties of KGM synergically interact with XG giving rise to gel formation; the synergism being maximum at a 1:1 ratio. By contrast, the American KGM does not show such effect forming only viscous solutions. Drug diffusion coefficients of theophylline and diltiazem HCl, with different molecular size and net charge, were evaluated in systems containing KGM/XG ratio 1:1. KGM/XG systems were more efficient than the XG alone dispersion for controlling drug diffusion of small molecules because of the gel formation. These results point out the potential of mixtures of some KGM types with XG to develop delivery systems capable of maintaining physical integrity and drug release control for up to 8-h period. PMID:17804182

Alvarez-Manceñido, Felipe; Landin, Mariana; Lacik, Igor; Martínez-Pacheco, Ramón

2008-02-12

255

Multiparticulate Formulation .. Approach to Colon Specific Drug Delivery: Current Perspectives  

Microsoft Academic Search

Colon specific drug delivery has gained increased importance not just for the delivery of drugs for the treatment of local diseases associated with the colon but also as potential site for the systemic delivery of therapeutic peptide and proteins. To achieve successful colon targeted drug delivery, a drug needs to be protected from degradation, release and\\/or absorption in the upper

Laila Fatima; Ali Asghar; Sajeev Chandran

256

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

2009-07-01

257

A microfluidic reciprocating intracochlear drug delivery system with reservoir and active dose control  

PubMed Central

Reciprocating microfluidic drug delivery, as compared to steady or pulsed infusion, has unique features which may be advantageous in many therapeutic applications. We have previously described a device, designed for wearable use in small animal models, which periodically infuses then withdraws a sub-microliter volume of drug solution to and from the endogenous fluid of the inner ear. This delivery approach results in zero net volume of liquid transfer while enabling mass transport of compounds to the cochlea by means of diffusion and mixing. We report here on an advanced wearable delivery system aimed at further miniaturization and complex dose protocols. Enhancements to the system include the incorporation of a planar micropump to generate reciprocating flow and a novel drug reservoir which maintains zero net volume delivery and permits programmable modulation of the drug concentration in the infused bolus. The reciprocating pump is fabricated from laminated polymer films and employs a miniature electromagnetic actuator to meet the size and weight requirements of a head-mounted in vivo guinea pig testing system. The reservoir comprises a long microchannel in series with a micropump, connected in parallel with the reciprocating flow network. We characterized in vitro the response and repeatability of the planar pump and compared the results with a lumped element simulation. We also characterized the performance of the reservoir, including repeatability of dosing and range of dose modulation. Acute in vivo experiments were performed in which the reciprocating pump was used to deliver a test compound to the cochlea of anesthetized guinea pigs to evaluate short-term safety and efficacy of the system. These advances are key steps toward realization of an implantable device for long-term therapeutic applications in humans. PMID:24302432

Kim, Ernest S.; Gustenhoven, Erich; Mescher, Mark J.; Pararas, Erin E. Leary; Smith, Kim A.; Spencer, Abigail J.; Tandon, Vishal; Borenstein, Jeffrey T.; Fiering, Jason

2014-01-01

258

Magnetically guided micro-droplet using biological magnetic material for smart drug delivery system.  

PubMed

Biodegradable polymer droplet containing magnetosome demonstrates active propulsion by magnetic field. Magnetosome is extracted from magnetotactic bacteria, AMB-1. Mixture of magnetosome and sodium alginate composes into droplet using the microfluidic device applied Plateau-Rayleigh instability principle. The magnetosome-contained droplet selects its route at the bifurcate microchannels by magnetic field. This shows tissue targeting potential of the proposed drug delivery system. PMID:25570227

Darong Oh; Suwon Lee; Jinhyuk Kim; Hongsoo Choi; Jongmo Seo; Kyo-In Koo

2014-08-01

259

A microfluidic reciprocating intracochlear drug delivery system with reservoir and active dose control.  

PubMed

Reciprocating microfluidic drug delivery, as compared to steady or pulsed infusion, has unique features which may be advantageous in many therapeutic applications. We have previously described a device, designed for wearable use in small animal models, that periodically infuses and then withdraws a sub-microliter volume of drug solution to and from the endogenous fluid of the inner ear. This delivery approach results in zero net volume of liquid transfer while enabling mass transport of compounds to the cochlea by means of diffusion and mixing. We report here on an advanced wearable delivery system aimed at further miniaturization and complex dosing protocols. Enhancements to the system include the incorporation of a planar micropump to generate reciprocating flow and a novel drug reservoir that maintains zero net volume delivery and permits programmable modulation of the drug concentration in the infused bolus. The reciprocating pump is fabricated from laminated polymer films and employs a miniature electromagnetic actuator to meet the size and weight requirements of a head-mounted in vivo guinea pig testing system. The reservoir comprises a long microchannel in series with a micropump, connected in parallel with the reciprocating flow network. We characterized in vitro the response and repeatability of the planar pump and compared the results with a lumped element simulation. We also characterized the performance of the reservoir, including repeatability of dosing and range of dose modulation. Acute in vivo experiments were performed in which the reciprocating pump was used to deliver a test compound to the cochlea of anesthetized guinea pigs to evaluate short-term safety and efficacy of the system. These advances are key steps toward realization of an implantable device for long-term therapeutic applications in humans. PMID:24302432

Kim, Ernest S; Gustenhoven, Erich; Mescher, Mark J; Pararas, Erin E Leary; Smith, Kim A; Spencer, Abigail J; Tandon, Vishal; Borenstein, Jeffrey T; Fiering, Jason

2014-02-21

260

Emulsomes Meet S-layer Proteins: An Emerging Targeted Drug Delivery System.  

PubMed

Here, the use of emulsomes as a drug delivery system is reviewed and compared with other similar lipidic nanoformulations. In particular, we look at surface modification of emulsomes using S-layer proteins, which are self-assembling proteins that cover the surface of many prokaryotic organisms. It has been shown that covering emulsomes with a crystalline S-layer lattice can protect cells from oxidative stress and membrane damage. In the future, the capability to recrystallize S-layer fusion proteins on lipidic nanoformulations may allow the presentation of binding functions or homing protein domains to achieve highly specific targeted delivery of drug-loaded emulsomes. Besides the discussion on several designs and advantages of composite emulsomes, the success of emulsomes for the delivery of drugs to fight against viral and fungal infections, dermal therapy, cancer, and autoimmunity is summarized. Further research might lead to smart, biocompatible emulsomes, which are able to protect and reduce the side effects caused by the drug, but at the same time are equipped with specific targeting molecules to find the desired site of action. PMID:25697368

Ucisik, Mehmet H; Sleytr, Uwe B; Schuster, Bernhard

2015-01-01

261

Crosslinked soy protein films and their application as ophthalmic drug delivery system.  

PubMed

In this research, the potential of soy protein (SPI) based-films as drug delivery devices for ocular therapy was developed. Hence, crosslinked films with a natural and non-cytotoxic crosslinking agent, genipin (Gen), coated with poly(lactic acid) (PLA), were prepared. Filmogenic solutions were loaded with timolol maleate (TM) as a model drug, to be used as drug delivery devices, a novel application for this material. The mechanical properties of the films were studied, observing that with the presence of PLA coating, more rigid materials with improved properties were obtained. Furthermore, the release behavior of TM was evaluated in aqueous medium, it being influenced by the degree of film crosslinking. Furthermore, it was determined that PLA coating decreased TM release rate compared to that of uncoated films. Similarly, this behavior was observed via indirect estimation of the release by assessing the hypotensive effectiveness of the films by in-vivo assays. Through intraocular pressure (IOP) determination tests in rabbits, it was demonstrated that, through the use of high crosslinked and coated films, a significant decrease in IOP could be achieved for prolonged time periods. These results suggest that the use of soy protein-based films as drug delivery systems is highly suitable. PMID:25842110

González, Agustín; Tártara, Luis I; Palma, Santiago D; Alvarez Igarzabal, Cecilia I

2015-06-01

262

Vaginal films for drug delivery.  

PubMed

Vaginal dosage forms have been studied in relation to many drugs as the vagina presents several advantages as a site for drug delivery, such as large surface area, rich blood supply, avoidance of the first-pass effect, relatively high permeability to several drugs, and self-insertion. Traditional vaginal dosage forms have been associated with disadvantages such as low residence time and discomfort and have been surpassed by newly designed drug delivery systems, particularly those based on bioadhesive polymers. Vaginal films are solid dosage forms that rapidly dissolve in contact with vaginal fluids and are unlikely to be associated with leakage and messiness. They have been studied for some female genital problems, aiming either contraceptive, antimicrobial, or microbicide effects. Precise and complex processes of manufacturing and characterization are required to achieve successful film formulation. Although scarce, the available user's acceptability studies show promising results. Vaginal films gather a lack of opportunities for both therapeutic and prophylactic actions, and therefore should be considered when designing and developing new vaginal drug delivery systems. PMID:23649325

Machado, Rita M; Palmeira-de-Oliveira, Ana; Martinez-De-Oliveira, José; Palmeira-de-Oliveira, Rita

2013-07-01

263

Development of Tri-component Copolymer Rods as Implantable Drug Delivery Systems for Liver Cancer Therapy  

Microsoft Academic Search

Tri-component copolymers of poly(?-caprolactone)- random-poly(D,L-lactide)-block-poly(ethylene glycol)-blockpoly( ?-caprolactone)-random-poly(D,L-lactide)\\u000a (PLCA-PEGPLCA or PLEC) were used as a material to develop cylindrical polymeric rods and were used as the implantable drug\\u000a delivery system. PLEC was successfully synthesized and the copolymer ratio and molecular weight were controllable. Trypan\\u000a blue was selected as a model drug and the release profiles of trypan blue were carried out

N. Nasongkla; P. Akarajiratun; S. Hongeng

264

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

2012-01-01

265

Recent advances in ocular drug delivery.  

PubMed

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

2013-11-01

266

Fabrication and evaluation of cationic exchange nanofibers for controlled drug delivery systems.  

PubMed

The number of ion exchange fibers in development has increased over the last several years. However, few studies have reported the use ion-exchange fibers in drug delivery system. In this study polystyrene nanofiber ion exchangers (PSNIE) were fabricated by electrospinning techniques, crosslinking and sulfonation. The degree of crosslinking and the ion exchange capacity (IEC) were determined. The morphology and diameter of the nanofiber mats were analyzed using scanning electron microscopy (SEM). Five cationic model drugs (dextromethorphan, chlorpheniramine, diphenhydramine, propranolol and salbutamol) were loaded into PSNIE. The loading capacity, release and release kinetics of the exchangers were investigated. PSNIE were successfully prepared by electrospinning and were allowed to crosslink for 10 min, resulting in a maximum IEC of 2.86±0.1 meq/g dry PSNIE. The diameter of the fibers after sulfonation was 464±35 nm. Dextromethorphan provided the highest loading in PSNIE while diphenhydramine gave the highest percentage release in both simulated gastric and intestinal fluid (SGF and SIF). The release kinetics of all drugs in SGF and SIF provided the best fit with the particle diffusion model. Our results showed that the development of a PSNIE-based drug delivery system was successful, and PSNIE were able to control drug release. PMID:23623792

Nitanan, Todsapon; Akkaramongkolporn, Prasert; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Panomsuk, Suwannee; Opanasopit, Praneet

2013-06-25

267

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

2011-01-01

268

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

2014-01-01

269

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

PubMed

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

2013-12-01

270

An encapsulated drug delivery system for recalcitrant urinary tract infection.  

PubMed

One of the hallmarks of urinary tract infection, a serious global disease, is its tendency to recur. Uropathogenic bacteria can invade cells lining the bladder, where they form longer-term intracellular reservoirs shielded from antibiotics, re-emerging at a later date to initiate flare-ups. In these cases, only lengthy systemic antibiotic treatment can eradicate all the reservoirs. Yet, long courses of antibiotics are not ideal, as they can lead to side effects and an increase in antibiotic resistance. Moreover, most antibiotics lose some potency by the time they reach the bladder, and many cannot permeate cells, so they cannot access intracellular reservoirs. Here, using coaxial electrohydrodynamic forming, we developed novel core-shell capsules containing antibiotics as a prototype for a future product that could be infused directly into the bladder. Gentamicin was encapsulated in a polymeric carrier (polymethylsilsesquioxane) and these capsules killed Enterococcus faecalis, a common chronic uropathogen, in vitro in a dose-responsive, slow-release manner. Capsules containing a fluorescent tracer dye in place of gentamicin penetrated human bladder cells and released their dye cargo with no apparent toxicity, confirming their ability to successfully permeate cells. These results suggest that such antibiotic capsules could prove useful in the treatment of recalcitrant UTI. PMID:24068180

Labbaf, Sheyda; Horsley, Harry; Chang, Ming-Wei; Stride, Eleanor; Malone-Lee, James; Edirisinghe, Mohan; Rohn, Jennifer L

2013-12-01

271

Comet Assay: A Method to Evaluate Genotoxicity of Nano-Drug Delivery System  

PubMed Central

Introduction Drug delivery systems could induce cellular toxicity as side effect of nanomaterials. The mechanism of toxicity usually involves DNA damage. The comet assay or single cell gel electrophoresis (SCGE) is a sensitive method for detecting strand damages in the DNA of a cell with applications in genotoxicity testing and molecular epidemiology as well as fundamental research in DNA damage and repair. Methods In the current study, we reviewed recent drug delivery researches related to SCGE. Results We found that one preference for choosing the assay is that comet images may result from apoptosis-mediated nuclear fragmentation. This method has been widely used over the last decade in several different areas. Overall cells, such as cultured cells are embedded in agarose on a microscope slide, lysed with detergent, and treated with high salt. Nucleoids are supercoiled DNA form. When the slide is faced to alkaline electrophoresis any breakages present in the DNA cause the supercoiling to relax locally and loops of DNA extend toward the anode as a ‘‘comet tail’’. Conclusion This article provides a relatively comprehensive review upon potentiality of the comet assay for assessment of DNA damage and accordingly it can be used as an informative platform in genotoxicity studies of drug delivery systems. PMID:23678412

Vandghanooni, Somayeh; Eskandani, Morteza

2011-01-01

272

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.

2003-12-01

273

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.

274

pH-enzyme di-dependent chronotherapeutic drug delivery system of theophylline for nocturnal asthma.  

PubMed

The purpose of this research work was to develop and evaluate a chronotherapeutic based colon-targeted drug delivery system of theophylline (THEO) exploiting pH-enzyme sensitive property for the prevention of episodic attack of asthma in early morning. Guar gum microspheres of theophylline were prepared by emulsification technique. Coating of microspheres was performed using solvent evaporation method with pH sensitive Eudragit(®) polymers. The particle size and surface morphology, entrapment efficiency and degree of swelling of microspheres were examined. The in vitro drug release studies were performed in pH progression medium and also in the presence of 2% rat caecal content. Theophylline was efficiently microencapsulated in guar gum microspheres at different polymer concentrations (1-4%). Fourier transform infrared (FT-IR)-spectroscopy confirmed the intermolecular interactions between guar gum and glutaraldehyde. Coating of guar gum microspheres by Eudragit led to decelerate the in vitro drug release of THEO. Moreover in vitro drug release studies also performed with 2% rat caecal content showed marked increment in drug release. The controlled release of THEO after a lag time was achieved with developed formulation for chronotherapeutic delivery. The pH dependent solubility behavior of Eudragit and gelling properties of guar gum are found to be responsible for delaying the release. PMID:21297298

Soni, Murari Lal; Namdeo, Kamta Prasad; Jain, Sunil Kumar; Gupta, Manish; Dangi, Jawahar Singh; Kumar, Manoj; Dangi, Yuvraj Singh

2011-01-01

275

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

2014-01-01

276

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.

2013-01-01

277

Comparison of high-resolution ultrasonic resonator technology and Raman spectroscopy as novel process analytical tools for drug quantification in self-emulsifying drug delivery systems  

Microsoft Academic Search

Self-emulsifying drug delivery systems (SEDDS) are complex mixtures in which drug quantification can become a challenging task. Thus, a general need is given for novel analytical methods and a particular interest lies in those techniques with the potential for process monitoring. This article aims to compare Raman spectroscopy with high-resolution ultrasonic resonator technology (URT) for drug quantification in SEDDS. Herein

Cordula Stillhart; Martin Kuentz

278

Enzyme responsive drug delivery system based on mesoporous silica nanoparticles for tumor therapy in vivo  

NASA Astrophysics Data System (ADS)

To reduce the toxic side effects of traditional chemotherapeutics in vivo, we designed and constructed a biocompatible, matrix metalloproteinases (MMPs) responsive drug delivery system based on mesoporous silica nanoparticles (MSNs). MMPs substrate peptide containing PLGLAR (sensitive to MMPs) was immobilized onto the surfaces of amino-functionalized MSNs via an amidation reaction, serving as MMPs sensitive intermediate linker. Bovine serum albumin was then covalently coupled to linker as end-cap for sealing the mesopores of MSNs. Lactobionic acid was further conjugated to the system as targeting motif. Doxorubicin hydrochloride was used as the model anticancer drug in this study. A series of characterizations revealed that the system was successfully constructed. The peptide-functionalized MSNs system demonstrated relatively high sensitivity to MMPs for triggering drug delivery, which was potentially important for tumor therapy since the tumor’s microenvironment overexpressed MMPs in nature. The in vivo experiments proved that the system could efficiently inhibit the tumor growth with minimal side effects. This study provides an approach for the development of the next generation of nanotherapeutics toward efficient cancer treatment.

Liu, Yun; Ding, Xingwei; Li, Jinghua; Luo, Zhong; Hu, Yan; Liu, Junjie; Dai, Liangliang; Zhou, Jun; Hou, Changjun; Cai, Kaiyong

2015-04-01

279

Nano-niosomes as nanoscale drug delivery systems: an illustrated review.  

PubMed

The field of nanochemistry research has shown a great progress in the developing of novel nanocarriers as potential drug delivery systems. Niosome is a class of molecular cluster formed by self-association of non-ionic surfactants in an aqueous phase. The unique structure of niosome presents an effective novel drug delivery system (NDDS) with ability of loading both hydrophilic and lipophilic drugs. Numerous research articles have been published in scientific journals, reporting valuable results of individual case studies in this context. However, surveying and discussing the recent, rapidly growing reported studies along with their theoretical principals is required for the fully understanding and exploring the great potential of this approach. To this aim, we have provided an illustrated and comprehensive study from the view of a supramolecular chemist, interested in the synthesizing and studying chemical aggregates on the nanoscale for the development of nanotechnological clusters including niosomes. First, a connectional review of the molecular structure and physicochemical properties of niosome forming non-ionic surfactants and additive agents have been discussed. Second, a systematic survey of niosome preparation and loading methods, administration routes, characterization of niosomes, their toxicity studies and mechanism of drug release; used in recent articles have been performed. PMID:24747765

Moghassemi, Saeid; Hadjizadeh, Afra

2014-07-10

280

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

1990-01-01

281

Nanomedicine and drug delivery: a mini review  

NASA Astrophysics Data System (ADS)

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

Mirza, Agha Zeeshan; Siddiqui, Farhan Ahmed

2014-02-01

282

Eudraginated polymer blends: a potential oral controlled drug delivery system for theophylline.  

PubMed

Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl(®)) formulation. Asmanyl(®) tablets showed faster absorption (t(max) 4.0 h) compared to the TPH formulation showing a t(max) value of 8.0 h. The C(max) and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl(®), revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline. PMID:22472450

Emeje, Martins; John-Africa, Lucy; Isimi, Yetunde; Kunle, Olobayo; Ofoefule, Sabinus

2012-03-01

283

Nanoparticle-cored dendrimers: functional hybrid nanocomposites as a new platform for drug delivery systems.  

PubMed

Nanoparticle-cored dendrimers (NCDs) are now offering themselves as versatile carriers because of their colloidal stability, tunable membrane properties and ability to encapsulate or integrate a broad range of drugs and molecules. This kind of hybrid nanocomposite aims to combine the advantages of stimuli-responsive dendritic coatings, in order to regulate the drug release behaviour under different conditions and improve the biocompatibility and in vivo half-time circulation of the inorganic nanoparticles. Size, surface chemistry and shape are key nanocarrier properties to evaluate. Here, we have reviewed the most recent advances of NCDs in drug delivery systems, compared their behaviour with non-dendritic stabilized nanoparticles and highlighted their challenges and promising applications in the future. PMID:25566989

Brunetti, V; Bouchet, L M; Strumia, M C

2015-02-19

284

A new delivery system for auristatin in STxB-drug conjugate therapy.  

PubMed

A key challenge in anticancer therapy is to gain control over the biodistribution of cytotoxic drugs. The most promising strategy consists in conjugating drugs to tumor-targeting carriers, thereby combining high cytotoxic activity and specific delivery. To target Gb3-positive cancer cells, we exploit the non-toxic B-subunit of Shiga toxin (STxB). Here, we have conjugated STxB to highly potent auristatin derivatives (MMA). A former linker was optimized to ensure proper drug-release upon reaching reducing environments in target cells, followed by a self-immolation step. Two conjugates were successfully obtained, and in vitro assays demonstrated the potential of this targeting system for the selective elimination of Gb3-positive tumors. PMID:25847766

Batisse, Cornélie; Dransart, Estelle; Ait Sarkouh, Rafik; Brulle, Laura; Bai, Siau-Kun; Godefroy, Sylvie; Johannes, Ludger; Schmidt, Frédéric

2015-05-01

285

Polymeric micelles as a drug delivery system enhance cytotoxicity of vinorelbine through more intercellular accumulation.  

PubMed

Polymeric micelles had been used as an efficacious carrier system for anti-cancer drug delivery. However, it is not clear whether the molecular mechanism of drug encapsulated in micelles is same as free drug. In this study, the mechanism of vinorelbine loaded in glycol-phosphatidylethanolamine (PEG-PE) micelles (M-Vino) on tumor cells was investigated. Compared with free vinorelbine (Free Vino), M-Vino was more effective in inhibiting the growth of tumor cells in vitro, inducing G(2)/M phase arrest and apoptosis of tumor cells. M-Vino showed a faster entry and higher accumulation in 4T1 cells than free vinorelbine. Therefore, M-Vino destabilized microtubules, induced cell death, and enhanced its cytotoxicity through more intercellular accumulation of vinorelbine. PMID:20307251

Lu, Xiaoyan; Zhang, Fayun; Qin, Lei; Xiao, Fengying; Liang, Wei

2010-05-01

286

Nanoparticle-cored dendrimers: functional hybrid nanocomposites as a new platform for drug delivery systems  

NASA Astrophysics Data System (ADS)

Nanoparticle-cored dendrimers (NCDs) are now offering themselves as versatile carriers because of their colloidal stability, tunable membrane properties and ability to encapsulate or integrate a broad range of drugs and molecules. This kind of hybrid nanocomposite aims to combine the advantages of stimuli-responsive dendritic coatings, in order to regulate the drug release behaviour under different conditions and improve the biocompatibility and in vivo half-time circulation of the inorganic nanoparticles. Size, surface chemistry and shape are key nanocarrier properties to evaluate. Here, we have reviewed the most recent advances of NCDs in drug delivery systems, compared their behaviour with non-dendritic stabilized nanoparticles and highlighted their challenges and promising applications in the future.

Brunetti, V.; Bouchet, L. M.; Strumia, M. C.

2015-02-01

287

Optimization of Drug Delivery Systems for Intraperitoneal Therapy to Extend the Residence Time of the Chemotherapeutic Agent  

PubMed Central

Intraperitoneal (IP) chemotherapy is an effective way of treating peritoneal carcinomatosis of colorectal origin after complete cytoreduction. Although IP therapy has been already performed for many years, no standardized treatment design has been developed in terms of schedule, residence time, drug, or carrier solution. Because of the fast clearance of the conventional intravenous (IV) drug delivery systems used for IP therapy, a lot of research is performed to optimize IP drug delivery and extend the residence time of the cytotoxic agent in the peritoneal cavity. This paper reviews the recent advances made in drug delivery systems for IP chemotherapy, discussing the use of microparticles, nanoparticles, liposomes, micelles, implants, and injectable depots for IP delivery. PMID:23589707

De Smet, L.; Ceelen, W.; Remon, J. P.; Vervaet, C.

2013-01-01

288

Design, development and optimization of oral colon targeted drug delivery system of azathioprine using biodegradable polymers.  

PubMed

The present study was aimed at designing a microflora triggered colon targeted drug delivery system (MCDDS) based on swellable polysaccharide, Sterculia gum in combination with biodegradable polymers with a view to specifically deliver azathioprine in the colonic region for the treatment of IBD with reduced systemic toxicity. The microflora degradation properties of Sterculia gum was investigated in rat caecal phosphate buffer medium. The polysaccharide tablet cores were coated to different film thicknesses with blends of Eudragit RLPO and chitosan and overcoated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid, SGF (pH 1.2), simulated intestinal fluid, SIF (pH 6.8) and simulated colonic fluid, SCF (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the Sterculia gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora activated environment. The degradation of chitosan was the rate-limiting factor for drug release in the colon. Drug release from the MCDDS was directly proportional to the concentration of the pore former (chitosan), but inversely related to the Eudragit RLPO coating thickness. PMID:23167303

Nath, Bipul; Nath, L K

2013-01-01

289

In vivo drug release behavior in dogs from a new colon-targeted delivery system  

Microsoft Academic Search

The colon-targeted delivery capsule (CTDC), a new capsule-type dosage form for colonic delivery of drugs, was investigated for the in vivo drug release behavior in dogs. A CTDC formulation with prednisolone as a model drug and theophylline as a marker substance for gastric emptying was prepared for this study. The enteric-coated capsule (ECC) formulation with a similar composition was also

Takashi Ishibashi; Harumi Hatano; Masao Kobayashi; Masakazu Mizobe; Hiroyuki Yoshino

1999-01-01

290

Local Intravascular Drug Delivery: In Vitro Comparison of Three Catheter Systems  

SciTech Connect

Purpose: The aim of this in vitro study was to compare different catheter systems for local drug delivery with respect to the penetration depth of a biotin marker solution delivered into the vessel wall. Methods: Post-mortem carotid arteries from pigs were locally infused with a biotin solution using three different catheter systems. With all catheters (microporous balloon catheter, hydrogel-coated balloon catheter, and spiral balloon catheter) we used the same pressure of 405 kPa (4 atm) and infusion times of 60, 90, and 300 sec. After infusion the arteries were histologically prepared and stained using a biotin-specific method. With a light microscope an observer, blinded to the catheter type, scored the amount of biotin within the vessel wall, measured as staining intensity, and the penetration depth of the biotin. Results: Delivery with the hydrogel-coated balloon catheter was limited to the intima and the innermost parts of the media. The spiral balloon and microporous balloon catheter showed both a deeper penetration and a larger amount of delivered biotin compared with the hydrogel catheter, with a slightly deeper penetration using the microporous catheter. The penetration depth showed a correlation with infusion time for the spiral balloon and microporous catheters, but not for the hydrogel-coated catheter. Conclusion: Different catheter designs lead to different patterns of local drug delivery. The differences in penetration depth and amount of the substance delivered to the vessel wall should be known and might be useful for targeting specific areas within the vessel wall.

Alfke, Heiko; Wagner, Hans-Joachim; Calmer, Christian; Klose, Klaus Jochen [Department of Diagnostic Radiology, University Hospital, Baldingerstrasse, D-35033 Marburg (Germany)

1998-01-15

291

Multiple drug delivery hydrogel system for spinal cord injury repair strategies.  

PubMed

The multifactorial pathological progress of spinal cord injury (SCI) is probably the main reason behind the absence of efficient therapeutic approaches. Hence, very recent highlights suggest the use of new multidrug delivery systems capable of local controlled release of therapeutic agents. In this work, a biocompatible hydrogel-based system was developed as multiple drug delivery tool, specifically designed for SCI repair strategies. Multiple release profiles were achieved by loading gel with a combination of low and high steric hindrance molecules. In vitro, in vivo and ex vivo release studies showed an independent combination of fast diffusion-controlled kinetics for smaller molecules together with slow diffusion-controlled kinetics for bigger ones. A preserved functionality of loaded substances was always achieved, confirming the absence of any chemical stable interactions between gel matrix and loaded molecules. Moreover, the relevant effect of the cerebrospinal fluid flux dynamics on the drug diffusion in the spinal cord tissue was here revealed for the first time: an oriented delivery of the released molecules in the spinal cord tract caudally to the gel site is demonstrated, thus suggesting a more efficient gel positioning rostrally to the lesion. PMID:22227024

Perale, Giuseppe; Rossi, Filippo; Santoro, Marco; Peviani, Marco; Papa, Simonetta; Llupi, Dorina; Torriani, Paola; Micotti, Edoardo; Previdi, Sara; Cervo, Luigi; Sundström, Erik; Boccaccini, Aldo R; Masi, Maurizio; Forloni, Gianluigi; Veglianese, Pietro

2012-04-30

292

Multilayer encapsulated mesoporous silica nanospheres as an oral sustained drug delivery system for the poorly water-soluble drug felodipine.  

PubMed

We used a combination of mesoporous silica nanospheres (MSN) and layer-by-layer (LBL) self-assembly technology to establish a new oral sustained drug delivery system for the poorly water-soluble drug felodipine. Firstly, the model drug was loaded into MSN, and then the loaded MSN were repeatedly encapsulated by chitosan (CHI) and acacia (ACA) via LBL self-assembly method. The structural features of the samples were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The encapsulating process was monitored by zeta-potential and surface tension measurements. The physical state of the drug in the samples was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The influence of the multilayer with different number of layers on the drug release rate was studied using thermal gravimetric analysis (TGA) and surface tension measurement. The swelling effect and the structure changes of the multilayer were investigated to explore the relationship between the drug release behavior and the state of the multilayer under different pH conditions. The stability and mucosa adhesive ability of the prepared nanoparticles were also explored. After multilayer coating, the drug release rate was effectively controlled. The differences in drug release behavior under different pH conditions could be attributed to the different states of the multilayer. And the nanoparticles possessed good stability and strong mucosa adhesive ability. We believe that this combination offers a simple strategy for regulating the release rate of poorly water-soluble drugs and extends the pharmaceutical applications of inorganic materials and polymers. PMID:25492202

Hu, Liang; Sun, Hongrui; Zhao, Qinfu; Han, Ning; Bai, Ling; Wang, Ying; Jiang, Tongying; Wang, Siling

2015-02-01

293

Nanoparticles for Targeted Drug Delivery  

E-print Network

Nanoparticles were synthesized and modified for target drug delivery. The research involved the aqueous synthesis of near infrared (NIR) sensitive Au-Au2S nanoparticles. An anti-cancer drug (cis-platin) ...

Chow, Gan-Moog

294

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

2011-01-01

295

The application of EDTA in drug delivery systems: doxorubicin liposomes loaded via NH4EDTA gradient  

PubMed Central

The applications of ethylenediaminetetraacetic acid (EDTA) have been expanded from the treatment of heavy metal poisoning to chelation therapies for atherosclerosis, heart disease, and cancers, in which EDTA reduces morbidity and mortality by chelating toxic metal ions. In this study, EDTA was used in a drug delivery system by adopting an NH4EDTA gradient method to load doxorubicin into liposomes with the goal of increasing therapeutic effects and decreasing drug-related cytotoxicity. The particle size of the optimum NH4EDTA gradient liposomes was 79.4±1.87 nm, and the entrapment efficiency was 95.54%±0.59%. In vitro studies revealed that liposomes prepared using an NH4EDTA gradient possessed long-term stability and delayed drug release. The in vivo studies also showed the superiority of the new doxorubicin formulation. Compared with an equivalent drug dose (5 mg/kg) prepared by (NH4)2SO4 gradient, NH4EDTA gradient liposomes showed no significant differences in tumor inhibition ratio, but cardiotoxicity and liposome-related immune organ damage were lower, and no drug-related deaths were observed. These results show that use of the NH4EDTA gradient method to load doxorubicin into liposomes could significantly reduce drug toxicity without influencing antitumor activity. PMID:25120359

Song, Yanzhi; Huang, Zhenjun; Song, Yang; Tian, Qingjing; Liu, Xinrong; She, Zhennan; Jiao, Jiao; Lu, Eliza; Deng, Yihui

2014-01-01

296

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

PubMed

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

2013-12-01

297

Towards nanoporous polymer thin film-based drug delivery systems , Vincent K.S. Hsiao a  

E-print Network

online 26 September 2008 Keywords: Porous polymer films Drug delivery Rhodamine B Ultrasound Pulsatile of Rhodamine B (drug model molecules) on both porous and non-porous thin films proved that nanopores enhanced Rhodamine B. Its ability to adsorb drug model molecules as well as the enhanced release of loaded molecules

298

Integration of drug, protein, and gene delivery systems with regenerative medicine.  

PubMed

Regenerative medicine has the potential to drastically change the field of health care from reactive to preventative and restorative. Exciting advances in stem cell biology and cellular reprogramming have fueled the progress of this field. Biochemical cues in the form of small molecule drugs, growth factors, zinc finger protein transcription factors and nucleases, transcription activator-like effector nucleases, monoclonal antibodies, plasmid DNA, aptamers, or RNA interference agents can play an important role to influence stem cell differentiation and the outcome of tissue regeneration. Many of these biochemical factors are fragile and must act intracellularly at the molecular level. They require an effective delivery system, which can take the form of a scaffold (e.g., hydrogels and electrospun fibers), carrier (viral and nonviral), nano- and microparticle, or genetically modified cell. In this review, we will discuss the history and current technologies of drug, protein, and gene delivery in the context of regenerative medicine. Next, we will present case examples of how delivery technologies are being applied to promote angiogenesis in nonhealing wounds or prevent angiogenesis in age related macular degeneration. Finally, we will conclude with a brief discussion of the regulatory pathway from bench to bedside for the clinical translation of these novel therapeutics. PMID:25787742

Lorden, Elizabeth R; Levinson, Howard M; Leong, Kam W

2015-04-01

299

Daunorubicin-TiO2 nanocomposites as a "smart" pH-responsive drug delivery system.  

PubMed

Daunorubicin (DNR) has a broad spectrum of anticancer activity, but is limited in clinical application due to its serious side effects. The aim of this study was to explore a novel "smart" pH-responsive drug delivery system (DDS) based on titanium dioxide (TiO(2)) nanoparticles for its potential in enabling more intelligent controlled release and enhancing chemotherapeutic efficiency of DNR. DNR was loaded onto TiO(2) nanoparticles by forming complexes with transition metal titanium to construct DNR-TiO(2) nanocomposites as a DDS. DNR was released from the DDS much more rapidly at pH 5.0 and 6.0 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. DNR-TiO(2) nanocomposites induced remarkable improvement in anticancer activity, as demonstrated by flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and nuclear 4',6-diamidino- 2-phenylindole staining. Furthermore, the possible signaling pathway was explored by western blot. For instance, in human leukemia K562 cells, it was demonstrated that DNR-TiO(2) nanocomposites increase intracellular concentration of DNR and enhance its anticancer efficiency by inducing apoptosis in a caspase-dependent manner, indicating that DNR-TiO(2) nanocomposites could act as an efficient DDS importing DNR into target cancer cells. These findings suggest that "smart" DNR delivery strategy is a promising approach to cancer therapy. PMID:22275838

Zhang, Haijun; Wang, Cailian; Chen, Baoan; Wang, Xuemei

2012-01-01

300

[Optimization and characterization of curcumin-piperine dual drug loaded self-microemulsifying drug delivery system by simplex lattice design].  

PubMed

The objective of the study was to prepare and evaluate the quality of curcumin-piperinedual drug loaded self-microemulsifying drug delivery system(Cur-PIP-SMEDDS). Simplex lattice design was constructed using optimal oil phase, surfactant and co-surfactant concentration as independent variables, and the curcumin and piperine were used as model drugs to optimize Cur-PIP-SMEDDS formulation. In the present study, the drug loadings of curcumin and piperine, mean particle size of Cur-PIP-SMEDDS were made as indicators, and the experiment design, model building and response surface analysis were established using Design Expert 8. 06 software to optimize and verify the composition of SMEDDS formulation. The quality of Cur-PIP-SMEDDS was evaluated by observing the appearance status, transmission electron microscope micrographs and determining particle diameter, electric potential, drug entrapment efficiency and drug loading of it. As a result, the optimal formulation of SMEDDS was CapryoL 90-Cremophor RH40-TranscutoL HP (10:60:30). The appearance of Cur-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation with uniform particle size distribution. The mean size of microemulsion droplet formed from Cur-PIP-SMEDDS was 15.33 nm, the drug loading of SMEDDS for Cur and PIP were 40.90 mg · g(-1) and 0.97 mg · g(-1), respectively, the drug entrapment efficiency were 94.98% and 90.96%, respectively. The results show that Cur-PIP-SMEDDS can increase the solubility and stability of curcumin significantly, in the expectation of enhancing the bioavailability of it. Taken together, these findings can provide the reference to a preferable choice of the Cur formulation and contribute to therapeutic application in clinical research. PMID:25751942

Li, Qiu-Ping; Dai, Jun-Dong; Zhai, Wen-Wen; Jiang, Qiao-Li

2014-10-01

301

Chronomodulated drug delivery system of urapidil for the treatment of hypertension  

PubMed Central

Introduction: Hypertension is a disease which shows circadian rhythm in the pattern of two peaks, one in the evening at about 7pm and other in the early morning between 4 am to 8 am. Conventional therapies are incapable to target those time points when actually the symptoms get worsened. To achieve drug release at two time points, chronomodulated delivery system may offer greater benefits. Materials and methods: The chronomodulated system comprised of dual approach; immediate release granules (IRG) and pulsatile release mini-tablets (PRM) filled in the hard gelatin capsule. The mini-tablets were coated using Eudragit S-100 which provided the lag time. To achieve the desired release, various parameters like coating duration and coat thickness were studied. The immediate release granules were evaluated for micromeritical properties and drug release, while mini-tablets were evaluated for various parameters such as hardness, thickness, friability, weight variation, drug content, and disintegration time and in-vitro drug release. Compatibility of drug-excipient was checked by fourier transform infrared spectroscopy and Differential scanning calorimetry studies and pellets morphology was done by Scanning electron microscopy studies. Results: The in-vitro release profile suggested that immediate release granules gives drug release within 20 min at the time of evening attack while the programmed pulsatile release was achieved from coated mini-tablets after a lag time of 9hrs, which was consistent with the demand of drug during early morning hour attack. Pellets found to be spherical in shape with smooth surface. Moreover compatibility studies illustrated no deleterious reaction between drug and polymers used in the study. Conclusions: The dual approach of developed chronomodulated formulation found to be satisfactory in the treatment of hypertension.

Chaudhary, Sona S.; Patel, Hetal K.; Parejiya, Punit B.; Shelat, Pragna K.

2015-01-01

302

Bioresponsive matrices in drug delivery  

Microsoft Academic Search

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

Jin-Oh You; Dariela Almeda; George JC Ye; Debra T Auguste

2010-01-01

303

The formalism of fractal aggregation phenomena of colloidal drug delivery systems.  

PubMed

Classical Newtonian Physics and Euclidean Geometry are currently used to describe biological phenomena and the processes of drug formulation, which are characterized by homogeneity and linearity. On the other hand, at the mesoscopic level, the principles and the laws of physics are quite different from the Classical Newtonian Physics and Euclidean approach especially at nanoscale dimension. The investigation of the aggregation process of liposomes is of paramount importance due to their applications in pharmaceutical nanotechnology as drug delivery systems and as membrane models, in biosciences. The physical stability and the aggregation process of colloidal systems as well as the surface phenomena are described using the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. The elucidation of the dimensionality of liposome aggregates obeys the fractal approach because the aggregation phenomena are irreversible. This approach can be correlated with the extended DLVO theory, which includes the hydration energy, too. PMID:21774618

Pippa, Natassa; Demetzos, Costas; Danezis, Emmanuel

2012-03-01

304

A pH-dependent colon targeted oral drug delivery system using methacrylic acid copolymers  

Microsoft Academic Search

Lactose-based placebo tablets were coated using various combinations of two methacrylic acid copolymers, Eudragit® L100-55 and Eudragit® S100, by spraying from aqueous systems. The Eudragit® L100-55–Eudragit® S100 combinations (w\\/w) studied were 1:0, 4:1, 3:2, 1:1, 2:3, 1:4, 1:5 and 0:1. The coated tablets were tested in vitro for their suitability for pH dependent colon targeted oral drug delivery. The same

M. Zahirul I Khan; Željko Prebeg; Nevenka Kurjakovi?

1999-01-01

305

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

2007-01-01

306

Smart drug delivery systems: back to the future vs. clinical reality.  

PubMed

Recent advances in nanotechnology and material science have re-ignited interest in drug delivery research. Arguably, however, hardly any of the systems developed and strategies proposed are really relevant for shaping the future (clinical) face of the nanomedicine field. Consequently, as outlined in this commentary, instead of making ever more carrier materials, and making nanomedicine both science-fiction and fiction-science, we should try to come up with rational and realistic concepts to make nanomedicines work, in particular in patients. PMID:23485339

Lammers, Twan

2013-09-15

307

Polysaccharides Based Colon Specific Drug delivery: A Review  

Microsoft Academic Search

Although oral delivery has become a widely accepted route of administration of therapeutic drugs, the gastrointestinal tract presents several formidable barriers to drug delivery. The delivery of drugs to the colon has a number of therapeutic implications in the field of drug deliv ery. In the recent times, the colon specific delive ry systems are also gaining importance not only

Ravi Kumar; M. B. Patil; Sachin R. Patil; Mahesh S. Paschapur

308

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

PubMed

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

2014-05-01

309

Investigations into Thermally Mediated Drug Delivery Using a Preclinical System for MRI-Guided Focused Ultrasound  

NASA Astrophysics Data System (ADS)

The objective of this research was to investigate the use of a preclinical system for MRI-guided focused ultrasound to achieve MRI-controlled hyperthermia and thermally-mediated drug delivery in vivo. Here we report results from ten rabbits, where a focused ultrasound (FUS) beam was scanned in a circular trajectory to heat 10-15 mm diameter regions in normal thigh to 43 °C for 20-30 minutes. MRI thermometry was used for closed-loop feedback control to achieve temporally and spatially uniform heating. Lyso-thermosensitive pegylated liposomal doxorubicin (ThermoDox®, Celsion Corporation, Columbia, MD) was infused intravenously during hyperthermia, and the tissue doxorubicin concentration was measured by the fluorescence intensity of homogenized tissue samples from heated and unheated thigh, obtained 2 hours after heating. Closed-loop control of FUS hyperthermia using MRI thermometry achieved temperature distributions with mean, T90 and T10 of 42.9 °C, 41.0 °C and 44.8 °C across the 10 mm diameter target, varying ±0.9 °C (SD) over 20 min. Drug concentrations in heated regions were, on average 15.3±8.1 (SD) times higher than in the unheated contralateral thigh. The results show the feasibility of using MRI-controlled FUS hyperthermia for preclinical studies of thermally mediated drug delivery with temperature-sensitive liposomes.

Staruch, Robert; Chopra, Rajiv; Hynynen, Kullervo

2011-09-01

310

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

2014-01-01

311

Multiscale modeling of transdermal drug delivery  

Microsoft Academic Search

This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis

Jee Eun Rim

2006-01-01

312

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

PubMed

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

2008-01-01

313

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.

314

Prospective of guar gum and its derivatives as controlled drug delivery systems  

Microsoft Academic Search

Guar gum is a non-ionic polysaccharide that is found abundantly in nature and has many properties desirable for drug delivery applications. However, due to its high swelling characteristics in aqueous solution, the use of guar gum as delivery carriers is limited. Guar gum can be modified by derivatization, grafting and network formation to improve its property profile for a wide

M. Prabaharan

2011-01-01

315

Self-nanoemulsifying drug delivery systems for oral insulin delivery: in vitro and in vivo evaluations of enteric coating and drug loading.  

PubMed

This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w/w), were readily dispersed in water to form nanoemulsions of 35 nm and vesicles of 300 nm. The association efficiency of non-complexed insulin in the dispersed SNEDDS was 18.6%, and was increased to 73.1% for insulin-phospholipid complex (at 10% loading level). The morphology of the dispersed SNEDDS changed from nanoemulsion droplets to vesicular structures with increasing complex loading levels. A pH-dependent insulin release profile was observed for SNEDDS filled into capsules coated with the enteric polymer, Eudragit(®) L100. Using a Caco-2 cell model, it was observed that the transport of insulin was enhanced by factors of 7.7- and 9.3- for SNEDDS loaded with 2.5 and 10% complex, respectively. In healthy fasted rats, administration of SNEDDS (10% complex) filled in enteric-coated capsules produced a 2.7-fold and 3.4-fold enhancement in the relative bioavailability and glucose reduction, respectively. This study shows the effectiveness of combining SNEDDS (loaded with insulin-phospholipid complex) with enteric-coated capsules for enhancing the oral absorption and efficacy of insulin. PMID:25455781

Li, Ping; Tan, Angel; Prestidge, Clive A; Nielsen, Hanne Mørck; Müllertz, Anette

2014-12-30

316

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

2014-01-01

317

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

2013-01-01

318

Combination of chemotherapy and photodynamic therapy using graphene oxide as drug delivery system.  

PubMed

Previous research indicated that graphene oxide (GO) can be used to deliver photosensitive anticancer drug, Hypocrellin A (HA), in photodynamic therapy (PDT). However, the anticancer activity of HA was obviously decreased after been loaded on GO. To solve this problem, a chemotherapy drug, 7-ethyl-10-hydroxycamptothecin (SN-38), was co-loaded on the HA loaded GO (HA/SN-38/GO) as a multimodal carrier for the synergistic combination of PDT and chemotherapy for cancer. In vitro results showed that the combination therapy exhibited a synergistic antiproliferative effect compared with PDT and chemotherapy alone. Therefore, HA/SN-38/GO delivery system has the potential to offer dual therapies for the synergistic combination of PDT and chemotherapy for the treatment of cancer. PMID:24792568

Zhou, Lin; Zhou, Lin; Wei, Shaohua; Ge, Xuefeng; Zhou, Jiahong; Jiang, Huijun; Li, Fuyou; Shen, Jian

2014-06-01

319

Bioactivity in glass/PMMA composites used as drug delivery system.  

PubMed

Gentamicin sulfate has been incorporated in composites prepared from a SiO2-CaO-P2O5 bioactive glass and polymethylmethacrylate. Data showed that these materials could be used as drug delivery system, keeping the bioactive behavior of the glass. The composites supply high doses of the antibiotic during the first hours when they are soaked in simulated body fluid (SBF). Thereafter, a slower drug release is produced, supplying 'maintenance' doses until the end of the experiment. The gentamicin release rate is related with the ionic Ca2+ and H3O+ exchange between composite and SBF. The porous structure of the composites allows the growth of hydroxycarbonate apatite on the surface and into the pores. PMID:11246964

Arcos, D; Ragel, C V; Vallet-Regí, M

2001-04-01

320

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

2011-01-01

321

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

322

Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations  

PubMed Central

Vesicles that are specifically designed to overcome the stratum corneum barrier in intact skin provide an efficient transdermal (systemic or local) drug delivery system. They can be classified into two main groups according to the mechanisms underlying their skin interaction. The first group comprises those possessing highly deformable bilayers, achieved by incorporating edge activators to the bilayers or by mixing with certain hydrophilic solutes. The vesicles of this group act as drug carriers that penetrate across hydrophilic pathways of the intact skin. The second group comprises those possessing highly fluid bilayers, owing to the presence of permeation enhancers. The vesicles of this group can act as carriers of drugs that permeate the skin after the barrier of the stratum corneum is altered because of synergistic action with the permeation enhancers contained in the vesicle structure. We have included a detailed overview of the different mechanisms of skin interaction and discussed the most promising preclinical applications of the last five years of Transfersomes® (IDEA AG, Munich, Germany), ethosomes, and invasomes as carriers of antitumoral and anti-inflammatory drugs applied by the topical route. PMID:23986634

Romero, Eder Lilia; Morilla, Maria Jose

2013-01-01

323

Enhanced oral bioavailability of dexibuprofen by a novel solid self-emulsifying drug delivery system (SEDDS).  

PubMed

The main objective of this study was to prepare a solid form of lipid-based self-emulsifying drug delivery system (SEDDS) by spray drying liquid SEDDS with an inert solid carrier Aerosil 200 to improve the oral bioavailability of poorly water-soluble drug dexibuprofen. The liquid SEDDS was a system that consisted of dexibuprofen, Labrasol, Capryol 90 and Labrafil M 1944 CS. The particle size analysis revealed no difference in the z-average particle diameter of the reconstituted emulsion between liquid and solid SEDDS. The solid SEDDS was characterized by SEM, DSC and XRD studies. In vivo results of solid SEDDS and dexibuprofen powder in rats at the dose of 10mg/kg showed that the initial plasma concentrations of drug in solid SEDDS were significantly higher than those of dexibuprofen powder (P<0.05). The solid SEDDS gave significantly higher AUC and Cmax than did dexibuprofen powder (P<0.05). In particular, the AUC of solid SEDDS was about twofold higher than that of dexibuprofen powder. Our results suggested that this solid SEDDS could be used as an effective oral solid dosage form to improve the bioavailability of poorly water-soluble drug dexibuprofen. PMID:19298857

Balakrishnan, Prabagar; Lee, Beom-Jin; Oh, Dong Hoon; Kim, Jong Oh; Hong, Myung Ja; Jee, Jun-Pil; Kim, Jung Ae; Yoo, Bong Kyu; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon

2009-08-01

324

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

PubMed

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

2014-09-01

325

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.

2009-01-01

326

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

2012-01-01

327

Response Surface Methodology for the Optimization of Celecoxib Self-microemulsifying Drug delivery System  

PubMed Central

The aim of the present study was to prepare, evaluate and optimize, self micro emulsifying drug delivery system of celecoxib. A 3 factor, 3 level factorial design was used for the optimization procedure with different amounts of Labrafil 2609 WL, Labrasol, and Cremophor EL as the independent variables. The response variable was selected on particle size (nm) of the droplets after dilution in 0.1N HCl. Particle size of the self micro-emulsifying drug delivery system depends on the quantity of above three independent variables. Three different levels of each independent variable were selected for the optimization. Mathematical equation and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the particle size after dilution was, Particle size (Y)= +27.83+76.07×A-23.62×B-43.83×C+52.72×A2+9.82×B2+27.20×C2-14.52×A×B-32.38×A×C+12.1×B×C, where, A=Labrafil 2609 WL, B= Labrasol, C= Cremophor EL, Y= particle size. The optimized model predicted a particle size of 28.33 nm with 0.16ml of labrafil 2609 WL, 0.17ml Labrasol and 0.22ml of Cremophor EL. The observed response were in close agreement with the predicted values of the optimized formulation. This demonstrates the reliability of the optimization procedure in predicting particle size of self microemulsifying delivery system for celecoxib. PMID:21394253

Shaji, Jessy; Lodha, Shital

2008-01-01

328

Determination of the physical state of norethindrone acetate containing transdermal drug delivery systems by isothermal microcalorimetry, X-ray diffraction, and optical microscopy  

Microsoft Academic Search

Transdermal drug delivery systems (TDDS) enable a controlled drug delivery to the skin. The low permeability of the stratum corneum necessitates a high drug concentration of the polymeric matrix and often requires supersaturation. This, however, promotes crystallisation of supersaturated systems. Isothermal microcalorimetry at 25°C, polarisation light microscopy, and X-ray powder diffraction (XRPD) were used to characterise the crystal growth of

Silvia Latsch; Torsten Selzer; Lothar Fink; Jörg Kreuter

2004-01-01

329

A novel pulsed drug-delivery system: polyelectrolyte layer-by-layer coating of chitosan–alginate microgels  

PubMed Central

Purpose The aim of this report was to introduce a novel “core-membrane” microgel drug-delivery device for spontaneously pulsed release without any external trigger. Methods The microgel core was prepared with alginate and chitosan. The semipermeable membrane outside the microgel was made of polyelectrolytes including polycation poly(allylamine hydrochloride) and sodium polystyrene sulfonate. The drug release of this novel system was governed by the swelling pressure of the core and the rupture of the outer membrane. Results The size of the core-membrane microgel drug-delivery device was 452.90 ± 2.71 ?m. The surface charge depended on the layer-by-layer coating of polyelectrolytes, with zeta potential of 38.6 ± 1.4 mV. The confocal microscope exhibited the layer-by-layer outer membrane and inner core. The in vitro release profile showed that the content release remained low during the first 2.67 hours. After this lag time, the cumulative release increased to 80% in the next 0.95 hours, which suggested a pulsed drug release. The in vivo drug release in mice showed that the outer membrane was ruptured at approximately 3 to 4 hours, as drug was explosively released. Conclusion These data suggest that the encapsulated substance in the core-membrane microgel delivery device can achieve a massive drug release after outer membrane rupture. This device was an effective system for pulsed drug delivery. PMID:23486565

Zhou, Guichen; Lu, Ying; Zhang, He; Chen, Yan; Yu, Yuan; Gao, Jing; Sun, Duxin; Zhang, Guoqing; Zou, Hao; Zhong, Yanqiang

2013-01-01

330

Novel Platforms for Oral Drug Delivery  

Microsoft Academic Search

The aim of this review is to provide the reader general and inspiring prospects on recent and promising fields of innovation\\u000a in oral drug delivery. Nowadays, inventive drug delivery systems vary from geometrically modified and modular matrices, more\\u000a close to “classic” pharmaceutical manufacturing processes, to futuristic bio micro-electro-mechanical systems (bioMEMS), based\\u000a on manufacturing techniques borrowed from electronics and other fields.

P. Colombo; F. Sonvico; G. Colombo; R. Bettini

2009-01-01

331

Coating metals on cellulose–polypyrrole composites: A new route to self-powered drug delivery system  

Microsoft Academic Search

A self-powered drug delivery system based on cellulose–polypyrrole (PPy) composite film was developed. The cellulose–PPy composite film was prepared by deposition of drug-contained PPy film on the inner and outer surfaces of a porous cellulose film. After coating a thin layer of active metal such as magnesium on the one side of the composite film, the drug stored in the

Dongtao Ge; Xiaoning Ru; Shimin Hong; Shuhui Jiang; Jing Tu; Jun Wang; Aifeng Zhang; Shan Ji; Vladimir Linkov; Bin Ren; Wei Shi

2010-01-01

332

Stimuli sensitive polymers and self regulated drug delivery systems: a very partial review.  

PubMed

Since the early days of the Journal of Controlled Release, there has been considerable interest in materials that can release drug on an "on-demand" basis. So called "stimuli-responsive" and "intelligent" systems have been designed to deliver drug at various times or at various sites in the body, according to a stimulus that is either endogenous or externally applied. In the past three decades, research along these lines has taken numerous directions, and each new generation of investigators has discovered new physicochemical principles and chemical schemes by which the release properties of materials can be altered. No single review could possibly do justice to all of these approaches. In this article, some general observations are made, and a partial history of the field is presented. Both open loop and closed loop systems are discussed. Special emphasis is placed on stimuli-responsive hydrogels, and on systems that can respond repeatedly. It is argued that the most success at present and in the foreseeable future is with systems in which biosensing and actuation (i.e. drug delivery) are separated, with a human and/or cybernetic operator linking the two. PMID:24984012

Siegel, Ronald A

2014-09-28

333

Facile fabrication of redox-responsive thiol-containing drug delivery system via RAFT polymerization.  

PubMed

A novel kind of redox-responsive polymeric drug delivery system has been designed and prepared successfully through the coupling of the multithiol branched polymers and thiol-containing drugs. The branched poly((S-(4-vinyl) benzyl S'-propyltrithiocarbonate)-co-(poly(ethylene glycol) methacrylate)) (poly(VBPT-co-PEGMA)) was synthesized by one-pot reaction via reversible addition-fragmentation chain transfer (RAFT) copolymerization. Subsequently, the hydrophobic thiol-containing anticancer drug 6-mercaptopurine (MP) was conjugated to poly(VBPT-co-PEGMA) by thiol-disulfide exchange reaction, resulting in the formation of poly(VBPT-co-PEGMA)-S-S-MP conjugate. Due to its amphiphilicity, poly(VBPT-co-PEGMA)-S-S-MP conjugate self-assembled into amphiphilic micelles in aqueous solution. Under a reductive environment, the disassembly of polymeric micelles resulted in the MP release. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements demonstrated that the poly(VBPT-co-PEGMA)-S-S-MP micelles could be taken up by Raji cells (a Burkitt lymphoma cell line). The viability of the Raji cells incubated with the glutathione (GSH) mediated poly(VBPT-co-PEGMA)-S-S-MP micelles was investigated by Cell Counting Kit-8 (CCK-8) assay. The experimental results showed that the viability of the glutathione monoester (GSH-OEt) pretreated cells was lower than that without pretreatment, while the viability of the buthionine sulfoximine (BSO) pretreated cells was higher than that without pretreatment. The poly(VBPT-co-PEGMA)-S-S-MP micelles could induce the apoptosis of Raji cells, and the apoptosis behavior was dose-dependent. This redox-responsive polymer-drug conjugate provides a promising platform for the delivery of thiol-containing biological molecules. PMID:24598057

Zhuang, Yuanyuan; Su, Yue; Peng, Yu; Wang, Dali; Deng, Hongping; Xi, Xiaodong; Zhu, Xinyuan; Lu, Yunfeng

2014-04-14

334

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

PubMed

Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the varying electric pulse amplitude, the amount of topical and transdermal drug delivery to the skin can be controlled. Furthermore, the newly developed monitoring system provides a tool for rapid real-time determination of both, transdermal and topical delivery, when the delivered molecule is fluorescent. PMID:24113487

Blagus, Tanja; Markelc, Bostjan; Cemazar, Maja; Kosjek, Tina; Preat, Veronique; Miklavcic, Damijan; Sersa, Gregor

2013-12-28

335

Lyophilised wafers as a drug delivery system for wound healing containing methylcellulose as a viscosity modifier.  

PubMed

Lyophilised wafers have potential as drug delivery systems for suppurating wounds. A dual series of wafers made from low molecular weight sodium alginate (SA) and xanthan gum (XG) respectively, modified with high molecular weight methylcellulose (MC) were produced. The swelling and flow properties of these wafers on model suppurating surfaces were both qualitatively and quantitatively investigated. The wafers instantaneously adhered to the surfaces, absorbing water and transforming from glassy, porous solids to highly viscous gels. The rate at which this occurred varied for the series studied with clear distinctions between the behaviour of SA and XG systems. For SA wafers there was a distinct relationship between the flow-rate and MC content. Increased amounts of MC decreased the rate at which the SA wafers flowed across a model gelatine surface. Flow rheometry was used to quantify the effect of increased MC content on both series of wafers and for the SA series, highlighted a substantial increase in apparent viscosity as a function of incremental increases in MC content. These results reflected those from the gelatine model. Observations of the reluctance of a swollen, unmodified XG wafer to flow compared with the relative ease of unmodified, low molecular weight SA was attributed to the yield stress characteristic of xanthan gels. XG is known to exhibit complex, loosely bound network structures in solution via the association of helical backbone structures. The inclusion of sodium fluorescein as a visible model for a soluble drug highlighted the potential of lyophilised wafers as useful drug delivery systems for suppurating wounds. PMID:15652198

Matthews, K H; Stevens, H N E; Auffret, A D; Humphrey, M J; Eccleston, G M

2005-01-31

336

Bioavailability assessment of hydroxymethylglutaryl coenzyme A reductase inhibitor utilizing pulsatile drug delivery system: a pilot study.  

PubMed

Abstract Chronotherapy or pulsatile drug delivery system could be achieved by increasing drug plasma concentration exactly at the time of disease incidence. Cholesterol synthesis shows a circadian rhythm being high at late night and early in the morning. Simvastatin (SIM) inhibits hydroxymethylglutaryl coenzyme A reductase, which is responsible for cholesterol synthesis. In this study, SIM lipid-based formulation filled in gelatin capsules and coated with aqueous Eudragit® S100 dispersion was prepared for chronotherapeutic treatment of hypercholesterolemia. The pharmacokinetic parameters of SIM capsules were studied in human volunteers after a single oral dose and compared with that of Zocor® tablets as a reference in a randomized cross-over study. Pharmacokinetic parameters such as AUC0-?, Cmax, Tmax, t1/2 and elimination rate constant were determined from plasma concentration-time profile for both formulations. The tested formulation had the ability to delay drug absorption and provide higher drug concentrations from 3 up to 10?h after oral administration compared to that of commercial tablets. The data in this study revealed that the prepared formulation could be effective in chronotherapeutic treatment of hypercholesterolemia. Moreover, the tested formulation was found to enhance SIM bioavailability by 29% over the reference tablets. PMID:25101831

Taha, Ehab I

2014-08-01

337

Self-Nanoemulsifying Drug Delivery System of Lutein: Physicochemical Properties and Effect on Bioavailability of Warfarin  

PubMed Central

Objective of present study was to prepare and characterize self-nanoemulsifying drug delivery system (SNEDDS) of lutein and to evaluate its effect on bioavailability of warfarin. The SNEDDS was prepared using an oil, a surfactant, and co-surfactants with optimal composition based on pseudo-ternary phase diagram. Effect of the SNEDDS on the bioavailability of warfarin was performed using Sprague Dawley rats. Lutein was successfully formulated as SNEDDS for immediate self-emulsification and dissolution by using combination of Peceol as oil, Labrasol as surfactant, and Transcutol-HP or Lutrol-E400 as co-surfactant. Almost complete dissolution was achieved after 15 min while lutein was not detectable from the lutein powder or intra-capsule content of a commercial formulation. SNEDDS formulation of lutein affected bioavailability of warfarin, showing about 10% increase in Cmax and AUC of the drug in rats while lutein as non-SNEDDS did not alter these parameters. Although exact mechanism is not yet elucidated, it appears that surfactant and co-surfactant used for SNEDDS formulation caused disturbance in the anatomy of small intestinal microvilli, leading to permeability change of the mucosal membrane. Based on this finding, it is suggested that drugs with narrow therapeutic range such as warfarin be administered with caution to avoid undesirable drug interaction due to large amount of surfactants contained in SNEDDS. PMID:24009877

Yoo, Juno; Baskaran, Rengarajan; Yoo, Bong-Kyu

2013-01-01

338

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

2005-01-01

339

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

PubMed

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

2015-02-01

340

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

PubMed

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

2010-01-01

341

Bleomycin Loaded Magnetite Nanoparticles Functionalized by Polyacrylic Acid as a New Antitumoral Drug Delivery System  

PubMed Central

Objective. To prepare, characterize, and analyze the release behavior of bleomycin-loaded magnetite nanoparticles (BLM-MNPs) coated with polyacrylic acid (PAA) as a new drug delivery system that can be specifically distributed in the tumor site. Methods. BLM-MNPs coated with PAA were prepared using a solvothermal approach. The particles were characterized using scanning electron microscope (SEM), vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FTIR). The loading and release behaviors of BLM-MNPs were examined by a mathematical formula and in vitro release profile at pH 7.5. Results. The sphere Fe3O4 nanoparticles with the size of approximately 30?nm exhibit a saturation magnetization of 87?emu/g. The noncoordinated carboxylate groups of PAA confer on the good dispersibility in the aqueous solution and lead to a good loading efficiency of BLM reaching 50% or higher. Approximately 98% of immobilized BLM could be released within 24?h, of which 22.4% was released in the first hour and then the remaining was released slowly and quantitatively in the next 23?hours. Conclusion. BLM-MNPs were prepared and characterized successfully. The particles show high saturation magnetization, high drug loading capacity, and favorable release property, which could contribute to the specific delivery and controllable release of BLM, and the BLM-MNPs could be a potential candidate for the development of treating solid tumors. PMID:23998124

2013-01-01

342

A thermal microjet system with tapered micronozzles fabricated by inclined UV lithography for transdermal drug delivery  

NASA Astrophysics Data System (ADS)

Transdermal drug delivery can be enabled by various methods that increase the permeability of the skin's outer barrier of stratum corneum, including skin exposure to heat and chemical enhancers, such as ethanol. Combining these approaches for the first time, in this study we designed a microdevice consisting of an array of microchambers filled with ethanol that is vaporized using an integrated microheater and ejected through a micronozzle contacting the skin surface. In this way, we hypothesize that the hot ethanol vapor can increase skin permeability upon contacting the skin surface. The tapered micronozzle and the microchamber designed for this application were realized using proximity-mode inclined rotational ultraviolet lithography, which facilitates easy fabrication of complex three-dimensional structures, convenient integration with other functional layers, low fabrication cost, and mass production. The resulting device had a micronozzle with an orifice inner and outer diameter of 220 and 320 µm, respectively, and an extruded height of 250 µm. When the microchamber was filled with an ethanol gel and activated, the resulting ethanol vapor jet increased the permeability of human cadaver epidermis to a model compound, calcein, by approximately 17 times, which is attributed to thermal and chemical disruption of stratum corneum structure. This thermal microjet system can serve as a tool not only for transdermal drug delivery, but also for a variety of biomedical applications.

Yoon, Yong-Kyu; Park, Jung-Hwan; Lee, Jeong-Woo; Prausnitz, Mark R.; Allen, Mark G.

2011-02-01

343

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

2006-01-01

344

Confocal Raman investigation of diffusion processes in monolithic type transdermal drug delivery systems.  

PubMed

Abstract Release from a transdermal drug delivery system (TDDS) can either be controlled by diffusion in the adhesive, by diffusion processes in the stratum corneum of the skin or a combination of both. In this study, diffusion processes in monolithic type TDDS were investigated using confocal Raman microscopy. An acrylic adhesive (Duro-Tak 180-129a), a rubber adhesive (Duro-Tak H1540) and a silicone adhesive (BIO-PSA 7-4202) were used. Skin permeation of the model drug Paeonol from these adhesives was investigated. Release studies on porcine cadaver skin were carried out. Solubility of Paeonol in the different adhesives was measured. Diffusion coefficients of the drug in the TDDSs were calculated from confocal Raman depth scans, the diffusion coefficient in the stratum corneum was calculated using tape stripping. Solubility of Paeonol in the acrylic adhesive was the highest with 30?g/L among the tested systems. Paeonol had a solubility of 6 and 9?g/L in the silicone and rubber based system. Diffusion coefficient rank order was BIO-PSA 7-4204?>?Duro-Tak 180-129a?>?Duro-Tak H1540. Release on porcine cadaver skin from the silicone was the highest followed by the rubber and the acrylic adhesive. During release studies on porcine skin with Duro-Tak H1540 no concentration gradient of Paeonol could be monitored in the Raman depth profiles, whereas in the stratum corneum an apparent diffusion gradient was detectable. Solubility of a drug in the adhesive dominated the release properties, high-diffusion coefficients of drugs in adhesives do not necessarily lead to high release rates from adhesives. PMID:24580682

Meyer, Stefanie; Heinsohn, Guido; Wolber, Rainer; Pörtner, Ralf; Nierle, Jens

2014-03-01

345

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

2011-01-01

346

Biotin-conjugated block copolymeric nanoparticles as tumor-targeted drug delivery systems  

Microsoft Academic Search

To achieve targeted drug delivery for chemotherapy, a ligand-mediated nanoparticulate drug carrier was designed, which could\\u000a identify a specific receptor on the surfaces of tumor cells. Biodegradable poly(ethylene oxide)\\/poly(?-caprolactone) (PEG\\/PCL)\\u000a amphiphilic block copolymers coupled to biotin ligands were synthesized with a variety of PEG\\/PCL compositions. Block copolymeric\\u000a nanoparticles harboring the anticancer drug paclitaxel were prepared via micelle formation in aqueous

So Yeon Kim; Seung Hea Cho; Young Moo Lee; Liang-Yin Chu

2007-01-01

347

Application of water-soluble diethylaminoethylcellulose in oral drug delivery systems  

Microsoft Academic Search

The aim of this work was to evaluate water-soluble cellulose derivatives with tertiary amino groups for controlled drug delivery in artificial gastric juices, as well as in bowel medium. Acetylsalicylic acid and p-acetaminophen were used as model drugs of acidic and non-ionic character, respectively. Tablets were prepared containing 86% (w\\/w) of the drug, lactose, polymeric component and 1% of magnesium

J Liesiene; J Matulioniene

2004-01-01

348

A novel folate-modified self-microemulsifying drug delivery system of curcumin for colon targeting  

PubMed Central

Background The objective of this study was to prepare, characterize, and evaluate a folate-modified self-microemulsifying drug delivery system (FSMEDDS) with the aim to improve the solubility of curcumin and its delivery to the colon, facilitating endocytosis of FSMEDDS mediated by folate receptors on colon cancer cells. Methods Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of curcumin-loaded SMEDDS was optimized by a simplex lattice experiment design. Then, three lipophilic folate derivatives (folate-polyethylene glycol-distearoylphosphatidylethanolamine, folate-polyethylene glycol-cholesteryl hemisuccinate, and folate-polyethylene glycol-cholesterol) used as a surfactant were added to curcumin-loaded SMEDDS formulations. An in situ colon perfusion method in rats was used to optimize the formulation of FSMEDDS. Curcumin-loaded FSMEDDS was then filled into colon-targeted capsules and the in vitro release was investigated. Cytotoxicity studies and cellular uptake studies was used in this research. Results The optimal formulation of FSMEDDS obtained with the established in situ colon perfusion method in rats was comprised of 57.5% Cremophor® EL, 32.5% Transcutol® HP, 10% Capryol™ 90, and a small amount of folate-polyethylene glycol-cholesteryl hemisuccinate (the weight ratio of folate materials to Cremophor EL was 1:100). The in vitro release results indicated that the obtained formulation of curcumin could reach the colon efficiently and release the drug immediately. Cellular uptake studies analyzed with fluorescence microscopy and flow cytometry indicated that the FSMEDDS formulation could efficiently bind with the folate receptors on the surface of positive folate receptors cell lines. In addition, FSMEDDS showed greater cytotoxicity than SMEDDS in the above two cells. Conclusion FSMEDDS-filled colon-targeted capsules are a potential carrier for colon delivery of curcumin. PMID:22275831

Zhang, Lin; Zhu, Weiwei; Yang, Chunfen; Guo, Hongxia; Yu, Aihua; Ji, Jianbo; Gao, Yan; Sun, Min; Zhai, Guangxi

2012-01-01

349

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

PubMed

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

2014-11-01

350

The Conjunctival Barrier in Ocular Drug Delivery  

Microsoft Academic Search

Within the context of topical and local drug delivery to the eye, the mammalian conjunctiva functions as a unique biological\\u000a barrier. Various model systems as in vitro tools have been refined and validated over the years to assess drug absorption\\u000a across the conjunctiva. Passive and active drug transport as well as endocytic routes of transconjunctival drug permeation\\u000a have been extensively

Hovhannes J. Gukasyan; Kwang-Jin Kim; Vincent H. L. Lee

351

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

PubMed

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

2011-08-01

352

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

PubMed

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

2013-05-13

353

In vivo evaluation of an oral self-microemulsifying drug delivery system (SMEDDS) for leuprorelin.  

PubMed

The objective of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) for the model peptide drug leuprorelin to prove a protective effect against luminal enzymatic metabolism. In order to incorporate leuprorelin into microemulsion droplets (o/w), the commercially available hydrophilic leuprolide acetate was modified by hydrophobic ion paring with sodium oleate. The obtained hydrophobic leuprolide oleate was dissolved in the SMEDDS formulation (30% (m/m) Cremophor EL, 30% (m/m) Capmul MCM, 10% (m/m) propylene glycol and 30% (m/m) Captex 355) in a concentration of 4 mg/g showing a mean droplet size of 50.1 nm when dispersed in a concentration of 1% (m/v) in phosphate buffer pH 6.8. The microemulsion was able to shield leuprolide oleate from enzymatic degradation by trypsin and ?-chymotrypsin, so that after 120 min 52.9% and 58.4%, respectively, of leuprolide oleate were still intact. Leuprolide acetate dissolved in an aqueous control solution was completely metabolized by trypsin within 60 min and by ?-chymotrypsin within 5 min. Moreover, an in vivo study in rats showed a 17.2-fold improved oral bioavailability of leuprolide oleate SMEDDS compared to a leuprolide acetate control solution. This is the first time, to our knowledge, that hydrophobic ion pairing is utilized in order to incorporate a peptide drug in SMEDDS and evidence of a protective effect of oil-in-water (o/w) microemulsion droplets against enzymatic degradation of a peptide drug was provided. According to these results, the system could be likely a novel platform technology to improve the oral bioavailability of peptide drugs. PMID:24879935

Hintzen, Fabian; Perera, Glen; Hauptstein, Sabine; Müller, Christiane; Laffleur, Flavia; Bernkop-Schnürch, Andreas

2014-09-10

354

Use of isothermal heat conduction microcalorimetry, X-ray diffraction, and optical microscopy for characterisation of crystals grown in steroid combination-containing transdermal drug delivery systems  

Microsoft Academic Search

The combined application of the steroids estradiol (E2) hemihydrate and norethindrone acetate (NEA) is desirable for hormone replacement therapy. Transdermal drug delivery systems (TDDS) enable a controlled delivery of these drugs to the skin. However, in order to attain high skin permeation rates the concentration of the dissolved drugs in the TDDSs has to be high. This often results in

Silvia Latsch; Torsten Selzer; Lothar Fink; Michael Horstmann; Jörg Kreuter

2004-01-01

355

Using in situ Raman spectroscopy to study the drug precipitation inhibition and supersaturation mechanism of Vitamin E TPGS from self-emulsifying drug delivery systems (SEDDS).  

PubMed

We are reporting a new methodology of using Raman spectroscopy for studying the drug surfactant interactions in self-emulsifying drug delivery systems (SEDDS). The physicochemical properties of surfactants could affect the performance of drugs from lipid delivery systems. Thus the purpose of our research was to study the drug surfactant interactions on a molecular level to understand the mechanism of supersaturation and precipitation inhibition. Two surfactants, Labrasol(®) and Vitamin E TPGS, were used to formulate several SEDDS. The optimized SEDDS were further evaluated by a kinetic solubility study and in situ Raman spectroscopy for two model drugs. It was found that both drugs precipitated from Labrasol(®) SEDDS whereas TPGS was able to inhibit precipitation and achieve high drug supersaturation levels. In situ Raman spectroscopy indicated that hydrogen bonding with TPGS was the main factor responsible for inhibiting precipitation. This study was able to correlate the structure and physicochemical properties of the drugs and surfactants to their ability to prevent drug precipitation. Our study brings up a possible new systematic approach by using Raman spectroscopy in the development and optimization of lipid based delivery systems. PMID:25767907

Raut, Shilpa; Karzuon, Basel; Atef, Eman

2015-05-10

356

Intranasal drug delivery for brain targeting.  

PubMed

Many drugs are not being effectively and efficiently delivered using conventional drug delivery approach to brain or central nervous system (CNS) due to its complexity. The brain and the central nervous system both have limited accessibility to blood compartment due to a number of barriers. Many advanced and effective approaches to brain delivery of drugs have emerged in recent years. Intranasal drug delivery is one of the focused delivery options for brain targeting, as the brain and nose compartments are connected to each other via the olfactory route and via peripheral circulation. Realization of nose to brain transport and the therapeutic viability of this route can be traced from the ancient times and has been investigated for rapid and effective transport in the last two decades. Various models have been designed and studied by scientists to establish the qualitative and quantitative transport through nasal mucosa to brain. The development of nasal drug products for brain targeting is still faced with enormous challenges. A better understanding in terms of properties of the drug candidate, nose to brain transport mechanism, and transport to and within the brain is of utmost importance. This review will discuss some pertinent issues to be considered and challenges to brain targeted intranasal drug delivery. A few marketed and investigational drug formulations will also be discussed. PMID:16305417

Vyas, Tushar K; Shahiwala, Aliasgar; Marathe, Sudhanva; Misra, Ambikanandan

2005-04-01

357

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

2012-01-01

358

Hydrosilylated Porous Silicon Particles Function as an Intravitreal Drug Delivery System for Daunorubicin  

PubMed Central

Abstract Purpose To evaluate in vivo ocular safety of an intravitreal hydrosilylated porous silicon (pSi) drug delivery system along with the payload of daunorubicin (DNR). Methods pSi microparticles were prepared from the electrochemical etching of highly doped, p-type Si wafers and an organic linker was attached to the Si-H terminated inner surface of the particles by thermal hydrosilylation of undecylenic acid. DNR was bound to the carboxy terminus of the linker as a drug-loading strategy. DNR release from hydrosilylated pSi particles was confirmed in the excised rabbit vitreous using liquid chromatography–electrospray ionization–multistage mass spectrometry. Both empty and DNR-loaded hydrosilylated pSi particles were injected into the rabbit vitreous and the degradation and safety were studied for 6 months. Results The mean pSi particle size was 30×46×15??m with an average pore size of 15?nm. Drug loading was determined as 22??g per 1?mg of pSi particles. An ex vivo drug release study showed that intact DNR was detected in the rabbit vitreous. An in vivo ocular toxicity study did not reveal clinical or pathological evidence of any toxicity during a 6-month observation. Hydrosilylated pSi particles, either empty or loaded with DNR, demonstrated a slow elimination kinetics from the rabbit vitreous without ocular toxicity. Conclusions Hydrosilylated pSi particles can host a large quantity of DNR by a covalent loading strategy and DNR can be slowly released into the vitreous without ocular toxicity, which would appear if an equivalent quantity of free drug was injected. PMID:23448595

Hartmann, Kathrin I.; Nieto, Alejandra; Wu, Elizabeth C.; Freeman, William R.; Kim, Jae Suk; Chhablani, Jay; Sailor, Michael J.

2013-01-01

359

Biodegradable nanoparticles mimicking platelet binding as a targeted and controlled drug delivery system.  

PubMed

This research aims to develop targeted nanoparticles as drug carriers to the injured arterial wall under fluid shear stress by mimicking the natural binding ability of platelets via interactions of glycoprotein Ib-alpha (GPIb?) of platelets with P-selectin of damaged endothelial cells (ECs) and/or with von Willebrand factor (vWF) of the subendothelium. Drug-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles were formulated using a standard emulsion method and conjugated with glycocalicin, the external fraction of platelet GPIb?, via carbodiimide chemistry. Surface-coated and cellular uptake studies in ECs showed that conjugation of PLGA nanoparticles, with GPIb, significantly increased nanoparticle adhesion to P-selectin- and vWF-coated surfaces as well as nanoparticle uptake by activated ECs under fluid shear stresses. In addition, effects of nanoparticle size and shear stress on adhesion efficiency were characterized through parallel flow chamber studies. The observed decrease in bound nanoparticle density with increased particle sizes and shear stresses is also explained through a computational model. Our results demonstrate that the GPIb-conjugated PLGA nanoparticles can be used as a targeted and controlled drug delivery system under flow conditions at the site of vascular injury. PMID:22172292

Kona, Soujanya; Dong, Jing-Fei; Liu, Yaling; Tan, Jifu; Nguyen, Kytai T

2012-02-28

360

Development and in vitro characterization of drug delivery system of rifapentine for osteoarticular tuberculosis  

PubMed Central

The study was to develop and evaluate the rifapentine-loaded poly(lactic acid-co-glycolic acid) (PLGA) microspheres (RPMs) for the treatment of osteoarticular tuberculosis to avoid critical side effects caused by oral regimens of antibiotics or intravenous antibiotics. The RPMs were spherical with rough surfaces, and elevated amounts of rifapentine in the formulation markedly increased the particle size and drug loading, while decreased the size distribution and entrapment efficiency. The highest drug loading and encapsulation efficiency of RPMs were 23.93%±3.93% and 88.49%±8.49%, respectively. After the initial rapid drug release, the release rate gradually decreased, and approximately 80% of the encapsulated rifapentine was released after 30 days of incubation. Moreover, RPMs could effectively inhibit the growth of Staphylococcus aureus. With increasing rifapentine content, the inhibition zones were continuously enlarged while the minimal inhibitory concentration values decreased. These results suggested that RPMs were bioactive and controlled release delivery systems for the treatment of osteoarticular tuberculosis. PMID:25834394

Wu, Jun; Zuo, Yi; Hu, Yunjiu; Wang, Jian; Li, Jidong; Qiao, Bo; Jiang, Dianming

2015-01-01

361

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

2013-01-01

362

Design and optimization of a new self-nanoemulsifying drug delivery system.  

PubMed

To improve the dissolution rate of ibuprofen, a model poorly water soluble drug, self-nanoemulsifying drug delivery systems (SNEDDS) were developed. Various surfactants and oils were screened as candidates for SNEDDS on the basis of droplet size of the resulting emulsions. The influence of the constituent structure, concentration and the composition of SNEDDS formulations, and the emulsifier HLB value, on the properties of the resulting emulsions was systematically investigated. Several SNEDDS formulations were employed to study the relationship between the emulsion droplet size and the dissolution rate of ibuprofen. The dissolution rate was accelerated by decreasing the nanoemulsion droplet size, and was significantly faster than that from a conventional tablet. The optimal SNEDDS formulation had a mean nanoemulsion droplet diameters of 58 nm in phosphate buffer, pH 6.8 (simulated intestinal fluid), and released ibuprofen more than 95% within 30 min. Therefore, these novel SNEDDS carriers appear to be useful for controlling the release rate of poorly water soluble drugs. PMID:19038395

Wang, Lijuan; Dong, Jinfeng; Chen, Jing; Eastoe, Julian; Li, Xuefeng

2009-02-15

363

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

2015-01-01

364

Application of Sterylglucoside-Containing Particles for Drug Delivery  

Microsoft Academic Search

Recent advances in biotechnology have promoted biomolecular targeting of drugs, peptides and genes in the treatment and management of major diseases and infections. Therapeutic development of drugs and delivery systems may have various objectives: Systemic drugs require optimal delivery and uptake at target sites; peptide drugs require alternative routes of administration, such as nasal or intestinal absorption; gene medicines need

Yoshie Maitani; Koji Nakamura; Kumi Kawano

365

Tuberculosis therapeutics: Engineering of nanomedicinal systems for local delivery of targeted drug cocktails  

NASA Astrophysics Data System (ADS)

In this thesis, a multifunctional nanocarrier drug delivery system was investigated and optimized to improve tuberculosis therapy by promoting the intracellular delivery of high payloads of antibiotics. To meet the needs of a patient population which continues to grow by close to 10 million people a year, innovative therapeutics must be formulated by robust and scalable processes. We use Flash NanoPrecipitation for the continuous precipitation of nanocarriers by block copolymer directed assembly, which enables the development of nanocarriers with tunable properties. Stable nanocarriers of Rifampicin and a hydrophobic Rifampicin prodrug have efficacy against tuberculosis in vitro that is equivalent to the soluble Rifampicin. To overcome poor in vivo efficacy of the recently discovered antitubercular drug SQ641, we co-encapsulate SQ641 and Cyclosporine A in a stable aqueous nanocarrier suspension, which enables drug administration and also enhances intracellular accumulation and antitubercular efficacy relative to SQ641 in solution. Since the mannose receptor is involved in the phagocytosis of tuberculosis bacilli, we modify the surface of nanocarriers with mannoside residues to target specific intracellular accumulation in macrophages. The surface density of mannoside terminated polyethylene glycol chains was controlled between 0 and 75% and in vitro cellular association reveals a 9% surface density is optimal for internalization mediated by the mannose receptor. We explore the preparation of large, porous aerosol carrier particles of with tunable deposition characteristics by spray freeze drying with ultrasonic atomization for direct dosing to the lungs. Nanocarriers are loaded at 3 - 50 wt% in mannitol particles with constant size, limited nanocarrier aggregation, and 63% dose delivered to the lungs, as determined by in vitro cascade impaction. There has been a lag in the development of new technologies to facilitate development and commercialization of therapeutic nanocarrier formulations. We present three translational technologies. (1) The intrinsic dissolution rates of drug nanocarriers are determined using a novel assay, based on high surface area lipid sink particles and magnetic separations, to improve in vitro/in vivo correlations. (2) The nanocarrier interaction with whole serum and the polymer surface conformation are correlated to in vivo clearance and general rules are proposed for the design of nanocarriers produced by Flash NanoPrecipitation with extended circulation times for targeted delivery. (3) In Hydrogen Bonding Coacervate Precipitation, polyethylene glycol coated nanocarriers are controllably flocculated with the addition of polyacids to enable rapid filtration and drying. In summary, this research outlines approaches to the customization of nanocarrier drug delivery systems to specifically improve outcomes in tuberculosis therapy. New assays and processing techniques for transitioning formulations from bench research to the clinic are developed. The methods are flexible and can be applied to target various diseases, coupled with rational design of nanocarrier payloads, surface functionality, and dosing route.

D'Addio, Suzanne M.

366

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

2009-08-03

367

Dissipative Particle Dynamics Method on PH-Responsive Polymeric Drug Delivery System  

NASA Astrophysics Data System (ADS)

The self-assembled morphologies formed by polymer in selective solvent could be potentially used as drug-delivery vehicles and has attracted great attention recently. In our work, the drug release mechanism of polymeric delivery vehicle (polymeric microsphere) is investigated with Dissipative particle dynamics simulation. Poly (Lactic Acid)-b-polyethylene glycol (PLA-b-PEG) diblock copolymer is the carrier while IBU is selected as the model drug. A core-shell spherical micelle with drug encapsulated in the core is obtained in our simulation. By changing the medium from neutral to acid, the drugs release via a diffuse mechanism. Both the formation mechanism of the encapsulant and the release mechanism for the drugs are studied in our work. For the formation process, it can be ascribed as the coalesce of the small clusters and the disperse of the drugs; while for the drug release behavior, the process can be divided for three stages: (1) swell of the polymeric carrier, (2) drug diffuse in the carrier and some acid molecules disperse into the carrier, (3) drug release towards the acid medium. Our results might provide a mesoscopic methodology for the evaluation and prediction for polymeric self-assemblies as a carrier for pharmaceutical interest.

Guo, Yingying

2013-03-01

368

Gene and drug delivery system and potential treatment into inner ear for protection and regeneration.  

PubMed

The most common type of hearing loss results from damage to the cochlea including lost hair cells (HCs) and spiral ganglion neurons (SGNs). In mammals, cochlear HC loss causes irreversible hearing impairment because this type of sensory cell cannot regenerate. The protection from SGN from degeneration has implications for cochlear implant to patients with severe deafness. This review summarizes the several treatments for HC regeneration based on experiments. We discuss how transgene expression of the neurotrophic factor can protect SGN from degeneration and describe potential new therapeutic interventions to reduce hearing loss. We also summarized viral vectors and introduced the gene and drug delivery system for regeneration and protection of cochlear HCs. Finally, we introduce the novel endoscopy we developed for local injection into cochlea. PMID:25339903

Kanzaki, Sho

2014-01-01

369

Therapeutic Trials Based on Combination of Drug Delivery System and Ultrasound  

NASA Astrophysics Data System (ADS)

The objective of this study is to show how therapeutically effective a combination of a drug delivery system (DDS) and ultrasound (US) is by introducing data from two related experiments. Fullerene (C60) was chemically modified by polyethylene glycol (PEG) for water-solubilization and tumour targeting. When the PEG-modified C60 was injected intravenously into tumour bearing mice, followed by US irradiation to the tumour site, a synergistic anti-tumour effect was observed. Following the intravenous injection of interferon (IFN) conjugated with pullulan which has an inherent affinity for the liver, and subsequent US irradiation to the liver, the activity level of an IFN-specific enzyme was significantly enhanced compared with that of the conjugate injection alone.

Tabata, Yasuhiko

2005-03-01

370

Gene and drug delivery system and potential treatment into inner ear for protection and regeneration  

PubMed Central

The most common type of hearing loss results from damage to the cochlea including lost hair cells (HCs) and spiral ganglion neurons (SGNs). In mammals, cochlear HC loss causes irreversible hearing impairment because this type of sensory cell cannot regenerate. The protection from SGN from degeneration has implications for cochlear implant to patients with severe deafness. This review summarizes the several treatments for HC regeneration based on experiments. We discuss how transgene expression of the neurotrophic factor can protect SGN from degeneration and describe potential new therapeutic interventions to reduce hearing loss. We also summarized viral vectors and introduced the gene and drug delivery system for regeneration and protection of cochlear HCs. Finally, we introduce the novel endoscopy we developed for local injection into cochlea. PMID:25339903

Kanzaki, Sho

2014-01-01

371

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

PubMed

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

2011-08-01

372

Magnetic Control of Potential Microrobotic Drug Delivery Systems: Nanoparticles, Magnetotactic Bacteria and Self-Propelled Microjets  

PubMed Central

Development of targeted drug delivery systems using magnetic microrobots increases the therapeutic indices of drugs. These systems have to be incorporated with precise motion controllers. We demonstrate closed-loop motion control of microrobots under the influence of controlled magnetic fields. Point-to-point motion control of a cluster of iron oxide nanoparticles (diameter of 250 nm) is achieved by pulling the cluster towards a reference position using magnetic field gradients. Magnetotactic bacterium (MTB) is controlled by orienting the magnetic fields towards a reference position. MTB with membrane length of 5 ?m moves towards the reference position using the propulsion force generated by its flagella. Similarly, self-propelled microjet with length of 50 ?m is controlled by directing the microjet towards a reference position by external magnetic torque. The microjet moves along the field lines using the thrust force generated by the ejecting oxygen bubbles from one of its ends. Our control system positions the cluster of nanoparticles, an MTB and a microjet at an average velocity of 190 ?m/s, 28 ?m/s, 90 ?m/s and within an average region-of-convergence of 132 ?m, 40 ?m, 235 ?m, respectively. PMID:24110932

Khalil, Islam S. M.; Magdanz, Veronika; Sanchez, Samuel; Schmidt, Oliver G.; Abelmann, Leon; Misra, Sarthak

2013-01-01

373

Drug Delivery Through the Skin: Molecular Simulations of Barrier Lipids to Design more Effective Noninvasive Dermal and Transdermal Delivery Systems for Small Molecules Biologics and Cosmetics  

SciTech Connect

The delivery of drugs through the skin provides a convenient route of administration that is often preferable to injection because it is noninvasive and can typically be self-administered. These two factors alone result in a significant reduction of medical complications and improvement in patient compliance. Unfortunately, a significant obstacle to dermal and transdermal drug delivery alike is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein and nucleotide therapeutic agents. Significant effort has already been devoted to obtain a functional understanding of the physical barrier properties imparted by the epidermis, specifically the membrane structures of the stratum corneum. However, structural observations of membrane systems are often hindered by low resolutions, making it difficult to resolve the molecular mechanisms related to interactions between lipids found within the stratum corneum. Several models describing the molecular diffusion of drug molecules through the stratum corneum have now been postulated, where chemical permeation enhancers are thought to disrupt the underlying lipid structure, resulting in enhanced permeability. Recent investigations using biphasic vesicles also suggested a possibility for novel mechanisms involving the formation of complex polymorphic lipid phases. In this review, we discuss the advantages and limitations of permeation-enhancing strategies and how computational simulations, at the atomic scale, coupled with physical observations can provide insight into the mechanisms of diffusion through the stratum corneum.

J Torin Huzil; S Sivaloganathan; M Kohandel; M Foldvari

2011-12-31

374

Controlled and continuous release ocular drug delivery systems: pros and cons.  

PubMed

Topical ocular drug administration is the most preferred route for treating conditions affecting the surface of the eye as well as anterior segment diseases; this is mainly due to the rapid and localised drug action and patient acceptability. However, the ocular bioavailability is typically less than 5% from conventional ophthalmic dosage forms such as eye drops. This is mainly due to the unique anatomical and physiological features of the eye. One of the effective pharmaceutical approaches is to provide a controlled and continuous drug release to the surface of the eye to compensate drug loss by nasolacrimal drainage and non-productive absorption of the topically applied drug. This review provides a critical appraisal (advantages and drawbacks) of the different drug delivery strategies that provides controlled and continuous drug supply to the surface of the eye; it covers research conducted over the past three decades. PMID:22640036

Abdelkader, Hamdy; Alany, Raid G

2012-07-01

375

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

E-print Network

Macromolecules in drug delivery Macromolecular targeting agents, carriers, and drugs 1gauthier@emt.inrs.ca #12;Why macromolecules in drug delivery? 2gauthier@emt.inrs.ca Classic chemotherapy Drug delivery? Targeting A carrier for small drugs A release mechanism (if necessary) Protection of drug cargo #12;How? 3

Barthelat, Francois

376

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

2012-01-01

377

An intra-cerebral drug delivery system for freely moving animals.  

PubMed

Microinfusions of drugs directly into the central nervous system of awake animals represent a widely used means of unravelling brain functions related to behaviour. However, current approaches generally use tethered liquid infusion systems and a syringe pump to deliver drugs into the brain, which often interfere with behaviour. We address this shortfall with a miniaturised electronically-controlled drug delivery system (20?×?17.5?×?5 mm³) designed to be skull-mounted in rats. The device features a micropump connected to two 8-mm-long silicon microprobes with a cross section of 250?×?250 ?m² and integrated fluid microchannels. Using an external electronic control unit, the device allows infusion of 16 metered doses (0.25 ?L each, 8 per silicon shaft). Each dosage requires 3.375 Ws of electrical power making the device additionally compatible with state-of-the-art wireless headstages. A dosage precision of 0.25?±?0.01 ?L was determined in vitro before in vivo tests were carried out in awake rats. No passive leakage from the loaded devices into the brain could be detected using methylene blue dye. Finally, the device was used to investigate the effects of the NMDA-receptor antagonist 3-((R)-2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid, (R)-CPP, administered directly into the prefrontal cortex of rats during performance on a task to assess visual attention and impulsivity. In agreement with previous findings using conventional tethered infusion systems, acute (R)-CPP administration produced a marked increase in impulsivity. PMID:22622711

Spieth, Sven; Schumacher, Axel; Holtzman, Tahl; Rich, P Dylan; Theobald, David E; Dalley, Jeffrey W; Nouna, Rachid; Messner, Stephan; Zengerle, Roland

2012-10-01

378

Two-dimensional finite element analysis of a polymer gel drug delivery system  

SciTech Connect

Hydrogels are being investigated as drug delivery mechanisms. Gels can be impregnated with a drug and then stimulated through various means to release it. Having the capability to numerically predict the dynamic behavior of these release process would benefit the design and control of the such a process. In the paper, a finite element analysis is used to simulate the dynamic behavior of an eroding polyelectrolyte gel. The gel is impregnated in a collapsed state. It is then subjected to a higher pH environment causing it to swell. When it has swollen to a specified extent, the gel erodes, thereby releasing the drug agent. Such gels are currently being investigated in drug delivery schemes to the colon.

Segalman, D.J.; Witkowski, W.R.

1993-12-31

379

In vitro efficacy and release study with anti-inflammatory drugs incorporated in adhesive transdermal drug delivery systems.  

PubMed

The topical application of two different anti-inflammatory extracts incorporated in adhesive transdermal drug delivery systems (TDDSs) was investigated. Therefore, anti-inflammatory properties and percutaneous absorption behavior of adhesive TDDSs were characterized in vitro conducting experiments with a dermatologically relevant human skin model. Anti-inflammatory efficacy against UV irradiation of both TDDSs was determined in vitro with EpiDerm™. The reduction of the release of proinflammatory cytokines by topically applied TDDSs was compared with the reduction during the presence of the specific cyclooxygenase inhibitor diclofenac in the culture medium. A similar anti-inflammatory efficacy of the topically applied TDDSs in comparison with the use of diclofenac in the culture medium should be achieved. Furthermore, percutaneous absorption in efficacy tests was compared with percutaneous absorption in diffusion studies with porcine cadaver skin. Both the topically applied TDDSs showed a significant anti-inflammatory activity. Permeation coefficients through the stratum corneum and the epidermis gained from the release studies on porcine cadaver skin (Magnolia: 2.23·10(-5) cm/h, licorice: 4.68·10(-6) cm/h) were approximately five times lower than the permeation coefficients obtained with the EpiDerm™ skin model (Magnolia: 9.48·10(-5) cm/h, licorice: 24.0·10(-6) cm/h). Therefore, an adjustment of drug doses during experiments with the EpiDerm™ skin model because of weaker skin barrier properties should be considered. PMID:24633817

Meyer, Stefanie; Peters, Nils; Mann, Tobias; Wolber, Rainer; Pörtner, Ralf; Nierle, Jens

2014-04-01

380

Designing colon-specific delivery systems for anticancer drug-loaded nanoparticles: an evaluation of alginate carriers.  

PubMed

Incorporation of drug-loaded nanoparticles (NPs) in colon-specific delivery systems shows potential for raising local drug concentrations, tumor targeting and improving chemotherapy. Alginate microcapsules (15-80 µm diameter) containing insoluble Eudragit(®) RS NPs as models were characterized precisely in terms of NP loading and release kinetics. High NP loading (22%, w/w of the dried microcapsules) combined with negligible release in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) suggested that high concentrations of NPs could be transported to the colon. However, NP aggregation was confirmed at extremely low concentration (0.0003%, w/v) in alginate solution (0.007%, w/v) and after release from alginate microcapsules. Indomethacin, a model anticolorectal cancer drug, was encapsulated in pH-responsive Eudragit(®) S100 NPs (116 nm, 5%, w/w drug loading) using the nanoprecipitation method. Approximately 90% of the drug load was released from the NPs in SGF and SIF before transfer to simulated colon fluid (SCF). However, incorporation of NPs in 2 mm alginate pellets resulted in a significantly higher fraction of the drug load (around 60%) being available for release in SCF. Delivery of isolated NPs to the colon for interaction with and uptake by cancer cells requires elimination of NP-excipient interactions that promote NP aggregation. NP-loaded alginate carriers, meanwhile, offer a promising strategy for delivery of anticancer drugs to tumor sites in the colon and reducing systemic side effects. PMID:24124007

Ma, Yiming; Coombes, Allan G A

2014-09-01

381

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

2014-01-01

382

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

PubMed

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

2014-01-01

383

Nanosuspensions in drug delivery  

Microsoft Academic Search

A surprisingly large proportion of new drug candidates emerging from drug discovery programmes are water insoluble, and therefore poorly bioavailable, leading to abandoned development efforts. These so-called 'brickdust' candidates can now be rescued by formulating them into crystalline nanosuspensions. In the process of overcoming issues involving solubility, additional pharmacokinetic benefits of the drugs so formulated have come to be appreciated.

Barrett E. Rabinow

2004-01-01

384

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

2013-01-01

385

Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain.  

PubMed

Abstract Context & Objective: The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug. Methods: Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, in vitro drug release, pharmacokinetics, in vivo and stability study. Results: Formulation under investigation has particle size 174.1?±?2.6?nm, zeta potential -18.65?±?1.13?mV and% EE 90.68?±?2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56?±?0.39% at end of 24?h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. In vivo studies revealed that effect of drug was enhanced by prepared lipid nanocarriers. Conclusions: IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations. PMID:25080227

Salunkhe, Sachin S; Bhatia, Neela M; Bhatia, Manish S

2014-07-31

386

In vitro and in vivo evaluation of a hydrogel reservoir as a continuous drug delivery system for inner ear treatment.  

PubMed

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

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

2014-01-01

387

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.

2009-01-01

388

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

2010-01-01

389

A thermal microjet system with tapered micronozzles fabricated by inclined UV lithography for transdermal drug delivery  

Microsoft Academic Search

Transdermal drug delivery can be enabled by various methods that increase the permeability of the skin's outer barrier of stratum corneum, including skin exposure to heat and chemical enhancers, such as ethanol. Combining these approaches for the first time, in this study we designed a microdevice consisting of an array of microchambers filled with ethanol that is vaporized using an

Yong-Kyu Yoon; Jung-Hwan Park; Jeong-Woo Lee; Mark R. Prausnitz; Mark G. Allen

2011-01-01

390

A pH-responsive mesoporous silica nanoparticles-based multi-drug delivery system for overcoming multi-drug resistance.  

PubMed

A type of pH-responsive nano multi-drug delivery systems (nano-MDDSs) with uniform particle size (100 ± 13 nm) and excellent monodispersity was developed by in situ co-self-assembly among water-insoluble anti-cancer drug (doxorubicin, DOX), surfactant micelles (CTAB) as chemosensitiver and silicon species forming drugs/surfactant micelles-co-loaded mesoporous silica nanoparticles (drugs@micelles@MSNs or DOX@CTAB@MSNs) via a micelles-MSNs self-assembly mechanism. The nano-MDDS DOX@CTAB@MSNs had a highly precise pH-responsive drug release behavior both in vitro and in vivo, and exhibited high drug efficiencies against drug-resistant MCF-7/ADR cells as well as drug-sensitive MCF-7 cells by the MSNs-mediated transmembrane delivery, the sustained drug release and the high anti-cancer and multi-drug resistance (MDR)-overcoming efficiencies. The MDR-overcoming mechanism was proved to be a synergistic cell cycle arrest/apoptosis-inducing effect resulted from the chemosensitization of the surfactant CTAB. These results demonstrated a very promising nano-MDDS for the pH-responsive controlled drug release and the cancer MDR overcoming. PMID:21816467

He, Qianjun; Gao, Yu; Zhang, Lingxia; Zhang, Zhiwen; Gao, Fang; Ji, Xiufeng; Li, Yaping; Shi, Jianlin

2011-10-01

391

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

2000-01-01

392

Refilling drug delivery depots through the blood.  

PubMed

Local drug delivery depots have significant clinical utility, but there is currently no noninvasive technique to refill these systems once their payload is exhausted. Inspired by the ability of nanotherapeutics to target specific tissues, we hypothesized that blood-borne drug payloads could be modified to home to and refill hydrogel drug delivery systems. To address this possibility, hydrogels were modified with oligodeoxynucleotides (ODNs) that provide a target for drug payloads in the form of free alginate strands carrying complementary ODNs. Coupling ODNs to alginate strands led to specific binding to complementary-ODN-carrying alginate gels in vitro and to injected gels in vivo. When coupled to a drug payload, sequence-targeted refilling of a delivery depot consisting of intratumor hydrogels completely abrogated tumor growth. These results suggest a new paradigm for nanotherapeutic drug delivery, and this concept is expected to have applications in refilling drug depots in cancer therapy, wound healing, and drug-eluting vascular grafts and stents. PMID:25139997

Brudno, Yevgeny; Silva, Eduardo A; Kearney, Cathal J; Lewin, Sarah A; Miller, Alex; Martinick, Kathleen D; Aizenberg, Michael; Mooney, David J

2014-09-01

393

Ultrasound-Mediated Gene and Drug Delivery Using a Microbubble-Liposome Particle System  

PubMed Central

Theranostic agents present a promising clinical approach for cancer detection and treatment. We herein introduce a microbubble and liposome complex (MB-Lipo) developed for ultrasound (US) imaging and activation. The MB-Lipo particles have a hybrid structure consisting of a MB complexed with multiple Lipos. The MB components are used to generate high echo signals in US imaging, while the Lipos serve as a versatile carrier of therapeutic materials. MB-Lipo allows high contrast US imaging of tumor sites. More importantly, the application of high acoustic pressure bursts MBs, which releases therapeutic Lipos and further enhances their intracellular delivery through sonoporation effect. Both imaging and drug release could thus be achieved by a single US modality, enabling in situ treatment guided by real-time imaging. The MB-Lipo system was applied to specifically deliver anti-cancer drug and genes to tumor cells, which showed enhanced therapeutic effect. We also demonstrate the clinical potential of MB-Lipo by imaging and treating tumor in vivo. PMID:25250094

Yoon, Young Il; Kwon, Yong-Su; Cho, Hee-Sang; Heo, Sun-Hee; Park, Kyeong Soon; Park, Sang Gyu; Lee, Soo-Hong; Hwang, Seung Il; Kim, Young Il; Jae, Hwan Jun; Ahn, Gook-Jun; Cho, Young-Seok; Lee, Hakho; Lee, Hak Jong; Yoon, Tae-Jong

2014-01-01

394

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.

2010-01-01

395

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

2010-01-01

396

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

PubMed

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

2014-11-18

397

Design, fabrication, and characterization of an electrochemically-based dose tracking system for closed-loop drug delivery.  

PubMed

A real-time integrated electrochemically-based dose tracking system for closed-loop drug delivery is presented. Thin film Pt sensors were integrated in an electrolytic MEMS drug delivery pump to allow dose tracking via electrochemical impedance measurement. Measurement electrode placement and composition were investigated. A bolus resolution of 230 nL was demonstrated. The sensor was calibrated for use with water (low conductivity) and 1 × PBS (high conductivity), the selected model aqueous drugs. The impedance response is dependent on delivered volume and not affected by actuation parameters. A graphical user interface was created for real-time impedance based dose tracking and leakage/blockage detection in the system. Drift in the impedance response of an idle system after perturbation (actuation) were investigated and mitigated through the use of Pt wire electrodes as opposed to thin film electrodes. PMID:23365943

Sheybani, Roya; Cabrera-Munoz, Nestor E; Sanchez, Tania; Meng, Ellis

2012-01-01

398

Magnetic Nanoparticles as Intraocular Drug Delivery System to Target Retinal Pigmented Epithelium (RPE)  

PubMed Central

One of the most challenging efforts in drug delivery is the targeting of the eye. The eye structure and barriers render this organ poorly permeable to drugs. Quite recently the entrance of nanoscience in ocular drug delivery has improved the penetration and half-life of drugs, especially in the anterior eye chamber, while targeting the posterior chamber is still an open issue. The retina and the retinal pigment epithelium/choroid tissues, located in the posterior eye chamber, are responsible for the majority of blindness both in childhood and adulthood. In the present study, we used magnetic nanoparticles (MNPs) as a nanotool for ocular drug delivery that is capable of specific localization in the retinal pigmented epithelium (RPE) layer. We demonstrate that, following intraocular injection in Xenopus embryos, MNPs localize specifically in RPE where they are retained for several days. The specificity of the localization did not depend on particle size and surface properties of the MNPs used in this work. Moreover, through similar experiments in zebrafish, we demonstrated that the targeting of RPE by the nanoparticles is not specific for the Xenopus species. PMID:24451140

Giannaccini, Martina; Giannini, Marianna; Calatayud, M. Pilar; Goya, Gerardo F.; Cuschieri, Alfred; Dente, Luciana; Raffa, Vittoria

2014-01-01

399

Microencapsulation: an acclaimed novel drug-delivery system for NSAIDs in arthritis.  

PubMed

Arthritis refers to different medical conditions associated with disorders of the primary structures that determine joint functioning, such as bones, cartilage, and synovial membranes. Drug discovery and delivery to retard the degeneration of joint tissues are challenging. Current treatment of different types of arthritis such as osteoarthritis, rheumatoid arthritis, septic arthritis, juvenile idiopathic arthritis, and ankylosing spondylitis involves the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, diclofenac, aceclofenac, ibuprofen, fl