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Sample records for drug delivery system

  1. Intracochlear Drug Delivery Systems

    PubMed Central

    Borenstein, Jeffrey T.

    2011-01-01

    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

  2. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

    Nanosize materials provide hopes, speculations and chances for an unprecedented change in drug delivery in near future. Nanotechnology is an emerging field to produce nanomaterials for drug delivery that can offer a new tool, opportunities and scope to provide more focused and fine-tuned treatment of diseases at a molecular level, enhancing the therapeutic potential of drugs so that they become less toxic and more effective. Nanodimensional drug delivery systems are of great scientific interest as they project their tremendous utility because of their capability of altering biodistribution of therapeutic agents so that they can concentrate more in the target tissues. Nanosize drug delivery systems generally focus on formulating bioactive molecules in biocompatible nanosystems such as nanocrystals, solid lipid nanoparticles, nanostructure lipid carriers, lipid drug conjugates, nanoliposomes, dendrimers, nanoshells, emulsions, nanotubes, quantum dots etc. Extensively versatile molecules like synthetic chemicals to naturally occurring complex macromolecules such as nucleic acids and proteins could be dispensed in such formulations maintaining their stability and efficacy. Empty viral capsids are being tried to deliver drug as these uniformly sized bionanomaterials can be utilized to load drug to improve solubility, reduce toxicity and provide site specific targeting. Nanomedicines offer a wide scope for delivery of smart materials from tissue engineering to more recently artificial RBCs. Nanocomposites are the future hope for tailored and personalized medicines as well as for bone repairing and rectification of cartilage impairment. Nanosize drug delivery systems are addressing the challenges to overcome the delivery problems of wide ranges of drugs through their narrow submicron particle size range, easily manipulatable surface characteristics in achievement of versatile tissue targeting (includes active and passive drug targeting), controlled and sustained drug release property to achieve increased therapeutic efficacy and reduced side effects. Nanoparticles and nanoliposomes are emerging areas of nanotechnologies that have already begun to make an impact over new modalities for cancer chemotherapy, diagnosis as well as gene delivery. Presently it is possible to reduce the particle size in such a way that the particles can be easily injected or inhaled and many types of human cells are capable to internalize them. A number of fabrications such as PEGylation, specific antibody conjugation, aptamer ligation, specific ligand binding etc. on the nanosize delivery devices makes them in the streamline of research to particularly target the diseased cells thus avoiding the healthy one. Potential of nanosize carriers to cross the blood brain barrier encourages us to build up a new strategy for delivery of therapeutically active agents to the brain. Nanotechnology is showing an emerging effect in chronic diseases such as diabetes, cancer, neurodegenerative diseases etc. Nanosize vaccines are having greater effect in production of better immunity against pathogens through direct administration of medication to the specialized dendritic cells in the immune systems. Lots of hopes and speculations are reigning around the scientists with nanosize drug delivery systems that may revolutionize the drug delivery with the better understanding of drug action mechanism and identification of biomarker associated with specific diseases. Nanosize drug delivery systems are emerging with the promising strategies for efficient targeted drug delivery. The proper designing of these systems can make them capable for being independent in the normal tissue environments and selective at the diseased pharmacological site. Nanomaterials as formulations are already in the market or in clinical trials. Investigation on nanostructural drug delivery is a highly growing field today as an extensive amount of research is on with an expectation to open up new avenues to drug delivery. No doubt the next era of drug therapy will be greater influenced by nanoscale dr

  3. Mucoadhesive drug delivery systems

    PubMed Central

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

    2011-01-01

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

  4. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. PMID:25703045

  5. Polymers for Drug Delivery Systems

    PubMed Central

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

    2012-01-01

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

  6. Microfabricated injectable drug delivery system

    DOEpatents

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

    2002-01-01

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

  7. Packaging for a drug delivery microelectromechanical system

    E-print Network

    Ho Duc, Hong Linh, 1978-

    2005-01-01

    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. ...

  8. Drug delivery systems from nose to brain.

    PubMed

    Misra, Ambikanandan; Kher, Gitanjali

    2012-09-01

    The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brain-barrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. Intranasal delivery offers a non-invasive and convenient method to bypass the BBB and delivery of therapeutics directly to the brain. The review discusses the potential of intranasal route to deliver drugs to the brain, the mechanisms and pathways of direct nose to brain drug transport, the various factors influencing transnasal drug absorption, the conventional and novel intranasal drug delivery systems, the various intranasal drug delivery techniques and devices, and examples of brain drug transport that have been feasible in treating various brain disorders. Moreover, products on the market, investigational drugs, and the author's perceptions about the prospect of intranasal delivery for treating brain disorders are also been discussed. PMID:23016642

  9. Intelligent hydrogels for drug delivery system.

    PubMed

    He, Liumin; Zuo, Qinhua; Xie, Shasha; Huang, Yuexin; Xue, Wei

    2011-09-01

    Intelligent hydrogel, also known as smart hydrogels, are materials with great potential for development in drug delivery system. Intelligent hydrogel also has the ability to perceive as a signal structure change and stimulation. The review introduces the temperature-, pH-, electric signal-, biochemical molecule-, light- and pressure- sensitive hydrogels. Finally, we described the application of intelligent hydrogel in drug delivery system and the recent patents involved for hydrogel in drug delivery. PMID:21834779

  10. Collagen macromolecular drug delivery systems

    SciTech Connect

    Gilbert, D.L.

    1988-01-01

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

  11. Kidney–targeted drug delivery systems

    PubMed Central

    Zhou, Peng; Sun, Xun; Zhang, Zhirong

    2014-01-01

    Kidney-targeted drug delivery systems represent a promising technology to improve drug efficacy and safety in the treatment of renal diseases. In this review, we summarize the strategies that have been employed to develop kidney-targeted drug delivery systems. We also describe how macromolecular carriers and prodrugs play crucial roles in targeting drugs to particular target cells in the kidney. New technologies render it possible to create renal targeting conjugates and other delivery systems including nanoparticles and liposomes present promising strategies to achieve the goal of targeting drugs to the kidney.

  12. Drug delivery systems: An updated review

    PubMed Central

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

    2012-01-01

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

  13. Radiation sterilization of new drug delivery systems

    PubMed Central

    Abuhano?lu, Gürhan

    2014-01-01

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

  14. Chitosan Microspheres in Novel Drug Delivery Systems

    PubMed Central

    Mitra, Analava; Dey, Baishakhi

    2011-01-01

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

  15. Novel drug delivery systems for glaucoma

    PubMed Central

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

    2011-01-01

    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

  16. Transdermal drug delivery system: patent reviews.

    PubMed

    Samad, Abdus; Ullah, Zabih; Alam, Mohammad I; Wais, Mohd; Shams, Mohammad Shabaz

    2009-06-01

    Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. Although the concept of transdermal drug delivery has been known since 1924, it took until 1979, as FDA approved the transdermal delivery of scopolamine, that transdermal delivery systems [TDDS] received broad attention as novel tool for controlled release. These drug delivery systems are designed for controlled release of drug through the skin into systemic circulation maintaining consistent efficacy and reducing dose of the drug and its related side effects. More than 200 patents have been granted by the United State patent alone, of which more than 35 TDD products have now been approved for sale in the US, and approximately 16 active ingredients have been approved for use globally. Statistics reveal a market of $ 12.7 billion in the year 2005 which is expected to increase by $ 21.5 billion in the year 2010 and $ 31.5 billion in the year 2015. Almost all major and minor pharmaceutical companies are developing TDDS. There is not a single review article which describes patents on different types of TDDS. Thus this review is designed for patents on the different type of TDDS which would be helpful for the researcher in the field of TDDS. PMID:19519574

  17. Nanotechnology in Biomaterials: Nanoparticulates as Drug Delivery Systems

    E-print Network

    Hasýrcý, Vasýf

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

  18. Lipid-Based Drug Delivery Systems

    PubMed Central

    Shrestha, Hina; Bala, Rajni; Arora, Sandeep

    2014-01-01

    The principle objective of formulation of lipid-based drugs is to enhance their bioavailability. The use of lipids in drug delivery is no more a new trend now but is still the promising concept. Lipid-based drug delivery systems (LBDDS) are one of the emerging technologies designed to address challenges like the solubility and bioavailability of poorly water-soluble drugs. Lipid-based formulations can be tailored to meet a wide range of product requirements dictated by disease indication, route of administration, cost consideration, product stability, toxicity, and efficacy. These formulations are also a commercially viable strategy to formulate pharmaceuticals, for topical, oral, pulmonary, or parenteral delivery. In addition, lipid-based formulations have been shown to reduce the toxicity of various drugs by changing the biodistribution of the drug away from sensitive organs. However, the number of applications for lipid-based formulations has expanded as the nature and type of active drugs under investigation have become more varied. This paper mainly focuses on novel lipid-based formulations, namely, emulsions, vesicular systems, and lipid particulate systems and their subcategories as well as on their prominent applications in pharmaceutical drug delivery. PMID:26556202

  19. Liposomes as delivery systems for antineoplastic drugs

    NASA Astrophysics Data System (ADS)

    Medina, Luis Alberto

    2014-11-01

    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.

  20. A wireless actuating drug delivery system

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  1. Intelligent, self-powered, drug delivery systems.

    PubMed

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

    2013-02-21

    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. PMID:23166050

  2. Recent technologies in pulsatile drug delivery systems

    PubMed Central

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

    2011-01-01

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

  3. Targeted drug delivery systems for pancreatic cancer.

    PubMed

    Khare, Vaibhav; Alam, Noor; Saneja, Ankit; Dubey, Ravindra Dhar; Gupta, Prem N

    2014-12-01

    Pancreatic cancer is usually diagnosed at the advanced stages, responds poorly to the available chemotherapeutics and constitutes the major factor for high mortality rate. Selective delivery of therapeutics to their cellular targets, without side effects is the foremost objective of the current investigations for effective treatment of pancreatic cancer. The development of the drugs which can selectively target pancreatic cancer along with carriers that can deliver drugs specifically to the rapidly dividing cells is considered as magic bullet for the efficient treatment of this fatal disease. This review describes various factors hampering the efficacy of drug targeting to pancreatic cancer including stromal fortress, hypocascularity, hyaluronan and interstitial fluid pressure, and exploration of various cellular targets for the site specific drug delivery. An account of burgeoning applications of novel drug delivery systems including nanoparticles, liposomes, quantum dots, micelles and drug conjugates in the management of pancreatic cancer is also provided. Additionally, potential of target based therapeutic agents and nanomedicines in clinical trials for the pancreatic cancer therapy are highlighted. PMID:26000366

  4. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

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

  5. Silk Electrogel Based Gastroretentive Drug Delivery System

    NASA Astrophysics Data System (ADS)

    Wang, Qianrui

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

  6. Biomedical Imaging in Implantable Drug Delivery Systems

    PubMed Central

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

    2015-01-01

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

  7. Non-viral drug delivery systems for immune modulation

    E-print Network

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

    2008-01-01

    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 ...

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

    PubMed Central

    Meng, Ellis; Hoang, Tuan

    2013-01-01

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

  9. Ultrasonic nebulization system for respiratory drug delivery.

    PubMed

    Wiedmann, T S; Ravichandran, A

    2001-01-01

    An ultrasonic spray system was tested for the production of aerosols for ultimate use in the respiratory delivery of drug to animals. A Sono-Tek ultrasonic spray system was mounted on top of a baffle to entrain aerosol particles within the carrier gas. Solvent was removed from the aerosol cloud by passing the droplets through drying columns composed of either charcoal or silica. The efficiency of removing ethanol and water were determined by measuring the outflow concentrations. Sodium fluorescein and sodium cromolyn dissolved in water were tested, and the effect of the liquid flow rate and drug concentration entering the atomizer on the output, and particle size distribution, were determined by the filter capture method, and by cascade impactor, respectively. Similar studies were conducted with budesonide and indomethacin dissolved in ethanol. The theoretical count median size distribution was calculated and compared with the experimental values calculated from the observed mass median aerodynamic diameter. The output rate expressed as the mass of aerosol collected in unit time increased nearly proportionately with the liquid flow rate (0.18-0.7 ml/min) and with the concentration of drug (0.19-12 mg/ml) entering the nebulizer. The mean particle size increased with solute concentration, but not by liquid flow rate. The calculated count median diameters were dependent on the type of solvent, but were independent of solute. At the high dose of cromolyn, there was very good agreement between the theoretical and observed. At lower doses, the observed size was larger than predicted, which was also true for the ethanol soluble solutes. The system has the potential of providing a wide range of dose levels for testing of drug delivery to animals including high doses with a controlled and relatively narrow particle size distribution. PMID:11247278

  10. Expert Review Functionalized Micellar Systems for Cancer Targeted Drug Delivery

    E-print Network

    Gao, Jinming

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

  11. Biopolymers as transdermal drug delivery systems in dermatology therapy.

    PubMed

    Basavaraj, K H; Johnsy, George; Navya, M A; Rashmi, R; Siddaramaiah

    2010-01-01

    The skin is considered a complex organ for drug delivery because of its structure. Drug delivery systems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drug delivery. Today, polymers have been proven to be successful for long-term drug delivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drug delivery systems, but as such the use of biopolymers as drug delivery systems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use. PMID:20499487

  12. Herbal Excipients in Novel Drug Delivery Systems

    PubMed Central

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

    2008-01-01

    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

  13. Progress toward a Colon Targeting Nanoparticle Based Drug Delivery System 

    E-print Network

    Yu, Xiao

    2012-07-16

    Hydrophobic drug paclitaxel nanoparticles (PAX NPs) and pH sensitive hydrogels were prepared in this study to build a colon targeting nanoparticle based drug delivery system for oral administration. Negative charged PAX NPs at the size of 110...

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

    PubMed

    Park, Kinam

    2014-09-28

    Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology. PMID:24794901

  15. 76 FR 51038 - Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... availability of a guidance for industry entitled ``Residual Drug in Transdermal and Related Drug Delivery... SERVICES Food and Drug Administration Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice....

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

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2016-01-01

    Many drugs have been designed to act on intracellular targets and to affect intracellular processes inside target cells. For the desired effects to be exerted, these drugs should permeate target cells and reach specific intracellular organelles. This subcellular drug targeting approach has been proposed for enhancement of accumulation of these drugs in target organelles and improved efficiency. This approach is based on drug encapsulation in drug delivery systems (DDSs) and/or their decoration with specific targeting moieties that are intended to enhance the drug/DDS accumulation in the intracellular organelle of interest. During recent years, there has been a constant increase in interest in DDSs targeted to specific intracellular organelles, and many different approaches have been proposed for attaining efficient drug delivery to specific organelles of interest. However, it appears that in many studies insufficient efforts have been devoted to quantitative analysis of the major formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and endosomal escape, intracellular trafficking, and efficiency of DDS delivery to the target organelle) and of the resulting pharmacological effects. Thus, in many cases, claims regarding efficient delivery of drug/DDS to a specific organelle and efficient subcellular targeting appear to be exaggerated. On the basis of the available experimental data, it appears that drugs/DDS decoration with specific targeting residues can affect their intracellular fate and result in preferential drug accumulation within an organelle of interest. However, it is not clear whether these approaches will be efficient in in vivo settings and be translated into preclinical and clinical applications. Studies that quantitatively assess the mechanisms, barriers, and efficiencies of subcellular drug delivery and of the associated toxic effects are required to determine the therapeutic potential of subcellular DDS targeting. PMID:26587994

  17. Design of controlled drug delivery system with optimal release characteristics

    NASA Astrophysics Data System (ADS)

    Wang, Xiaopeng; Chen, Tianning; Yang, Zhanxiao; Wang, Wanjun

    2006-01-01

    The biodegradable controlled-release system with large array of micro chambers is a new controlled drug delivery system. The structure of the system is designed using the MEMS technology, combining the drug release condition and the biodegradable characteristic of the polymer. This type of drug delivery system has some unique advantages in controlled long-term drug delivery, such as more drug loading than the matrices release systems, easier control the release rate, and so on. It is necessary to optimum the structure for the long-term drug delivery. This paper founds the simulated modeling which can simulate the erosion and the drug delivery from this controlled-release system. Further more the thickness of the chamber's wall is taken as the design variable. An optimized modeling for the drug delivery from the biodegradable controlled-release system is developed. This model can optimize the structure of the controlled release system for the desired release characteristics. The results indicate that this method can be used to design the drug delivery system based on the biodegradable polymer.

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

    PubMed Central

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

    2012-01-01

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

  19. Drug delivery systems. 1. site-specific drug delivery using liposomes as carriers.

    PubMed

    Ranade, V V

    1989-08-01

    Drug delivery systems, offering controlled delivery of biologically active agents, are rapidly gaining importance in pharmaceutical research and development. To achieve controlled drug delivery, i.e., the administration of drugs so that optimal amount reaches the target site to cure or control the disease state, increasingly sophisticated systems containing different carriers have been developed. Macromolecules represent one of the carriers involved, and they have taken on a significantly prominent role in various modes of administration of therapeutic agents. Among macromolecules, for example, synthetic copolymers, polysaccharides, liposomes, polyanions and antibodies, as drug carriers, liposomes have proved most effective for diseases affecting the reticuloendothelial system and blood cells in particular. Liposomes, which are vesicles consisting of one or more concentrically ordered assemblies of phospholipids bilayers, range in size from a nanometer to several micrometers. Phospholipids such as egg phosphatidylcholine, phosphatidylserine, synthetic dipalmitoyl-DL-alpha-phosphatidylcholine or phosphatidylinositol, have been used in conjunction with cholesterol and positively or negatively charged amphiphiles such as stearylamine or phosphatidic acid. Alteration of surface charge has been shown to enhance drug incorporation and also influence drug release. Because of the multifold characteristics as drug carriers, liposomes have been investigated extensively as carriers of anticancer agents for the past several years. Liposomal entrapments include a variety of pharmacologically active compounds such as antimalarial, antiviral, anti-inflammatory and anti-fungal agents as well as antibiotics, prostaglandins, steroids and bronchodilators to name a few. The liposomal entrapment has been shown to have considerable effect on the pharmacokinetics and tissue distribution of administered drugs. Despite the potential value of liposomes as unique carriers, the major obstacles are the first order targeting of a systemically given liposomes, physical stability and manufacture of the liposomal products and these problems still remain to be overcome. Drug delivery systems evolving in the 1980s have become increasingly dependent on fundamental cell-biology and receptor-mediated endocytotic mechanisms. Drug delivery systems during the 1990s may take advantage of the specificity of receptor-mediated uptake mechanisms as well as polymer chemistry and cell-biology in order to introduce more precise and efficient target-specific delivery systems that are based especially on the liposome technology. PMID:2674208

  20. Design Strategies and Applications of Circulating Cell-Mediated Drug Delivery Systems

    E-print Network

    Yang, Jian

    Design Strategies and Applications of Circulating Cell-Mediated Drug Delivery Systems Yixue Su Hallowell Building, University Park, Pennsylvania 16802, United States ABSTRACT: Drug delivery systems, particularly nanomaterial- based drug delivery systems, possess a tremendous amount of potential to improve

  1. Bioavailability of phytochemicals and its enhancement by drug delivery systems

    PubMed Central

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

    2013-01-01

    Issues of poor oral bioavailability of cancer chemopreventives have hindered progress in cancer prevention. Novel delivery systems that modulate the pharmacokinetics of existing drugs, such as nanoparticles, cyclodextrins, niosomes, liposomes and implants, could be used to enhance the delivery of chemopreventive agents to target sites. The development of new approaches in prevention and treatment of cancer could encompass new delivery systems for approved and newly investigated compounds. In this review, we discuss some of the delivery approaches that have already made an impact by either delivering a drug to target tissue or increasing its bioavailability by many fold. PMID:23435377

  2. 76 FR 51038 - Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ...DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0246] Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems; Availability AGENCY: Food...

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

    PubMed Central

    2013-01-01

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

  4. Mucoadhesive and thermogelling systems for vaginal drug delivery.

    PubMed

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

    2015-09-15

    This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described. PMID:25683694

  5. Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

    PubMed Central

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

    2014-01-01

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

  6. Formulation and Stability Aspects of Nanosized Solid Drug Delivery Systems.

    PubMed

    Szabo, Peter; Zelko, Romana

    2015-01-01

    Nano drug delivery systems are considered as useful means to remedy the problems of drugs of poor solubility, permeability and bioavailability, which became one of the most troublesome questions of the pharmaceutical industry. Different types of nanosized drug delivery systems have been developed and investigated for oral administration, providing auspicious solutions for drug development. In this paper nanosized drug delivery systems intended for oral administration are discussed based on the chemical nature of the carrier of drug molecules. Lipid nanoparticles comprising solid lipid nanoparticles, improved nanostructured lipid carriers and nanostructured silica- lipid hybrid particles have become popular in the formulation of lipophilic drugs of poor oral bioavailability. Polymeric nanoparticles including nanospheres and nanocapsules and polymeric fibrous systems have also emerged as potential drug delivery systems owing to their unique structure. The feasibility of surface functionalization of mesoporous materials and gold nanoparticles enables high level of control over particle characteristics making inorganic nanoparticles an exceptional formulation approach. The authors paid particular attention to the functionality-related stability of the reviewed delivery systems. PMID:26027571

  7. Targeted electrohydrodynamic printing for micro-reservoir drug delivery systems

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  8. Interactive mixture as a rapid drug delivery system.

    PubMed

    Lee, Chin Chiat; Ong, Charlene Li Ching; Heng, Paul Wan Sia; Chan, Lai Wah; Wong, Tin Wui

    2008-02-01

    The effectiveness of an interactive mixture as a rapid drug delivery system is compared with that of a solid dispersion. The influences of drug load, particle size, and crystallinity of these test systems are investigated. The interactive mixtures and solid dispersions were prepared from polyethylene glycol (PEG) 3350 and hydrophobic nifedipine drug by means of physical mixing and melting methods, respectively. The formed products were subjected to drug particle size and crystallinity analyses, and dissolution tests. In comparison with the interactive mixtures, the solid dispersions with low drug load were more effective as a rapid drug delivery system, as the size of a given batch of drug particles was markedly reduced by the molten PEG 3350. The rate and extent of drug dissolution were mainly promoted by decreasing effective drug particle size. However, these were lower in the solid dispersions than in the interactive mixtures when a high load of fine drug particles was used as the starting material. This was attributed to drug coarsening during the preparation of the solid dispersion. Unlike solid dispersions, the interactive mixtures could accommodate a high load of fine drug particles without compromising its capacity to enhance the rate and extent of drug dissolution. The interactive mixture is appropriate for use to deliver a fine hydrophobic drug in a formulation requiring a high drug load. PMID:18302040

  9. Coacervate delivery systems for proteins and small molecule drugs

    PubMed Central

    Johnson, Noah R; Wang, Yadong

    2015-01-01

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

  10. Pulsatile Drug Delivery System Based on Electrohydrodynamic Method

    E-print Network

    Zheng, Yi; Hu, Junqiang; Gao, Wenle

    2012-01-01

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

  11. Electrohydrodynamics: A facile technique to fabricate drug delivery systems

    PubMed Central

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

    2009-01-01

    Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drug delivery systems (DDS) through a one-step process. The nano-structured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial-electrospinning/electrospraying, a relatively new technique of fabricating core-shell fibers/particles have added to the versatility of these DDS by affording a near zero-order drug release kinetics, dampening of burst release, and applicability to a wider range of bioactive agents. Controllable electrospinning/spraying of fibers and particles and subsequent drug release from these chiefly polymeric vehicles depends on well-defined solution and process parameters. The additional drug delivery capability from electrospun fibers can further enhance the material’s functionality in tissue engineering applications. This review discusses the state-of-the-art of using electrohydrodynamic technique to generate nano-fiber/particles as drug delivery devices. PMID:19651167

  12. 3-dimensional (3D) fabricated polymer based drug delivery systems.

    PubMed

    Moulton, Simon E; Wallace, Gordon G

    2014-11-10

    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

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

    PubMed Central

    Upadhyay, Ravi Kant

    2014-01-01

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

  14. Nanoscale drug delivery systems and the blood–brain barrier

    PubMed Central

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

    2014-01-01

    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

  15. Crystallization Methods for Preparation of Nanocrystals for Drug Delivery System.

    PubMed

    Gao, Yuan; Wang, Jingkang; Wang, Yongli; Yin, Qiuxiang; Glennon, Brian; Zhong, Jian; Ouyang, Jinbo; Huang, Xin; Hao, Hongxun

    2015-01-01

    Low water solubility of drug products causes delivery problems such as low bioavailability. The reduced particle size and increased surface area of nanocrystals lead to the increasing of the dissolution rate. The formulation of drug nanocrystals is a robust approach and has been widely applied to drug delivery system (DDS) due to the significant development of nanoscience and nanotechnology. It can be used to improve drug efficacy, provide targeted delivery and minimize side-effects. Crystallization is the main and efficient unit operation to produce nanocrystals. Both traditional crystallization methods such as reactive crystallization, anti-solvent crystallization and new crystallization methods such as supercritical fluid crystallization, high-gravity controlled precipitation can be used to produce nanocrystals. The current mini-review outlines the main crystallization methods addressed in literature. The advantages and disadvantages of each method were summarized and compared. PMID:26027573

  16. A clinical perspective on mucoadhesive buccal drug delivery systems

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  18. Using DNA nanotechnology to produce a drug delivery system

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

    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.

  19. Pouch drug delivery systems for dermal and transdermal administration.

    PubMed

    Zailer, Jana; Touitou, Elka

    2014-12-01

    In this work, we have designed and investigated a new carrier for dermal and transdermal drug delivery. The delivery system is composed of high (>60 %) ethanol concentration, phospholipid, polymer, and water. The system forms a structured matrix following non-occluded application on the skin. We call these structured carriers as pouch drug delivery systems (PDDS). The pouch-structured matrix was characterized by electron microscopy, (31)P-NMR and FTIR. The new delivery system exhibits a number of properties adequate for the design of improved dermal and transdermal drug administration for various treatments. Lidocaine PDDS dry faster and has an enhanced dermal drug delivery when compared to a clinical-used product. These proprieties are important for the prevention of premature ejaculation. Results obtained in pharmacodynamics test carried out with brotizolam PDDS in a mice-sleeping model and with ibuprofen PDDS in fevered rats indicated a prolonged hypnotic and antipyretic effect, respectively. The carrier was found nonirritant in tests carried out on EpiDerm(TM) skin model. PMID:25787204

  20. Medicated chewing gum, a novel drug delivery system

    PubMed Central

    Aslani, Abolfazl; Rostami, Farnaz

    2015-01-01

    New formulations and technologies have been developed through oral drug delivery systems’ researches. Such researches display significance of oral route amongst patients. We’ve reviewed all the features associated with medicated chewing gum as a modern drug delivery by introducing the history, advantages and disadvantages, methods of manufacturing, composition differences, evaluation tests and examples of varieties of medicated chewing gums. Acceptance of medicated chewing gum has been augmented through years. The advantages and therapeutic benefits of chewing gum support its development as we can see new formulations with new drugs contained have been produced from past and are going to find a place in market by formulation of new medicated chewing gums. Potential applications of medicated chewing gums are highly widespread as they will be recognized in future. Nowadays standards for qualifying chewing gums are the same as tablets. Patient-centered studies include medicated chewing gums as a delivery system too which creates compliance for patients. PMID:26109999

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

    E-print Network

    Mavroidis, Constantinos

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

  2. Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery

    PubMed Central

    Torchilin, Vladimir P.

    2015-01-01

    The use of nanoparticulate pharmaceutical drug delivery systems (NDDSs) to enhance the in vivo effectiveness of drugs is now well established. The development of multifunctional and stimulus-sensitive NDDSs is an active area of current research. Such NDDSs can have long circulation times, target the site of the disease and enhance the intracellular delivery of a drug. This type of NDDS can also respond to local stimuli that are characteristic of the pathological site by, for example, releasing an entrapped drug or shedding a protective coating, thus facilitating the interaction between drug-loaded nanocarriers and target cells or tissues. In addition, imaging contrast moieties can be attached to these carriers to track their real-time biodistribution and accumulation in target cells or tissues. Here, I highlight recent developments with multifunctional and stimuli-sensitive NDDSs and their therapeutic potential for diseases including cancer, cardiovascular diseases and infectious diseases. PMID:25287120

  3. Novel targeted bladder drug-delivery systems: a review

    PubMed Central

    Zacchè, Martino Maria; Srikrishna, Sushma; Cardozo, Linda

    2015-01-01

    The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects. Prolonged exposure of the diseased tissue to the drug is of crucial importance. Drug-delivery systems (DDSs) have been introduced to control rate, time, and place of release. Drugs can easily reach the bladder through a catheter, while systemically administered agents may undergo extensive metabolism. Continuous urine filling and subsequent washout hinder intravesical drug delivery (IDD). Moreover, the low permeability of the urothelium, also described as the bladder permeability barrier, poses a major challenge in the development of the IDD. DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance. This review focuses on novel DDSs to treat bladder conditions such as overactive bladder, interstitial cystitis, bladder cancer, and recurrent urinary tract infections. The rationale and strategies for both systemic and local delivery methods are discussed, with emphasis on new formulations of well-known drugs (oxybutynin), nanocarriers, polymeric hydrogels, intravesical devices, encapsulated DDSs, and gene therapy. We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy. PMID:26649286

  4. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

    PubMed Central

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

    2014-01-01

    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

  5. Carrier-Based Drug Delivery System for Treatment of Acne

    PubMed Central

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

    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

  6. Polymer-based biodegradable drug delivery systems in pain management.

    PubMed

    Al Malyan, Mohamed; Becchi, Chiara; Nikkola, Lila; Viitanen, Petrus; Boncinelli, Sergio; Chiellini, Federica; Ashammakhi, Nureddin

    2006-03-01

    Pain is an unpleasant sensory experience commonly produced by damage to bodily tissues and it is one of the most significant public health problems, because 21.5% of the world population is estimated to suffer from pain. It results in a total loss of more than 165 billion US dollars each year in the United States alone. Pain reflects a mixture of various pathophysiologic, psychologic, and genetic contributions. When undertreated, pain usually results in serious immune and metabolic upset. Therefore, it requires wide understanding and intensive effort for a better management. Currently, pain control is limited by the modest efficiency of the used drugs, the serious side effects of these drugs, and the inefficacy of conventional drug administration. By the introduction of the technology of biodegradable controlled-release devices into clinical practice, pain control not only benefits from these novel methods for a better delivery of various drugs, but the side effects of the drugs are reduced because use of the devices improves patient compliance. Biodegradable controlled-release devices are polymer-based devices that are designed to deliver drugs locally in a predesigned manner. Recently, there was a high interest in developing these devices for the delivery of different drugs used for pain control. This paper first highlights the dimensions and basics of the problem of pain. Then, it presents an overview of the biodegradable polymers that are used in drug delivery systems and summarizes the studies carried out on these systems in the field of pain management. We refer to our experience in developing a device for multimodal drug delivery, including the use of nanotechnology. Future perspectives are also presented. PMID:16633180

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

    PubMed Central

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

    2010-01-01

    Many promising therapeutic agents are limited by their inability to reach the systemic circulation, due to the excellent barrier properties of biological membranes, such as the stratum corneum (SC) of the skin or the sclera/cornea of the eye and others. The outermost layer of the skin, the SC, is the principal barrier to topically-applied medications. The intact SC thus provides the main barrier to exogenous substances, including drugs. Only drugs with very specific physicochemical properties (molecular weight < 500 Da, adequate lipophilicity, and low melting point) can be successfully administered transdermally. Transdermal delivery of hydrophilic drugs and macromolecular agents of interest, including peptides, DNA, and small interfering RNA is problematic. Therefore, facilitation of drug penetration through the SC may involve by-pass or reversible disruption of SC molecular architecture. Microneedles (MNs), when used to puncture skin, will by-pass the SC and create transient aqueous transport pathways of micron dimensions and enhance the transdermal permeability. These micropores are orders of magnitude larger than molecular dimensions, and, therefore, should readily permit the transport of hydrophilic macromolecules. Various strategies have been employed by many research groups and pharmaceutical companies worldwide, for the fabrication of MNs. This review details various types of MNs, fabrication methods and, importantly, investigations of clinical safety of MN. PMID:20297904

  8. Advances in topical drug delivery system: micro to nanofibrous structures.

    PubMed

    Joshi, Mangala; Butola, B S; Saha, Kasturi

    2014-01-01

    This paper is a review of the latest developments in the field of topical drug delivery via which the drug is directly applied onto the skin with high selectivity and efficiency. Advances in microfiber-based medical textiles such as sutures and wound dressings, especially those containing a drug or an antimicrobial agent, have been covered briefly. A special focus is on recent developments in the area of nanofibrous drug delivery systems, which have several advantages due to their large surface area to volume ratio, high porosity and flexibility. The electrospinning technique to produce nanofibers has also been discussed with reference to latest advances such as multiple needles, needleless and coaxial forms of electrospinning. The applications of nanofibers in different areas such as wound dressing, periodontal and anticancer treatment have also been discussed. PMID:24730303

  9. Potential and problems in ultrasound-responsive drug delivery systems

    PubMed Central

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

    2013-01-01

    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

  10. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

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

  11. Polymer based drug delivery systems for mycobacterial infections.

    PubMed

    Pandey, Rajesh; Khuller, G K

    2004-07-01

    In the last decade, polymer based technologies have found wide biomedical applications. Polymers, whether synthetic (e.g. polylactide-co-glycolide or PLG) or natural (e.g. alginate, chitosan etc.), have the property of encapsulating a diverse range of molecules of biological interest and bear distinct therapeutic advantages such as controlled release of drugs, protection against the premature degradation of drugs and reduction in drug toxicity. These are important considerations in the long-duration treatment of chronic infectious diseases such as tuberculosis in which patient non-compliance is the major obstacle to successful chemotherapy. Antitubercular drugs, singly or in combination, have been encapsulated in polymers to provide controlled drug release and the system also offers the flexibility of selecting various routes of administration such as oral, subcutaneous and aerosol. The present review highlights the approaches towards the preparation of polymeric antitubercular drug delivery systems, emphasizing how the route of administration may influence drug bioavailability as well as the chemotherapeutic efficacy. In addition, the pros and cons of the various delivery systems are also discussed. PMID:16305383

  12. 75 FR 45640 - Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... industry entitled ``Residual Drug in Transdermal and Related Drug Delivery Systems.'' This draft guidance... of a draft guidance for industry entitled ``Residual Drug in Transdermal and Related Drug Delivery... SERVICES Food and Drug Administration Draft Guidance for Industry on Residual Drug in Transdermal...

  13. Development of a Light Actuated Drug Delivery-on-Demand System

    E-print Network

    Linsley, Chase Schilling

    2015-01-01

    Engineering Polymer Systems for Improved Drug Delivery, Johndrug and delivery vehicle to control release. For instance, cyclodextrin- based polymersdelivery of the drug pilocarpine from the Ocusert ® system – a slow- release polymer

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

    MedlinePLUS

    ... Lupus in Mice A drug delivery system using nanoparticle technology that allows for better targeting of specific ... be effectively programmed to seek specific cells. Although nanoparticle drug delivery systems have been used experimentally to ...

  15. Floating drug delivery of nevirapine as a gastroretentive system.

    PubMed

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

    2010-10-01

    A multiple-unit floating drug delivery system based on gas formation technique was developed, in order to prolong the gastric residence time and to increase the overall bioavailability of the dosage form. The floating bead formulations were prepared by dispersing nevirapine together with calcium carbonate in a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping the dispersion into an acidified solution of calcium chloride. Calcium alginate beads were formed, as the alginate underwent ionotropic gelation by calcium ions, and carbon dioxide developed from the reaction of carbonate salts with acid. The obtained beads were able to float due to CO(2)-gas formation and the gas entrapment by the polymeric membrane. The prepared beads were evaluated for percent drug loading, drug entrapment efficiency, morphology, surface topography, buoyancy, in-vitro release, and release kinetics. The formulations were optimized for different weight ratios of the gas-forming agent and sodium alginate. The beads containing higher amounts of calcium carbonate demonstrated an instantaneous, complete, and excellent floating ability over a period of 24 hours. The increased amount of the gas forming agent did not affect the time to float, but increased the drug release from the floating beads, while increasing the coating level of the gas-entrapped membrane, increased the time to float, and slightly retarded the drug release. Good floating properties and sustained drug release were achieved. Finally, these floating beads seemed to be a promising gastroretentive drug delivery system. PMID:21264092

  16. Exosome mimetics: a novel class of drug delivery systems

    PubMed Central

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

    2012-01-01

    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

  17. 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...

  18. Silicon Nanowires for Bioadhesion and Drug Delivery

    E-print Network

    Fischer, Kathleen Elizabeth

    2010-01-01

    Generation Adhesive Drug Delivery Systems. Nano Letters 9,Drug Delivery Goals for Oral Delivery Micro- and Nanoparticles Microparticles Nanoparticles Bioadhesion Chemical Bioadhesives Physical Adhesives Nano-

  19. Chronopharmaceutical Drug Delivery Systems: Hurdles, Hype or Hope??

    PubMed Central

    Youan, Bi-Botti C.

    2010-01-01

    The current advances in chronobiology and the knowledge gained from chronotherapy of selected diseases strongly suggest that “the one size fits all at all times” approach to drug delivery is no longer substantiated, at least for selected bioactive agents and disease therapy or prevention. Thus, there is a critical and urgent need for chronopharmaceutical research (e.g., design and evaluation of robust, spatially and temporally controlled drug delivery systems that would be clinically intended for chronotherapy by different routes of administration). This review provides a brief overview of current delivery system intended for chronotherapy. In theory, such an ideal “magic pill” preferably with affordable cost, would improve the safety, efficacy and patient compliance of old and new drugs. However, currently, there are three major hurdles for the successful transition of such system from laboratory to patient bedside. These include the challenges to identify adequate (i) rhythmic biomaterials and systems, (ii) rhythm engineering modeling, perhaps using system biology and (iii) regulatory guidance. PMID:20438781

  20. Kinetic limitations of cooperativity based drug delivery systems

    E-print Network

    Nicholas A. Licata; Alexei V. Tkachenko

    2008-03-07

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

  1. Preclinical testing of drug delivery systems to bone.

    PubMed

    van Griensven, Martijn

    2015-11-01

    Bone defects do not heal in 5-10% of the fractures. In order to enhance bone regeneration, drug delivery systems are needed. They comprise a scaffold with or without inducing factors and/or cells. To test these drug delivery systems before application in patients, they finally need to be tested in animal models. The choice of animal model depends on the main research question; is a functional or mechanistic evaluation needed? Furthermore, which type of bone defects are investigated: load-bearing (i.e. orthopedic) or non-load-bearing (i.e. craniomaxillofacial)? This determines the type of model and in which type of animal. The experiments need to be set-up using the 3R principle and must be reported following the ARRIVE guidelines. PMID:26212157

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

    PubMed Central

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

    2014-01-01

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

  3. Therapeutic opportunities in colon-specific drug-delivery systems.

    PubMed

    Patel, Mayur; Shah, Tejal; Amin, Avani

    2007-01-01

    Oral colon-specific drug-delivery systems have recently gained importance for delivering a variety of therapeutic agents. The major obstacles to delivering drugs to the colon are the absorption and degradation pathways in the upper gastrointestinal tract. However, a successfully designed colon-targeted system can overcome these obstacles. Targeting drugs to the colon has proven quite valuable in a variety of disorders, and the colon has proven to be a potential site for local as well as systemic administration of drugs. Colon targeting has proven beneficial for local action in a variety of disease conditions, such as inflammatory bowel disease, irritable bowel syndrome, and colonic cancer. Aminosalicylates, corticosteroids, immunosuppressive agents, cationized antioxidant enzymes, genetically engineered bacteria to produce cytokines, nicotine, and other drugs have exhibited significantly enhanced efficacy when delivered to the colon. Targeting drugs to cancer cells through receptors and ligands have opened up new avenues in the treatment of colonic cancer. Colon targeting has also proven useful for systemic action of protein-peptide drugs such as insulin, calcitonin, and met-enkaphalin and even for other nonpeptide drugs such as cardiovascular and antiasthmatic agents. This review also presents various approaches for targeting orally administered dosage forms to the colon. The use of a prodrug approach, bioadhesive polymers, and coating with pH-sensitive and biodegradable polymers has been, to an extent, highly successful in delivering the targeted formulations to the site of action. Biodegrable hydrogels such as amylose, chondroitin sulphate, chitosan, inulin, guar gum, and pectin have also been successfully used to achieve oral colon-targeted delivery. PMID:17725524

  4. Formulation and Evaluation of Floating Drug Delivery System of Famotidine

    PubMed Central

    Satishbabu, B. K.; Sandeep, V. R.; Ravi, R. B.; Shrutinag, R.

    2010-01-01

    A multiple unit oral floating drug delivery system of famotidine was developed to prolong gastric residence time, target stomach mucosa and increase drug bioavailability. Drug and polymer compatibility was studied by subjecting physical mixtures of drug and polymers to differential scanning calorimetry. Cod liver oil entrapped calcium alginate beads containing famotidine, capable of floating in the gastric condition were formulated and evaluated. The gel beads were prepared by emulsion gelation method by employing sodium alginate alone and mixture of sodium alginate and hydrophilic copolymers such as carbopol 934P and hydroxypropylmethylcellulose K15M grade in three different ratios. The effect of selected factors, such as percentage of oil and amount of copolymers on floating properties was investigated. The beads were evaluated for percent drug loading, drug entrapment efficiency, buoyancy and in vitro drug release. The in vitro drug release study of the beads was carried out in simulated gastric media employing a modified Rosette-Rice test apparatus. Wherein, the apparatus was further modified by incorporating a water jacket to the apparatus to circulate hot water to maintain 37±2° for throughout the release study. All the oil entrapped calcium alginate beads floated if a sufficient amount of oil was used. Beads formulated employing sodium alginate alone could not sustain the drug release up to 8 h, whereas beads formulated with mixture of sodium alginate and copolymers demonstrated sustained release of famotidine up to 8 h. The results suggested that cod liver oil entrapped calcium alginate beads were promising as a carrier for intragastric floating drug delivery of famotidine. PMID:21969746

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

    E-print Network

    Peppas, Nicholas A.

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

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

    E-print Network

    Peppas, Nicholas A.

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

  7. Synthetic microbes as drug delivery systems.

    PubMed

    Claesen, Jan; Fischbach, Michael A

    2015-04-17

    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

  8. Synthetic Microbes As Drug Delivery Systems

    PubMed Central

    2015-01-01

    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

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

    PubMed

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

    2014-09-01

    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

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

    E-print Network

    Lin, Liwei

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

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

    E-print Network

    Capecchi, Mario R.

    Utah-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 therapeutics, controlled release, and targeted drug delivery from University of Utah's Department

  12. Nanobiotechnology and its applications in drug delivery system: a review.

    PubMed

    Khan, Imran; Khan, Momin; Umar, Muhammad Naveed; Oh, Deog-Hwan

    2015-12-01

    Nanobiotechnology holds great potential in various regimes of life sciences. In this review, the potential applications of nanobiotechnology in various sectors of nanotechnologies, including nanomedicine and nanobiopharmaceuticals, are highlighted. To overcome the problems associated with drug delivery, nanotechnology has gained increasing interest in recent years. Nanosystems with different biological properties and compositions have been extensively investigated for drug delivery applications. Nanoparticles fabricated through various techniques have elevated therapeutic efficacy, provided stability to the drugs and proved capable of targeting the cells and controlled release inside the cell. Polymeric nanoparticles have shown increased development and usage in drug delivery as well as in diagnostics in recent decades. PMID:26647817

  13. Design and Optimization of Floating Drug Delivery System of Acyclovir

    PubMed Central

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

    2010-01-01

    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

  14. Design and optimization of floating drug delivery system of acyclovir.

    PubMed

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

    2010-09-01

    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 3(2) 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% (t(50%)) and 70% (t(70%)) 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 t(50%) and t(70%) 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

  15. 75 FR 45640 - Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ...DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0246] Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems; Availability AGENCY: Food...

  16. Chitosan in nasal delivery systems for therapeutic drugs.

    PubMed

    Casettari, Luca; Illum, Lisbeth

    2014-09-28

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

  17. Formulation and evaluation of Ketoconazole niosomal gel drug delivery system

    PubMed Central

    Shirsand, SB; Para, MS; Nagendrakumar, D; Kanani, KM; Keerthy, D

    2012-01-01

    Purpose: Niosomes play an increasingly important role in drug delivery as they can reduce toxicity and modify pharmacokinetic and bio-availability. Topically applied niosomes can increase the residence time of drugs in the stratum corneum and epidermis, while reducing the systemic absorption of the drug. It can act as drug containing reservoirs and the modification of the vesicular compositions or surface properties can adjust the drug release rate and the affinity for the target site. Ketoconazole is a broad spectrum Imidazole derivative useful in the treatment of superficial and systemic fungal infections. Materials and Methods: In order to improve the low skin penetration and to minimize the side effects associated with topical conventional drug administration, Ketoconazole niosomes were prepared by a thin film hydration method using different ratios of non-ionic surfactants (Span 40, 60 and Tween 60) along with cholesterol (CHO). The formulations were evaluated for size, shape, entrapment efficiency and in vitro drug release. Results: Niosomes appeared spherical in shape and size range was found to be 4.86 ± 1.24-7.38 ± 3.64 ?m. The entrapment efficiency was found in the range of 55.14 ± 2.29-78.63 ± 0.91% and in vitro drug release in the range of 46.63 ± 0.95-72.37 ± 0.59% in 24 h. Ketoconazole niosomes formulated with Span 60 and CHO in the ratio of 1:0.2 were found to be promising and were incorporated into 1% Carbopol gel. The formulated gel was evaluated for various physicochemical parameters and antifungal activity. The in vitro drug release study was carried out using phosphate buffer saline pH 7.4 and was found to be 36.18 ± 1.50% in 12 h. Conclusion: Gel formulation containing niosomes loaded with Ketoconazole showed prolonged action than formulations containing Ketoconazole in non-niosomal form and it can be developed successfully to improve the antifungal activity. PMID:23580936

  18. Synthesis and characterization of modified starch/polybutadiene as novel transdermal drug delivery system.

    PubMed

    Saboktakin, Mohammad Reza; Akhyari, Shahab; Nasirov, Fizuli A

    2014-08-01

    Transdermal drug delivery systems are topically administered medicaments in the form of patches that deliver drugs for systemic effects at a predetermined and controlled rate. It works very simply in which drug is applied inside the patch and it is worn on skin for long period of time. Polymer matrix, drug, permeation enhancers are the main components of transdermal drug delivery systems. The objective of the present study was to develop the modified starch and 1,4-cis polybutadiene nanoparticles as novel polymer matrix system. We have been studied the properties of a novel transdermal drug delivery system with clonidine as drug model. PMID:24887550

  19. Progress in Psoriasis Therapy via Novel Drug Delivery Systems

    PubMed Central

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

    2014-01-01

    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

  20. Smart drug delivery systems: from fundamentals to the clinic.

    PubMed

    Alvarez-Lorenzo, Carmen; Concheiro, Angel

    2014-07-25

    Forty years after the first reports on stimuli-responsive phase transitions in synthetic hydrogels, the first medicines based on responsive components are approaching the market. Sensitiveness to internal or external signals of the body can be achieved by means of materials (mostly polymers, but also lipids and metals) that modify their properties as a function of the intensity of the signal and that enable the transduction into changes in the delivery system that affect its ability to host/release a therapeutic substance. Integration of responsive materials into implantable depots, targetable nanocarriers and even insertable medical devices can endow them with activation-modulated and feedback-regulated control of drug release. This review offers a critical overview of therapeutically-interesting stimuli to trigger drug release and the evolution of responsive materials suitable as functional excipients, illustrated with recent examples of formulations in clinical trials or already commercially available, which can provide a perspective on the current state of the art on smart drug delivery systems. PMID:24805962

  1. Cubic and Hexagonal Liquid Crystals as Drug Delivery Systems

    PubMed Central

    Chen, Yulin; Ma, Ping; Gui, Shuangying

    2014-01-01

    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

  2. Rosin: a naturally derived excipient in drug delivery systems.

    PubMed

    Kumar, Shobhit; Gupta, Satish Kumar

    2013-01-01

    Natural polymers are primarily attractive because they are biodegradable, inexpensive, and readily available. The most important benefit of natural polymers is that they are capable for chemical modifications. One such biopolymer, rosin, and its derivatives have been pharmaceutically evaluated as microencapsulating materials, film forming agent and as binding agent in formulation of tablets. They are also employed in formulation of chewing gum bases and cosmetics. This review article provides an overview of pharmaceutical use of rosin and its derivatives as excipient in dosage forms as well as novel drug delivery systems. PMID:23808195

  3. A review of drug delivery systems for capsule endoscopy.

    PubMed

    Munoz, Fredy; Alici, Gursel; Li, Weihua

    2014-05-01

    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

  4. Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

    PubMed

    Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

    2016-01-01

    Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace. PMID:26354801

  5. Evaluation of metal nanoparticles for drug delivery systems.

    PubMed

    Adeyemi, Oluyomi S; Sulaiman, Faoziyat A

    2015-04-01

    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

  6. Cell or Cell Membrane-Based Drug Delivery Systems

    PubMed Central

    Tan, Songwei; Wu, Tingting; Zhang, Dan; Zhang, Zhiping

    2015-01-01

    Natural cells have been explored as drug carriers for a long period. They have received growing interest as a promising drug delivery system (DDS) until recently along with the development of biology and medical science. The synthetic materials, either organic or inorganic, are found to be with more or less immunogenicity and/or toxicity. The cells and extracellular vesicles (EVs), are endogenous and thought to be much safer and friendlier. Furthermore, in view of their host attributes, they may achieve different biological effects and/or targeting specificity, which can meet the needs of personalized medicine as the next generation of DDS. In this review, we summarized the recent progress in cell or cell membrane-based DDS and their fabrication processes, unique properties and applications, including the whole cells, EVs and cell membrane coated nanoparticles. We expect the continuing development of this cell or cell membrane-based DDS will promote their clinic applications. PMID:26000058

  7. Formulation and evaluation of nano based drug delivery system for the buccal delivery of acyclovir.

    PubMed

    Al-Dhubiab, Bandar E; Nair, Anroop B; Kumria, Rachna; Attimarad, Mahesh; Harsha, Sree

    2015-12-01

    Oral bioavailability of acyclovir is limited, primarily because of low permeability across the gastrointestinal membrane. The purpose of this study is the prospective evaluation of buccal films impregnated with acyclovir loaded nanospheres as a drug delivery system to improve systemic bioavailability. Acyclovir polymeric nanospheres were prepared by double emulsion solvent evaporation technique. Nanospheres were embedded into buccoadhesive films (A1-A4) comprising of different concentrations of polymers (Eudragit RL 100, HPMC K15 and carbopol 974P). Films were characterized for physico-mechanical properties, mucoadhesive strength, hydration, drug release and ex vivo permeation. In vivo studies were carried out on rabbits to assess the pharmacokinetic profile of buccal film (A3) as compared to oral therapy. The prepared films demonstrated excellent physical properties, adequate hydration and buccoadhesive strength. In vitro drug release data inferred that the drug release was dependent on the composition of film. Ex vivo permeation studies indicated greater flux in film A3. In vivo studies revealed a significant enhancement in absorption of acyclovir (P<0.0001) with Cmax (?3 folds) and AUC0-? (?8 folds, P<0.0001) when compared to oral dosing. Moreover, the extended Tmax value (6h) signifies the potential of the prepared film to prolong acyclovir delivery. Given the promising results, the study concludes that the developed buccal film (A3) impregnated with acyclovir loaded nanospheres could be a promising approach for effective delivery of acyclovir. PMID:26547315

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

    PubMed Central

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

    2014-01-01

    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

  9. Drug and gene co-delivery systems for cancer treatment.

    PubMed

    Yang, Zhe; Gao, Di; Cao, Zhong; Zhang, Chao; Cheng, Du; Liu, Jie; Shuai, Xintao

    2015-07-01

    Cancer remains a major killer and a leading cause of death in the world; thus, a growing number of new treatments have been focused on cancer therapy over the past few decades. Chemotherapy, which is thought to be a powerful strategy for cancer treatment, has been widely used in clinical therapy in recent years. However, due to the complexity of cancer, a single therapeutic approach is insufficient for the suppression of cancer growth and migration. Therefore, increasing attention has been paid to the use of smart multifunctional carriers and combinatorially delivers chemotherapeutic drugs and functional genes in order to maximize therapeutic efficiency. Combination therapy using selected drugs and genes can not only overcome multidrug resistance and inhibit the cellular anti-apoptotic process but also achieve a synergistic therapeutic effect. Because multifunctional nanocarriers are important for achieving these goals, this review will illustrate and discuss some advanced biomaterial nanocarriers for co-delivering therapeutic genes and drugs, including multifunctional micelles, liposomes, polymeric conjugates and inorganic nanoparticles. In addition, the challenges and future perspectives for co-delivery systems, containing therapeutic drugs and genes to achieve better therapeutic effects for cancer treatment will be discussed. PMID:26221938

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. Cubosomes as targeted drug delivery systems - a biopharmaceutical approach.

    PubMed

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

    2014-01-01

    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

  13. The use of gelatin in a multiple drug delivery system

    NASA Astrophysics Data System (ADS)

    Morgan, Abby W.

    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.

  14. Development and characterization of a novel nanoemulsion drug-delivery system for potential application in oral delivery of protein drugs

    PubMed Central

    Sun, Hongwu; Liu, Kaiyun; Liu, Wei; Wang, Wenxiu; Guo, Chunliang; Tang, Bin; Gu, Jiang; Zhang, Jinyong; Li, Haibo; Mao, Xuhu; Zou, Quanming; Zeng, Hao

    2012-01-01

    Background: The stability of protein drugs remains one of the key hurdles to their success in the market. The aim of the present study was to design a novel nanoemulsion drug-delivery system (NEDDS) that would encapsulate a standard-model protein drug – bovine serum albumin (BSA) – to improve drug stability. Methods: The BSA NEDDS was prepared using a phase-inversion method and pseudoternary phase diagrams. The following characteristics were studied: morphology, size, zeta potential, drug loading, and encapsulation efficiency. We also investigated the stability of the BSA NEDDS, bioactivity of BSA encapsulated within the NEDDS, the integrity of the primary, secondary, and tertiary structures, and specificity. Results: The BSA NEDDS consisted of Cremophor EL-35, propylene glycol, isopropyl myristate, and normal saline. The average particle diameter of the BSA NEDDS was about 21.8 nm, and the system showed a high encapsulation efficiency (>90%) and an adequate drug-loading capacity (45 mg/mL). The thermodynamic stability of the system was investigated at different temperatures and pH levels and in room-temperature conditions for 180 days. BSA NEDDS showed good structural integrity and specificity for the primary, secondary, and tertiary structures, and good bioactivity of the loaded BSA. Conclusions: BSA NEDDS showed the properties of a good nanoemulsion-delivery system. NEDDS can greatly enhance the stability of the protein drug BSA while maintaining high levels of drug bioactivity, good specificity, and integrity of the primary, secondary, and tertiary protein structures. These findings indicate that the nanoemulsion is a potential formulation for oral administration of protein drugs. PMID:23118537

  15. 75 FR 45640 - Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... SERVICES Food and Drug Administration Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance...

  16. Polymeric nanoparticles for targeted drug delivery system for cancer therapy.

    PubMed

    Masood, Farha

    2016-03-01

    A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed. PMID:26706565

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

    E-print Network

    Davis, Ben G.

    Drug delivery systems based on sugar-macromolecule conjugates Benjamin G Davis* & Mark A Robinson in Drug Discovery & Development 2002 5(2): 279-288 PharmaPress Ltd ISSN 1367-6733 The specificity-tuning of active drug delivery through their great ability to undergo site- specific modification

  18. Layered double hydroxide nanocomposite for drug delivery systems; bio-distribution, toxicity and drug activity enhancement.

    PubMed

    Kura, Aminu Umar; Hussein, Mohd Zobir; Fakurazi, Sharida; Arulselvan, Palanisamy

    2014-01-01

    The production of layered double hydroxide(LDH) nanocomposite as an alternative drug delivery system against various ailments is on the increase. Their toxicity potential is usually dose and time dependent with particle sizes, shapes and surface charge playing some role both in the in vitro and in vivo studies. The reticular endothelial system of especially the liver and spleen were shown to sequestrate most of these nanocomposite, especially those with sizes greater than 50 nm. The intracellular drug delivery by these particles is mainly via endocytotic pathways aided by the surface charges in most cases. However, structural modification of these nanocomposite via coating using different types of material may lower the toxicity where present. More importantly, the coating may serve as targeting ligand hence, directing drug distribution and leading to proper drug delivery to specific area of need; it equally decreases the unwanted nanocomposite accumulation in especially the liver and spleen. These nanocomposite have the advantage of wider bio-distribution irrespective of route of administration, excellent targeted delivery potential with ease of synthetic modification including coating. PMID:25177361

  19. Single compartment drug delivery

    PubMed Central

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

    2014-01-01

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

  20. Advanced Drug-Delivery Systems of Curcumin for Cancer Chemoprevention

    PubMed Central

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

    2011-01-01

    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

  1. Design of anti-bacterial drug and anti-mycobacterial drug for drug delivery system.

    PubMed

    Yanagihara, Katsunori

    2002-01-01

    Liposome-encapsulated drugs often exhibit reduced toxicity and have also been shown to enhance retention of drugs in the tissues. Thus, encapsulation of drugs in liposomes has often resulted in an improved overall therapeutic efficacy. The results of efficacy of liposome-encapsulated ciplofloxacin or azithromycin for therapy of intracellular M. avium infection show enhanced cellular delivery of liposome-encapsulated antibiotics and suggest that efficiency of intracellular targeting is sufficient to mediate enhanced antimycobacterial effects. The antitubercular drugs encapsulated in lung specific stealth liposomes have enhanced efficacies against tuberculosis infection in mice. These results from stealth liposome study indicate that antitubercular drugs encapsulated in liposome may provide therapeutic advantages over the existing chemotherapeutic regimen for tuberculosis. Liposomes with encapsulated amikacin are able to protect collagen almost completely from adherence of bacterial cells of all strains examined and prevent from invading of bacteria. PMID:12069384

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

    E-print Network

    Campbell, Sue Ann

    loop feedback system can be influenced in a precisely controllable manner. 1 Introduction EndocrineDynamic Feedback and the Design of Closed-loop Drug Delivery Systems John Milton1,2 , Sue Ann´eal, Montr´eal, Canada Abstract A closed-loop drug delivery system is constructed in which external negative

  3. Synthesis and Characterization of a Magnetically Responsive Polymeric Drug Delivery System

    E-print Network

    Yu, Shi

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

  4. The origins and evolution of "controlled" drug delivery systems.

    PubMed

    Hoffman, Allan S

    2008-12-18

    This paper describes the earliest days when the "controlled drug delivery" (CDD) field began, the pioneers who launched this exciting and important field, and the key people who came after them. It traces the evolution of the field from its origins in the 1960s to (a) the 1970s and 1980s, when numerous macroscopic "controlled" drug delivery (DD) devices and implants were designed for delivery as mucosal inserts (e.g., in the eye or vagina), as implants (e.g., sub-cutaneous or intra-muscular), as ingestible capsules (e.g., in the G-I tract), as topical patches (e.g., on the skin), and were approved for clinical use, to (b) the 1980s and 1990s when microscopic degradable polymer depot DD systems (DDS) were commercialized, and to (c) the currently very active and exciting nanoscopic era of targeted nano-carriers, in a sense bringing to life Ehrlich's imagined concept of the "Magic Bullet". The nanoscopic era began with systems proposed in the 1970s, that were first used in the clinic in the 1980s, and which came of age in the 1990s, and which are presently evolving into many exciting and clinically successful products in the 2000s. Most of these have succeeded because of the emergence of three key technologies: (1) PEGylation, (2) active targeting to specific cells by ligands conjugated to the DDS, or passive targeting to solid tumors via the EPR effect. The author has been personally involved in the origins and evolution of this field for the past 38 years (see below), and this review includes information that was provided to him by many researchers in this field about the history of various developments. Thus, this paper is based on his own personal involvements in the CDD field, along with many historical anecdotes provided by the key pioneers and researchers in the field. Because of the huge literature of scientific papers on CDD systems, this article attempts to limit examples to those that have been approved for clinical use, or are currently in clinical trials. Even so, it is impossible to know of and include all such examples and to properly credit all the key people who helped to bring the various technologies and devices to the clinic. The author apologizes in advance for all omissions. PMID:18817820

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

    PubMed Central

    2015-01-01

    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

  6. Role of Components in the Formation of Self-microemulsifying Drug Delivery Systems

    PubMed Central

    Gurram, A. K.; Deshpande, P. B.; Kar, S. S.; Nayak, Usha Y.; Udupa, N.; Reddy, M. S.

    2015-01-01

    Pharmaceutical research is focused in designing novel drug delivery systems to improve the bioavailability of poorly water soluble drugs. Self-microemulsifying drug delivery systems, one among the lipid-based dosage forms were proven to be promising in improving the oral bioavailability of such drugs by enhancing solubility, permeability and avoiding first-pass metabolism via enhanced lymphatic transport. Further, they have been successful in avoiding both inter and intra individual variations as well as the dose disproportionality. Aqueous insoluble drugs, in general, show greater solubility in lipid based excipients, and hence they are formulated as lipid based drug delivery systems. The extent of solubility of a hydrophobic drug in lipid excipients i.e. oil, surfactant and co-surfactant (components of self-microemulsifying drug delivery systems) greatly affects the drug loading and in producing stable self-microemulsifying drug delivery systems. The present review highlighted the influence of physicochemical factors and structural features of the hydrophobic drug on its solubility in lipid excipients and an attempt was made to explore the role of each component of self-microemulsifying drug delivery systems in the formation of stable microemulsion upon dilution. PMID:26180269

  7. Poly(D, L-lactide-co-glycolide)/Poly(ethylenimine) Blend Matrix System for pH Sensitive Drug Delivery

    E-print Network

    Gao, Jinming

    utility of a PLGA/ PEI matrix and its potential application in pH responsive drug delivery. © 2006 Wiley(d,l-lactide-co-glycolide); poly(ethylenimine); pH sensitive drug delivery INTRODUCTION Drug delivery systems in which drug release delivery2­4 and selective drug delivery to the stomach5,6 or intestine.7 Changes in pH are also known

  8. Advances in polyelectrolyte multilayer nanofilms as tunable drug delivery systems

    PubMed Central

    Jiang, Bingbing; Barnett, John B; Li, Bingyun

    2009-01-01

    There has been considerable interest in polyelectrolyte multilayer nanofilms, which have a variety of applications ranging from optical and electrochemical materials to biomedical devices. Polyelectrolyte multilayer nanofilms are constructed from aqueous solutions using electrostatic layer-by-layer self-assembly of oppositely-charged polyelectrolytes on a solid substrate. Multifunctional polyelectrolyte multilayer nanofilms have been studied using charged dyes, metal and inorganic nanoparticles, DNA, proteins, and viruses. In the past few years, there has been increasing attention to developing polyelectrolyte multilayer nanofilms as drug delivery vehicles. In this mini-review, we present recent developments in polyelectrolyte multilayer nanofilms with tunable drug delivery properties, with particular emphasis on the strategies in tuning the loading and release of drugs in polyelectrolyte multilayer nanofilms as well as their applications. PMID:24198464

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

    E-print Network

    Bogyo, Matthew

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

  10. Mesoporous silica nanoparticles in target drug delivery system: A review

    PubMed Central

    Bharti, Charu; Nagaich, Upendra; Pal, Ashok Kumar; Gulati, Neha

    2015-01-01

    Due to lack of specification and solubility of drug molecules, patients have to take high doses of the drug to achieve the desired therapeutic effects for the treatment of diseases. To solve these problems, there are various drug carriers present in the pharmaceuticals, which can used to deliver therapeutic agents to the target site in the body. Mesoporous silica materials become known as a promising candidate that can overcome above problems and produce effects in a controllable and sustainable manner. In particular, mesoporous silica nanoparticles (MSNs) are widely used as a delivery reagent because silica possesses favorable chemical properties, thermal stability, and biocompatibility. The unique mesoporous structure of silica facilitates effective loading of drugs and their subsequent controlled release of the target site. The properties of mesoporous, including pore size, high drug loading, and porosity as well as the surface properties, can be altered depending on additives used to prepare MSNs. Active surface enables functionalization to changed surface properties and link therapeutic molecules. They are used as widely in the field of diagnosis, target drug delivery, bio-sensing, cellular uptake, etc., in the bio-medical field. This review aims to present the state of knowledge of silica containing mesoporous nanoparticles and specific application in various biomedical fields. PMID:26258053

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

    PubMed

    Mahnama, Ali; Nourbakhsh, Ahmad; Ghorbaniasl, Ghader

    2014-01-01

    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

  12. Dual stimuli-responsive multi-drug delivery system for the individually controlled release of anti-cancer drugs.

    PubMed

    Xiao, Wang; Zeng, Xuan; Lin, Hang; Han, Kai; Jia, Hui-Zhen; Zhang, Xian-Zheng

    2015-01-28

    A dual stimuli-responsive multi-drug delivery system was developed for "cancer cocktail therapy". Upon UV irradiation, microcapsules could rapidly release the small-molecule drugs, and thereafter the macromolecular drugs would be released in the presence of MMP in the tumor cells. This system will find great potential as a novel chemotherapeutic combination for cancer treatment. PMID:25494173

  13. An Overview of Clinical and Commercial Impact of Drug Delivery Systems

    PubMed Central

    Anselmo, Aaron C.; Mitragotri, Samir

    2014-01-01

    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

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

    PubMed

    Anselmo, Aaron C; Mitragotri, Samir

    2014-09-28

    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

  15. Fluorescent graphene quantum dots as traceable, pH-sensitive drug delivery systems

    PubMed Central

    Qiu, Jichuan; Zhang, Ruibin; Li, Jianhua; Sang, Yuanhua; Tang, Wei; Rivera Gil, Pilar; Liu, Hong

    2015-01-01

    Graphene quantum dots (GQDs) were rationally fabricated as a traceable drug delivery system for the targeted, pH-sensitive delivery of a chemotherapeutic drug into cancer cells. The GQDs served as fluorescent carriers for a well-known anticancer drug, doxorubicin (Dox). The whole system has the capacity for simultaneous tracking of the carrier and of drug release. Dox release is triggered upon acidification of the intracellular vesicles, where the carriers are located after their uptake by cancer cells. Further functionalization of the loaded carriers with targeting moieties such as arginine-glycine-aspartic acid (RGD) peptides enhanced their uptake by cancer cells. DU-145 and PC-3 human prostate cancer cell lines were used to evaluate the anticancer ability of Dox-loaded RGD-modified GQDs (Dox-RGD-GQDs). The results demonstrated the feasibility of using GQDs as traceable drug delivery systems with the ability for the pH-triggered delivery of drugs into target cells. PMID:26604747

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

    PubMed Central

    Philip, Anil K.; Philip, Betty

    2010-01-01

    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

  17. Formulation and evaluation of galantamine gel as drug reservoir in transdermal patch delivery system.

    PubMed

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

    2015-01-01

    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. PMID:25853145

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

    PubMed Central

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

    2015-01-01

    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. PMID:25853145

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

    PubMed

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

    2011-12-01

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

  20. Delivery of drugs to intracellular organelles using drug delivery systems: Analysis of research trends and targeting efficiencies.

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2015-12-30

    Targeting of drug delivery systems (DDSs) to specific intracellular organelles (i.e., subcellular targeting) has been investigated in numerous publications, but targeting efficiency of these systems is seldom reported. We searched scientific publications in the subcellular DDS targeting field and analyzed targeting efficiency and major formulation parameters that affect it. We identified 77 scientific publications that matched the search criteria. In the majority of these studies nanoparticle-based DDSs were applied, while liposomes, quantum dots and conjugates were used less frequently. The nucleus was the most common intracellular target, followed by mitochondrion, endoplasmic reticulum and Golgi apparatus. In 65% of the publications, DDSs surface was decorated with specific targeting residues, but the efficiency of this surface decoration was not analyzed in predominant majority of the studies. Moreover, only 23% of the analyzed publications contained quantitative data on DDSs subcellular targeting efficiency, while the majority of publications reported qualitative results only. From the analysis of publications in the subcellular targeting field, it appears that insufficient efforts are devoted to quantitative analysis of the major formulation parameters and of the DDSs' intracellular fate. Based on these findings, we provide recommendations for future studies in the field of organelle-specific drug delivery and targeting. PMID:26516100

  1. From drug delivery systems to drug release, dissolution, IVIVC, BCS, BDDCS, bioequivalence and biowaivers.

    PubMed

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

    2010-09-01

    This is a summary report of the conference on drug absorption and bioequivalence issues held in Titania Hotel in Athens (Greece) from the 28(th) to the 30(th) of May 2009. The conference included presentations which were mainly divided into three sections. The first section focused on modern drug delivery systems such as polymer nanotechnology, cell immobilization techniques to deliver drugs into the brain, nanosized liposomes used in drug eluting stents, encapsulation of drug implants in biocompatible polymers, and application of differential scanning calorimetry as a tool to study liposomal stability. The importance of drug release and dissolution were also discussed by placing special emphasis on camptothecins and oral prolonged release formulations. The complexity of the luminal environment and the value of dissolution in lyophilized products were also highlighted. The second session of the conference included presentations on the Biopharmaceutics Classification Scheme (BCS), the Biopharmaceutics Drug Disposition Classification System (BDDCS), and the role of transporters in the classification of drugs. The current status of biowaivers and a modern view on non-linear in vitro-in vivo (IVIVC) correlations were also addressed. Finally, this section ended with a special topic on biorelevant dissolution media and methods. The third day of the conference was dedicated to bioequivalence. Emphasis was placed on high within-subject variability and its impact on study design. Two unresolved issues of bioequivalence were also discussed: the use of generic antiepileptic drugs and the role of metabolites in bioequivalence assessment. Finally, the conference closed with a presentation of the current regulatory status of WHO and EMEA. PMID:20635193

  2. Nanocapsules: The Weapons for Novel Drug Delivery Systems

    PubMed Central

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

    2012-01-01

    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

  3. Medical applications of implantable drug delivery microdevices based on MEMS (Micro-Electro-Mechanical-Systems).

    PubMed

    Elman, N M; Upadhyay, U M

    2010-06-01

    Drug delivery microdevices based on MEMS (Micro-Electro-Mechanical-Systems) represent the next generation of active implantable drug delivery systems. MEMS technology has enabled the scaling down of current delivery modalities to the micrometer and millimeter size. The complementary use of biocompatible materials makes this technology potentially viable for a wide variety of clinical applications. Conditions such as brain tumors, chronic pain syndromes, and infectious abscess represent specialized clinical diseases that will likely benefit most from such drug delivery microdevices. Designing MEMS microdevices poses considerable technical and clinical challenges as devices need to be constructed from biocompatible materials that are harmless to human tissue. Devices must also be miniaturized and capable of delivering adequate pharmacologic payload. Balancing these competing needs will likely lead to the successful application of MEMS drug delivery devices to various medical conditions. This work reviews the various factors that must be considered in optimizing MEMS microdevices for their appropriate and successful application to medical disease. PMID:20201795

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

    PubMed

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

    2013-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

    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.

  6. Alternating current electrospinning for preparation of fibrous drug delivery systems.

    PubMed

    Balogh, Attila; Cselkó, Richárd; Démuth, Balázs; Verreck, Geert; Mensch, Jürgen; Marosi, György; Nagy, Zsombor Kristóf

    2015-11-10

    Alternating current electrospinning (ACES) was compared to direct current electrospinning (DCES) for the preparation of drug-loaded nanofibrous mats. It is generally considered that DCES is the solely technique to produce nanofibers using the electrostatic force from polymer solutions, however, less studied and also capable ACES provides further advantages such as increased specific productivities. A poorly water-soluble drug (carvedilol) was incorporated into the fibers based on three different polymeric matrices (an acid-soluble terpolymer (Eudragit(®) E), a base-soluble copolymer (Eudragit(®) L 100-55) and a nonionic homopolymer (polyvinylpyrrolidone K90)) to improve the dissolution of the weak base drug under different pH conditions. Morphology and fiber diameter evaluation showed similar electrospun fibers regardless the type of the high voltage and the major differences in feeding rates. The amorphous ACES and DCES fibers provided fast and total drug dissolutions in all cases. The presented results show that ACES can be a more feasible novel alternative to formulate fibers for drug delivery purposes. PMID:26320549

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

    PubMed

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

    2013-07-29

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

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

    PubMed

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

    2015-02-01

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

  9. Intranasal delivery of systemic-acting drugs: small-molecules and biomacromolecules.

    PubMed

    Fortuna, Ana; Alves, Gilberto; Serralheiro, Ana; Sousa, Joana; Falcão, Amílcar

    2014-09-01

    As a non-invasive route, intranasal administration offers patient comfort and compliance which are hurdled in parenteral drug therapy. In addition, the current recognition that the high permeability and vascularization of nasal mucosa coupled to the avoidance of the first-pass elimination and/or gastrointestinal decomposition ensure higher systemic drug absorption than oral route has contributed to the growing interest for intranasal delivery of drugs that require considerable systemic exposure to exert their therapeutic actions (systemic-acting drugs). Nevertheless, several features may hamper drug absorption through the nasal mucosa, particularly the drug molecular weight and intrinsic permeability, and, therefore, several strategies have been employed to improve it, propelling a constant challenge during nasal drug (formulation) development. This review will firstly provide an anatomical, histological and mechanistic overview of drug systemic absorption after nasal administration and the relevant aspects of the therapeutic interest and limitations of the intranasal systemic delivery. The current studies regarding the nasal application of systemic-acting small drugs (analgesic drugs, cardiovascular drugs and antiviral drugs) and biomacromolecular drugs (peptide/protein drugs and vaccines) will also be outlined, addressing drug pharmacokinetics and pharmacodynamic improvements. PMID:24681294

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

    PubMed Central

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

    2013-01-01

    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

  11. Enzymatic action of phospholipase A? on liposomal drug delivery systems.

    PubMed

    Hansen, Anders H; Mouritsen, Ole G; Arouri, Ahmad

    2015-08-01

    The overexpression of secretory phospholipase A2 (sPLA2) in tumors has opened new avenues for enzyme-triggered active unloading of liposomal antitumor drug carriers selectively at the target tumor. However, the effects of the liposome composition, drug encapsulation, and tumor microenvironment on the activity of sPLA2 are still not well understood. We carried out a physico-chemical study to characterize the sPLA2-assisted breakdown of liposomes using dye-release assays in the context of drug delivery and under physiologically relevant conditions. The influence of temperature, lipid concentration, enzyme concentration, and drug loading on the hydrolysis of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC, Tm=42°C) liposomes with snake venom sPLA2 was investigated. The sensitivity of human sPLA2 to the liposome composition was checked using binary lipid mixtures of phosphatidylcholine (PC) and phosphatidylglycerol (PG) phospholipids with C14 and C16 acyl chains. Increasing temperature (36-41°C) was found to mainly shorten the enzyme lag-time, whereas the effect on lipid hydrolysis rate was modest. The enzyme lag-time was also found to be inversely dependent on the lipid-to-enzyme ratio. Drug encapsulation can alter the hydrolysis profile of the carrier liposomes. The activity of human sPLA2 was highly sensitive to the phospholipid acyl-chain length and negative surface charge density of the liposomes. We believe our work will prove useful for the optimization of sPLA2-susceptible liposomal formulations as well as will provide a solid ground for predicting the hydrolysis profile of the liposomes in vivo at the target site. PMID:26056930

  12. Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems.

    PubMed

    Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Badshah, Shaikh Atik; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

    2015-01-01

    Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems. PMID:26473828

  13. Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

    PubMed Central

    Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Atik Badshah, Shaikh; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

    2015-01-01

    Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems. PMID:26473828

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

    PubMed

    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

    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

  15. Drug delivery systems--2. Site-specific drug delivery utilizing monoclonal antibodies.

    PubMed

    Ranade, V V

    1989-10-01

    Monoclonal antibodies (MAbs) are purified antibodies produced by a single clone of cells. They are engineered to recognize and bind to a single specific antigen. Accordingly, when administered, MAbs home in on a particular circulating protein or on cells that bear the correct antigenic signature on their surfaces. It is the specificity of MAbs that has made them valuable tools for health professions. Following the discovery of Kohler and Milstein regarding the method of somatic cell hybridization, a number of investigators have successfully adopted this technique to obtain T-lymphocyte hybrid cell lines by fusion of activated T (thymus derived) lymphocytes with a T lymphoma cell line leading to an immortalization of a specific differentiated function. The hybrids thus obtained were subsequently shown to produce homogeneous effector molecules with a wide variety of immune functions such as enhancement or suppression of antibody responses, generation of helper T cells, suppressor T cells and cytotoxic T cells. Study of these regulatory molecules has been further shown to provide a greater insight into the genetic, biochemical and molecular mechanisms responsible for cellular development, and the interaction and triggering of various cell types. The successful application of hybridoma technology has now resulted into several advances in the understanding the mechanism and treatment of diseases, especially cancer and development of vaccines, promotion of organ transplantation and therapy against parasites as well. Since monoclonal antibodies could be made in unlimited supply, they have been used in genetic studies such as mRNA and gene isolation, chromosomal isolation of specific genes, immunoglobulin structure, detection of new or rare immunoglobulin gene products, structural studies of enzymes and other proteins and structural and population studies of protein polymorphisms. In some instances, the monoclonal antibodies have been found to replace conventional antisera for studies of chromosome structure and function, gene mapping, embryogenesis, characterization and biosynthesis of developmental and differentiation antigens. These antigens are those that are specific for various cell types and tissues, species specific antigen, antigens involved in chemotaxis, immunogenetics and clinical genetics including genetically inherited disorders, chromosome aberrations and transplantation antigens. Besides these monoclonal antibodies, their complexes have recently been investigated as exquisitely sensitive probes to be guided to target cells or organs. They have been used to deliver cytotoxic drugs to malignant cells or enzymes to specific cell types.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2687335

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

    PubMed Central

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

    2011-01-01

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

  17. Fast disintegrating tablets: Opportunity in drug delivery system

    PubMed Central

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

    2011-01-01

    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

  18. Bioactive and bioresponsive nanoparticle surface modifications for vaccine and systemic drug delivery

    E-print Network

    Clawson, Corbin Zean

    2011-01-01

    A Robust Drug Delivery Platform. ACS Nano. 2008;2(8):1696-Drug Delivery and Tissue Engineering: From Discovery to Applications. Nanodrug delivery platform. We call the new nanoparticle based theranostic platform Nano

  19. Design, fabrication and characterization of drug delivery systems based on lab-on-a-chip technology.

    PubMed

    Nguyen, Nam-Trung; Shaegh, Seyed Ali Mousavi; Kashaninejad, Navid; Phan, Dinh-Tuan

    2013-11-01

    Lab-on-a-chip technology is an emerging field evolving from the recent advances of micro- and nanotechnologies. The technology allows the integration of various components into a single microdevice. Microfluidics, the science and engineering of fluid flow in microscale, is the enabling underlying concept for lab-on-a-chip technology. The present paper reviews the design, fabrication and characterization of drug delivery systems based on this amazing technology. The systems are categorized and discussed according to the scales at which the drug is administered. Starting with the fundamentals on scaling laws of mass transfer and basic fabrication techniques, the paper reviews and discusses drug delivery devices for cellular, tissue and organism levels. At the cellular level, a concentration gradient generator integrated with a cell culture platform is the main drug delivery scheme of interest. At the tissue level, the synthesis of smart particles as drug carriers using lab-on-a-chip technology is the main focus of recent developments. At the organism level, microneedles and implantable devices with fluid-handling components are the main drug delivery systems. For drug delivery to a small organism that can fit into a microchip, devices similar to those of cellular level can be used. PMID:23726943

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

    PubMed Central

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

    2012-01-01

    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

  1. Controlled Release System for Localized and Sustained Drug Delivery Applications

    NASA Astrophysics Data System (ADS)

    Rodriguez, Lidia Betsabe

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

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

    E-print Network

    Zheng, Yi; Hu, Junqiang; Lin, Qiao

    2012-01-01

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

  3. Organ-on-a-Chip Platforms for Studying Drug Delivery Systems

    PubMed Central

    Bhise, Nupura S.; Ribas, João; Manoharan, Vijayan; Zhang, Yu Shrike; Polini, Alessandro; Massa, Solange; Dokmeci, Mehmet R.; Khademhosseini, Ali

    2014-01-01

    Novel microfluidic tools allow new ways to manufacture and test drug delivery systems. Organ-on-a-chip systems – microscale recapitulations of complex organ functions – promise to improve the drug development pipeline. This review highlights the importance of integrating microfluidic networks with 3D tissue engineered models to create organ-on-a-chip platforms, able to meet the demand of creating robust preclinical screening models. Specific examples are cited to demonstrate the use of these systems for studying the performance of drug delivery vectors and thereby reduce the discrepancies between their performance at preclinical and clinical trials. We also highlight the future directions that need to be pursued by the research community for these proof-of-concept studies to achieve the goal of accelerating clinical translation of drug delivery nanoparticles. PMID:24818770

  4. Bioresponsive matrices in drug delivery

    PubMed Central

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

    Ling, Peixue; Zhang, Tianmin

    2013-01-01

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

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

    PubMed Central

    2011-01-01

    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

  9. Role of pressure-sensitive adhesives in transdermal drug delivery systems.

    PubMed

    Lobo, Shabbir; Sachdeva, Sameer; Goswami, Tarun

    2016-01-01

    Transdermal drug delivery systems (TDDS) are employed for the delivery of drugs across skin into the systemic circulation. Pressure-sensitive adhesive (PSA) is one of the most critical components used in a TDDS. The primary function of PSA is to help in adhesion of patch to skin, but more importantly it acts as a matrix for the drug and other excipients. Hence, apart from adhesion of the patch, PSA also affects other critical quality attributes of the TDDS such as drug delivery, flux through skin and physical and chemical stability of the finished product. This review article provides a summary of the adhesives used in various types of TDDS. In particular, this review will cover the design types of TDDS, categories of PSAs and their evaluation and regulatory aspects. PMID:26652621

  10. Modular reservoir concept for MEMS-based transdermal drug delivery systems

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

    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.

  11. Dendrimer-coupled sonophoresis-mediated transdermal drug-delivery system for diclofenac

    PubMed Central

    Huang, Bin; Dong, Wei-Jiang; Yang, Gao-Yi; Wang, Wei; Ji, Cong-Hua; Zhou, Fei-Ni

    2015-01-01

    The purpose of the present study was to develop a novel transdermal drug-delivery system comprising a polyamidoamine dendrimer coupled with sonophoresis to enhance the permeation of diclofenac (DF) through the skin. The novel transdermal drug-delivery system was developed by using a statistical Plackett–Burman design. Hairless male Wistar rat skin was used for the DF-permeation study. Coupling media concentration, ultrasound-application time, duty cycle, distance from probe to skin, and a third-generation polyamidoamine-dendrimer concentration were selected as independent variables, while in vitro drug release was selected as a dependent variable. Independent variables were found to be statistically significant (P<0.05). DF gel without dendrimer and ultrasound treatment to skin (passive delivery, run 13) showed 56.69 µg/cm2 cumulative drug permeated through the skin, while the DF-dendrimer gel without sonophoresis treatment (run 14) showed 257.3 µg/cm2 cumulative drug permeated through the skin after 24 hours. However, when the same gel was applied to sonophoresis-treated skin, drastic permeation enhancement was observed. In the case of run 3, the cumulative drug that permeated through the skin was 935.21 µg/cm2. It was concluded that dendrimer-coupled sonophoresis-mediated transdermal drug delivery system has the potential to enhance the permeation of DF through the skin. PMID:26229447

  12. Novel in vivo imaging analysis of an inner ear drug delivery system: Drug availability in inner ear following different dose of systemic drug injections.

    PubMed

    Kanzaki, Sho; Watanabe, Kotaro; Fujioka, Masato; Shibata, Shinsuke; Nakamura, Masaya; Okano, Hirotaka James; Okano, Hideyuki; Ogawa, Kaoru

    2015-12-01

    Systemic application of drugs is commonly used in clinical situations. Some of these drugs are ototoxic. Since there are few studies on in vivo monitoring of drug delivery dynamics, the time course or bioavailability of drugs in the inner ear of live animals following systemic drug application remains unknown. For instance, it is unknown whether the volume of a drug delivered systemically correlates with its inner ear pharmacokinetics. We previously established a new in vivo imaging system to monitor drug delivery in live mice. In the present study, we used this system to compare drug concentration in the inner ear over time after systemic drug injections. We used transgenic GFAP-Luc mice that harbor a firefly luciferase gene expression cassette regulated by 12 kb of murine GFAP promoter and human beta-globin intron 2. Luciferin delivered into the inner ear of these mice reacts with luciferase, and the resulting signals are detected in GFAP-expressing cells in the cochlear nerve. Thus, we assessed in the inner ear the intensity and duration of luciferin/luciferase signals after systemic injections of different volumes of luciferin. An IVIS(®) imaging system was used to observe signals, and these signals were compared to the drug dynamics of luciferin delivered through subcutaneous (sc) injections. The volume of sc-injected drug correlated significantly with photon counts measured in the inner ear. Photons were detected almost immediately after injection, peaking 20 min after injection. Drug concentration did not affect inner ear signals. Luciferin injected systemically appeared in the inner ear between highest and lowest concentration. Drug volume is an important parameter to know if the inner ear requires a higher level of the drug. We observed that it is the volume of a drug-not its concentration-that is the important factor. Indeed, the more volume of a drug injected systemically increased the concentration of that drug in the inner ear. This study provides a better understanding of in vivo drug delivery dynamics measured in the inner ear. Further studies will show whether a high dosage of drug is effective or not. This article is part of a Special Issue entitled . PMID:26435094

  13. Intranasal drug delivery to the central nervous system: present status and future outlook.

    PubMed

    Tayebati, Seyed Khosrow; Nwankwo, Innocent Ejike; Amenta, Francesco

    2013-01-01

    Pharmacological treatment of disorders affecting the central nervous system (CNS) is a complex task. Different parameters may negatively influence effective targeting of the CNS and drug compliance, for example, poor brain-blood barrier (BBB) permeability, patient forgetfulness or neglect, and lack of collaboration between caregivers and patients. Pharmaceutical science is constantly looking for new administration strategies for efficient drug delivery to the CNS that could obviate these problems. Drugs can reach the brain through the skin, nasal cavity and oral cavity, and while effective transport of drugs from skin and nasal cavity to the CNS has been documented, these studies did not stimulate the introduction of a substantial number of new drug formulations to treat CNS disorders. Nasal drug delivery, generally used to administer locally acting molecules, is not common for systemic administration, although the possibility and importance of such systemic administration is suggested by several studies. This paper reviewed different anatomical and pharmaceutical factors related to drug administration through the nasal route, and explored whether nasal delivery of selected CNS drugs could improve their pharmacokinetics and patient compliance. This route offers attractive advantages, and pharmaceutical scientists and anatomists should collaborate to improve CNS drug compliance and to increase the number of compounds that can be administered intranasally. PMID:23116337

  14. Colon-targeted oral drug delivery systems: design trends and approaches.

    PubMed

    Amidon, Seth; Brown, Jack E; Dave, Vivek S

    2015-08-01

    Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS. PMID:26070545

  15. Texosome-based drug delivery system for cancer therapy: from past to present

    PubMed Central

    Mahmoodzadeh Hosseini, Hamideh; Halabian, Raheleh; Amin, Mohsen; Imani Fooladi, Abbas Ali

    2015-01-01

    Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Malfunction of the immune system, particularly in the tumor microenvironment, causes tumor growth and enhances tumor progression. Thus, cancer immunotherapy can be an appropriate approach to provoke the systemic immune system to combat tumor expansion. Texosomes, which are endogenous nanovesicles released by all tumor cells, contribute to cell-cell communication and modify the phenotypic features of recipient cells due to the texosomes’ ability to transport biological components. For this reason, texosome-based delivery system can be a valuable strategy for therapeutic purposes. To improve the pharmaceutical behavior of this system and to facilitate its use in medical applications, biotechnology approaches and mimetic techniques have been utilized. In this review, we present the development history of texosome-based delivery systems and discuss the advantages and disadvantages of each system. PMID:26487960

  16. Rhythmomimetic drug delivery

    E-print Network

    Calderer, M Carme; Siegel, Ronald A; Yao, Lingxing

    2015-01-01

    We present modeling, analysis and numerical simulation of a prototype glucose driven drug delivery device based on chemomechanical interactions and volume phase transitions in polyelectrolyte gels. The device consists of two fluid compartments, an external cell (I) mimicking the physiological environment, and a closed chamber (II), separated by a hydrogel membrane. Cell I, which is held at constant pH and ionic strength, provides a constant supply of glucose to cell II, and also serves as clearance station for reaction products. Cell II contains the drug to be delivered to the body, an enzyme that catalyzes conversion of glucose into hydrogen ions, and a piece of marble to remove excess hydrogen ions that would otherwise overwhelm the system. When the membrane is swollen, glucose flux into Cell II is high, leading to rapid production of hydrogen ions. However, the hydrogen ions are not immediately released to Cell I but react, instead, with the negatively charged carboxyl groups of the membrane, which collaps...

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

    PubMed Central

    Bose, Susmita; Tarafder, Solaiman

    2012-01-01

    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

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

    E-print Network

    Saltzman, Wendy

    Effective and well-tolerated drug delivery and restraint systems are essential for studies and restraint systems for small primates are not as well developed (Blum et al. 1983, O'Byrne 1988, O over the larger, less fecund and slower-maturing macaques Novel restraint system for neuroendocrine

  19. Exosome nanotechnology: an emerging paradigm shift in drug delivery: exploitation of exosome nanovesicles for systemic in vivo delivery of RNAi heralds new horizons for drug delivery across biological barriers.

    PubMed

    Lakhal, Samira; Wood, Matthew J A

    2011-10-01

    The demonstration that dendritic cell (DC)-derived exosomes can be exploited for targeted RNAi delivery to the brain after systemic injection provides the first proof-of-concept for the potential of these naturally occurring vesicles as vehicles of drug delivery. As well as being amenable to existing in vivo targeting strategies already in use for viruses and liposomes, this novel approach offers the added advantages of in vivo safety and low immunogenicity. Fulfilment of the potential of exosome delivery methods warrants a better understanding of their biology, as well as the development of novel production, characterisation, targeting and cargo-loading nanotechnologies. Ultimately, exosome-mediated drug delivery promises to overcome important challenges in the field of therapeutics, such as delivery of drugs across otherwise impermeable biological barriers, such as the blood brain barrier, and using patient-derived tissue as a source of individualised and biocompatible therapeutic drug delivery vehicles. PMID:21932222

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

    PubMed

    Jain, Dharmendra; Bar-Shalom, Daniel

    2014-12-01

    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

  1. Pathogen-inspired drug delivery to the central nervous system

    PubMed Central

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

    2014-01-01

    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

  2. A multifunctional metal-organic framework based tumor targeting drug delivery system for cancer therapy.

    PubMed

    Wang, Xiao-Gang; Dong, Zhi-Yue; Cheng, Hong; Wan, Shuang-Shuang; Chen, Wei-Hai; Zou, Mei-Zhen; Huo, Jia-Wei; Deng, He-Xiang; Zhang, Xian-Zheng

    2015-10-14

    Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free "green" post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects. PMID:26372069

  3. The recent progresses on the improved therapy of melanoma by novel drug delivery systems.

    PubMed

    Taymouri, Somayeh; Varshosaz, Jaleh

    2014-01-01

    Melanoma is a life threatening disease with a growing incidence rate. It is estimated that 9840 patients will die from melanoma in 2014. Despite numerous attempts for treating metastatic melanoma, conventional therapies including systemic chemotherapy or immunotherapy, either as single agents or combined, have not been promising. The most cytotoxic agents have low molecular weight, which leads to rapid excretion, nonspecific distribution, and poor therapeutic index. Therefore, they may even increase toxicity due to their non-specific action on healthy tissue that can exacerbate the malady. To provide optimum effective concentration, multiple-dose drug administration is required, which again can increase the incidence of adverse effects. Recent developments in drug delivery systems are able to improve the drug efficacy and safety, and offer more promising approaches in treating melanoma. Recent researches have shed more light on the advantages of novel drug loaded carrier systems versus free drugs. Most of these animal studies, reported improvement in treatment efficacy and survival rate using novel carrier systems. This is related to the ability of these systems in enhancing the anticancer effect by modifying drug pharmacokinetics and biodistribution, selective target delivery of the agents to the diseased tissue and their ability to cross the biological barriers. In this paper, it is attempted to illustrate the potentials of novel strategies in treatment of melanoma incorporating drug delivery systems versus conventional therapies. PMID:24947545

  4. A multifunctional metal-organic framework based tumor targeting drug delivery system for cancer therapy

    NASA Astrophysics Data System (ADS)

    Wang, Xiao-Gang; Dong, Zhi-Yue; Cheng, Hong; Wan, Shuang-Shuang; Chen, Wei-Hai; Zou, Mei-Zhen; Huo, Jia-Wei; Deng, He-Xiang; Zhang, Xian-Zheng

    2015-09-01

    Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects.Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects. Electronic supplementary information (ESI) available: Synthesis procedure, 1HNMR, ESI-MS and additional data. See DOI: 10.1039/c5nr04045k

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

    PubMed

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

    2012-12-01

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

  6. Dual acid-responsive supramolecular nanoparticles as new anticancer drug delivery systems.

    PubMed

    Wang, Chunran; Chen, Xiaofei; Yao, Xuemei; Chen, Li; Chen, Xuesi

    2015-12-15

    Considering the specific pH gradients of tumour microenvironments, a dual acid-responsive drug delivery system, which can respond to the tumor extracellular and intercellular pH stimuli, has been fabricated via simple host-guest recognition. Firstly, we synthesise 2,4,6-trimethoxybenzaldehyde modified dextran (Dex-TMBA) and mPEG-imine-?-cyclodextrin (PIC), respectively. And then, through the host-guest recognition between the cyclodextrin (CD) of PIC and the benzene ring of Dex-TMBA, a kind of dual acid-responsive supramolecular drug delivery system can be fabricated. Under neutral pH conditions, anticancer drugs can be loaded by forming supramolecular nanoparticles via the host-guest recognition. While, at tumor extracellular pH (?6.8), the acid-labile benzoic-imine of PIC cleaves and the nanoparticles are amino positively charged to facilitate cell internalization. Subsequently, due to the hydrolysis of acetal bonds in Dex-TMBA under significantly increased acidity in subcellular compartments such as the endosomes (?5.3), the loaded doxorubicin releases from the endocytosed drug delivery. This dual acid-responsive nanoparticles can efficiently load and release drugs, acting as drug delivery systems for enhancing anticancer efficiency. PMID:26438891

  7. Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease

    PubMed Central

    Fonseca-Santos, Bruno; Gremião, Maria Palmira Daflon; Chorilli, Marlus

    2015-01-01

    Alzheimer’s disease is a neurological disorder that results in cognitive and behavioral impairment. Conventional treatment strategies, such as acetylcholinesterase inhibitor drugs, often fail due to their poor solubility, lower bioavailability, and ineffective ability to cross the blood–brain barrier. Nanotechnological treatment methods, which involve the design, characterization, production, and application of nanoscale drug delivery systems, have been employed to optimize therapeutics. These nanotechnologies include polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and liquid crystals. Each of these are promising tools for the delivery of therapeutic devices to the brain via various routes of administration, particularly the intranasal route. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease. PMID:26345528

  8. Ultrasonic drug delivery in Oncology.

    PubMed

    Udroiu, Ion

    2015-01-01

    Ultrasound-assisted drug delivery is an emerging technique that has the advantage of being non-invasive, efficiently and specifically targeted and controllable. While systemic drugs often show detrimental side effects, their ultrasound-triggered local release at the selected tissue may improve safety and specifity of therapy. An increasing amount of animal and preclinical studies demonstrates how ultrasound can also be used for increasing the efficacy of chemotherapeutic drug release to solid tumors. In particular, this technique may be functional to reach uniform delivery of chemotherapeutic agents throughout tumors, which is naturally restricted by their abnormal vascularization and interstitial pressure. This review deals with the physical mechanisms of ultrasound, the different kinds of drug carriers (microbubbles, liposomes and micelles) and the biological phenomena useful for cancer treatment (hyperthermia, sonoporation, enhanced extravasation, sonophoresis and blood-brain barrier disruption), showing how much ultrasonic drug delivery is a promising method in the oncological field. PMID:26011326

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

    PubMed Central

    Ramteke, Kuldeep Hemraj; Nath, Lilakant

    2014-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2010-10-01

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

  11. Optimal periodic control of a drug delivery system Subbarao Varigonda 1

    E-print Network

    Georgiou, Tryphon T.

    2007 #12;reproductive disorders in both males and females, must be treated with periodic pulses (periodOptimal periodic control of a drug delivery system Subbarao Varigonda 1 , Tryphon T. Georgiou 2. A simple pharmacokinetic-pharmacodynamic (PKPD) model of a system exhibiting tolerance is considered

  12. An Implantable MEMS Micropump System for Drug Delivery in Small Animals

    PubMed Central

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

    2012-01-01

    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

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

    PubMed

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

    2012-06-01

    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

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

    PubMed Central

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

    2012-01-01

    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

  15. Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute.

    PubMed

    Wokovich, Anna M; Prodduturi, Suneela; Doub, William H; Hussain, Ajaz S; Buhse, Lucinda F

    2006-08-01

    Transdermal drug delivery systems (TDDS), also known as "patches," are dosage forms designed to deliver a therapeutically effective amount of drug across a patient's skin. The adhesive of the transdermal drug delivery system is critical to the safety, efficacy and quality of the product. In the Drug Quality Reporting System (DQRS), the United States Food and Drug Administration (FDA) has received numerous reports of "adhesion lacking" for transdermal drug delivery systems. This article provides an overview of types of transdermals, their anatomy, the role of adhesion, the possible adhesion failure modes and how adhesion can be measured. Excerpts from FDA reports on the lack of adhesion of transdermal system products are presented. Pros and cons of in vitro techniques, such as peel adhesion, tack and shear strength, in vivo techniques used to evaluate adhesive properties are discussed. To see a decrease in "adhesion lacking" reports, adhesion needs to become an important design parameter and suitable methods need to be available to assess quality and in vivo performance. This article provides a framework for further discussion and scientific work to improve transdermal adhesive performance. PMID:16797171

  16. Novel controlled drug delivery system for multiple drugs based on electrospun nanofibers containing nanomicelles.

    PubMed

    Hu, Jun; Zeng, Fangfa; Wei, Junchao; Chen, Yong; Chen, Yiwang

    2014-01-01

    This research described a novel composite electrospun nanofibers, which were consisted of MPEG-b-PLA micelles, chitosan, and PEO, realizing controlled release of both hydrophobic and hydrophilic drugs. 5-FU and Cefradine used as model drugs were successfully loaded in the nanofibers. The in vitro studies showed there was a low initial burst release of 5-FU from micelles-loaded nanofibers, and the final release proportion was about 91.4% after continually releasing for 109?h. In vitro cytotoxicity studies revealed that 5-FU-loaded nanofibers restrained HepG-2 cells efficiently, and the cell viability was 45.9% after three days of cultivation in solutions containing micelles-loaded nanofibers with 21.6 ?g 5-FU. All results suggested that micelles-loaded nanofibers with two kinds of drugs can be used as an effective controlled drug delivery vehicle and may have a bright future in cancer chemotherapy or clinical treatments. PMID:24160558

  17. Development of Drug Delivery Systems Based on Layered Hydroxides for Nanomedicine

    PubMed Central

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

    2014-01-01

    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

  18. Microsponges based novel drug delivery system for augmented arthritis therapy

    PubMed Central

    Osmani, Riyaz Ali M.; Aloorkar, Nagesh H.; Ingale, Dipti J.; Kulkarni, Parthasarathi K.; Hani, Umme; Bhosale, Rohit R.; Jayachandra Dev, Dandasi

    2015-01-01

    The motive behind present work was to formulate and evaluate gel containing microsponges of diclofenac diethylamine to provide prolonged release for proficient arthritis therapy. Quasi-emulsion solvent diffusion method was implied using Eudragit RS-100 and microsponges with varied drug–polymer ratios were prepared. For the sake of optimization, diverse factors affecting microparticles physical properties were too investigated. Microsponges were characterized by SEM, DSC, FT-IR, XRPD and particle size analysis, and evaluated for morphology, drug loading, in vitro drug release and ex vivo diffusion as well. There were no chemical interactions between drug and polymers used as revealed by compatibility studies outcomes. The drug polymer ratio reflected notable effect on drug content, encapsulation efficiency and particle size. SEM results revealed spherical microsponges with porous surface, and had 7.21 ?m mean particle size. The microsponges were then incorporated in gel; which exhibited viscous modulus along with pseudoplastic behavior. In vitro drug release results depicted that microsponges with 1:2 drug–polymer ratio were more efficient to give extended drug release of 75.88% at the end of 8 h; while conventional formulation get exhausted incredibly earlier by releasing 81.11% drug at the end of 4 h only. Thus the formulated microsponge-based gel of diclofenac diethylamine would be a promising alternative to conventional therapy for safer and efficient treatment of arthritis and musculoskeletal disorders. PMID:26594124

  19. Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review

    PubMed Central

    Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon

    2015-01-01

    Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy. PMID:26078967

  20. Capillary Physiology and Drug Delivery in Central

    E-print Network

    Timmer, Jens

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

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

    PubMed Central

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

    2013-01-01

    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

  2. Non-invasive systemic drug delivery: developability considerations for alternate routes of administration.

    PubMed

    Mathias, Neil R; Hussain, Munir A

    2010-01-01

    Over the past few decades alternate routes of administration have gained significant momentum and attention, to complement approved drug products, or enable those that cannot be delivered by the oral or parenteral route. Intranasal, buccal/sublingual, pulmonary, and transdermal routes being the most promising non-invasive systemic delivery options. Considering alternate routes of administration early in the development process may be useful to enable new molecular entities (NME) that have deficiencies (extensive first-pass metabolism, unfavorable physicochemical properties, gastro-intestinal adverse effects) or suboptimal pharmacokinetic profiles that are identified in preclinical studies. This review article describes the various delivery considerations and extraneous factors in developing a strategy to pursue an alternate route of administration for systemic delivery. The various delivery route options are outlined with their pros and cons; key criteria and physicochemical attributes that would make a drug a suitable candidate are discussed; approaches to assess delivery feasibility, toxicity at the site of delivery, and overall developability potential are described; and lastly, product trends and their disease implications are highlighted to underscore treatment precedence that help to build scientific rationale for the pursuit of an alternate route of administration. PMID:19499570

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

    E-print Network

    Ljubljana, University of

    -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

  4. Nanoencapsulation for drug delivery

    PubMed Central

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

    2014-01-01

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

  5. A modified emulsion gelation technique to improve buoyancy of hydrogel tablets for floating drug delivery systems.

    PubMed

    Yom-Tov, Ortal; Seliktar, Dror; Bianco-Peled, Havazelet

    2015-10-01

    The use of buoyant or floating hydrogel tablets is of particular interest in the sustained release of drugs to the stomach. They have an ability to slow the release rates of drugs by prolonging their absorption window in the upper part of the gastrointestinal (GI) tract. In this study we synthesized bioactive hydrogels that have sustainable release rates for drugs in the stomach based on a hydrogel preparation technique that employs emulsifying surfactants. The emulsion gelation technique, which encapsulates oil droplets within the hydrogels during crosslinking, was used to decrease their specific gravity in aqueous environments, resulting in floating drug release depots. Properties such as swelling, buoyancy, density and drug release were manipulated by changing the polymer concentrations, surfactant percentages and the oil:polymer ratios. The relationship between these properties and the hydrogel's floating lag time was documented. The potential for this material to be used as a floating drug delivery system was demonstrated. PMID:26117764

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

    PubMed Central

    Zhang, Xiao-Yu; Lu, Wei-Yue

    2014-01-01

    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

  7. Two-photon triggered drug delivery system: a new way to prevent posterior capsule opacification

    NASA Astrophysics Data System (ADS)

    Kim, H.-C.; Härtner, S.; Hampp, N.

    2006-02-01

    One of the major complications of cataract surgery is posterior capsule opacification caused by proliferation and migration of residual lens epithelial cells into the visual axis. In this study we present a novel approach to treat posterior capsule opacification in a non-invasive manner. A polymer-drug conjugate has been developed which is suitable for manufacturing functional intraocular lenses equipped with a drug delivery system. The therapeutic molecules, 5-fluorouracil, were attached through a photolabile linkage to the acrylic polymer backbone of the intraocular lens material. The controlled release of 5-fluorouracil is accomplished by two-photon induced cleavage of the linkage which is stable in ordinary conditions. The properties of the therapeutic system are characterized and the function is demonstrated in in vitro tests. The utilization of two-photon-absorption processes in drug delivery may provide a powerful tool to prevent posterior capsule opacification.

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

    PubMed Central

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

    2014-01-01

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

  9. Evaluation of hydroxypropyl methylcellulose matrix systems as swellable gastro-retentive drug delivery systems (GRDDS).

    PubMed

    Matharu, Amol S; Motto, Michael G; Patel, Mahendra R; Simonelli, Anthony P; Dave, Rutesh H

    2011-01-01

    Utilizing gastro-retentive drug delivery systems (GRDDS) to increase absorption of weakly basic drugs by extending their transit time is a promising approach. Swellable systems were evaluated for this purpose. Such systems demonstrate dual mechanism of release-diffusion and erosion. GRDDS requires maintaining its dimensions, which demands diffusion as a predominant mechanism of release (Fickian). In this work, dypyridamole, a weakly basic drug, together with various grades of hydroxypropyl methylcellulose and different excipients were evaluated for release and swelling properties. Dissolution data were analyzed by curve fitting to various models to estimate predominant release mechanism. It was found that matrices containing a swellable diluent like microcrystalline cellulose demonstrated predominantly Fickian mechanism of release, whereas soluble diluents (lactose and mannitol) contributed to a mixed mechanism of release. Addition of copovidone increased the swelling and survivability, whereas sodium chloride altered the erosion behavior. A correlation between matrix weight loss and drug release was obtained, which further consolidated the analysis. Correlation for the soluble excipients was linear, whereas that for the swellable excipient was nonlinear, implying predominance of Fickian release mechanism for the latter. Hence, the selection of excipients can influence matrix survivability and release kinetics, which can be used for developing GRDDS. PMID:20572054

  10. Rhythmomimetic drug delivery

    E-print Network

    M. Carme Calderer; Yoichiro Mori; Ronald A. Siegel; Lingxing Yao

    2015-01-06

    We present modeling, analysis and numerical simulation of a prototype glucose driven drug delivery device based on chemomechanical interactions and volume phase transitions in polyelectrolyte gels. The device consists of two fluid compartments, an external cell (I) mimicking the physiological environment, and a closed chamber (II), separated by a hydrogel membrane. Cell I, which is held at constant pH and ionic strength, provides a constant supply of glucose to cell II, and also serves as clearance station for reaction products. Cell II contains the drug to be delivered to the body, an enzyme that catalyzes conversion of glucose into hydrogen ions, and a piece of marble to remove excess hydrogen ions that would otherwise overwhelm the system. When the membrane is swollen, glucose flux into Cell II is high, leading to rapid production of hydrogen ions. However, the hydrogen ions are not immediately released to Cell I but react, instead, with the negatively charged carboxyl groups of the membrane, which collapses when a critical pH is reached in Cell II, substantially attenuating glucose transport and $\\textrm {H}^+$ production. Subsequent diffusion of attached $\\textrm {H}^+$ ions increases again the concentration of negative carboxyl groups in the membrane, causing the gel to re-swell, and the process is poised to repeat itself. Since drug release can only occur when the membrane is swollen, release occurs in rhythmic pulses that are coherent with the pH oscillations in Cell II and swelling oscillations of the membrane. The work to analyze them combines multiscale methods with tools from dynamical systems to show existence of sustained oscillations for a robust set of material parameters. The predictions of the model are in good agreement with earlier experimental results obtained with a laboratory device.

  11. 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 ...

  12. Nanotopography applications in drug delivery.

    PubMed

    Walsh, Laura A; Allen, Jessica L; Desai, Tejal A

    2015-12-01

    Refinement of micro- and nanofabrication in the semiconductor field has led to innovations in biomedical technologies. Nanotopography, in particular, shows great potential in facilitating drug delivery. The flexibility of fabrication techniques has created a diverse array of topographies that have been developed for drug delivery applications. Nanowires and nanostraws deliver drug cytosolically for in vitro and ex vivo applications. In vivo drug delivery is limited by the barrier function of the epithelium. Nanowires on microspheres increase adhesion and residence time for oral drug delivery, while also increasing permeability of the epithelium. Low aspect ratio nanocolumns increase paracellular permeability, and in conjunction with microneedles increase transdermal drug delivery of biologics in vivo. In summary, nanotopography is a versatile tool for drug delivery. It can deliver directly to cells or be used for in vivo delivery across epithelial barriers. This editorial highlights the application of nanotopography in the field of drug delivery. PMID:26512871

  13. Synthesis and characterization of novel dual-responsive nanogels and their application as drug delivery systems

    NASA Astrophysics Data System (ADS)

    Peng, Jinrong; Qi, Tingting; Liao, Jinfeng; Fan, Min; Luo, Feng; Li, He; Qian, Zhiyong

    2012-03-01

    In this study, a temperature/pH dual-response nanogel based on NIPAm, MAA, and PEGMA was synthesized via emulsion polymerization and characterized by 1H-NMR, FT-IR, TEM and DLS. By introducing a novel initiator, through which PEG-AIBN-PEG was synthesized, it was revealed that the PEG segments from PEG-AIBN-PEG with a dosage of initiator had a significant influence over the macro-state and stability of the nanogels. In order to optimize the feeding prescription for better application as a drug delivery system, the effect of the co-monomer contents on the response to stimuli (temperature and pH value) and cytotoxicity of the nanogels has been studied in detail. The results demonstrated that the responsiveness, reversibility and volume phase transition critical value of the nanogels could be controlled by adjusting the feeding ratio of the co-monomers in the synthesis process. MTT assay results revealed that nanogels with appropriate compositions showed good biocompatibility and relatively low toxicity. Most importantly, by studying the drug loading behavior, it was found that the dimensions of the drug molecules had a considerable influence on the drug loading efficiency and loading capacity of the nanogels, and that the mechanism by which drug molecule sizes influence the drug loading behavior of nanogels needs further investigation. The results indicated that such PNMP nanogels might have potential applications in drug delivery and other medical applications, but that the drug loading mechanism must be further developed.

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

    Kaur, Randeep; Badea, Ildiko

    2013-01-01

    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

  16. Insights into the novel three 'D's of epilepsy treatment: drugs, delivery systems and devices.

    PubMed

    Pathan, Shadab A; Jain, Gaurav K; Akhter, Sohail; Vohora, Divya; Ahmad, Farhan J; Khar, Roop K

    2010-09-01

    Here, we review three 'D's--drugs, delivery systems and devices--that can selectively target not only brain regions but also abnormal cells in the epileptic nervous system. This review also offers insights into the novel molecular targets that enabled the development of new antiepileptic drugs with improved efficacy. Nanotechnology-based delivery systems and alert, diagnostic, surgical and brain stimulation devices designed for the control and management of epilepsy are also discussed. Although the application of the three 'D's continues to be valuable, this review also considers computer-aided software systems, with special emphasis on seizure detection and management. Finally, challenges that still loiter in the field and future prospects that, once accomplished, could lead to cures for epilepsy are addressed. PMID:20603226

  17. Multifunctional HER2-antibody conjugated polymeric nanocarrier-based drug delivery system for multi-drug-resistant breast cancer therapy.

    PubMed

    Vivek, Raju; Thangam, Ramar; NipunBabu, Varukattu; Rejeeth, Chandrababu; Sivasubramanian, Srinivasan; Gunasekaran, Palani; Muthuchelian, Krishnasamy; Kannan, Soundarapandian

    2014-05-14

    Nanotechnology-based medical approaches have made tremendous potential for enhancing the treatment efficacy with minimal doses of chemotherapeutic drugs against cancer. In this study, using tamoxifen (Tam), biodegradable antibody conjugated polymeric nanoparticles (NPs) was developed to achieve targeted delivery as well as sustained release of the drug against breast cancer cells. Poly(D,L-lactic-co-glycolic acid) (PLGA) NPs were stabilized by coating with poly(vinyl alcohol) (PVA), and copolymer polyvinyl-pyrrolidone (PVP) was used to conjugate herceptin (antibody) with PLGA NPs for promoting the site-specific intracellular delivery of Tam against HER2 receptor overexpressed breast cancer (MCF-7) cells. The Tam-loaded PVP-PLGA NPs and herceptin-conjugated Tam-loaded PVP-PLGA NPs were characterized in terms of morphology, size, surface charge, and structural chemistry by dynamic light scattering (DLS), Transmission electron microscopy (TEM), ? potential analysis, 1H nuclear magnetic resonance (NMR), and Fourier transform infrared (FT-IR) spectroscopy. pH-based drug release property and the anticancer activity (in vitro and in vivo models) of the herceptin conjugated polymeric NPs were evaluated by flow cytometry and confocal image analysis. Besides, the extent of cellular uptake of drug via HER2 receptor-mediated endocytosis by herceptin-conjugated Tam-loaded PVP-PLGA NPs was examined. Furthermore, the possible signaling pathway of apoptotic induction in MCF-7 cells was explored by Western blotting, and it was demonstrated that drug-loaded PLGA NPs were capable of inducing apoptosis in a caspase-dependent manner. Hence, this nanocarrier drug delivery system (DDS) not only actively targets a multidrug-resistance (MDR) associated phenotype (HER2 receptor overexpression) but also improves therapeutic efficiency by enhancing the cancer cell targeted delivery and sustained release of therapeutic agents. PMID:24780315

  18. Iontophoretic drug delivery.

    PubMed

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

    2004-03-27

    The composition and architecture of the stratum corneum render it a formidable barrier to the topical and transdermal administration of therapeutic agents. The physicochemical constraints severely limit the number of molecules that can be considered as realistic candidates for transdermal delivery. Iontophoresis provides a mechanism to enhance the penetration of hydrophilic and charged molecules across the skin. The principal distinguishing feature is the control afforded by iontophoresis and the ability to individualize therapies. This may become significant as the impact of interindividual variations in protein expression and the effect on drug metabolism and drug efficacy is better understood. In this review we describe the underlying mechanisms that drive iontophoresis and we discuss the impact of key experimental parameters-namely, drug concentration, applied current and pH-on iontophoretic delivery efficiency. We present a comprehensive and critical review of the different therapeutic classes and molecules that have been investigated as potential candidates for iontophoretic delivery. The iontophoretic delivery of peptides and proteins is also discussed. In the final section, we describe the development of the first pre-filled, pre-programmed iontophoretic device, which is scheduled to be commercialized during the course of 2004. PMID:15019750

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

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

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

    2011-01-01

    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

  1. Investigating the Effect of Adding Drug (Lidocaine) to a Drug Delivery System Using Small-Angle X-Ray Scattering

    NASA Astrophysics Data System (ADS)

    Balogh, Joakim; Pedersen, Jan Skov

    The effect on a model drug delivery system when adding a drug, lidocaine, has been studied. Temperature and concentration dependence of a nonionic microemulsion with part of the oil, 1 and %[vol.]10, substituted with drug has been investigated. A nonionic oil-in-water microemulsion consisting of CH3(CH2)11(OCH2CH2)5OH, (C12E5), decane, water and the drug (lidocaine) that has been used to substitute part of the oil was studied. The microscopic differences have been derived from small-angle X-ray scattering (SAXS) data and the results are compared with light scattering data. Using these results together with the macroscopic differences, as observed in the phase diagram (lowering of phase boundaries), between the systems with and without lidocaine can be explained.

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

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

    2015-01-01

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

  4. Controlled and Extended Release of a Model Protein from a Microsphere-Hydrogel Drug Delivery System.

    PubMed

    Osswald, Christian R; Kang-Mieler, Jennifer J

    2015-11-01

    In extended ocular drug delivery applications, it is necessary to exert control over the release characteristics of the drug. Design considerations must be made to limit the initial burst (IB) and ensure complete release of drug from the drug delivery system (DDS). In this study, ovalbumin was used as a model protein to explore the effects on release of polymer formulation and fabrication technique in poly(lactic-co-glycolic acid) (PLGA) microspheres. Furthermore, the effect on release of suspending these microspheres in an injectable, thermo-responsive poly(N-isopropylacrylamide)-based hydrogel was determined. To characterize release, ovalbumin was radiolabeled with iodine-125. Regardless of polymer formulation or fabrication technique, pulsatile release was achieved with a second burst occurring after ~70 days for microspheres alone. Suspending PLGA 75:25 microspheres within hydrogel reduced the IB by ~75%, delayed the second burst by 28 days, and extended release out to ~200 days with steadier, consistent release throughout compared to microspheres alone. The combined microsphere-hydrogel DDS remains injectable through small-gauge needles and may have many applications, namely ocular drug delivery to the posterior segment. PMID:25835212

  5. Self-emulsifying drug delivery systems: an approach to enhance oral bioavailability.

    PubMed

    Kohli, Kanchan; Chopra, Sunny; Dhar, Deepika; Arora, Saurabh; Khar, Roop K

    2010-11-01

    Self-emulsifying drug delivery systems are a vital tool in solving low bioavailability issues of poorly soluble drugs. Hydrophobic drugs can be dissolved in these systems, enabling them to be administered as a unit dosage form for per-oral administration. When such a system is released in the lumen of the gastrointestinal tract, it disperses to form a fine emulsion (micro/nano) with the aid of GI fluid. This leads to in situ solubilization of drug that can subsequently be absorbed by lymphatic pathways, bypassing the hepatic first-pass effect. This article presents an exhaustive account of various literature reports on diverse types of self-emulsifying formulations with emphasis on their formulation, characterization and in vitro analysis, with examples of currently marketed preparations. PMID:20727418

  6. Autonomous Rhythmic Drug Delivery Systems Based on Chemical and Biochemomechanical Oscillators

    NASA Astrophysics Data System (ADS)

    Siegel, Ronald A.

    While many drug delivery systems target constant, or zero-order drug release, certain drugs and hormones must be delivered in rhythmic pulses in order to achieve their optimal effect. Here we describe studies with two model autonomous rhythmic delivery systems. The first system is driven by a pH oscillator that modulates the ionization state of a model drug, benzoic acid, which can permeate through a lipophilic membrane when the drug is uncharged. The second system is based on a nonlinear negative feedback instability that arises from coupling of swelling of a hydrogel membrane to an enzymatic reaction, with the hydrogel controlling access of substrate to the enzyme, and the enzyme's product controlling the hydrogel's swelling state. The latter system, whose autonomous oscillations are driven by glucose at constant external activity, is shown to deliver gonadotropin releasing hormone (GnRH) in rhythmic pulses, with periodicity of the same order as observed in sexually mature adult humans. Relevant experimental results and some mathematical models are reviewed.

  7. Collagen Coated Nanoliposome as a Targeted and Controlled Drug Delivery System

    NASA Astrophysics Data System (ADS)

    Krishnamoorthy, G.; Stephen, P.; Prabhu, M.; Sehgal, P. K.; Sadulla, S.

    2010-10-01

    The collagen coated nanoliposome (CCNL) have been prepared and characterized in order to develop a targeted and controlled drug delivery system. The zeta potential (ZP) measurement, Fourier transform infrared (FT-IR) spectral and Scanning Electron Microscopy (SEM) and Cell viability assay data showed that the collagen coated nanoliposome particle size and charges, structural interaction and surface morphology and high bio-cyto-compatibility of collagen coated nanoliposome. The particle sizes of nanoliposome (NL) and collagen coated nanoliposome are 20-300 nm and 0.1-10 ?m respectively. The introduction of triple helical, coiled coil and fibrous protein of collagen into nanoliposome can improves the stability of nanoliposome, resistant to phospholipase activities and decreasing the phagocytosis of liposomes by reticuloendothelial system. The collagen coated nanoliposome is expected to be used as for targeted and controlled drug delivery system, and tissue engineering application.

  8. An implantable device for localized drug delivery and sensing

    E-print Network

    Daniel, Karen D

    2009-01-01

    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 ...

  9. Transmucosal macromolecular drug delivery.

    PubMed

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

    2005-01-01

    Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, the use of nanoparticulate carriers represents a challenging but promising strategy. The present paper aims to compare the characteristics and potential of nanostructures based on the mucoadhesive polysaccharide chitosan (CS). These are CS nanoparticles, CS-coated oil nanodroplets (nanocapsules) and CS-coated lipid nanoparticles. The characteristics and behavior of CS nanoparticles and CS-coated lipid nanoparticles already reported [A. Vila, A. Sanchez, M. Tobio, P. Calvo, M.J. Alonso, Design of biodegradable particles for protein delivery, J. Control. Rel. 78 (2002) 15-24; R. Fernandez-Urrusuno, P. Calvo, C. Remunan-Lopez, J.L. Vila-Jato, M.J. Alonso, Enhancement of nasal absorption of insulin using chitosan nanoparticles, Pharm. Res. 16 (1999) 1576-1581; M. Garcia-Fuentes, D. Torres, M.J. Alonso, New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin (submitted for publication).] are compared with those of CS nanocapsules originally reported here. The three types of systems have a size in the nanometer range and a positive zeta potential that was attributed to the presence of CS on their surface. They showed an important capacity for the association of peptides such as insulin, salmon calcitonin and proteins, such as tetanus toxoid. Their mechanism of interaction with epithelia was investigated using the Caco-2 model cell line. The results showed that CS-coated systems caused a concentration-dependent reduction in the transepithelial resistance of the cell monolayer. Moreover, within the range of concentrations investigated, these systems were internalized in the monolayer in a concentration-dependent manner. This uptake was slightly enhanced by the presence of the CS coating but, as compared with previously published results [M. Garcia-Fuentes, C. Prego, D. Torres, M.J. Alonso, Triglyceride-chitosan nanostructures for oral calcitonin delivery: evaluation in the Caco-2 cell model and in vivo (submitted for publication)], highly dependent on the nature of the lipid core. Nevertheless, these differences in the uptake of the CS-coated systems (solid lipid core or oily core) by the Caco-2 cells did not have a consequence in the in vivo behaviour. Indeed, both CS-coated systems (nanocapsules and CS-coated nanoparticles) showed an important capacity to enhance the intestinal absorption of the model peptide, salmon calcitonin, as shown by the important and long-lasting decrease in the calcemia levels observed in rats. PMID:15588901

  10. Development of a multilayered association polymer system for sequential drug delivery

    NASA Astrophysics Data System (ADS)

    Chinnakavanam Sundararaj, Sharath kumar

    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.

  11. Development and lyophilization of itraconazole loaded poly(butylcyanoacrylate) nanospheres as a drug delivery system.

    PubMed

    ?uri?, Anamarija; Keller, Benjamin-Luca; Reul, Regina; Möschwitzer, Jan; Fricker, Gert

    2015-10-12

    Itraconazole is a poorly soluble drug which is used in the treatment of systemic fungal infections. However, there is little reported literature about itraconazole loaded delivery systems used for targeted delivery. Therefore, poly(butyl cyanoacrylate) nanospheres (PBCA-NSP) have been developed as a potential delivery system for transport of itraconazole. One possible application of itraconazole loaded PBCA-NSP could be to treat cryptococcal meningitis. An oil-in-water (o/w) emulsion solvent evaporation was performed for formulation generation. Manufacturing optimization was achieved using design of experiments (DoE) methodology. The average size of PBCA-NSPs varied between 60 and 80 nm. Encapsulation efficiency (EE (%)), absolute drug loading (AL (%)) and release rate of itraconazole from PBCA-NSP in vitro were measured by reversed phase high-performance liquid chromatography (RP-HPLC). EE of 87% could be achieved when the AL of 17.6% was intended. Lyophilization of itraconazole loaded PBCA-NSP was needed to increase the stability of formulations, which was achieved by evaluating different sugar cryoprotectants. In this study, PBCA-NSPs were successfully generated as a delivery system for itraconazole providing a promising approach to improve the therapy of fungal infections of specific organs such as the brain infection cryptococcal meningitis. PMID:26171880

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

    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.

  13. Computational design of nanoparticle drug delivery systems for selective targeting

    NASA Astrophysics Data System (ADS)

    Duncan, Gregg A.; Bevan, Michael A.

    2015-09-01

    Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ?R, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ?L. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting diseased cells and tissues.Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ?R, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ?L. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting diseased cells and tissues. Electronic supplementary information (ESI) available: Movie showing simulation renderings of targeted (?L = 1820/?m2, KD = 120 ?M) nanoparticle selective binding to cancer (?R = 256/?m2) vs. healthy (?R = 64/?m2) cell surfaces. Target membrane proteins have linear color scale depending on binding energy ranging from white when unbound (URL = 0) to red when tightly bound (URL = UM). See DOI: 10.1039/c5nr03691g

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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

  16. Nanoparticles for Brain Drug Delivery

    PubMed Central

    Masserini, Massimo

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-07-01

    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).

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

    PubMed

    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

    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

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

    PubMed Central

    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

    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

  20. Nanoscale drug delivery systems for enhanced drug penetration into solid tumors: current progress and opportunities.

    PubMed

    Waite, Carolyn L; Roth, Charles M

    2012-01-01

    Poor penetration of anticancer drags into solid tumors significantly limits their efficacy. This phenomenon has long been observed for small-molecule chemotherapeutics, and it can be even more pronounced for nanoscale therapies. Nanoparticles have enormous potential for the treatment of cancer due to their wide applicability as drug delivery and imaging vehicles and their size-dependent accumulation into solid tumors by the enhanced permeability and retention (EPR) effect. Further, synthetic nanoparticles can be engineered to overcome barriers to drag delivery. Despite their promise for the treatment of cancer, relatively little work has been done to study and improve their ability to diffuse into solid tumors following passive accumulation in the tumor vasculature. In this review, we present the complex issues governing efficient penetration of nanoscale therapies into solid tumors. The current methods available to researchers to study nanoparticle penetration into malignant tumors are described, and the most recent works studying the penetration of nanoscale materials into solid tumors are summarized. We conclude with an overview of the important nanoparticle design parameters governing their tumor penetration, as well as by highlighting critical directions in this field. PMID:22428797

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

    PubMed Central

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

    2015-01-01

    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

  2. The study of a remote-controlled gastrointestinal drug delivery and sampling system.

    PubMed

    Cui, Jianguo; Zheng, Xiaolin; Hou, Wensheng; Zhuang, YinPing; Pi, Xitian; Yang, Jun

    2008-09-01

    A micromachined capsule based on microelectromechanical systems (MEMS) technology is introduced in this paper. It is an effective tool for diagnosing and treating gastrointestinal diseases. The microcapsule can carry out real-time drug release and the gastrointestinal fluid sampling in the gastrointestinal tract. According to the structural and metabolic characters of the gastrointestinal tract, the configuration of the microcapsule was designed as a cylinder. This nondigestible oral device can smoothly pass through the gastrointestinal tract for drug delivery and liquid sampling. The working mechanism of the capsule was the mechanic movement mode of a piston, which was regulated through a MEMS calorific element. The action of drug delivery and gastrointestinal fluid sampling in the gastrointestinal tract was performed wirelessly. The remote control device can be connected with a computer through a serial port (RS-232), and it can be used in telemedicine applications. Some experimental research has been carried out to validate the design. The experimental results indicated that the microcapsule can achieve drug delivery and liquid sample reliably. PMID:18817502

  3. Design and Characterization of Silicone and Surfactant Based Systems for Topical Drug Delivery.

    PubMed

    Oyafuso, Márcia Helena; Carvalho, Flávia Chiva; Chiavacci, Leila Aparecida; Gremião, Maria Palmira Daflon; Chorilli, Marlus

    2015-01-01

    Nanotechnology offers advantages for new drug delivery design by providing drug targeting while minimizing the side effects. Polyoxyethylene 20 cetyl alcohol (CETETH-20) is a surfactant that may form nanostructured systems, such as liquid crystals, when in contact with water/oil, which are structurally similar to biological membranes and may improve skin interaction. The aim of this study was to develop and characterize CETETH 20-based nanostructured systems by combining CETETH-20 with water and different oily phases, including PEG-12-dimethicone for topical drug administration. The systems were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheology, texture profile analyses (TPA), in vitro cytotoxicity and histopathological analyses of rabbits' skin. Lamellar, hexagonal and cubic phases were identified and their viscoelastic moduli varied according to each phase. The stiffness of the cubic phase was 3-fold higher and twice more adhesive than the hexagonal phase. The formulations did not affect the normal macrophages cells, neither promoted skin irritation. They were spontaneously obtained by simply mixing the components, which corroborates for an ease scaled-up. These results suggest that systems composed of CETETH 20, PEG-12-dimethicone and water are a promising new approach for designing nanostructured topical drug delivery systems. PMID:26328446

  4. The Biocompatibility of Nanodiamonds and Their Application in Drug Delivery Systems

    PubMed Central

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

    2012-01-01

    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

  5. Magnetic Resonance-Guided Drug Delivery.

    PubMed

    Mikhail, Andrew S; Partanen, Ari; Yarmolenko, Pavel; Venkatesan, Aradhana M; Wood, Bradford J

    2015-11-01

    The use of clinical imaging modalities for the guidance of targeted drug delivery systems, known as image-guided drug delivery (IGDD), has emerged as a promising strategy for enhancing antitumor efficacy. MR imaging is particularly well suited for IGDD applications because of its ability to acquire images and quantitative measurements with high spatiotemporal resolution. The goal of IGDD strategies is to improve treatment outcomes by facilitating planning, real-time guidance, and personalization of pharmacologic interventions. This article reviews basic principles of targeted drug delivery and highlights the current status, emerging applications, and future paradigms of MR-guided drug delivery. PMID:26499281

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

    SciTech Connect

    Chen, S.; Wong, S.; Zhao, X.; Chen, J.; Chen, J.; Kuznetsova, L.; Ojima, I.

    2010-05-01

    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 and (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.

  7. An electrically controlled drug delivery system based on conducting poly(3,4-ethylenedioxypyrrole) matrix.

    PubMed

    Krukiewicz, Katarzyna; Zawisza, Patrycja; Herman, Artur P; Turczyn, Roman; Boncel, Slawomir; Zak, Jerzy K

    2016-04-01

    As numerous therapeutic agents are not well tolerated when administrated systemically, localized and controlled delivery can help to decrease their toxicity by applying an optimized drug concentration at extended exposure time. Among different types of drug delivery systems, conjugated polymers are considered as promising materials due to their biocompatibility, electrical conductivity and ability to undergo controllable redox reactions. In this work poly(3,4-ethylenedioxypyrrole), PEDOP, matrix is described for the first time as a reservoir of a model drug, ibuprofen (IBU). Drug immobilization process is performed in situ, during the electrochemical polymerization of 10mM EDOP in the presence of 5-50mM IBU. The loading efficiency of polymer matrix is dependent on IBU concentration and reaches 25.0±1.3?g/cm(2). The analysis of PEDOP-IBU chemical structure based on Raman spectroscopy, energy dispersive spectroscopy and surface morphology data provided by scanning electron microscopy shows that IBU is accumulated in the structure of matrix and evidently influences its morphology. IBU is then released in a controlled way under the influence of applied potential (-0.7V vs. Ag/AgCl). It is demonstrated that the judicious choice of the synthesis conditions leads to a tailored loading efficiency of PEDOP matrix and to a tunable drug release. PMID:26606716

  8. Curcumin-piperine mixtures in self-microemulsifying drug delivery system for ulcerative colitis therapy.

    PubMed

    Li, Qiuping; Zhai, Wenwen; Jiang, Qiaoli; Huang, Ruixue; Liu, Lehuan; Dai, Jundong; Gong, Weihong; Du, Shouying; Wu, Qing

    2015-07-25

    Curcumin (CUR) is a poorly water-soluble drug and its absorption is very low. In this study, CUR and piperine (PIP) were co-encapsulated into the nanoformulation called self-microemulsifying drug delivery system (SMEDDS) to improve the stability and water-solubility of CUR and enhance its anti-colitis activity. The formulation of CUR-PIP-SMEDDS was prepared to encapsulate two hydrophobic components CUR and PIP, and then was characterized by assessing appearance, morphology, particle size, zeta potential and drug encapsulation efficiency. The appearance of CUR-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation. The mean size of microemulsion droplet formed from CUR-PIP-SMEDDS was 15.87 ± 0.76 nm, and the drug encapsulation efficiency of SMEDDS for CUR and PIP were (94.34 ± 2.18)% and (90.78 ± 2.56)%, respectively. The vitro stability investigation of CUR-PIP-SMEDDS in colon tissue suggested that using SMEDDS as a delivery vehicle and co-encapsulated with PIP, CUR was more stable than drug solution in colons site. Meanwhile, the anti-inflammatory activity of CUR-PIP-SMEDDS was evaluated on DSS-induced colitis model. The results showed that CUR-PIP-SMEDDS exhibited definite anti-colitis activity by directing CUR-PIP-SMEDDS to inflammatory colon tissue through retention enema administration. Our study illustrated that the developed CUR-PIP-SMEDDS formulation was a potential carrier for developing colon-specific drug delivery system of CUR for ulcerative colitis treatment. PMID:25957703

  9. The synthesis and application of two mesoporous silica nanoparticles as drug delivery system with different shape

    NASA Astrophysics Data System (ADS)

    Wang, Jiayi; Wang, Zhuyuan; Chen, Hui; Zong, Shenfei; Cui, Yiping

    2015-05-01

    Mesoporous silica nanospheres(MSNSs) have been obtained utilizing the conventional reverse micelles synthesis method while the mesoporous silica nanorods(MSNRs) have been acquired by means of changing certain parameters. Afterwards, the prepared mesoporous silica nanospheres and nanorods were used as drug carriers to load and release the classical cancer therapeutic drug—DOX. According to the absorption spectra, the encapsulation efficiency of the mesoporous silica nanospheres is almost as high as that of the nanospheres. Different from the familiar encapsulation efficiency, the release characteristic curves of the mesoporous silica nanospheres and nanorods possessed certain differences during the release process. Finally incellular fluorescence imaging was achieved to observe the endocytosis of the mesoporous silica materials. Our results show that although both of the two kinds of nanoparticles possess favourable properties for loading and releasing drugs, the mesoporous silica nanospheres perform better in dispersity and controlled release than the nanorods, which probably endow them the potential as incellular drug delivery system.

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

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

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

    PubMed Central

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

    2014-01-01

    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

  12. [Colloid-physical characterization of supramolecular drug delivery systems].

    PubMed

    Süle, András; Csempesz, Ferenc

    2008-01-01

    Cyclodextrins are well-known biocompatible oligosaccharides capable of forming inclusion complexes with suitable guest molecules. They can be expediently used as solubilizers for hydrophobic pharmacon molecules in aqueous solutions. In this study, the effect of colloidal and non-colloidal additives on the solubility of statins is described. Two statin-derivatives (lovastatin and simvastatin), beta-cyclodextrin (-CD) and randomly methylated beta-cyclodextrin (RAMEB) were used as complexing agents. Those pharmacons are widely used in the management of cardiovascular diseases involving high or elevated blood cholesterol levels. Complexation of the highly lipophilic statin molecules with beta-CD and RAMEB was studied in the presence and the absence of dissolved polyvinyl-pyrrolidone (PVP). For the characterization of the stability of statin-CD complexes, association constant of binary associates have been calculated. It was found that inclusion complexation can beneficially enhance the solubility of both statin-derivatives. In binary statin-CD solutions predominantly associates of 1:1 molar ratio form, which show significant surface activity. In polymer-containing ternary systems, the solubility of the pharmacons can further be increased. This phenomenon can presumably be explained with the formation of statin-CD-polymer ternary associates of supramolecular structure. In such supramolecular assemblies the amphiphilic statin-CD complexes are likely bound to the macromolecules' chains. The wetting properties of solid, dried and powdered complexes were studied by immersion enthalpy measurements. Both in binary and ternary systems a significant increase in the immersion enthalpy values could be detected, which indicates that the complexes exhibit fairly hydrophilic character. PMID:18807385

  13. Synthesis of oxidant prone nanosilver to develop H2O2 responsive drug delivery system.

    PubMed

    Muhammad, Faheem; Wang, Aifei; Miao, Lu; Wang, Pengyuan; Li, Qin; Liu, Jia; Du, Jianshi; Zhu, Guangshan

    2015-01-13

    Our immune system uses toxicity of hydrogen peroxide to kill off bacterial invaders. In this contribution, we intended to integrate ROS producing capability of immune system with oxidant-sensitive nature of antibacterial silver nanoparticles (Ag NPs) to develop an oxidant drug delivery system. Prior to execute this strategy, we have developed an efficient one-pot synthetic protocol to produce ultrasmall (5 nm), water-stable, and oxidant-prone Ag NPs. Notably, the yield of as-synthesized Ag NPs is 10-fold higher than standard citrate reduction route. The resulting therapeutically active and well-dispersed Ag NPs are used as nanolids to cap the drug loaded nanochannels of porous silica. Upon exposing to H2O2, dissolution-accompanied aggregation of Ag nanolids unleashes the encapsulated therapeutic entities from channels of nanocarrier. Combination of antibacterial and anti-inflammatory drugs in single nanocarriers can potentially augment the effectiveness of various therapies. PMID:25486873

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

    E-print Network

    Mescher, Mark J.

    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 ...

  15. Persistent Spinal Headache After Removal of Intrathecal Drug Delivery System: A Case Report and Review of Literature

    PubMed Central

    Kurnutala, Lakshmi N.; Kim, David; Sayeed, Huma; Sibai, Nabil

    2015-01-01

    Introduction: To report and discuss the spinal headache following insertion and removal of intrathecal drug delivery system in patients with chronic pain disorders. Case Presentation: Intrathecal drug delivery system (IDDS) was initially used for the management of chronic malignant pain; it has since been used to manage pain from other nonmalignant conditions as well. Spinal headache is one of the complications during the trial, permanent placement and after removal of intrathecal drug delivery catheter systems. A 48-year-male patient with chronic pain disorder developed a refractory spinal headache after removing the intrathecal drug delivery system requiring a surgical intervention to resolve the problem. Conclusions: Conservative management is successful in the vast majority of patients with spinal headache. Interventional procedures are required in a small fraction of patients for symptomatic relief. PMID:26587409

  16. Optical properties of the chemotherapy drugs used in the central nervous system lymphoma therapy: monitoring drug delivery

    NASA Astrophysics Data System (ADS)

    Myllylä, T.; Popov, A.; Surazy?ski, L.; Oinas, J.; Bibikova, O.; Bykov, A.; Wróbel, M. S.; Gnyba, M.; Jedrzejewska-Szczerska, M.; Meglinski, I.; Kuittinen, O.

    2015-07-01

    Our aim is to optically monitor the delivery of the chemotherapy drugs for brain tumours, particularly used in the central nervous system (CNS) lymphoma therapy. In vivo monitoring would help to optimize the treatment and avoiding unnecessary medications. Moreover, it would be beneficial to be able to measure which of the multi-regimen drugs actually do penetrate and how well into the brain tissue. There exist several potential optical measurement techniques to be utilised for the purpose. The most desired method would allow the detection of the drugs without using optical biomarkers as a contrast agent. In this case, for non-invasive sensing of the drug in the brain cortex, the drug should have a reasonably strong optical absorption band somewhere in the range between 600 nm and 1700 nm, and not directly coincident with the strong bands of haemoglobin or water. Alternatively, mid-infrared (MIR) range has the potential for invasive drug monitoring techniques. In this paper, we report the optical properties of several chemotherapy drugs used in CNS lymphoma therapy, such as rituximabi, cyclophosphamide and etoposide. We measured their transmittance and reflectance spectra in near-infrared (NIR) range, particularly 900 nm - 2500 nm, to be considered when choosing the in vivo monitoring method to be developed. The absorption and scattering coefficients were retrieved from the measurements and applying Beer's law. For the measurement of the sum of total transmission and reflection in NIR range we used integrating sphere with spektralo to enable calculation of the scattering coefficient.

  17. Facile synthesis of chitosan/ZnO bio-nanocomposite hydrogel beads as drug delivery systems.

    PubMed

    Yadollahi, Mehdi; Farhoudian, Sana; Barkhordari, Soroush; Gholamali, Iman; Farhadnejad, Hassan; Motasadizadeh, Hamidreza

    2016-01-01

    ZnO nanoparticles were synthesized in situ during the formation of physically cross-linked chitosan hydrogel beads using sodium tripolyphosphate as the cross-linker. The aim of the study was to investigate whether these nanocomposite beads have the potential to be used in drug delivery applications. The formation of ZnO nanoparticles (ZnONPs) in the hydrogels was confirmed by X-ray diffraction and scanning electron microscopy studies. SEM micrographs revealed the formation of ZnONPs with size range of 10-25nm within the hydrogel matrix. Furthermore, the swelling and drug release properties of the beads were studied. The prepared nanocomposite hydrogels showed a pH sensitive swelling behavior. The ZnO nanocomposite hydrogels have rather higher swelling ratio in different aqueous solutions in comparison with neat hydrogel. In vitro drug release test was carried out to prove the effectiveness of this novel type of nanocomposite beads as a controlled drug delivery system. A prolonged and more controlled drug releases were observed for ZnONPs containing chitosan beads, which increased by the increase in ZnONPs content. PMID:26433177

  18. Protease-mediated drug delivery

    NASA Astrophysics Data System (ADS)

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

    2003-12-01

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

  19. From silk spinning in insects and spiders to advanced silk fibroin drug delivery systems.

    PubMed

    Werner, Vera; Meinel, Lorenz

    2015-11-01

    The natural process of silk spinning covers a fascinating versatility of aggregate states, ranging from colloidal solutions through hydrogels to solid systems. The transition among these states is controlled by a carefully orchestrated process in vivo. Major players within the natural process include the control of spatial pH throughout passage of the silk dope, the composition and type of ions, and fluid flow mechanics within the duct, respectively. The function of these input parameters on the spinning process is reviewed before detailing their impact on the design and manufacture of silk based drug delivery systems (DDS). Examples are reported including the control of hydrogel formation during storage or significant parameters controlling precipitation in the presence of appropriate salts, respectively. The review details the use of silk fibroin (SF) to develop liquid, semiliquid or solid DDS with a focus on the control of SF crystallization, particle formation, and drug-SF interaction for tailored drug load. PMID:25801494

  20. Computers and Chemical Engineering 29 (2005) 22902296 Modelling and control of drug delivery systems

    E-print Network

    Grossmann, Ignacio E.

    2005-01-01

    model for delivery of drugs under anesthesia and an advanced model based control algorithm for insulin delivery for Type 1 diabetes. The model for anesthesia involves choice of three drugs isoflurane, dopamine computational software and hardware platform. © 2005 Elsevier Ltd. All rights reserved. Keywords: Anesthesia

  1. Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids.

    PubMed

    Grassin-Delyle, Stanislas; Buenestado, Amparo; Naline, Emmanuel; Faisy, Christophe; Blouquit-Laye, Sabine; Couderc, Louis-Jean; Le Guen, Morgan; Fischler, Marc; Devillier, Philippe

    2012-06-01

    Intranasal administration is a non-invasive route for drug delivery, which is widely used for the local treatment of rhinitis or nasal polyposis. Since drugs can be absorbed into the systemic circulation through the nasal mucosa, this route may also be used in a range of acute or chronic conditions requiring considerable systemic exposure. Indeed, it offers advantages such as ease of administration, rapid onset of action, and avoidance of first-pass metabolism, which consequently offers for example an interesting alternative to intravenous, subcutaneous, oral transmucosal, oral or rectal administration in the management of pain with opioids. Given these indisputable interests, fentanyl-containing formulations have been recently approved and marketed for the treatment of breakthrough cancer pain. This review will outline the relevant aspects of the therapeutic interest and limits of intranasal delivery of drugs, with a special focus on opioids, together with an in-depth discussion of the physiological characteristics of the nasal cavity as well as physicochemical properties (lipophilicity, molecular weight, ionisation) and pharmaceutical factors (absorption enhancers, devices for application) that should be considered for the development of nasal drugs. PMID:22465159

  2. Nanoemulsion-templated shell-crosslinked nanocapsules as drug delivery systems.

    PubMed

    He, Wei; Lu, Yi; Qi, Jianping; Chen, Lingyun; Hu, Fuqiang; Wu, Wei

    2013-03-10

    A novel biocompatible shell-crosslinked nanocapsule system was developed based on nanoemulsion templates stabilized by a class of food proteins. The nanoemulsion templates were prepared using a combination of mechanical mixing and high-pressure homogenization, while the nanocapsule shell formed simultaneously through calcium ions-induced crosslinking of the food proteins. These core-shell structured nanocapsules with a particle size of about 200 nm showed high drug-loading capacity and well improved stability in comparison with their nanoemulsion counterpart. The nanocapsule suspension can be freeze-fried directly; and the solidified nanocapsules can be well reconstituted in water, retaining their original particle size. It is concluded that the nanoemulsion-templated core-shell structured nanocapsules can be used as novel drug delivery systems with high loading capacity for poorly water-soluble drugs as well as well improved long-term and storage stability. Furthermore, the presence of surface food proteins introduces carboxyl and amine moieties, which enables the nanocapsules to anchor ligands, suggesting its potential application in targeting drug delivery, bioimaging and therapeutics. PMID:23396257

  3. Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.

    PubMed

    Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles W; Owen, Andrew; Sinko, Patrick J

    2015-12-10

    The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel delivery systems will help iterate towards prevention, functional cure and eventually the eradication of HIV infection. PMID:26315816

  4. Nanomedicine and drug delivery: a mini review

    NASA Astrophysics Data System (ADS)

    Mirza, Agha Zeeshan; Siddiqui, Farhan Ahmed

    2014-02-01

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

  5. Self-microemulsifying drug delivery system (SMEDDS) - challenges and road ahead.

    PubMed

    Dokania, Shambhu; Joshi, Amita K

    2015-09-01

    Self-microemulsifying drug delivery system (SMEDDS) has emerged as a vital strategy to formulate poor water soluble compounds for bioavailability enhancement. However, certain limitations are associated with SMEDDS formulations which include in vivo drug precipitation, formulation handling issues, limited lymphatic uptake, lack of predictive in vitro tests and oxidation of unsaturated fatty acids. These limitations restrict their potential usage. Inclusion of polymers or precipitation inhibitors within lipid based formulations helps to maintain drug supersaturation after dispersion. This, thereby, improves the bioavailability and reduces the variability on exposure. Also, formulating solid SMEDDS helps to overcome liquid handling and stability problems. Usage of medium chain triglycerides (MCT) and suitable antioxidants to minimize oxidation of unsaturated fatty acids are few of the steps to overcome the limitations associated with SMEDDS. The review discussed here, in detail, the limitations of SMEDDS and suitable measures that can be taken to overcome them. PMID:24670091

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

    PubMed Central

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

    2013-01-01

    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

  7. Formulation of solid self-nanoemulsifying drug delivery systems using N-methyl pyrrolidone as cosolvent.

    PubMed

    Agrawal, Anuj G; Kumar, Ashok; Gide, Paraag S

    2015-04-01

    Atorvastatin calcium (ATRC) is a poor water soluble drug used for treatment of hypercholesterolemia. This research is aimed to improve solubility and dissolution rate of ATRC by formulating into solid self-nanoemulsifying drug delivery system (S-SNEDDS) using N-methyl pyrrolidone (NMP) as cosolvent. Solubility of ATRC was determined in various vehicles. Ternary phase diagrams were constructed to identify stable nanoemulsion region. SNEDDS formulations were evaluated for robustness to dilution, thermodynamic stability study, % transmittance, self-emulsification time, globule size and transmission electron microscopy. The optimized liquid SNEDDS showed robust to all dilutions exhibiting no signs of phase separation or precipitation for 24?h. Liquid SNEDDS was transformed into S-SNEDDS using different adsorbents. Differential scanning calorimetry and scanning electron microscopy studies unravel the transformation of native crystalline state to amorphous state/solubilized state. In vitro dissolution study of S-SNEDDS was found to be significantly higher in comparison to that from plain drug, irrespective of pH (p?drug. In conclusion, S-SNEDDS prepared using NMP as cosolvent provides an effective approach for improved oral delivery of ATRC. PMID:24517575

  8. Preparation, characterization, and evaluation of gatifloxacin loaded solid lipid nanoparticles as colloidal ocular drug delivery system.

    PubMed

    Kalam, Mohd Abul; Sultana, Yasmin; Ali, Asgar; Aqil, Mohd; Mishra, Anil K; Chuttani, Krishna

    2010-04-01

    This article describes the preparation and characterization of solid lipid nanoparticles (SLNs) prepared with stearic acid (SLN-A) and a mixture of stearic acid and Compritol (SLN-B) as lipid matrix and poloxamer-188 as surfactant, using sodium taurocholate and ethanol as co-surfactant mixture, with a view to applying the SLN in topical ocular drug delivery. The SLNs were prepared by o/w microemulsion technique and characterized by time-resolved particle size analysis, polydispersity index, zeta(zeta)-potential, differential scanning calorimetry (DSC), IR-spectroscopy, and wide-angle X-ray diffractometry (WAXD). The results obtained in these studies were compared with SLN prepared with stearic acid alone. IR, WAXD, and DSC studies revealed low-crystalline SLN and were having positive zeta-potentials after three-months of storage. Results indicated mixed lipid-matrix produced SLN with low-crystallinity and smaller particle sizes and higher drug entrapment compared with SLN prepared with stearic acid alone, therefore SLN-B would be suitable for the preparation of nanosuspension. Nanosuspensions were subjected to rheological and physicochemical evaluation, in vitro drug release and ex vivo corneal permeation studies and their effect were evaluated on corneal hydration-level. SLN composed of stearic acid and compritol would prove to be a good ocular drug delivery system considering the smaller particle size, particle size stability, and physiologically tolerable components. PMID:19839712

  9. Molecular recognition and controlled release in drug delivery systems based on nanostructured lipid surfactants

    NASA Astrophysics Data System (ADS)

    Angius, R.; Murgia, S.; Berti, D.; Baglioni, P.; Monduzzi, M.

    2006-08-01

    Several monoolein/water (MO/W) based liquid crystalline (LC) nanostructured mesophases have been revisited in view of the new trends of modern drug delivery formulations. The shape and amphiphilic character of the investigated lipid molecules address the preferential polar-apolar interfacial curvature and the delicate interplay of different intermolecular forces that drive self-assembly and thermodynamic stability of the nanostructures. Here some preliminary results related to the release of the antiviral drug 1-amine-adamantane hydrochloride, solubilized in the aqueous domain of bicontinuous cubic and reverse hexagonal LC phases, suggest these MO based LC phases as possible nano-depot systems for long term controlled release. Drug release was followed by conductivity measurements during a period of ten days. An effective and targeted drug delivery often requires a specific molecular recognition. With this aim, the possibility to entrap suitable molecules such as lauroylcholine (LCh, a cationic surfactant having a peptide-like polar head that can 'recognize' membrane proteins) and adenosine monophosphate disodium salt (NaAMP, an electrolyte that can 'recognize' purine receptors) has been tested. The addition of LCh to MO/W cubic gyroid (CG) LC phase causes a cubic-lamellar phase transition. The addition of NaAMP still allows the formation of the CG nanostructure. In the presence of both NaAMP and LCh again a CG LC phase forms. The bicontinuous CG LC phases have been characterized by NMR and SAXS.

  10. A robust, electrochemically driven microwell drug delivery system for controlled vasopressin release.

    PubMed

    Chung, Aram J; Huh, Yun Suk; Erickson, David

    2009-08-01

    Micro-electro-mechanical-system (MEMS) based implantable drug delivery devices represent a promising approach to achieving more precise dosing, faster release and better localization of therapeutic compounds than is possible with existing technology. Despite recent advancements, there remain challenges in being able to build systems that enable active control over the dose rate and release time, in a robust, low power but simple to fabricate package. Here we demonstrate an implantable micro-reservoir device that enables delivery of dose volumes as high as 15 microl using an electrochemically based transport mechanism. This approach allows for a significant reduction in the amount of time required for drug delivery as well as reducing the dependence on the external physiological conditions. We present the overall design, operating principle and construction of the device, and experimental results showing the volume transport rate as a function of the strength of the applied electric field. The concentration profile vs. time, the power consumption, and ejection efficiency are also investigated. To demonstrate the medical utility of the device we also characterize the in-vitro release of vasopressin. PMID:19353273

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

    SciTech Connect

    Alfke, Heiko; Wagner, Hans-Joachim; Calmer, Christian; Klose, Klaus Jochen

    1998-01-15

    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.

  12. Electrospun polycaprolactone nanofibers as a potential oromucosal delivery system for poorly water-soluble drugs.

    PubMed

    Potr?, Tanja; Baumgartner, Saša; Roškar, Robert; Planinšek, Odon; Lavri?, Zoran; Kristl, Julijana; Kocbek, Petra

    2015-07-30

    The number of poorly water-soluble drug candidates is rapidly increasing; this represents a major challenge for the pharmaceutical industry. As a consequence, novel formulation approaches are required. Furthermore, if such a drug candidate is intended for the therapy of a specific group of the population, such as geriatric or pediatric, the formulation challenge is even greater, with the need to produce a dosage form that is acceptable for specific patients. Therefore, the goal of our study was to explore electrospun polycaprolactone (PCL) nanofibers as a novel nanodelivery system adopted for the oromucosal administration of poorly water-soluble drugs. The nanofibers were evaluated in comparison with polymer films loaded with ibuprofen or carvedilol as the model drugs. Scanning electron microscopy revealed that the amount of incorporated drug affects the diameter and the morphology of the nanofibers. The average fiber diameter increased with a higher drug loading, whereas the morphology of the nanofibers was noticeably changed in the case of nanofibers with 50% and 60% ibuprofen. The incorporation of drugs into the electrospun PCL nanofibers was observed to reduce their crystallinity. Based on the morphology of the nanofibers and the films, and the differential scanning calorimetry results obtained in this study, it can be assumed that the drugs incorporated into the nanofibers were partially molecularly dispersed in the PCL matrix and partially in the form of dispersed nanocrystals. The incorporation of both model drugs into the PCL nanofibers significantly improved their dissolution rates. The PCL nanofibers released almost 100% of the incorporated ibuprofen in 4h, whereas only up to 77% of the incorporated carvedilol was released during the same time period, indicating the influence of the drug's properties, such as molecular weight and solubility, on its release from the PCL matrix. The obtained results clearly demonstrated the advantages of the new nanodelivery system compared to the drug-loaded polymer films that were used as the reference formulation. As a result, electrospinning was shown to be a very promising nanotechnology-based approach to the formulation of poorly water-soluble drugs in order to enhance their dissolution. In addition, the great potential of the produced drug-loaded PCL nanofiber mats for subsequent formulation as oromucosal drug delivery systems for children and the elderly was confirmed. PMID:25910438

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

    PubMed

    Sinha, Vivek Ranjan; Sethi, Shilpa

    2015-05-01

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

  14. Ultrasound mediated nanoparticle drug delivery

    NASA Astrophysics Data System (ADS)

    Mullin, Lee B.

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

  15. Nanoparticles for Targeted Drug Delivery

    E-print Network

    Chow, Gan-Moog

    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) ...

  16. Development of a novel injectable drug delivery system for subconjunctival glaucoma treatment.

    PubMed

    Voss, Karsten; Falke, Karen; Bernsdorf, Arne; Grabow, Niels; Kastner, Christian; Sternberg, Katrin; Minrath, Ingo; Eickner, Thomas; Wree, Andreas; Schmitz, Klaus-Peter; Guthoff, Rudolf; Witt, Martin; Hovakimyan, Marina

    2015-09-28

    In this study we present the development of an injectable polymeric drug delivery system for subconjunctival treatment of primary open angle glaucoma. The system consists of hyaluronic acid sodium salt (HA), which is commonly used in ophthalmology in anterior segment surgery, and an isocyanate-functionalized 1,2-ethylene glycol bis(dilactic acid) (ELA-NCO). The polymer mixtures with different ratios of HA to ELA-NCO (1/1, 1/4, and 1/10 (v/v)) were investigated for biocompatibility, degradation behavior and applicability as a sustained release system. For the latter, the lipophilic latanoprost ester pro-drug (LA) was incorporated into the HA/ELA-NCO system. In vitro, a sustained LA release over a period of about 60days was achieved. In cell culture experiments, the HA/ELA-NCO (1/1, (v/v)) system was proven to be biocompatible for human and rabbit Tenon's fibroblasts. Examination of in vitro degradation behavior revealed a total mass loss of more than 60% during the observation period of 26weeks. In vivo, LA was continuously released for 152days into rabbit aqueous humor and serum. Histological investigations revealed a marked leuko-lymphocytic infiltration soon after subconjunctival injection. Thereafter, the initial tissue reaction declined concomitantly with a continuous degradation of the polymer, which was completed after 10months. Our study demonstrates the suitability of the polymer resulting from the reaction of HA with ELA-NCO as an injectable local drug delivery system for glaucoma therapy, combining biocompatibility and biodegradability with prolonged drug release. PMID:26160303

  17. A novel floating controlled release drug delivery system prepared by hot-melt extrusion.

    PubMed

    Vo, Anh Q; Feng, Xin; Morott, Joseph T; Pimparade, Manjeet B; Tiwari, Roshan V; Zhang, Feng; Repka, Michael A

    2016-01-01

    Floating dosage forms are an important formulation strategy for drugs with a narrow absorption window and low intestinal solubility, and for localized gastric treatment. Novel floating pellets were prepared using the hot-melt extrusion (HME) technology. Uniformly foamed strands were created by liquid injection pumping and screw configuration modification. The ammonio methacrylate copolymer (Eudragit® RSPO) foaming structure was formed by a liquid-vapor phase transition inside the strand upon die exiting resulting from the sudden decrease in external pressure, vaporizing the liquid ethanol and vacating the extruded material. This generated uniform vacuous regions in the extrudate. The pellets' internal structure was investigated using scanning electron microscopy (SEM). The formulation constituents' and processing parameters' effects on the drug release profiles, floating force, and the pellets' micromeritic properties were evaluated by design of experiments: all formulations showed zero lag time and excellent floating strength, indicating immediate-floating pellet formation. The pellets' drug release profiles were controlled by multiple independent variables at different time points (?24h). Drug loading significantly affected drug release within the first hour, the hydroxypropyl methylcellulose (HPMC) content thereafter. Understanding the variables' effects on the formulations allows for the tailoring of this delivery system to obtain various drug release profiles. PMID:26643801

  18. Organosilicate-polymer drug delivery systems: controlled release and enhanced mechanical properties.

    PubMed

    Cypes, Stephen H; Saltzman, W Mark; Giannelis, Emmanuel P

    2003-06-24

    Dexamethasone-loaded poly(ethylene-co-vinyl acetate) (EVAc) nanocomposites were fabricated via solution-casting with three different organosilicates for study in a drug delivery system. X-ray diffraction (XRD) showed that all three nanocomposites were in an intercalated morphology. Release studies of dexamethasone into phosphate-buffered saline revealed that the presence of silicates reduced the rate of drug release, and this reduction was a function of volume fraction of silicate in the composite, as well as the aspect ratio of the silicate layers. It was also found that the presence of silicate in a nanocomposite resulted in an increase in the Young's modulus as compared to the pure polymer, and this increase was also a function of the volume fraction of silicate present as well as the aspect ratio of the silicate layers. Silicates are a viable additive to EVAc drug delivery systems, providing controlled release characteristics as well as enhanced mechanical properties in an economically and biologically safe manner. PMID:12810299

  19. Brain aging and Parkinson's disease: New therapeutic approaches using drug delivery systems.

    PubMed

    Rodríguez-Nogales, C; Garbayo, E; Carmona-Abellán, M M; Luquin, M R; Blanco-Prieto, M J

    2016-02-01

    The etiology and pathogenesis of Parkinson's disease (PD) is unknown, aging being the strongest risk factor for brain degeneration. Understanding PD pathogenesis and how aging increases the risk of disease would aid the development of therapies able to slow or prevent the progression of this neurodegenerative disorder. In this review we provide an overview of the most promising therapeutic targets and strategies to delay the loss of dopaminergic neurons observed both in PD and aging. Among them, handling alpha-synuclein toxicity, enhancing proteasome and lysosome clearance, ameliorating mitochondrial disruptions and modifying the glial environment are so far the most promising candidates. These new and conventional drugs may present problems related to their labile nature and to the difficulties in reaching the brain. Thus, we highlight the latest types of drug delivery system (DDS)-based strategies for PD treatment, including DDS for local and systemic drug delivery. Finally, the ongoing challenges for the discovery of new targets and the opportunities for DDS-based therapies to improve and efficacious PD therapy will be discussed. PMID:26653838

  20. Strategies of targeting oral drug delivery systems to the colon and their potential use for the treatment of colorectal cancer.

    PubMed

    Krishnaiah, Yellela S R; Khan, Mansoor A

    2012-01-01

    Colorectal cancer (CRC) is the third most common cause of cancer-related death in both men and women. Often, surgical intervention remains the choice in treating CRC. Traditional dosage forms used for treating CRC deliver drug to wanted as well as unwanted sites of drug action resulting in several adverse side effects. Targeted oral drug delivery systems are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific delivery of a drug to colon increases its concentration at the target site, and thus requires a lower dose with reduced incidence of side effects. The major obstacle to be overcome for successful targeting of drug to colon through oral route is that drug absorption/degradation must be avoided in stomach and small intestine before the dosage form reaches colon. The review includes discussion of physiological factors that must be considered when targeting drugs directly to colorectal region, an outline on drugs used for treatment and prevention of CRC, and a brief description of various types of colon-targeted oral drug delivery systems. The focus is on the assessment of various formulation approaches being investigated for oral colon-specific delivery of drugs used in the treatment and prevention of CRC. PMID:22681390

  1. Development of chitosan nanoparticles as drug delivery system for a prototype capsid inhibitor.

    PubMed

    Xue, Meiyan; Hu, Steven; Lu, Yifei; Zhang, Yu; Jiang, Xutao; An, Sai; Guo, Yubo; Zhou, Xue; Hou, Huimin; Jiang, Chen

    2015-11-30

    Oral delivery of biopharmaceutics drug disposition classification system (BDDCS) Class II or IV drugs with poor aqueous solubility and poor enzymatic and/or metabolic stability is very challenging. Bay41-4109, a member of the heteroaryldihydropyrimidine (HAP) family, inhibits HBV replication by destabilizing capsid assembly. It pertains to class II of the BDDCS which has a practically insoluble solubility which is 38?g/mL (LYSA) and the oral delivery resulted in low bioavailability. The purpose of the current research work was to develop and evaluate Bay41-4109 loaded chitosan nanoparticles to increase the solubility and bioavailability for treatment of HBV. The Bay41-4109 nanoparticles were prepared by gelation of chitosan with tripolyphosphate (TPP) through ionic cross-linking. A three-factor three-level central composite design (CCD) was introduced to perform the experiments. A quadratic polynomial model was generated to predict and evaluate the independent variables with respect to the dependent variables. Bay41-4109 was encapsulated in the chitosan nanoparticles were demonstrated by PLM, FTIR, DSC, XRD and TEM etc. The in vivo results suggest that Bay41-4109 nanoparticles have better bioavailability and would be a promising approach for oral delivery of Bay41-4109 for the treatment of HBV. PMID:26428629

  2. Novel magnetic/ultrasound focusing system enhances nanoparticle drug delivery for glioma treatment.

    PubMed

    Chen, Pin-Yuan; Liu, Hao-Li; Hua, Mu-Yi; Yang, Hung-Wei; Huang, Chiung-Yin; Chu, Po-Chun; Lyu, Lee-Ang; Tseng, I-Chou; Feng, Li-Ying; Tsai, Hong-Chieh; Chen, Shu-Mei; Lu, Yu-Jen; Wang, Jiun-Jie; Yen, Tzu-Chen; Ma, Yunn-Hwa; Wu, Tony; Chen, Jyh-Ping; Chuang, Jih-Ing; Shin, Jyh-Wei; Hsueh, Chuen; Wei, Kuo-Chen

    2010-10-01

    Malignant glioma is a common and severe primary brain tumor with a high recurrence rate and an extremely high mortality rate within 2 years of diagnosis, even when surgical, radiological, and chemotherapeutic interventions are applied. Intravenously administered drugs have limited use because of their adverse systemic effects and poor blood-brain barrier penetration. Here, we combine 2 methods to increase drug delivery to brain tumors. Focused ultrasound transiently permeabilizes the blood-brain barrier, increasing passive diffusion. Subsequent application of an external magnetic field then actively enhances localization of a chemotherapeutic agent immobilized on a novel magnetic nanoparticle. Combining these techniques significantly improved the delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea to rodent gliomas. Furthermore, the physicochemical properties of the nanoparticles allowed their delivery to be monitored by magnetic resonance imaging (MRI). The resulting suppression of tumor progression without damaging the normal regions of the brain was verified by MRI and histological examination. This noninvasive, reversible technique promises to provide a more effective and tolerable means of tumor treatment, with lower therapeutic doses and concurrent clinical monitoring. PMID:20663792

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

    PubMed

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

    2002-10-01

    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 or array that could operate with a similar frequency and intensity range as a commercial sonicator used in previous transdermal ultrasound insulin experiments, but without the weight and mass of a sonicator probe. To obtain this intensity range, a cymbal transducer design was chosen because of its light, compact structure and low resonance frequency in water. To increase the spatial ultrasound field for drug delivery across skin, two arrays, each comprising of four cymbal transducers, were constructed. The first array, designated the standard array, used four cymbals transducer elements in parallel. A second array (named the stack array) used four cymbal transducers that used stacked piezoelectric discs to drive the titanium flextensional caps. Under similar driving conditions, the standard array produced intensities comparable to those achieved using a commercial sonicator. PMID:12403144

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

    PubMed Central

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

    2008-01-01

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

  5. Chronomodulated drug delivery system of urapidil for the treatment of hypertension

    PubMed Central

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

    2015-01-01

    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. PMID:25838996

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

    PubMed

    Lammers, Twan

    2013-09-15

    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

  7. Smart Polymers in Nasal Drug Delivery

    PubMed Central

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

    2015-01-01

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

  8. Smart Polymers in Nasal Drug Delivery.

    PubMed

    Chonkar, Ankita; Nayak, Usha; Udupa, N

    2015-01-01

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

  9. Preparation and performance evaluation of emulsomes as a drug delivery system for silybin.

    PubMed

    Zhou, Xiaodan; Chen, Zhipeng

    2015-12-01

    We developed silybin (SIL) emulsomes and evaluated their physicochemical properties and the in vivo pharmacokinetics of SIL delivered by emulsomes in rats. SIL emulsomes were prepared using the thin film dispersion method. SIL emulsomes were evaluated for their entrapment efficiency, particle size, zeta potential, morphology, in vitro release, and in vivo drug delivery in rats. The entrapment efficiency was above 80 %. The average particle size and zeta potential were 364.1 ± 20 nm and -34 ± 8 mV, respectively. Morphological analysis revealed that the SIL emulsomes were spherical in shape. Compared to an SIL solution, emulsomes produced sustained release of SIL for up to 48 h after an initial burst release in vitro. The pharmacokinetics of SIL emulsomes in rats were evaluated after intravenous injection, and the results were compared with those obtained for the control SIL solution. Following SIL delivery by emulsomes, the area under the curve was 2.2-fold higher and the mean residence time was 2.5-fold higher than the corresponding values recorded using SIL solution. Hence, emulsomes might represent a promising system for improving the bioavailability of lipophilic drugs. Moreover, emulsomes produce sustained drug release, which is advantageous in the clinical setting. PMID:26152876

  10. Raman microscopic imaging of cells and applications monitoring the uptake of drug delivery systems

    NASA Astrophysics Data System (ADS)

    Matthäus, Christian; Chernenko, Tatyana; Quintero, Luis; Milan, Lara; Kale, Amit; Amiji, Mansoor; Torchilin, Vladimir; Diem, Max

    2008-04-01

    Raman spectroscopy, in combination with optical microscopy provides a new non-invasive method to asses and image cellular processes. Based on the spectral signatures of a cell's components, it is possible to image cellular organelles such as the nucleus, chromatin, mitochondria or lipid bodies, at the resolution of conventional microscopy. Several multivariate algorithms, for example hierarchical cluster analysis or orthogonal subspace projection, may be used to reconstruct an image of a cell. The noninvasive character of the technique, as well as the associated chemical information, may offer advantages over other imaging techniques such as fluorescence microscopy. Currently of particular interest are uptake and intracellular fate of various pharmaceutical nanocarriers, which are widely used for drug delivery purposes, including intracellular drug and gene delivery. We have imaged the uptake and distribution patterns of several carrier systems over time. In order to distinguish the species of interest from their cellular environment spectroscopically, the carrier particles or the drug load itself may be labeled with deuterium. Here, we introduce the concept of Raman imaging in combination with vertex component data analysis to follow the uptake of nanocarriers based on phospholipids as well as biodegradable polymers.

  11. Raman Micro-spectral Imaging of Cells and Intracellular Drug Delivery Using Nanocarrier Systems

    NASA Astrophysics Data System (ADS)

    Matthäus, Christian; Chernenko, Tatyana; Quintero, Luis; Miljkovi?, Miloš; Milane, Lara; Kale, Amit; Amiji, Mansoor; Torchilin, Vladimir; Diem, Max

    Raman spectroscopy in combination with optical microscopy provides a new non-invasive method to examine and image cellular processes. Based on the spectral parameters of a cell's components it is possible to image cellular organelles, such as the nucleus, chromatin, mitochondria, or lipid bodies, at the resolution of conventional microscopy. Several multivariate or spectral de-mixing algorithms, for example, hierarchical cluster analysis or orthogonal subspace projection, may be used to reconstruct an image of a cell. The non-invasive character of the technique as well as the associated chemical information may offer advantages over other imaging techniques such as fluorescence microscopy. Currently of particular interest are the uptake and intracellular fate of various pharmaceutical nanocarriers, which are widely used for drug delivery purposes, including intracellular drug and gene delivery. We have imaged the uptake and distribution patterns of several carrier systems over time. In order to distinguish the species of interest from their cellular environment spectroscopically, the carrier particles or the drug load itself may be labeled with deuterium. The first part of the chapter will briefly introduce the concept of Raman imaging in combination with multivariate data analysis on some simple cell models, after which the results of the uptake studies are discussed.

  12. Tumor Endothelial Cell-Specific Drug Delivery System Using Apelin-Conjugated Liposomes

    PubMed Central

    Kawahara, Hiroki; Naito, Hisamichi; Takara, Kazuhiro; Wakabayashi, Taku; Kidoya, Hiroyasu; Takakura, Nobuyuki

    2013-01-01

    Background A drug delivery system specifically targeting endothelial cells (ECs) in tumors is required to prevent normal blood vessels from being damaged by angiogenesis inhibitors. The purpose of this study was to investigate whether apelin, a ligand for APJ expressed in ECs when angiogenesis is taking place, can be used for targeting drug delivery to ECs in tumors. Methods and Results Uptake of apelin via APJ stably expressed in NIH-3T3 cells was investigated using TAMRA (fluorescent probe)-conjugated apelin. Both long and short forms of apelin (apelin 36 and apelin 13) were taken up, the latter more effectively. To improve efficacy of apelin- liposome conjugates, we introduced cysteine, with its sulfhydryl group, to the C terminus of apelin 13, resulting in the generation of apelin 14. In turn, apelin 14 was conjugated to rhodamine-encapsulating liposomes and administered to tumor-bearing mice. In the tumor microenvironment, we confirmed that liposomes were incorporated into the cytoplasm of ECs. In contrast, apelin non-conjugated liposomes were rarely found in the cytoplasm of ECs. Moreover, non-specific uptake of apelin-conjugated liposomes was rarely detected in other normal organs. Conclusions ECs in normal organs express little APJ; however, upon hypoxic stimulation, such as in tumors, ECs start to express APJ. The present study suggests that apelin could represent a suitable tool to effectively deliver drugs specifically to ECs within tumors. PMID:23799018

  13. Self-microemulsifying drug delivery system for improved oral bioavailability of oleanolic acid: design and evaluation

    PubMed Central

    Yang, Rui; Huang, Xin; Dou, Jinfeng; Zhai, Guangxi; Su, Lequn

    2013-01-01

    Oleanolic acid is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) has been developed to enhance the solubility and oral bioavailability of oleanolic acid. The formulation design was optimized by solubility assay, compatibility tests, and pseudoternary phase diagrams. The morphology, droplet size distribution, zeta potential, viscosity, electrical conductivity, and refractive index of a SMEDDS loaded with oleanolic acid were studied in detail. Compared with oleanolic acid solution, the in vitro release of oleanolic acid from SMEDDS showed that the drug could be released in a sustained manner. A highly selective and sensitive high-performance liquid chromatographymass spectrometry method was developed for determination of oleanolic acid in rat plasma. This method was used for a pharmacokinetic study of an oleanolic acid-loaded SMEDDS compared with the conventional tablet in rats. Promisingly, a 5.07-fold increase in oral bioavailability of oleanolic acid was achieved for the SMEDDS compared with the marketed product in tablet form. Our studies illustrate the potential use of a SMEDDS for delivery of oleanolic acid via the oral route. PMID:23966781

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

    PubMed Central

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

    2014-01-01

    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

  15. Intravenous drug delivery in neonates: lessons learnt.

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2008-01-01

    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

  17. Soy matrix drug delivery systems obtained by melt-processing techniques.

    PubMed

    Vaz, Cláudia M; van Doeveren, Patrick F N M; Reis, Rui L; Cunha, António M

    2003-01-01

    The aim of this study was to develop new soy protein drug delivery matrix systems by melt-processing techniques, namely, extrusion and injection moulding. The soy matrix systems with an encapsulated drug (theophylline, TH) were previously compounded by extrusion performed at two different pH values, (i) pH 4 (SIpDtp) and (ii) pH 7 (SIDtp), and further injection-moulded into a desired shape. During the extrusion process the matrixes SIDtp were also cross-linked with glyoxal (0.6X-SIDtp) and reinforced with a bioactive filler, hydroxylapatite (SI-HADtp). The obtained mouldings were used to study the drug-release mechanisms from the plastic soy-TH matrixes. In an isotonic saline solution (ISS) buffered at pH 5.0 (200 mM acetate buffer), the resulting release kinetics could be described using the Fick's second law of diffusion. Because the diffusion coefficients were found to be constant and the boundary conditions to be stationary, these systems are drug-diffusion controlled. Conversely, the dominant phenomena in an isotonic saline solution buffered at pH 7.4 (200 mM Tris/HCl buffer) are more complex. In fact, because of the higher polymer solubility, the resulting matrix is time-variant. So, the drug release is affected by swelling, drug diffusion, and polymer dissolution, being faster when compared to ISS-200 mM acetate buffer, pH 5.0. The changes in the formulation composition affecting the correspondent release rates were also investigated. At pH 7.4, increasing the cross-linking degree of the polymer matrix (via reaction with glyoxal or heat treatment) or decreasing the net charge (extruding at pH near its isoelectric point) led to lower release rates. The incorporation of ceramic filler caused the opposite effect. Because of the low solubility of the matrix at pH 5.0, no significant variations were detected with variations in the selected formulations. These systems, based on a nonstandard protein-based material, seem to be very promising to be used as carriers for drug delivery. PMID:14606876

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

    NASA Astrophysics Data System (ADS)

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

    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.

  19. Development of polysaccharide-based colon targeted drug delivery systems for the treatment of amoebiasis.

    PubMed

    Mundargi, Raghavendra C; Patil, Sangamesh A; Agnihotri, Sunil A; Aminabhavi, Tejraj M

    2007-03-01

    The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, beta-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30-40% drug release during the initial 4-5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18-24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations. PMID:17454058

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2013-01-01

    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

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

    PubMed

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

    2014-12-30

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

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

    PubMed

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

    2014-09-01

    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

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

    PubMed Central

    Romero, Eder Lilia; Morilla, Maria Jose

    2013-01-01

    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

  5. Inner ear drug delivery via a reciprocating perfusion system in the guinea pig

    PubMed Central

    Chen, Zhiqiang; Kujawa, Sharon G.; McKenna, Michael J.; Fiering, Jason O.; Mescher, Mark J.; Borenstein, Jeffrey T.; Leary Swan, Erin E.; Sewell, William F.

    2007-01-01

    Rapid progress in understanding the molecular mechanisms associated with cochlear and auditory nerve degenerative processes offers hope for the development of gene-transfer and molecular approaches to treat these diseases in patients. For therapies based on these discoveries to become clinically useful, it will be necessary to develop safe and reliable mechanisms for the delivery of drugs into the inner ear, bypassing the blood–labyrinthine barrier. Toward the goal of developing an inner ear perfusion device for human use, a reciprocating microfluidic system that allows perfusion of drugs into the cochlear perilymph through a single inlet hole in scala tympani of the basal turn was developed. The performance of a prototype, extracorporeal reciprocating perfusion system in guinea pigs is described. Analysis of the cochlear distribution of compounds after perfusion took advantage of the place-dependent generation of responses to tones along the length of the cochlea. Perfusion with a control artificial perilymph solution had no effect. Two drugs with well-characterized effects on cochlear physiology, salicylate (5 mM) and DNQX (6,7-Dinitroquinoxaline-2,3-dione; 100 and 300 ?M), reversibly altered responses. The magnitude of drug effect decreased with distance from the perfusion pipette for up to 10 mm, and increased with dose and length of application. PMID:16274830

  6. Theranostic system for drug delivery and pharmacokinetic imaging based on nanosecond pulsed light-induced photomechanical and photoacoustic effects

    NASA Astrophysics Data System (ADS)

    Tsunoi, Yasuyuki; Sato, Shunichi; Kawauchi, Satoko; Akutsu, Yusuke; Miyagawa, Yoshihiro; Araki, Koji; Shiotani, Akihiro; Terakawa, Mitsuhiro

    2015-11-01

    For efficient and side effects-free pharmacological treatment, we here propose a theranostic system that enables transvascular drug delivery by photomechanical waves (PMWs) and photoacoustic (PA) imaging of the drug distribution; both functions are based on nanosecond laser pulses and can therefore be integrated in one system. Through optical fibers arranged around an ultrasound sensor, low-energy and high-energy nanosecond light pulses were transmitted respectively for PA imaging and PMW-based drug delivery by temporal switching. With the system, we delivered a test drug (Evans blue) to tumors in mice and visualized distributions of both the blood vessels and drug in the tissue in vivo, showing the validity of the system.

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

    PubMed Central

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

    2014-01-01

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

  8. A graphene quantum dot-based FRET system for nuclear-targeted and real-time monitoring of drug delivery

    NASA Astrophysics Data System (ADS)

    Chen, Hui; Wang, Zhuyuan; Zong, Shenfei; Chen, Peng; Zhu, Dan; Wu, Lei; Cui, Yiping

    2015-09-01

    A graphene quantum dot-based FRET system is demonstrated for nuclear-targeted drug delivery, which allows for real-time monitoring of the drug release process through FRET signals. In such a system, graphene quantum dots (GQDs) simultaneously serve as the carriers of drugs and donors of FRET pairs. Additionally, a peptide TAT as the nuclear localization signal is conjugated to GQDs, which facilitates the transportation of the delivery system to the nucleus. We have demonstrated that: (a) both the conjugated TAT and small size of GQDs contribute to targeting the nucleus, which results in a significantly enhanced intranuclear accumulation of drugs; (b) FRET signals being extremely sensitive to the distance between donors and acceptors are capable of real-time monitoring of the separation process of drugs and GQDs, which is more versatile in tracking the drug release dynamics. Our strategy for the assembly of a FRET-based drug delivery system may be unique and universal for monitoring the dynamic release process. This study may give more exciting new opportunities for improving the therapeutic efficacy and tracking precision.A graphene quantum dot-based FRET system is demonstrated for nuclear-targeted drug delivery, which allows for real-time monitoring of the drug release process through FRET signals. In such a system, graphene quantum dots (GQDs) simultaneously serve as the carriers of drugs and donors of FRET pairs. Additionally, a peptide TAT as the nuclear localization signal is conjugated to GQDs, which facilitates the transportation of the delivery system to the nucleus. We have demonstrated that: (a) both the conjugated TAT and small size of GQDs contribute to targeting the nucleus, which results in a significantly enhanced intranuclear accumulation of drugs; (b) FRET signals being extremely sensitive to the distance between donors and acceptors are capable of real-time monitoring of the separation process of drugs and GQDs, which is more versatile in tracking the drug release dynamics. Our strategy for the assembly of a FRET-based drug delivery system may be unique and universal for monitoring the dynamic release process. This study may give more exciting new opportunities for improving the therapeutic efficacy and tracking precision. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03454j

  9. Microneedle delivery for improved efficacy of antiretroviral and antibiotic drugs

    E-print Network

    Stauber, Zachary Jason

    2012-01-01

    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 ...

  10. Stimuli Sensitive Polymers and Self Regulated Drug Delivery Systems: A Very Partial Review

    PubMed Central

    Siegel, Ronald A.

    2014-01-01

    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

  11. Self-microemulsifying drug delivery system for improved oral bioavailability of dipyridamole: preparation and evaluation.

    PubMed

    Guo, Feng; Zhong, Haijun; He, Jing; Xie, Baogang; Liu, Fen; Xu, Helin; Liu, Minmin; Xu, Chunlian

    2011-07-01

    Dipyridamole shows poor and variable bioavailability after oral administration due to pHdependent solubility, low biomembrane permeability as well as being a substrate of P-glycoprotein. In order to improve the oral absorption of dipyridamole, a self-microemulsifying drug delivery system (SMEDDS) for dipyridamole was prepared and evaluated in vitro and in vivo. The optimum formulation was 18% oleic acid, 12% Labrafac lipophile WL 1349, 42% Solutol HS 15 and 28% isopropyl alcohol. It was found that the performance of self-microemulsification with the combination of oleic acid and Labrafac lipophile WL 1349 increased compared with just one oil. The results obtained from an in vitro dissolution assay indicated that dipyridamole in SMEDDS dissolved rapidly and completely in pH 6.8 aqueous media, while the commercial drug tablet was less soluble. An oral bioavailability study in rats showed that dipyridamole in the SMEDDS formulation had a 2.06-fold increased absorption compared with the simple drug suspension. It was evident that SMEDDS may be an effective approach to improve the oral absorption for drugs having pH-dependent solubility. PMID:21811918

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

    SciTech Connect

    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

    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.

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

    PubMed Central

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

    2013-01-01

    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

  14. Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases

    PubMed Central

    Smola, Malgorzata; Vandamme, Thierry; Sokolowski, Adam

    2008-01-01

    The purpose of this review is to discuss the impact of nanocarriers administered by pulmonary route to treat and to diagnose respiratory and non respiratory diseases. Indeed, during the past 10 years, the removal of chlorofluorocarbon propellants from industrial and household products intended for the pulmonary route has lead to the developments of new alternative products. Amongst these ones, on one hand, a lot of attention has been focused to improve the bioavailability of marketed drugs intended for respiratory diseases and to develop new concepts for pulmonary administration of drugs and, on the other hand, to use the pulmonary route to administer drugs for systemic diseases. This has led to some marketed products through the last decade. Although the introduction of nanotechnology permitted to step over numerous problems and to improve the bioavailability of drugs, there are, however, unresolved delivery problems to be still addressed. These scientific and industrial innovations and challenges are discussed along this review together with an analysis of the current situation concerning the industrial developments. PMID:18488412

  15. Microparticle-loaded neonatal porcine Sertoli cells for cell-based therapeutic and drug delivery system.

    PubMed

    Giovagnoli, S; Mancuso, F; Vannini, S; Calvitti, M; Piroddi, M; Pietrella, D; Arato, I; Falabella, G; Galli, F; Moretti, M; Neri, L M; Bodo, M; Capitani, S; Cameron, D F; Ricci, M; Luca, G; Calafiore, R

    2014-10-28

    Neonatal porcine Sertoli cells (NPSC) are immune privileged cells showing innate phagocytic and antibacterial activities. NPSC have been shown capable of immunoaltering the body's response and possess lung homing capacity. These properties encourage investigation of NPSC as functional components of cell-based therapeutic protocols to treat lung infections and related complications. In this work, for the first time, NPSC were tailored to carry an antibiotic drug loaded into poly(d,l lactic) acid microparticles (MP). A loading protocol was developed, which afforded 30% drug uptake and high stability over time, with little or no effects on NPSC viability, morphology, reactive oxygen species production and DNA integrity. FSH receptor integrity, and TGF? (transforming growth factor ?) and AMH (anti-Müllerian hormone) expressions were unchanged after 1month of cryopreservation. Protein tyrosine kinase activation due to phagocytosis may have had resulted in changes in inhibin B expression. The activity of MP-loaded or NPSC alone against Pseudomonas aeruginosa was maintained throughout 1month of storage. NPSC couple an innate antibacterial activity with the capacity to embody drug loaded MP. We showed for the first time that engineered NPSC can be cryopreserved with no loss of their basic properties, thereby possibly representing a novel approach for cell-based therapeutic and drug delivery system. PMID:25111130

  16. Repeated in vivo electrochemical activation and the biological effects of microelectromechanical systems drug delivery device.

    PubMed

    Shawgo, Rebecca S; Voskerician, Gabriela; Duc, Hong Linh Ho; Li, Yawen; Lynn, Aaron; MacEwan, Matthew; Langer, Robert; Anderson, James M; Cima, Michael J

    2004-12-15

    The repeated activation of a microelectromechanical systems (MEMS) drug delivery device was studied in vivo in rats to examine the effect of implantation on the device operation and the effect of electrochemical activation on the inflammatory and wound-healing response. The MEMS devices were fabricated from a silicon wafer into which reservoirs were etched and covered with gold membranes. The membranes were electrochemically removed when an anodic voltage was applied. Devices were implanted subcutaneously both with and without stainless steel mesh cages for 4, 7, 14, 21, or 28 days before activation. Devices were activated every other day for five activations. Leukocyte concentrations indicated that both the application of voltage and the gold corrosion products elevated the inflammatory response which was resolved within 48 h after each activation. The efficiency of gold membrane removal was not impaired throughout the implantation, although a bimodal distribution of background current densities was observed after long implantation times. The thickness of the fibrous capsule surrounding the MEMS devices was similar between activated and control devices explanted at each time point. It was concluded that the repeated activation of MEMS drug delivery devices was successful and the activation produced an acceptable biological response that resolved promptly. PMID:15508122

  17. Design and evaluation of a novel matrix type multiple units as biphasic gastroretentive drug delivery systems.

    PubMed

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

    2008-01-01

    A biphasic gastroretentive floating drug delivery system with multiple-unit mini-tablets based on gas formation technique was developed to maintain constant plasma level of a drug concentration within the therapeutic window. The system consists of loading dose as uncoated core units, and prolonged-release core units are prepared by direct compression process; the latter were coated with three successive layers, one of which is seal coat, an effervescent (sodium bicarbonate) layer, and an outer polymeric layer of polymethacrylates. The formulations were evaluated for quality control tests, and all the parameters evaluated were within the acceptable limits. The system using Eudragit RL30D and combination of them as polymeric layer could float within acceptable time. The drug release was linear with the square root of time. The rapid floating and the controlled release properties were achieved in this present study. When compared with the theoretical release profile, the similarity factor of formulation with coating of RS:RL (1:3)-7.5%, was observed to be 74, which is well fitted into zero-order kinetics confirming that the release from formulation is close to desired release profile. The stability samples showed no significant change in dissolution profiles (p > 0.05). In vivo gastric residence time was examined by radiograms, and it was observed that the units remained in the stomach for about 5 h. PMID:19115111

  18. Novel polyoxazolines polymer drug delivery platform

    E-print Network

    Novel polyoxazolines polymer drug delivery platform Reference Number B68084 Introduction Oral and parenteral drug administration dominate the drug delivery market. The global market for oral drug delivery enhanced products was estimated to be worth around US$51 billion in 2009. Parenteral drug delivery

  19. Design and In Vitro Characterization of Buccoadhesive Drug Delivery System of Insulin

    PubMed Central

    Sahni, J.; Raj, S.; Ahmad, F. J.; Khar, R. K.

    2008-01-01

    A buccoadhesive drug delivery system of Insulin was prepared by solvent casting technique and characterized in vitro by surface pH, bioadhesive strength, drug release and skin permeation studies. Sodium carboxymethylcellulose-DVP was chosen as the controlled release matrix polymer. The optimized formulation J4 contained Sodium carboxy methyl cellulose-DVP 2% (w/v), insulin (50 IU/film), propylene glycol (0.25 ml) and Isopropyl alcohol: water (1:4) as solvent system. Bioadhesive strength of the prepared patches was measured on a modified physical balance using bovine cheek pouch as the model membrane. In vitro release studies were carried out at 37 ± 2° using phosphate buffer pH 6.6, in a modified dissolution apparatus fabricated for the purpose. Cumulative amount of drug released from the optimized formulation J4 was 91.64% in 6 hours. In vitro permeation studies were carried out on J4 at 37 ± 2° using Franz diffusion cell. Cumulative amount of drug permeated from J4 was 6.63% in 6 hours. In order to enhance the permeation of protein drug, different permeation enhancers were evaluated. The results suggested that sodium deoxycholate 5% (w/v) was the best permeation enhancer among those evaluated. It enhanced the permeation of insulin from 6.63% to 10.38% over a period of 6 hours. The optimized patches were also satisfactory in terms of surface pH and bioadhesive strength. It can also be easily concluded that the system is a success as compared to the conventional formulations with respect to invasiveness, requirement of trained persons for administration and most importantly, the first pass metabolism. PMID:20390082

  20. In vitro and in vivo evaluation of a self-microemulsifying drug delivery system for the poorly soluble drug fenofibrate.

    PubMed

    Cho, Young-Dae; Park, Young-Joon

    2014-02-01

    Fenofibrate is indicated in hypercholesterolemia and hypertriglyceridemia alone or combined (types IIa, IIb, III, IV, and V dyslipidemias). However, due to its low solubility in water, it has low bioavailability after oral administration. In order to improve the dissolution rate, fenofibrate was formulated into a self-microemulsifying drug delivery system (SMEDDS). We used pseudoternary phase diagrams to evaluate the area of microemulsification, and an in vitro dissolution test was used to investigate the dissolution rate of fenofibrate. The optimized formulation for in vitro dissolution and bioavailability assessment consisted of propylene glycol laurate (Lauroglycol FCC) (60 %), macrogol-15-hydroxystearate (Solutol HS 15) (27 %), and diethylene glycol monoethyl ether (Transcutol-P) (13 %). The mean droplet size of the oil phase in the microemulsion formed by the SMEDDS was 131.1 nm. The dissolution rate of fenofibrate from SMEDDS was significantly higher than that of the reference tablet. In vivo pharmacokinetics study of fenofibrate in beagles administered SMEDDS-A form resulted in a 3.7-fold increase in bioavailability as compared with the reference drug. Our studies suggested that the fenofibrate containing SMEDDS composition can effectively increase the solubility and oral bioavailability of poorly water-soluble drugs. PMID:23754165

  1. Hazard effects of nanoparticles in central nervous system: Searching for biocompatible nanomaterials for drug delivery.

    PubMed

    Leite, Paulo Emílio Corrêa; Pereira, Mariana Rodrigues; Granjeiro, José Mauro

    2015-10-01

    Nanostructured materials are widely used in many applications of industry and biomedical fields. Nanoparticles emerges as potential pharmacological carriers that can be applied in the regenerative medicine, diagnosis and drug delivery. Different types of nanoparticles exhibit ability to cross the brain blood barrier (BBB) and accumulate in several brain areas. Then, efforts have been done to develop safer nanocarrier systems to treat disorders of central nervous system (CNS). However, several in vitro and in vivo studies demonstrated that nanoparticles of different materials exhibit a wide range of neurotoxic effects inducing neuroinflammation and cognitive impairment. For this reason, polymeric nanoparticles arise as a promisor alternative due to their biocompatible and biodegradable properties. After an overview of CNS location and neurotoxic effects of translocated nanoparticles, this review addresses the use of polymeric nanoparticles to the treatment of neuroinfectious diseases, as acquired immunodeficiency syndrome (AIDS) and meningitis. PMID:26116398

  2. A three-drug nanoscale drug delivery system designed for preferential lymphatic uptake for the treatment of metastatic melanoma.

    PubMed

    Doddapaneni, Bhuvana S; Kyryachenko, Sergiy; Chagani, Sharmeen E; Alany, Raid G; Rao, Deepa A; Indra, Arup K; Alani, Adam W G

    2015-12-28

    Metastatic melanoma has a high mortality rate due to lymphatic progression of the disease. Current treatment is surgery followed by radiation and intravenous chemotherapy. However, drawbacks for current chemotherapeutics lie in the fact that they develop resistance and do not achieve therapeutic concentrations in the lymphatic system. We hypothesize that a three-drug nanoscale drug delivery system, tailored for lymphatic uptake, administered subcutaneously, will have decreased drug resistance and therefore offer better therapeutic outcomes. We prepared and characterized nanoparticles (NPs) with docetaxel, everolimus, and LY294002 in polyethyleneglycol-block-poly(?-caprolactone) (PEG-PCL) polymer with different charge distributions by modifying the ratio of anionic and neutral end groups on the PEG block. These NPs are similarly sized (~48nm), with neutral, partially charged, or fully charged surface. The NPs are able to load ~2mg/mL of each drug and are stable for 24h. The NPs are assessed for safety and efficacy in two transgenic metastatic melanoma mouse models. All the NPs were safe in both models based on general appearance, weight changes, death, and blood biochemical analyses. The partially charged NPs are most effective in decreasing the number of melanocytes at both the proximal (sentinel) lymph node (LN) and the distal LN from the injection site. The neutral NPs are efficacious at the proximal LN, while the fully charged NPs have no effect on either LNs. Thus, our data indicates that the NP surface charge and lymphatic efficacy are closely tied to each other and the partially charged NPs have the highest potential in treating metastatic melanoma. PMID:26578440

  3. Routes for Drug Delivery to the Retina: Topical, Transscleral, Suprachoroidal and Intravitreal Gas Phase Delivery.

    PubMed

    Yamada, Norihiro; Olsen, Timothy W

    2016-01-01

    Local drug delivery to the posterior segment, particularly the macula, represents a significant challenge. In this chapter, we review current challenges, barriers and limitations. Due to the local drug delivery to the retina and macula, systemic side effects are limited. In this chapter, we also discuss the historical approaches, key aspects of ideal drug delivery systems, the use of animal models to study pharmacokinetics, and the principles of transscleral, suprachoroidal and gas phase drug delivery. PMID:26501685

  4. Supercritical fluid technology for enhanced drug delivery.

    PubMed

    Pathak, Pankaj; Meziani, Mohammed J; Sun, Ya-Ping

    2005-07-01

    The rapid advances in the development of formulation and delivery systems based on micron-sized and nanoscale drug particles will create significant benefits to the pharmaceutical industry. Complementary to traditional methods, supercritical fluid techniques have found many useful, and sometimes unique, applications in the production and processing of drug particles. In this article background information is provided on a variety of supercritical fluid techniques relevant to drug formulation and delivery, recent advances and novel applications are highlighted, and the successful development of a new supercritical fluid rapid expansion technique for producing exclusively nanoscale drug particles will be discussed. Challenges and opportunities for further development and future applications are also reviewed. PMID:16296799

  5. Calcium phosphate ceramics in drug delivery

    NASA Astrophysics Data System (ADS)

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

    2011-04-01

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

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

    PubMed

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

    2015-12-10

    UV light has been extensively employed in drug delivery because of its versatility, ease of manipulation, and ability to induce chemical changes on the therapeutic carrier. Here we review the mechanisms by which UV light affects drug delivery systems. We will present the challenges facing UV-induced drug delivery and some of the proposed solutions. PMID:26208426

  7. Trojan particles: Large porous carriers of nanoparticles for drug delivery

    E-print Network

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

  8. Enhancement of the oral bioavailability of breviscapine by nanoemulsions drug delivery system.

    PubMed

    Ma, Yan; Li, HaiGang; Guan, ShiXia

    2015-02-01

    Aim to design an effective breviscapine nanoscale drug delivery system to realize the improvement of its oral bioavailability. Based on the investigations of the stabilities in the gastrointestinal tract (GIT), permeation and efflux across the cell membrane, the breviscapine nanoemulsion (NE) was formulated and evaluated in vitro and in vivo. The globule size and polydispersity index of the NE was 45.6?nm and 0.105, and the efficient encapsulation was 95.2%. In vitro, the drug release from NEs in pH 6.8 PBS fit to the first-order kinetics. The Caco-2 cell transport experiments showed that the breviscapine NE facilitated the improvement of the apparent permeability coefficient (Papp) from the apical side to basilar side compared with the free drug. In vivo, the relative bioavailability of breviscapine NE reached to 249.7%. All the studies implicated that the NE carrier contributed to the enhancement of the oral absorption of breviscapine due to the improved stability and permeation in the GIT. The nanoemulsions technology is better for the poor permeable and unstable active agents in GIT as well as helps the industrial scale process. PMID:25113432

  9. Development and Evaluation of Liquid and Solid Self-Emulsifying Drug Delivery Systems for Atorvastatin.

    PubMed

    Czajkowska-Ko?nik, Anna; Szekalska, Marta; Amelian, Aleksandra; Szyma?ska, Emilia; Winnicka, Katarzyna

    2015-01-01

    The objective of this work was to design and characterize liquid and solid self-emulsifying drug delivery systems (SEDDS) for poorly soluble atorvastatin. To optimize the composition of liquid atorvastatin-SEDDS, solubility tests, pseudoternary phase diagrams, emulsification studies and other in vitro examinations (thermodynamic stability, droplet size and zeta potential analysis) were performed. Due to the disadvantages of liquid SEDDS (few choices for dosage forms, low stability and portability during the manufacturing process), attempts were also made to obtain solid SEDDS. Solid SEDDS were successfully obtained using the spray drying technique from two optimized liquid formulations, CF3 and OF2. Despite liquid SEDDS formulation, CF3 was characterized by lower turbidity, higher percentage transmittance and better self-emulsifying properties, and based on the in vitro dissolution study it can be concluded that better solubilization properties were exhibited by solid formulation OF2. Overall, the studies demonstrated the possibility of formulating liquid and solid SEEDS as promising carriers of atorvastatin. SEDDS, with their unique solubilization properties, provide the opportunity to deliver lipophilic drugs to the gastrointestinal tract in a solubilized state, avoiding dissolution-a restricting factor in absorption rate of BCS Class 2 drugs, including atorvastatin. PMID:26610464

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

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

    2015-01-01

    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

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

    PubMed Central

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

    2013-01-01

    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

  13. Formulation, optimization, and evaluation of self-emulsifying drug delivery systems of nevirapine

    PubMed Central

    Chintalapudi, Ramprasad; Murthy, T. E. G. K.; Lakshmi, K. Rajya; Manohar, G. Ganesh

    2015-01-01

    Background: The aim of the present study was to formulate and optimize the self-emulsifying drug delivery systems (SEDDS) of nevirapine (NVP) by use of 22 factorial designs to enhance the oral absorption of NVP by improving its solubility, dissolution rate, and diffusion profile. SEDDS are the isotropic mixtures of oil, surfactant, co-surfactant and drug that form oil in water microemulsion when introduced into the aqueous phase under gentle agitation. Materials and Methods: Solubility of NVP in different oils, surfactants, and co-surfactants was determined for the screening of excipients. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations with the help of data obtained through the maximum micro emulsion region containing combinations of oil, surfactant, and co-surfactant. The formulations of SEDDS were optimized by 22 factorial designs. Results: The optimum formulation of SEDDS contains 32.5% oleic acid, 44.16% tween 20, and 11.9% polyethylene glycol 600 as oil, surfactant, and co-surfactant respectively. The SEDDS was evaluated for the following drug content, self-emulsification time, rheological properties, zeta potential, in vitro diffusion studies, thermodynamic stability studies, and in vitro dissolution studies. An increase in dissolution was achieved by SEDDS compared to pure form of NVP. Conclusion: Overall, this study suggests that the dissolution and oral bioavailability of NVP could be improved by SEDDS technology. PMID:26682191

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

    PubMed

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

    2013-04-01

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

  15. Systematic Development of Self-Emulsifying Drug Delivery Systems of Atorvastatin with Improved Bioavailability Potential

    PubMed Central

    Khan, Fariba; Islam, Md. Saiful; Roni, Monzurul Amin; Jalil, Reza-Ul

    2012-01-01

    The aim of this study was to prepare and characterize a self-emulsifying drug delivery system (SEDDS) with a high drug load of poorly water-soluble atorvastatin for the enhancement of dissolution and oral bioavailability. Solubility of atorvastatin in oil, surfactant, and cosurfactant was determined. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations. A high drug load (10% w/w) was achieved with a combination of oleic acid, Tween 80, and polyethylene glycol 400, ensuring the maximum dissolution property (in the case of SES6). Effects of lipids and surfactants on physical properties of SEDDS such as in vitro emulsification efficiency in terms of self-emulsification time, emulsion droplet size, and percent transmittance were measured. Multiple regression analysis revealed that a higher amount of surfactants significantly increased dissolution of ATV while decreasing emulsion droplet size and emulsification time. About a four-fold increase in dissolution was achieved by SEDDS compared to pure ATV powder. Overall, this study suggests that dissolution and oral bioavailability of ATV could be improved by SEDDS technology. PMID:23264948

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

    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.

  17. Think global--act local: intravitreal drug delivery systems in chronic noninfectious uveitis.

    PubMed

    Hazirolan, Dicle; Pleyer, Uwe

    2013-01-01

    The eye is probably the most attractive site of the body for treatment using locally delivered therapeutic agents. An ideal indication for such an approach is noninfectious posterior uveitis. Since intraocular structures of the posterior segment are difficult to reach and are otherwise accessible only by systemic treatment, current interest is focused on the pros and cons of intravitreal drug delivery. Because of its chronic and recurrent nature, the long-term release of anti-inflammatory agents is a major treatment goal. Intravitreal injections, intravitreal implants and biodegradable devices are the most commonly used and approved approaches to deliver various agents to the vitreous. Because of their broad and potent effects, corticosteroids (CS) have been the first-line candidates for intraocular delivery. An increasing spectrum of CS preparations including nondegradable and biodegradable devices is currently available. Since repeated and long-term applications bear the risk of steroid-related complications such as increased intraocular pressure and cataract, alternative agents are currently being tested. Intravitreal injection of methotrexate, anti-VEGF (vascular endothelial growth factor), anti-TNF? (tumor necrosis factor ?) and sirolimus have also been applied in patients with conflicting results. Intravitreal treatment has significantly reduced the incidence of adverse effects compared to systemic application, but due to greater ocular side effects there are still some limitations. PMID:23258374

  18. Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy

    PubMed Central

    Fan, Yuchen; Moon, James J.

    2015-01-01

    Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes of adoptive T cell transfer-based therapies. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges facing cancer vaccines and immunotherapy. Nanoparticle systems have been shown to improve targeted delivery of tumor antigens and therapeutics against immune checkpoint molecules, amplify immune activation via the use of new stimuli-responsive or immunostimulatory materials, and augment the efficacy of adoptive cell therapies. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to potentiate cancer immunotherapies, including cancer vaccines with subunit antigens (e.g., oncoproteins, mutated neo-antigens, DNA and mRNA antigens) and whole-cell tumor antigens, dendritic cell-based vaccines, artificial antigen-presenting cells, and immunotherapeutics based on immunogenic cell death, immune checkpoint blockade, and adoptive T-cell therapy. PMID:26350600

  19. Engineering Design and Molecular Dynamics of Mucoadhesive Drug Delivery Systems as Targeting Agents

    PubMed Central

    Serra, Laura; Doménech, Josep; Peppas, Nicholas

    2009-01-01

    The goal of this critical review is to provide a critical analysis of the chain dynamics responsible for the action of micro- and nanoparticles of mucoadhesive biomaterials. The objective of using bioadhesive controlled drug delivery devices is to prolong their residence at a specific site of delivery, thus enhancing the drug absorption process. These mucoadhesive devices can protect the drug during the absorption process in addition to protecting it on its route to the delivery site. The major emphasis of recent research on mucoadhesive biomaterials has been on the use of adhesion promoters, which would enhance the adhesion between synthetic polymers and mucus. The use of adhesion promoters such as linear or tethered polymer chains is a natural result of the diffusional characteristics of adhesion. Mucoadhesion depends largely on the structure of the synthetic polymer gels used in controlled release applications. PMID:18976706

  20. Drug Delivery: Engineering Melanin Nanoparticles as an Efficient Drug-Delivery System for Imaging-Guided Chemotherapy (Adv. Mater. 34/2015).

    PubMed

    Zhang, Ruiping; Fan, Quli; Yang, Min; Cheng, Kai; Lu, Xiaomei; Zhang, Lei; Huang, Wei; Cheng, Zhen

    2015-09-01

    Naturally occurring melanin-based nanoparticles (MNPs) are developed as a highly efficient and biocompatible nanoplatform for drug delivery for cancer imaging-guided treatment. Specifically the FDA-approved drug Sorafenib, which has high hydrophobicity, is successfully loaded into MNPs to prepare a water-soluble nanocomplex for positron emission tomography (PET) and photoacoustic-imaging-guided tumor therapy, as described by Q. Fan, Z. Cheng, and co-workers on page 5063. Image credit: Zhen Cheng and Quli Fan. PMID:26344842

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

    NASA Astrophysics Data System (ADS)

    D'Addio, Suzanne M.

    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.

  2. Brain tumor-targeted drug delivery strategies

    PubMed Central

    Wei, Xiaoli; Chen, Xishan; Ying, Man; Lu, Weiyue

    2014-01-01

    Despite the application of aggressive surgery, radiotherapy and chemotherapy in clinics, brain tumors are still a difficult health challenge due to their fast development and poor prognosis. Brain tumor-targeted drug delivery systems, which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue, are a promising new approach to brain tumor treatments. Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues, potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery. In this review, we briefly describe the physiological characteristics of brain tumors, including blood–brain/brain tumor barriers, the tumor microenvironment, and tumor stem cells. We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.

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

    PubMed

    Kanzaki, Sho

    2014-01-01

    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

  4. Protein-Based Nanomedicine Platforms for Drug Delivery

    SciTech Connect

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

    2009-08-03

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

  5. Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

    PubMed Central

    Kalomiraki, Marina; Thermos, Kyriaki; Chaniotakis, Nikos A

    2016-01-01

    Dendrimers are large polymeric structures with nanosize dimensions (1–10 nm) and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific “architecture” and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases.

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

    PubMed

    Abdelkader, Hamdy; Alany, Raid G

    2012-07-01

    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

  7. An implantable MEMS drug delivery device for rapid delivery in ambulatory emergency care.

    PubMed

    Elman, N M; Ho Duc, H L; Cima, M J

    2009-06-01

    We introduce the first implantable drug delivery system based on MEMS (Micro-Electro-Mechanical-Systems) technology specifically designed as a platform for treatment in ambulatory emergency care. The device is named IRD(3) (implantable rapid drug delivery device) and allows rapid delivery of drugs. Vasopressin was used as a model drug for in vitro tests as it is a commonly used drug for cardiac resuscitation. Experimental results reveal that the IRD(3) provides an effective method for rapid delivery without significant drug degradation. Several medical uses and delivery modalities for IRD(3) are proposed. PMID:19169826

  8. 'Genipin' - the natural water soluble cross-linking agent and its importance in the modified drug delivery systems: an overview.

    PubMed

    Manickam, Balamurugan; Sreedharan, Rajesh; Elumalai, Manogaran

    2014-01-01

    One of the popular approaches in controlling drug delivery from the polymeric carriers is suitably achieved by the inclusion of crosslinking agents into the formulations at different concentrations. Nevertheless, addition of the chemical crosslinkers such as glutaraldehyde, formaldehyde etc, used in the drug delivery systems causes very serious cytotoxic reactions. These chemical crosslinking agents did not offer any significant advantageous effects when compared to the natural crosslinking agents for instance genipin, which is quite less toxic, biocompatible and offers very stable crosslinked products. Based on the earlier reports the safety of this particular natural crosslinker is very well established, since it has been widely used as a Chinese traditional medicine for long-time, isolated from fruits of the plant Gardenia jasminoides Ellis. This concise article largely portrayed the value of this unique natural crosslinker, utilized in controlling the drug delivery from the various formulations. PMID:24041312

  9. 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

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

    2011-12-31

    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.

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

    SciTech Connect

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

    1993-12-31

    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.

  11. Evolutionary game based control for biological systems with applications in drug delivery.

    PubMed

    Li, Xiaobo; Lenaghan, Scott C; Zhang, Mingjun

    2013-06-01

    Control engineering and analysis of biological systems have become increasingly important for systems and synthetic biology. Unfortunately, no widely accepted control framework is currently available for these systems, especially at the cell and molecular levels. This is partially due to the lack of appropriate mathematical models to describe the unique dynamics of biological systems, and the lack of implementation techniques, such as ultra-fast and ultra-small devices and corresponding control algorithms. This paper proposes a control framework for biological systems subject to dynamics that exhibit adaptive behavior under evolutionary pressures. The control framework was formulated based on evolutionary game based modeling, which integrates both the internal dynamics and the population dynamics. In the proposed control framework, the adaptive behavior was characterized as an internal dynamic, and the external environment was regarded as an external control input. The proposed open-interface control framework can be integrated with additional control algorithms for control of biological systems. To demonstrate the effectiveness of the proposed framework, an optimal control strategy was developed and validated for drug delivery using the pathogen Giardia lamblia as a test case. In principle, the proposed control framework can be applied to any biological system exhibiting adaptive behavior under evolutionary pressures. PMID:23295892

  12. Development of a virus-mimicking nanocarrier for drug delivery systems: The bio-nanocapsule.

    PubMed

    Somiya, Masaharu; Kuroda, Shun'ichi

    2015-12-01

    As drug delivery systems, nanocarriers should be capable of executing the following functions: evasion of the host immune system, targeting to the diseased site, entering cells, escaping from endosomes, and releasing payloads into the cytoplasm. Since viruses perform some or all of these functions, they are considered naturally occurring nanocarriers. To achieve biomimicry of the hepatitis B virus (HBV), we generated the "bio-nanocapsule" (BNC)-which deploys the human hepatocyte-targeting domain, fusogenic domain, and polymerized-albumin receptor domain of HBV envelope L protein on its surface-by overexpressing the L protein in yeast cells. BNCs are capable of delivering various payloads to the cytoplasm of human hepatic cells specifically in vivo, which is achieved via formation of complexes with various materials (e.g., drugs, nucleic acids, and proteins) by electroporation, fusion with liposomes, or chemical modification. In this review, we describe BNC-related technology, discuss retargeting strategies for BNCs, and outline other virus-inspired nanocarriers. PMID:26482188

  13. Characterization of hot-melt extruded drug delivery systems for onychomycosis.

    PubMed

    Mididoddi, Praveen K; Repka, Michael A

    2007-04-01

    The objectives of this investigation were to study the physico-chemical properties of hot-melt extruded (HME) films for onychomycosis and to determine the stability of the model antifungal drug incorporated within these films. The influence of etching and instrument variables on the bioadhesion of these drug delivery systems for the human nail was also studied. Six 250 g batches (F1-F6) of hydroxypropyl cellulose (HPC) and/or poly(ethylene oxide) films containing ketoconazole (20%) were extruded using a Killion extruder (Model KLB-100). The thermal properties of HME films were investigated using differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) was used to examine the surface morphology of the films and X-ray diffraction (XRD) was used to investigate the crystalline properties of the drugs, physical mixtures as well as the HME films. Stability studies were performed on the films stored at 25 degrees C/60%RH. The bioadhesive properties of these films were investigated on the human nail (ex vivo) using a Texture Analyzer. The nail samples tested were either non-treated (control) or treated with an etching gel. The parameters measured were peak adhesion force (PAF) and area under the curve (AUC). The Hansen solubility parameter was calculated using a combination of Hoy and Hoftyzer/Van Krevelen methods to estimate the likelihood of drug-polymer miscibility. SEM provided direct physical evidence of the physical state of the drug within the films. The theoretical post-extrusion content of ketoconazole remaining in the six film batches ranged from 90.3% (+/-2.2) to 102.4% (+/-9.0) for up to 6 months and from 83.9% (+/-3.6) to 91.6% (+/-3.0) for up to 12 months. Bioadhesion studies of HPC film tested on 'etched' nails recorded significantly higher PAF and AUC than that of the non-treated 'control' nails. Ketoconazole was found to be relatively stable during the extrusion process. Melting points corresponding to the crystalline drugs were not observed in the processed films. The Hansen solubility parameters predicted miscibility between the polymers and the drug. The predictions of the solubility parameters were in agreement with DSC, XRD and SEM results. Bioadhesion measurements of the film on the human nail substrate were generally higher for the etched nails than that of the control nails. PMID:17045468

  14. Antioxidant Gallic Acid-Functionalized Biodegradable in Situ Gelling Copolymers for Cytoprotective Antiglaucoma Drug Delivery Systems.

    PubMed

    Lai, Jui-Yang; Luo, Li-Jyuan

    2015-09-14

    In clinical ophthalmology, oxidative stress has been proposed as the initiating cause of ocular hypertension, which is one of the risk factors for glaucomatous damage and disease progression. In an attempt to improve the therapeutic efficacy of intracamerally administered pilocarpine, herein, a cytoprotective antiglaucoma drug delivery system composed of antioxidant gallic acid (GA)-functionalized gelatin-g-poly(N-isopropylacrylamide) (GN) biodegradable in situ gelling copolymer was developed for the first time. Analyses by UV-vis and Fourier transform infrared spectroscopies showed the formation of biopolymer-antioxidant covalent linkages in GNGA structures through a radical reaction in the presence of water-soluble redox initiators. The synthesized GNGA polymers with strong free radical scavenging effectiveness exhibited appropriate phase transition temperature and degradation rate as injectable bioerodible depots for minimally invasive pilocarpine delivery to the ocular anterior chamber. During the 2-week in vitro study, the sustained releases of sufficient amounts of pilocarpine for a therapeutic action in alleviating ocular hypertension could be achieved under physiological conditions. Results of cell viability, intracellular reactive oxygen species level, and intracellular calcium concentration indicated that the incorporation of antioxidant GA into GN structure can enhance cytoprotective effects of carrier materials against hydrogen peroxide-induced oxidative stress in lens epithelial cultures. Effective pharmacological responses (i.e., reduction of intraocular pressure and preservation of corneal endothelial cell morphology and density) in rabbits receiving intracameral GNGA injections containing pilocarpine were evidenced by clinical observations. The findings of in vivo studies also support the hypothesis that the GNGA carriers are more advantageous over their GN counterparts for the improvement of total antioxidant status in glaucomatous eyes with chronic ocular hypertension. The synthesized multifunctional molecules may be further used as potential polymer therapeutics for intraocular delivery of bioactive agents. PMID:26248008

  15. Polymeric conjugates for drug delivery

    PubMed Central

    Larson, Nate; Ghandehari, Hamidreza

    2012-01-01

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

  16. Evaluation of critical formulation parameters in design and differentiation of self-microemulsifying drug delivery systems (SMEDDSs) for oral delivery of aciclovir.

    PubMed

    Jankovi?, Jovana; Djekic, Ljiljana; Dobri?i?, Vladimir; Primorac, Marija

    2016-01-30

    The study investigated the influence of formulation parameters for design of self-microemulsifying drug delivery systems (SMEDDSs) comprising oil (medium chain triglycerides) (10%), surfactant (Labrasol(®), polysorbate 20, or Kolliphor(®) RH40), cosurfactant (Plurol(®) Oleique CC 497) (q.s. ad 100%), and cosolvent (glycerol or macrogol 400) (20% or 30%), and evaluate their potential as carriers for oral delivery of a poorly permeable antivirotic aciclovir (acyclovir). The drug loading capacity of the prepared formulations ranged from 0.18-31.66mg/ml. Among a total of 60 formulations, three formulations meet the limits for average droplet size (Z-ave) and polydispersity index (PdI) that have been set for SMEDDSs (Z-ave?100nm, PdI<0.250) upon spontaneous dispersion in 0.1M HCl and phosphate buffer pH 7.2. SMEDDSs with the highest aciclovir loading capacity (24.06mg/ml and 21.12mg/ml) provided the in vitro drug release rates of 0.325mgcm(-2)min(-1) and 0.323mgcm(-2)min(-1), respectively, and significantly enhanced drug permeability in the parallel artificial membrane permeability assay (PAMPA), in comparison with the pure drug substance. The results revealed that development of SMEDDSs with enhanced drug loading capacity and oral delivery potential, required optimization of hydrophilic ingredients, in terms of size of hydrophilic moiety of the surfactant, surfactant-to-cosurfactant mass ratio (Km), and log P of the cosolvent. PMID:26611669

  17. Engineering Melanin Nanoparticles as an Efficient Drug-Delivery System for Imaging-Guided Chemotherapy.

    PubMed

    Zhang, Ruiping; Fan, Quli; Yang, Min; Cheng, Kai; Lu, Xiaomei; Zhang, Lei; Huang, Wei; Cheng, Zhen

    2015-09-01

    In order to promote imaging-guided chemotherapy for preclinical and clinical applications, endogenous nanosystems with both contrast and drug-delivery properties are highly desired. Here, the simple use of melanin is first reported, and this biopolymer with good biocompatibility and biodegradability, binding ability to drugs and ions, and intrinsic photoacoustic properties, can serve as an efficient endogenous nanosystem for imaging-guided tumor chemotherapy in living mice. PMID:26222210

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

    PubMed

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

    2015-02-01

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

  19. Ungual and transungual drug delivery.

    PubMed

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

    2012-08-01

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

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

    PubMed Central

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

    2014-01-01

    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

  1. Switchable selectivity for gating ion transport with mixed polyelectrolyte brushes: approaching 'smart' drug delivery systems

    NASA Astrophysics Data System (ADS)

    Motornov, Mikhail; Tam, Tsz Kin; Pita, Marcos; Tokarev, Ihor; Katz, Evgeny; Minko, Sergiy

    2009-10-01

    A pH-responsive mixed polyelectrolyte brush from tethered polyacrylic acid (PAA) and poly(2-vinylpyridine) (P2VP) (PAA:P2VP = 69:31 by weight) was prepared and used for selective gating transport of anions and cations across the thin film. An ITO glass electrode was modified with the polymer brush and used to study the switchable permeability of the mixed brush triggered by changes in pH of the aqueous environment in the presence of two soluble redox probes: [Fe(CN)6]4- and [Ru(NH3)6]3+. The responsive behavior of the brush was also investigated using the in situ ellipsometric measurements of the brush swelling, examination of the brush morphology with atomic force microscopy (AFM), and contact angle measurements of the brush samples extracted from aqueous solutions at different pH values. The mixed brush demonstrated a bipolar permselective behavior. At pH<3 the positively charged P2VP chains enabled the electrochemical process for the negatively charged redox probe, [Fe(CN)6]4-, while the redox process for the positively charged redox probe was effectively inhibited. On the contrary, at pH>6 a reversible redox process for the positively charged redox probe, [Ru(NH3)6]3+, was observed, while the redox process for the negatively charged redox species, [Fe(CN)6]4-, was fully inhibited. Stepwise changing the pH value and recording cyclic voltammograms for the intermediate states of the polymer brush allowed electrochemical observation of the brush transition from the positively charged state, permeable for the negatively charged species, to the negatively charged state, permeable for the positively charged species. The data of ellipsometric, AFM and contact angle measurements are in accord with the electrochemical study. The discovered properties of the brush could be used for the development of 'smart' sensors and drug delivery systems, for example, a smart drug delivery capsule which could release negatively charged molecules of drugs in acidic conditions, while positively charged molecules of drugs will be released in neutral conditions.

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

    ERIC Educational Resources Information Center

    Schwalbe, Michelle Kristin

    2010-01-01

    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…

  3. Nanodisk: a versatile drug delivery platform

    E-print Network

    Ghosh, Mistuni

    2012-01-01

    makes ND a promising nano-platform for in vivo drug deliveryof nanotechnology on drug delivery. ACS Nano. Ryan RO.nano-scale level to improve bioavailability, increase plasma circulation time and achieve tissue specific drug delivery

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

    PubMed

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

    2013-10-15

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

  5. Impact of surface coated magnetite used in magnetic drug delivery system on immune response

    NASA Astrophysics Data System (ADS)

    Oaku, Yoshihiro; Tamada, Junya; Mishima, Fumihito; Akiyama, Yoko; Osako, Mariana Kiomy; Koriyama, Hiroshi; Nakagami, Hironori; Nishijima, Shigehiro

    2015-05-01

    Magnetic drug delivery system (MDDS) is a technique to effectively accumulate drugs, which are combined with ferromagnetic particles, into the affected area using magnetic force control. This study intends to apply MDDS for immunotherapy by enhancing immune responses by a surface treatment of a ferromagnetic particle. The objective of this study is to give the adjuvant effect to a ferromagnetic particle by the surface treatment with alum, which is known as one of the common adjuvants that activates inflammasome pathway. First, magnetite was prepared as a ferromagnetic particle and coated with alum. Alum-coated magnetite increased the expression of caspase-1, which is an activated indicator of inflammasome, in the culture of human monocyte cell (THP-1 cell). To evaluate the potential of the surface coated particles, the particles were subcutaneously injected to mice with a peptide vaccine. As a result, the antibody titer was increased by the surface coated particles as assessed by ELISA. Although a magnetic force has not yet applied in this study, the administration experiment to mice using magnetic force control is our next step. In conclusion, we modified the immune response to magnetite by coating the surface with alum. This can lead to a clinical application for vaccine therapy in future.

  6. Numerical simulations of crystal growth in a transdermal drug delivery system

    NASA Astrophysics Data System (ADS)

    Zeng, Jianming; Jacob, Karl I.; Tikare, Veena

    2004-02-01

    Grain growth by precipitation and Ostwald ripening in an unstressed matrix of a dissolved crystallizable component was simulated using a kinetic Monte Carlo model. This model was used previously to study Ostwald ripening in the high crystallizable component regime and was shown to correctly simulate solution, diffusion and precipitation. In this study, the same model with modifications was applied to the low crystallizable regime of interest to the transdermal drug delivery system (TDS) community. We demonstrate the model's utility by simulating precipitation and grain growth during isothermal storage at different supersaturation conditions. The simulation results provide a first approximation for the crystallization occurring in TDS. It has been reported that for relatively higher temperature growth of drug crystals in TDS occurs only in the middle third of the polymer layer. The results from the simulations support these findings that crystal growth is limited to the middle third of the region, where the availability of crystallizable components is the highest, for cluster growth at relatively high temperature.

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

    PubMed

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

    2014-01-01

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

  8. Sulfisoxazole/cyclodextrin inclusion complex incorporated in electrospun hydroxypropyl cellulose nanofibers as drug delivery system.

    PubMed

    Aytac, Zeynep; Sen, Huseyin Sener; Durgun, Engin; Uyar, Tamer

    2015-04-01

    Herein, hydroxypropyl-beta-cyclodextrin (HP?CD) inclusion complex (IC) of a hydrophobic drug, sulfisoxazole (SFS) was incorporated in hydroxypropyl cellulose (HPC) nanofibers (HPC/SFS/HP?CD-IC-NF) via electrospinning. SFS/HP?CD-IC was characterized by DSC to investigate the formation of inclusion complex and the stoichiometry of the complex was determined by Job's plot. Modeling studies were also performed on SFS/HP?CD-IC using ab initio technique. SEM images depicted the defect free uniform fibers and confirmed the incorporation of SFS/HP?CD-IC in nanofibers did not alter the fiber morphology. XRD analyses showed amorphous distribution of SFS/HP?CD-IC in the fiber mat. Release studies were performed in phosphate buffered saline (PBS). The results suggest higher amount of SFS released from HPC/SFS/HP?CD-IC-NF when compared to free SFS containing HPC nanofibers (HPC/SFS-NF). This was attributed to the increased solubility of SFS by inclusion complexation. Sandwich configurations were prepared by placing HPC/SFS/HP?CD-IC-NF between electrospun PCL nanofibrous mat (PCL-HPC/SFS/HP?CD-IC-NF). Consequently, PCL-HPC/SFS/HP?CD-IC-NF exhibited slower release of SFS as compared with HPC/SFS/HP?CD-IC-NF. This study may provide more efficient future strategies for developing delivery systems of hydrophobic drugs. PMID:25769282

  9. Progress in antiretroviral drug delivery using nanotechnology

    PubMed Central

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-01-01

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

  10. One-pot synthesis of antibacterial chitosan/silver bio-nanocomposite hydrogel beads as drug delivery systems.

    PubMed

    Yadollahi, Mehdi; Farhoudian, Sana; Namazi, Hassan

    2015-08-01

    Silver nanoparticles were synthesized in situ during the formation of physically crosslinked chitosan hydrogel beads using sodium tripolyphosphate as the crosslinker. The aim of the study was to investigate whether these nanocomposite beads have the potential to be used in drug delivery applications. The formation of silver nanoparticles (AgNPs) in the hydrogels was confirmed by X-ray diffraction and scanning electron microscopy studies. Furthermore, the antibacterial and swelling properties of the beads were studied. The nanocomposite hydrogels demonstrated good antibacterial effects against Escherichia coli and Staphylococcus aureus bacteria. AgNPs caused an increase in the swelling capacity of the beads. In vitro drug release test was carried out to prove the effectiveness of this novel type of nanocomposite beads as a controlled drug delivery system. Prolonged and more controlled drug releases were observed for AgNPs containing chitosan beads, which increased by the increase in AgNPs content. PMID:25931399

  11. Expanding Alternative Delivery Systems.

    ERIC Educational Resources Information Center

    Baltzer, Jan A.

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

  12. A cyclically actuated electrolytic drug delivery device.

    PubMed

    Yi, Ying; Buttner, Ulrich; Foulds, Ian G

    2015-09-01

    This work, focusing on an implantable drug delivery system, presents the first prototype electrolytic pump that combines a catalytic reformer and a cyclically actuated mode. These features improve the release performance and extend the lifetime of the device. Using our platinum (Pt)-coated carbon fiber mesh that acts as a catalytic reforming element, the cyclical mode is improved because the faster recombination rate allows for a shorter cycling time for drug delivery. Another feature of our device is that it uses a solid-drug-in-reservoir (SDR) approach, which allows small amounts of a solid drug to be dissolved in human fluid, forming a reproducible drug solution for long-term therapies. We have conducted proof-of-principle drug delivery studies using such an electrolytic pump and solvent blue 38 as the drug substitute. These tests demonstrate power-controlled and pulsatile release profiles of the chemical substance, as well as the feasibility of this device. A drug delivery rate of 11.44 ± 0.56 ?g min(-1) was achieved by using an input power of 4 mW for multiple pulses, which indicates the stability of our system. PMID:26198777

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

    PubMed

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

    2012-01-01

    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

  14. Nanothermodynamics mediates drug delivery.

    PubMed

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

    2015-01-01

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

  15. Bufalin loaded biotinylated chitosan nanoparticles: an efficient drug delivery system for targeted chemotherapy against breast carcinoma.

    PubMed

    Tian, Xin; Yin, Hongzhuan; Zhang, Shichen; Luo, Ying; Xu, Kai; Ma, Ping; Sui, Chengguang; Meng, Fandong; Liu, Yunpeng; Jiang, Youhong; Fang, Jun

    2014-08-01

    Bufalin is a traditional oriental medicine which is known to induce apoptosis in many tumor cells, and it is thus considered as a new anticancer therapeutic. By now, most of the studies of bufalin are in vitro, however in vivo evaluations of its therapeutic efficacy are less and are in great demand for its development toward anticancer drug. One of the problems probably hampering the development of bufalin is the lack of tumor selectivity, which may reduce the therapeutic effect as well as showing side effects. To overcome this drawback, in this study, we designed a tumor-targeted drug delivery system of bufalin based on enhanced permeability and retention (EPR) effect, by using biotinylated chitosan, resulting in bufalin encapsulating nanoparticles (Bu-BCS-NPs) with mean hydrodynamic size of 171.6 nm, as evidenced by dynamic light scattering and transmission electron microscope. Bu-BCS-NPs showed a relative slow and almost linear release of bufalin, and about 36.8% of bufalin was released in 24 h when dissolved in sodium phosphate buffer. Compared to native bufalin, Bu-BCS-NPs exhibited a stronger cytotoxicity against breast cancer MCF-7 cells (IC50 of 0.582 ?g/ml vs 1.896 ?g/ml of native bufalin). Similar results were also obtained in intracellular reactive oxygen species production, apoptosis induction, and decrease in mitochondria membrane potential. These results may contribute to the rapid intracellular uptake of nanoparticles, partly benefiting from the highly expressed biotin receptors in tumor cells. In vivo studies using MCF-7 tumor models in nude mice confirmed the remarkable therapeutic effect of Bu-BCS-NPs. These findings suggest the potential of Bu-BCS-NPs as an anticancer drug with tumor targeting property. PMID:24846793

  16. Preparation and In Vitro Evaluation of a Stomach Specific Drug Delivery System based on Superporous Hydrogel Composite

    PubMed Central

    Chavda, H. V.; Patel, C. N.

    2011-01-01

    This study discusses efforts made to design drug-delivery system based on superporous hydrogel composite for sustained delivery of ranitidine hydrochloride. The characterization studies involve measurement of apparent density, porosity, swelling studies, mechanical strength studies, and scanning electron microscopy. Scanning electron microscopic images clearly showed the formation of interconnected pores, capillary channels, and the cross-linked sodium carboxymethylcellulose molecules around the peripheries of pores. The prepared system floated and delivered the ranitidine hydrochloride for about 17 h. The release profile of ranitidine hydrochloride was studies by changing the retardant polymer in the system. To ascertain the drug release kinetics, the dissolution profiles were fitted to different mathematical models that include zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas, Weibull, and Hopfenberg models. The in vitro dissolution from system was explained by Korsmeyer-Peppas model. The diffusion exponent values in Korsmeyer-Peppas model range between 0.48±0.01 and 0.70±0.01, which appears to indicate an anomalous non-Fickian transport. It is concluded that the proposed mechanically stable floating drug-delivery system based on superporous hydrogel composite containing sodium carboxymethylcellulose as a composite material is promising for stomach specific delivery of ranitidine hydrochloride. PMID:22131619

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

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

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

  18. Drug Delivery Strategies of Chemical CDK Inhibitors.

    PubMed

    Alvira, Daniel; Mondragón, Laura

    2016-01-01

    The pharmacological use of new therapeutics is often limited by a safe and effective drug-delivery system. In this sense, new chemical CDK inhibitors are not an exception. Nanotechnology may be able to solve some of the main problems limiting cancer treatments such as more specific delivery of therapeutics and reduction of toxic secondary effects. It provides new delivery systems able to specifically target cancer cells and release the active molecules in a controlled fashion. Specifically, silica mesoporous supports (SMPS) have emerged as an alternative for more classical drug delivery systems based on polymers. In this chapter, we describe the synthesis of a SMPS containing the CDK inhibitor roscovitine as cargo molecule and the protocols for confirmation of the proper cargo release of the nanoparticles in cell culture employing cell viability, cellular internalization, and cell death induction studies. PMID:26231714

  19. A remotely operated drug delivery system with an electrolytic pump and a thermo-responsive valve.

    PubMed

    Yi, Ying; Zaher, Amir; Yassine, Omar; Kosel, Jurgen; Foulds, Ian G

    2015-09-01

    Implantable drug delivery devices are becoming attractive due to their abilities of targeted and controlled dose release. Currently, two important issues are functional lifetime and non-controlled drug diffusion. In this work, we present a drug delivery device combining an electrolytic pump and a thermo-responsive valve, which are both remotely controlled by an electromagnetic field (40.5?mT and 450?kHz). Our proposed device exhibits a novel operation mechanism for long-term therapeutic treatments using a solid drug in reservoir approach. Our device also prevents undesired drug liquid diffusions. When the electromagnetic field is on, the electrolysis-induced bubble drives the drug liquid towards the Poly (N-Isopropylacrylamide) (PNIPAM) valve that consists of PNIPAM and iron micro-particles. The heat generated by the iron micro-particles causes the PNIPAM to shrink, resulting in an open valve. When the electromagnetic field is turned off, the PNIPAM starts to swell. In the meantime, the bubbles are catalytically recombined into water, reducing the pressure inside the pumping chamber, which leads to the refilling of the fresh liquid from outside the device. A catalytic reformer is included, allowing more liquid refilling during the limited valve's closing time. The amount of body liquid that refills the drug reservoir can further dissolve the solid drug, forming a reproducible drug solution for the next dose. By repeatedly turning on and off the electromagnetic field, the drug dose can be cyclically released, and the exit port of the device is effectively controlled. PMID:26339328

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

    PubMed

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

    2015-02-01

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

  1. Microscopies at the Nanoscale for Nano-Scale Drug Delivery Systems.

    PubMed

    Dini, Luciana; Panzarini, Elisa; Mariano, Stefania; Passeri, Daniele; Reggente, Melania; Rossi, Marco; Vergallo, Cristian

    2015-01-01

    One of the frontier of nanoscience is undoubtedly represented by the use of nanotechnologies in the pharmaceutical research. During the last decades a big family of nanostructures that have a surface-acting action, such as NanoParticles (NPs), lipid nanocarriers and many more, have been developed to be used as Drug Delivery Systems (DDSs). However, these nanocarriers opened also new frontiers in nanometrology, requiring an accurate morphological characterization, near atomic resolution, before they are really available to clinicians to ascertain their elemental composition, to exclude the presence of contaminants introduced during the synthesis procedure and to ensure biocompatibility. Classical Transmission (TEM) and Scanning Electron Microscopy (SEM) techniques frequently have to be adapted for an accurate analysis of formulation morphology, especially in case of hydrated colloidal systems. Specific techniques such as environmental scanning microscopy and/or cryo preparation are required for their investigation. Analytical Electron Microscopy (AEM) techniques such as Electron Energy-Loss Spectroscopy (EELS) or Energy-Dispersive X-ray Spectroscopy (EDXS) are additional assets to determine the elemental composition of the systems. Here we will discuss the importance of Electron Microscopy (EM) as a reliable tool in the pharmaceutical research of the 21(st) century, focalizing our attention on advantages and limitations of different kind of NPs (in particular silver and carbon NPs, cubosomes) and vesicles (liposomes and niosomes). PMID:26028043

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

    SciTech Connect

    Lee, Don Haeng; Kang, Sung-Gwon Jeong, Seok; Yoon, Chang Jin; Choi, Jung-Ah; Byun, Ju Nam; Park, Jae Hyung; Lee, Kyu Back

    2006-10-15

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

  3. Microbubble-Assisted Ultrasound for Drug Delivery in the Brain and Central Nervous System.

    PubMed

    Burgess, Alison; Hynynen, Kullervo

    2016-01-01

    The blood-brain barrier is a serious impediment to the delivery of pharmaceutical treatments for brain diseases, including cancer, neurodegenerative and neuropsychatric diseases. Focused ultrasound, when combined with microbubbles, has emerged as an effective method to transiently and locally open the blood-brain barrier to promote drug delivery to the brain. Focused ultrasound has been used to successfully deliver a wide variety of therapeutic agents to pre-clinical disease models. The requirement for clinical translation of focused ultrasound technology is considered. PMID:26486344

  4. Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system

    NASA Astrophysics Data System (ADS)

    McDannold, Nathan; Zhang, Yongzhi; Power, Chanikarn; Arvanitis, Costas D.; Vykhodtseva, Natalia; Livingstone, Margaret

    2015-05-01

    The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. The method presents new opportunities for the use of drugs and for the study of the brain.

  5. Comparative study on solid self-nanoemulsifying drug delivery and solid dispersion system for enhanced solubility and bioavailability of ezetimibe

    PubMed Central

    Rashid, Rehmana; Kim, Dong Wuk; Yousaf, Abid Mehmood; Mustapha, Omer; Din, Fakhar ud; Park, Jong Hyuck; Yong, Chul Soon; Oh, Yu-Kyoung; Youn, Yu Seok; Kim, Jong Oh; Choi, Han-Gon

    2015-01-01

    Background The objective of this study was to compare the physicochemical characteristics, solubility, dissolution, and oral bioavailability of an ezetimibe-loaded solid self-nanoemulsifying drug delivery system (SNEDDS), surface modified solid dispersion (SMSD), and solvent evaporated solid dispersion (SESD) to identify the best drug delivery system with the highest oral bioavailability. Methods For the liquid SNEDDS formulation, Capryol 90, Cremophor EL, and Tween 80 were selected as the oil, surfactant, and cosurfactant, respectively. The nanoemulsion-forming region was sketched using a pseudoternary phase diagram on the basis of reduced emulsion size. The optimized liquid SNEDDS was converted to solid SNEDDS by spray drying with silicon dioxide. Furthermore, SMSDs were prepared using the spray drying technique with various amounts of hydroxypropylcellulose and Tween 80, optimized on the basis of their drug solubility. The SESD formulation was prepared with the same composition of optimized SMSD. The aqueous solubility, dissolution, physicochemical properties, and pharmacokinetics of all of the formulations were investigated and compared with the drug powder. Results The drug existed in the crystalline form in SMSD, but was changed into an amorphous form in SNEDDS and SESD, giving particle sizes of approximately 24, 6, and 11 µm, respectively. All of these formulations significantly improved the aqueous solubility and dissolution in the order of solid SNEDDS ? SESD > SMSD, and showed a total higher plasma concentration than did the drug powder. Moreover, SESD gave a higher area under the drug concentration time curve from zero to infinity than did SNEDDS and SMSD, even if they were not significantly different, suggesting more improved oral bioavailability. Conclusion Among the various formulations tested in this study, the SESD system would be strongly recommended as a drug delivery system for the oral administration of ezetimibe with poor water solubility. PMID:26491288

  6. Microfabrication Technologies for Oral Drug Delivery

    PubMed Central

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

    2012-01-01

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

  7. Assessment of drug delivery devices.

    PubMed

    Batista, Elsa; Almeida, Nelson; Furtado, Andreia; Filipe, Eduarda; Sousa, Luis; Martins, Rui; Lucas, Peter; Petter, Harm Tido; Snijder, Roland; Timmerman, Annemoon

    2015-08-01

    For critical drug delivery, it is important to have a constant and well-known infusion rate delivered by the complete infusion set-up (pump, tubing, and accessories). Therefore, various drug delivery devices and accessories were tested in this article in terms of their infusion accuracy, start-up delay, response time, and dependency on the viscosity. These measurements were performed as part of the European funded research project MeDD. The obtained results show that the infusion accuracy of the devices is flow rate and accessory depended, especially for low flow rates. Viscosity does not have a significant impact on the flow rate accuracy. PMID:25945719

  8. Engineered Polymers for Advanced Drug Delivery

    PubMed Central

    Kim, Sungwon; Kim, Jong-Ho; Jeon, Oju; Kwon, Ick Chan; Park, Kinam

    2009-01-01

    Engineered polymers have been utilized for developing advanced drug delivery systems. The development of such polymers has caused advances in polymer chemistry, which, in turn, has resulted in smart polymers that can respond to changes in environmental condition, such as temperature, pH, and biomolecules. The responses vary widely from swelling/deswelling to degradation. Drug-polymer conjugates and drug-containing nano/micro-particles have been used for drug targeting. Engineered polymers and polymeric systems have also been used in new areas, such as molecular imaging as well as in nanotechnology. This review examines the engineered polymers that have been used as traditional drug delivery and as more recent applications in nanotechnology. PMID:18977434

  9. Nanotechnology-based drug delivery systems and herbal medicines: a review

    PubMed Central

    Bonifácio, Bruna Vidal; da Silva, Patricia Bento; Ramos, Matheus Aparecido dos Santos; Negri, Kamila Maria Silveira; Bauab, Taís Maria; Chorilli, Marlus

    2014-01-01

    Herbal medicines have been widely used around the world since ancient times. The advancement of phytochemical and phytopharmacological sciences has enabled elucidation of the composition and biological activities of several medicinal plant products. The effectiveness of many species of medicinal plants depends on the supply of active compounds. Most of the biologically active constituents of extracts, such as flavonoids, tannins, and terpenoids, are highly soluble in water, but have low absorption, because they are unable to cross the lipid membranes of the cells, have excessively high molecular size, or are poorly absorbed, resulting in loss of bioavailability and efficacy. Some extracts are not used clinically because of these obstacles. It has been widely proposed to combine herbal medicine with nanotechnology, because nanostructured systems might be able to potentiate the action of plant extracts, reducing the required dose and side effects, and improving activity. Nanosystems can deliver the active constituent at a sufficient concentration during the entire treatment period, directing it to the desired site of action. Conventional treatments do not meet these requirements. The purpose of this study is to review nanotechnology-based drug delivery systems and herbal medicines. PMID:24363556

  10. Improved Antioxidant Capacity of Optimization of a Self-Microemulsifying Drug Delivery System for Resveratrol.

    PubMed

    Chen, Ying; Zhang, Huiyong; Yang, Jing; Sun, Haiyan

    2015-01-01

    The use of nano-encapsulated resveratrol (RSV) in self-micro-emulsified drug delivery systems (SMEDDS) formulations was investigated. Self-emulsifying grading tests were used to establish the optimal ratio of oil, surfactant, and co-surfactant. The optimized system was further investigated for the droplet size and zeta potential at the different medium pH values by a Malvern Zetasizer and transmission electron microscopy (TEM). The antioxidant capacity and cytotoxicity of the formulation were detected by DCFH-DA and a CCK-8 assays. The results showed that the nano-emulsion based on ethyl oleate, Tween-80, and PEG-400 (35:40:25, w/w/w) was the most stable formulation due to the small droplet size (approximately 50 nm) and high zeta potential in a neutral environment. Furthermore, this formulation also exhibited a greater antioxidant capacity with less toxicity than free RSV. Taken together, considering these results and the simple fabrication process, this formulation could be used to deliver nutritional food supplements in a stable, efficient, and safe manner. PMID:26633319

  11. Peristaltic transport of magneto-nanoparticles submerged in water: Model for drug delivery system

    NASA Astrophysics Data System (ADS)

    Abbasi, F. M.; Hayat, T.; Alsaedi, A.

    2015-04-01

    Recent development in biomedical engineering has enabled the use of the magnetic nanoparticles in modern drug delivery systems with great utility. Nanofluids composed of magnetic nanoparticles have the characteristics to be manipulated by external magnetic field and are used to guide the particles up the bloodstream to a tumor with magnets. In this study we examine the mixed convective peristaltic transport of copper-water nanofluid under the influence of constant applied magnetic field. Nanofluid is considered in an asymmetric channel. Aside from the effect of applied magnetic field on the mechanics of nanofluid, its side effects i.e. the Ohmic heating and Hall effects are also taken into consideration. Heat transfer analysis is performed in presence of viscous dissipation and heat generation/absorption. Mathematical modeling is carried out using the lubrication analysis. Resulting system of equations is numerically solved. Impact of embedded parameters on the velocity, pressure gradient, streamlines and temperature of nanofluid is examined. Effects of applied magnetic field in presence and absence of Hall effects are studied and compared. Results depict that addition of copper nanoparticles reduces the velocity and temperature of fluid. Heat transfer rate at the boundary enhances by increasing the nanoparticles volume fraction. Increase in the strength of applied magnetic field tends to decrease/increase the velocity/temperature of nanofluid. Further presence of Hall effects reduces the variations brought in the state of fluid when strength of applied magnetic field is increased.

  12. Stabilization Challenges and Formulation Strategies Associated with Oral Biologic Drug Delivery Systems.

    PubMed

    Truong-Le, Vu; Lovalenti, Phillip M; Abdul-Fattah, Ahmad M

    2015-10-01

    Delivery of proteins to mucosal tissues of GI tract typically utilize formulations which protect against proteolysis and target the mucosal tissues. Using case studies from literature and the authors' own work, the in-process stability and solid state storage stability of biopharmaceuticals formulated in delivery systems designed for oral delivery to the GI tract will be reviewed. Among the range of delivery systems, biodegradable polymer systems for protection and controlled release of proteins have been the most studied; hence these systems will be covered in greater depth. These delivery systems include polymeric biodegradable microspheres or nanospheres that contain proteins or vaccines, which are designed to reduce the number of administrations/inoculations and the total protein dose required to achieve the desired biological effect. Specifically, this review will include a landscape survey of the systems that have been studied, the manufacturing processes involved, stability through the manufacturing process, key pharmaceutical formulation parameters that impact stability of the encased proteins, and storage stability of the encapsulated proteins in these delivery systems. PMID:26277263

  13. Supplementary Data Drug delivery

    E-print Network

    Seroude, Laurent

    to polymerize and dry at room temperature for 12 to 36 hours depending on the ambient humidity. 2. "Yeast paste (0.01% molasses/8.2% cornmeal/3.4% killed yeast/0.94% agar/0.18% benzoic acid/0.66% propionic acic" delivery: Appropriate volumes of 25 mg/ml RU486 stock solution was mixed with yeast paste (60.4% water, 39

  14. Fluorescent Microscope System to Monitor Real-Time Interactions between Focused Ultrasound, Echogenic Drug Delivery Vehicles, and Live Cell Membranes

    PubMed Central

    Ibsen, Stuart; Benchimol, Michael; Esener, Sadik

    2012-01-01

    Rapid development in the field of ultrasound triggered drug delivery has made it essential to study the real-time interaction between the membranes of live cells and the membranes of echogenic delivery vehicles under exposure to focused ultrasound. The objective of this work was to design an analysis system that combined fluorescent imagining, high speed videography, and definable pulse sequences of focused ultrasound to allow for real time observations of both cell and vehicle membranes. Documenting the behavior of the membranes themselves has not previously been possible due to limitations with existing optical systems used to understand the basic physics of microbubble/ultrasound interaction and the basic interaction between microbubbles and cells. The performance of this new system to monitor membrane behavior was demonstrated by documenting the modes of vehicle fragmentation at different ultrasound intensity levels. At 1.5 MPa the membranes were shown to completely fragment while at intensities below 1 MPa there is a popping and slow unfolding. The interaction between these vehicles and cell membranes was also documented by the removal of fluorescent particles from the surfaces of live cells out to 20 ?m from the microbubble location. The fluid flow created by microstreaming around ensonated microbubbles was documented at video recording speeds from 60 to 18,000 frames per second. This information about membrane behavior allows the chemical and physical properties of the drug delivery vehicle to be designed along with the ultrasound pulse sequence to cause the most efficient drug delivery. PMID:22749476

  15. Microneedles for medical point of care diagnostics and drug delivery

    E-print Network

    Siefert, Chris

    Microneedles for medical point of care diagnostics and drug delivery Ronen Polsky Department Diagnostic Device Portable Handheld Medical Analyzer Diagnostic/Drug Delivery Sense/Respond System #12 delivery device. #12;Commercial Applications Point of Care Diagnostics/Home Health Care Sports Medicine

  16. Skin-compatible lecithin drug delivery systems for fluconazole: effect of phosphatidylethanolamine and oleic acid on skin permeation.

    PubMed

    Hoeller, Sonja; Klang, Victoria; Valenta, Claudia

    2008-05-01

    The purpose of the present study was to evaluate skin-compatible drug delivery systems for fluconazole. Pseudoternary phase diagrams were constructed, composed of different soybean lecithins/oil/isopropanol and water. The role of the various lecithin compositions was expressed in the different resulting isotropic areas. Based on these phase diagrams, two systems were chosen as drug delivery systems for fluconazole. The influence of phosphatidylethanolamine and of the oil component on the skin permeation of fluconazole was investigated. The more phosphatidylethanolamine, the greater was the fluconazole skin permeation, independent of the hydrophilicity of the system. The influence of oleic acid and isopropylmyristate as the oil component was compared and a greater penetration enhancing effect was found for the microemulsion containing oleic acid. PMID:18416934

  17. Current perspectives on intrathecal drug delivery

    PubMed Central

    Bottros, Michael M; Christo, Paul J

    2014-01-01

    Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain and spasticity. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. Recent expert panel consensus guidelines have provided care paths in the treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data for pain relief, adverse effect reduction, and cost-effectiveness with cancer pain control are compelling, the evidence is less clear for noncancer pain, other than spasticity. Physicians should be aware of mechanical, pharmacological, surgical, and patient-specific complications, including possible granuloma formation. Newer intrathecal drug delivery systems may allow for better safety and quality of life outcomes. PMID:25395870

  18. Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system

    PubMed Central

    Wang, Hua; Liu, Jun; Tao, Shan; Chai, Guihong; Wang, Jianwei; Hu, Fu-Qiang; Yuan, Hong

    2015-01-01

    Purpose Nanoparticles (NPs) that target bone tissue were developed using poly(lactic-co-glycolic acid) (PLGA) copolymers and tetracycline (TC)-based bone-targeting moieties. These NPs are expected to enable the transport of drugs, such as simvastatin (SIM), for the treatment of osteoporosis. Methods The molecular structures of TC–PLGA were validated by 1H-NMR, and the SIM-loaded NPs were prepared using the solvent emulsification method. The surface properties, cytotoxicity, cellular uptake, cell mineralization, bone targeting potential, and animal pharmacodynamics of the TC–PLGA NPs were evaluated and compared to those of PLGA NPs. Results It was confirmed that the average particle size of the NPs was approximately 220 nm. In phosphate-buffered saline (PBS, pH 7.4), the SIM-loaded NPs exhibited a cumulative release of up to 80% within 72 hours. An in vitro cell evaluation indicated that the NPs had an excellent cellular uptake capacity and showed great biocompatibility with MC3T3-E1 cells, thereby reducing the cytotoxic effects of SIM. The cell mineralization assay showed that the SIM-loaded NPs induced osteogenic differentiation and mineralized nodule formation in MC3T3-E1 cells, thereby achieving the same effect as SIM. Preliminary findings from in vitro and in vivo bone affinity assays indicated that the TC–PLGA NPs may display increased bone-targeting efficiency compared to PLGA NPs lacking a TC moiety. The use of SIM-loaded TC–PLGA NPs in treating osteoporosis was tested through animal pharmacodynamics analyses performed in ovariectomized rats, and the results suggested that the SIM-loaded TC–PLGA NPs can improve the curative effects of SIM on the recovery of bone mineral density compared to either SIM-loaded PLGA NPs or SIM alone. Conclusion Bone-targeting NPs, which were based on the conjugation of TC to PLGA copolymers, have the ability to target bone. These NPs may be developed as a delivery system for hydrophobic drugs, and they are expected to improve the curative effects of drugs, reduce the administered drug doses, and reduce side effects in other organs. PMID:26388691

  19. Thermomechanical Properties, Antibiotic Release, and Bioactivity of a Sterilized Cyclodextrin Drug Delivery System

    PubMed Central

    Halpern, Jeffrey M.; Gormley, Catherine A.; Keech, Melissa; von Recum, Horst A.

    2014-01-01

    Various local drug delivery devices and coatings are being developed as slow, sustained release mechanism for drugs, yet the polymers are typically not evaluated after commercial sterilization techniques. We examine the effect that commercial sterilization techniques have on the physical, mechanical, and drug delivery properties of polyurethane polymers. Specifically we tested cyclodextrin-hexamethyl diisocyanate crosslinked polymers before and after autoclave, ethylene oxide, and gamma radiation sterilization processes. We found that there is no significant change in the properties of polymers sterilized by ethylene oxide and gamma radiation compared to non-sterilized polymers. Polymers sterilized by autoclave showed increased tensile strength (p<0.0001) compared to non-sterilized polymers . In the release of drugs, which were loaded after the autoclave sterilization process, we observed a prolonged release (p<0.05) and a prolonged therapeutic effect (p<0.05) but less drug loading (p<0.0001) compared to non-sterilized polymers. The change in the release profile and tensile strength in polymers sterilized by autoclave was interpreted as being caused by additional crosslinking from residual, unreacted, or partially-reacted crosslinker contained within the polymer. Autoclaving therefore represents additional thermo-processing to modify rate and dose from polyurethanes and other materials. PMID:24949201

  20. Research of Ultrasound-Mediated Transdermal Drug Delivery System Using Cymbal-Type Piezoelectric Composite Transducer

    NASA Astrophysics Data System (ADS)

    Huan, Huiting; Gao, Chunming; Liu, Lixian; Sun, Qiming; Zhao, Binxing; Yan, Laijun

    2015-06-01

    Transdermal drug delivery (TDD) implemented by especially low-frequency ultrasound is generally known as sonophoresis or phonophoresis which has drawn considerable wide attention. However, TDD has not yet achieved its full potential as an alternative to conventional drug delivery methods due to its bulky instruments. In this paper, a cymbal-type piezoelectric composite transducer (CPCT) which has advantages over a traditional ultrasound generator in weight, flexibility, and power consumption, is used as a substitute ultrasonicator to realize TDD. First, theoretical research on a CPCT based on the finite element analysis was carried out according to which a series of applicable CPCTs with bandwidths of 20 kHz to 100 kHz were elaborated. Second, a TDD experimental setup was built with previously fabricated CPCTs aimed at the administration of glucose. Finally, the TDD performance of glucose molecule transport in porcine skin was measured in vitro by quantifying the concentration of glucose, and the time variation curves were subsequently obtained. During the experiment, the driving wave form, frequency, and power consumption of the transducers were selected as the main elements which determined the efficacy of glucose delivery. The results indicate that the effectiveness of the CPCT-based delivery is constrained more by the frequency and intensity of ultrasound rather than the driving waveform. The light-weight, flexibility, and low-power consumption of a CPCT can potentially achieve effective TDD.

  1. Lipid-based intravesical drug delivery systems with controlled release of trospium chloride for the urinary bladder.

    PubMed

    Haupt, M; Thommes, M; Heidenreich, A; Breitkreutz, J

    2013-09-10

    The overactive bladder (OAB) is a common disease with an overactivity of the detrusor muscle in the bladder wall. Besides peroral administration of anticholinergic drugs and bladder irrigations, there is a need for a sustained release formulation in the urinary bladder. In order to realise a local long-term treatment of the overactive urinary bladder, lipidic drug delivery systems were prepared. Requirements for an intravesical application are a long-term controlled release of trospium chloride, a high drug loading and small sized drug carriers to permit an insertion through the urethra into the urinary bladder. The drug delivery systems were manufactured by using compression (mini-tablets), solid lipid extrusion (extrudates) and a melting and casting technique (mini-moulds) with different amounts of trospium chloride and glyceryl tristearate as matrix former. Drug release depended on the drug loading and the preparation method. Mini-tablets and lipidic extrudates showed a drug release over five days, whereas that from mini-moulds was negligibly small. The appearance of polymorphic transformations during processing and storage was investigated by using differential scanning calorimetry and X-ray diffraction. In contrast to mini-tablets and mini-moulds, lipidic extrudates showed no polymorphic transformations. In summary, lipids are suitable matrix formers for a highly water-soluble drug, like trospium chloride. Despite a drug loading of up to 30%, it was feasible to achieve a drug release ranging from several days up to weeks. In addition, small dosage forms with a size of only a few millimetres were realised. Therefore, an insertion and excretion through the urethra is possible and the requirements for an intravesical application are fulfilled. PMID:23732944

  2. Polysaccharides for colon targeted drug delivery.

    PubMed

    Chourasia, M K; Jain, S K

    2004-01-01

    Colon targeted drug delivery has the potential to deliver bioactive agents for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. Various strategies, currently available to target the release of drugs to colon, include formation of prodrug, coating of pH-sensitive polymers, use of colon-specific biodegradable polymers, timed released systems, osmotic systems, and pressure controlled drug delivery systems. Among the different approaches to achieve targeted drug release to the colon, the use of polymers especially biodegradable by colonic bacteria holds great promise. Polysaccharidases are bacterial enzymes that are available in sufficient quantity to be exploited in colon targeting of drugs. Based on this approach, various polysaccharides have been investigated for colon-specific drug release. These polysaccharides include pectin, guar gum, amylose, inulin, dextran, chitosan, and chondroitin sulphate. This family of natural polymers has an appeal to drug delivery as it is comprised of polymers with a large number of derivatizable groups, a wide range of molecular weights, varying chemical compositions, and, for the most part, low toxicity and biodegradability yet high stability. The most favorable property of these materials is their approval as pharmaceutical excipients. PMID:15200012

  3. Magnetic manipulation of superparamagnetic nanoparticles in a microfluidic system for drug delivery applications

    NASA Astrophysics Data System (ADS)

    Agiotis, L.; Theodorakos, I.; Samothrakitis, S.; Papazoglou, S.; Zergioti, I.; Raptis, Y. S.

    2016-03-01

    Magnetic nanoparticles (MNPs), such as superparamagnetic iron oxide nanoparticles (SPIONS), have attracted major interest, due to their small size and unique magnetic properties, for drug delivery applications. In this context, iron oxide nanoparticles of magnetite (Fe3O4) (150 nm magnetic core diameter), were used as drug carriers, aiming to form a magnetically controlled nano-platform. The navigation capabilities of the iron oxide nanoparticles in a microfluidic channel were investigated by simulating the magnetic field and the magnetic force applied on the magnetic nanoparticles inside a microfluidic chip. The simulations have been performed using finite element method (ANSY'S software). The optimum setup which intends to simulate the magnetic navigation of the nanoparticles, by the use of MRI-type fields, in the human circulatory system, consists of two parallel permanent magnets to produce a homogeneous magnetic field, in order to ensure the maximum magnetization of the magnetic nanoparticles, an electromagnet for the induction of the magnetic gradients and the creation of the magnetic force and a microfluidic setup so as to simulate the blood flow inside the human blood vessels. The magnetization of the superparamagnetic nanoparticles and the consequent magnetic torque developed by the two permanent magnets, together with the mutual interactions between the magnetized nanoparticles lead to the creation of rhabdoid aggregates in the direction of the homogeneous field. Additionally, the magnetic gradients introduced by the operation of the electromagnet are capable of directing the aggregates, as a whole, to the desired direction. By removing the magnetic fields, the aggregates are disrupted, due to the super paramagnetic nature of the nanoparticles, avoiding thus the formation of undesired thrombosis.

  4. Drug delivery system innovation and Health Technology Assessment: Upgrading from Clinical to Technological Assessment.

    PubMed

    Panzitta, Michele; Bruno, Giorgio; Giovagnoli, Stefano; Mendicino, Francesca R; Ricci, Maurizio

    2015-11-30

    Health Technology Assessment (HTA) is a multidisciplinary health political instrument that evaluates the consequences, mainly clinical and economical, of a health care technology; the HTA aim is to produce and spread information on scientific and technological innovation for health political decision making process. Drug delivery systems (DDS), such as nanocarriers, are technologically complex but they have pivotal relevance in therapeutic innovation. The HTA process, as commonly applied to conventional drug evaluation, should upgrade to a full pharmaceutical assessment, considering the DDS complexity. This is useful to study more in depth the clinical outcome and to broaden its critical assessment toward pharmaceutical issues affecting the patient and not measured by the current clinical evidence approach. We draw out the expertise necessary to perform the pharmaceutical assessment and we propose a format to evaluate the DDS technological topics such as formulation and mechanism of action, physicochemical characteristics, manufacturing process. We integrated the above-mentioned three points in the Evidence Based Medicine approach, which is data source for any HTA process. In this regard, the introduction of a Pharmaceutics Expert figure in the HTA could be fundamental to grant a more detailed evaluation of medicine product characteristics and performances and to help optimizing DDS features to overcome R&D drawbacks. Some aspects of product development, such as manufacturing processes, should be part of the HTA as innovative manufacturing processes allow new products to reach more effectively patient bedside. HTA so upgraded may encourage resource allocating payers to invest in innovative technologies and providers to focus on innovative material properties and manufacturing processes, thus contributing to bring more medicines in therapy in a sustainable manner. PMID:26399633

  5. A nanomedicine-promising approach to provide an appropriate colon-targeted drug delivery system for 5-fluorouracil

    PubMed Central

    Singh, Sima; Kotla, Niranjan G; Tomar, Sonia; Maddiboyina, Balaji; Webster, Thomas J; Sharma, Dinesh; Sunnapu, Omprakash

    2015-01-01

    Targeted drug delivery plays a significant role in disease treatment associated with the colon, affording therapeutic responses for a prolonged period of time with low side effects. Colorectal cancer is the third most common cancer in both men and women with an estimated 102,480 cases of colon cancer and 40,340 cases of rectal cancer in 2013 as reported by the American Cancer Society. In the present investigation, we developed an improved oral delivery system for existing anticancer drugs meant for colon cancer via prebiotic and probiotic approaches. The system comprises three components, namely, nanoparticles of drug coated with natural materials such as guar gum, xanthan gum (that serve as prebiotics), and probiotics. The natural gums play a dual role of protecting the drug in the gastric as well as intestinal conditions to allow its release only in the colon. In vitro results obtained from these experiments indicated the successful targeted delivery of 5-fluorouracil to the colon. Electron microscopy results demonstrated that the prepared nanoparticles were spherical in shape and 200 nm in size. The in vitro release data indicated that the maximum release occurs at pH 7.2 and 7.4 with 93% of the drug released in the presence of 4% (w/v) of rat cecal content. In vivo results conclude a practical mechanism to maintain the integrity and intactness of the intestinal/colonic microflora, in the face of a “chemical attack” by oral colon-targeted drug delivery for colon cancer treatment. PMID:26648721

  6. Foaming of amorphous drug delivery systems prepared by hot melt mixing and extrusion

    NASA Astrophysics Data System (ADS)

    Terife, Graciela

    Currently there is considerable interest from both academe and pharmaceutical industry in exploring foaming processes and their products in drug delivery applications. However, there is still little knowledge of the impact of the morphology of the foamed structures on the performance of drug products in spite of some publications in this area. Therefore, the main objective of this dissertation is to gain a fundamental understanding of the correlation between foam morphology and performance of amorphous drug delivery systems, which are comprised of an Active Pharmaceutical Ingredient (API) and Polymer excipient. The Hot Melt Extrusion (HME) process is used to compound the following API / polymer binary systems: Indomethacin (INM) with SoluplusRTM (PVCap-PVAc-PEG); Carbamazepine (CBZ) with PVCap-PVAc-PEG; and INM with EudragitRTM EPO. Comprehensive characterization of these binary systems carried out by combining Differential Scanning Calorimetry, Fourier Transform Infrared spectroscopy, X-Ray Diffraction, and Scanning Electron Microscopy, shows that in all HME-prepared and foamed samples the APIs are amorphous and dissolved in the polymer excipients. The most important contributions of this dissertation can be grouped into three areas: (a) an understanding of the mechanisms by which foamed dosage forms can lead to faster API release, as well as the key morphological aspects of the cellular structures to achieve this, (b) an understanding of the correlation between the mechanism controlling the release of an API from an amorphous dosage and the enhancement in its release rate upon foaming, and (c) an understanding of the impact of the morphology of the cellular structures in the milling efficiency of HME products and the dissolution performance of the particles produced. In the first area, foamed amorphous solid solutions with three different morphologies are produced through the batch foaming process. A strong correlation between foam morphology and the enhancement in API release rate is observed. A significant increase in API release rate is achieved by fast disintegration. Through a very broad distribution of wall thicknesses, internal stresses are generated due to different local swelling rates in the sample. In this sense, such foam morphologies act as disintegrant-less disintegrants, speeding up API release and release rates. In the second area, the release controlling mechanisms of INM and CBZ from the amorphous systems are identified by using the Power Law model. Three distinct mechanisms are observed: relaxation controlled, anomalous transport, and diffusion controlled. In all cases, the release rates of the APIs are increased upon foaming. However, in cases where the API release is relaxation-controlled, the foamed structures show to have the strongest impact at the initial stages of its in vitro release. Finally, the Foam Hot Melt Extrusion process is used to produce foamed amorphous solid solutions with two different morphologies. Their performance in terms of milling efficiency and in vitro dissolution behavior is compared to that of the unfoamed extrudates of the same composition. The milling efficiency is increased appreciably through foamed extrudates, and smaller particles with narrower particle size distributions are obtained compared to un-foamed extrudates. Additionally, it is found that the enhancement of the release rate exhibited by milled foamed extrudates is the most significant for the particles produced by milling the lower density foam extrudates.

  7. Polysaccharides in colon-specific drug delivery.

    PubMed

    Sinha, V R; Kumria, R

    2001-08-14

    Natural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon. The rationale for the development of a polysaccharide based delivery system for colon is the presence of large amounts of polysaccharidases in the human colon as the colon is inhabited by a large number and variety of bacteria which secrete many enzymes e.g. beta-D-glucosidase, beta-D-galactosidase, amylase, pectinase, xylanase, beta-D-xylosidase, dextranase, etc. Various major approaches utilizing polysaccharides for colon-specific delivery are fermentable coating of the drug core, embedding of the drug in biodegradable matrix, formulation of drug-saccharide conjugate (prodrugs). A large number of polysaccharides have already been studied for their potential as colon-specific drug carrier systems, such as chitosan, pectin, chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylose and locust bean gum. Recent efforts and approaches exploiting these polysaccharides in colon-specific drug delivery are discussed. PMID:11472812

  8. Amphiphilic linear-dendritic block copolymers for drug delivery

    E-print Network

    Nguyen, Phuong, Ph. D. Massachusetts Institute of Technology

    2007-01-01

    Polymeric drug delivery systems have been widely used in the pharmaceutical industry. Such systems can solubilize and sequester hydrophobic drugs from degradation, thereby increasing circulation half-life and efficacy. ...

  9. Enhanced solubility and oral bioavailability of ?-tocotrienol using a self-emulsifying drug delivery system (SEDDS).

    PubMed

    Alqahtani, Saeed; Alayoubi, Alaadin; Nazzal, Sami; Sylvester, Paul W; Kaddoumi, Amal

    2014-08-01

    The aim of this study was to evaluate the in vitro and in vivo performance of ?-tocotrienol (?-T3) incorporated in a self-emulsifying drug delivery system (SEDDS) and to compare its enhanced performance to a commercially available product, namely Tocovid Suprabio™ (hereafter Tocovid), containing tocotrienols. The solubilization of ?-T3 was tested in a dynamic in vitro lipolysis model followed by in vitro cellular uptake study for the lipolysis products. In addition, in vitro uptake studies using Caco2 cells were conducted at different concentrations of ?-T3 prepared as SEDDS, Tocovid, or mixed micelles. ?-T3 incorporated in SEDDS or Tocovid was orally administered to rats at different doses and absolute oral bioavailability from both formulations were determined. The dynamic in vitro lipolysis experiment showed about two fold increase in the solubilization of ?-T3 prepared as SEDDS compared to Tocovid, which correlated with higher cellular uptake in the subsequent uptake studies. In vitro cellular uptake and in vivo oral bioavailability studies have shown a twofold increase in the cellular uptake and oral bioavailability of ?-T3 incorporated in SEDDS compared to Tocovid as a result of improvement in its solubility and passive uptake as confirmed by in vitro studies. In conclusion, incorporation of ?-T3 in SEDDS formulation enhanced ?-T3 solubilization and passive permeability, thus its cellular uptake and oral bioavailability when compared to Tocovid. PMID:24934591

  10. Encapsulation of 10-hydroxy camptothecin in supramolecular hydrogel as an injectable drug delivery system.

    PubMed

    Li, Ruixin; Shu, Chang; Wang, Wei; Wang, Xiaoliang; Li, Hui; Xu, Danke; Zhong, Wenying

    2015-07-01

    10-Hydroxy camptothecin (HCPT) has been proven to be a cell cycle-specific chemotherapeutic agent, which is a necessary choice to inhibit tumor residue growth and prevent tumor metastasis after surgery. But it suffers from light decomposition, poor solubility, relatively low bioavailability, and some side effects, which are the major obstacles toward its clinical use. Integration of hydrophobic HCPT with hydrophilic hydrogel is a facile approach to change the disadvantageous situation of HCPT. In this study, a novel supramolecular hydrogelator with improved synthetic strategy was triggered by chemical hydrolysis, and then self-assembled to hydrogel. Taking advantage of the high-equilibrium solubility of HCPT in hydrogelator solution, this hydrogel was utilized to load HCPT via encapsulation as an effective carrier. HCPT hydrogels were characterized by several techniques including transmission electronic microscopy, rheology, and UV spectroscopy. In vitro release experiment indicated HCPT hydrogel could maintain long term and sustained release of HCPT at high accumulated rate. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay showed that HCPT hydrogel had an optimized anticancer efficacy. Besides, with prominent physical properties of carrier, HCPT hydrogel possessed satisfactory stability, syringeability, and recoverability, demonstrating itself as a potential localized injectable drug delivery system. PMID:25980666

  11. In vitro characterization of insulin containing thiomeric microparticles as nasal drug delivery system.

    PubMed

    Deutel, Britta; Laffleur, Flavia; Palmberger, Thomas; Saxer, Andreas; Thaler, Marlene; Bernkop-Schnürch, Andreas

    2016-01-01

    This study focused on a novel two step preparation method for the generation of insulin containing thiomer microparticles. The first step utilized the interpolymer complexation between poly(vinyl pyrrolidone) (PVP) and poly(acrylic acid) (PAA) or poly(acrylic acid)-cysteine (PAA-Cys), respectively, in the presence of insulin. Thereafter lyophilized coprecipitates were micronized via air jet mill. Particles were evaluated regarding size, morphology, insulin release and the effect on ciliary beat frequency of human nasal epithelial cells in vitro. Results displayed mean particle sizes of 2.6±1.6?m and 2.8±1.7?m for PAA/PVP/insulin and PAA-Cys/PVP/insulin microparticles, respectively, in a range where volitional impaction of particles on nasal epithelium takes place. Multi unit dosage forms showed in addition release for the incorporated insulin and nasal safety as to results of ciliary beat frequency studies (CBF). The introduced jet milled microparticles might in conclusion display a safe nasal insulin drug delivery system leading to improved absorption. PMID:26517960

  12. Electrospinning of PVA/chitosan nanocomposite nanofibers containing gelatin nanoparticles as a dual drug delivery system.

    PubMed

    Fathollahipour, Shahrzad; Abouei Mehrizi, Ali; Ghaee, Azadeh; Koosha, Mojtaba

    2015-12-01

    Nanofibrous core-sheath nanocomposite dual drug delivery system based on poly(vinyl alcohol) (PVA)/chitosan/lidocaine hydrochloride loaded with gelatin nanoparticles were successfully prepared by the electrospinning method. Gelatin nanoparticles were prepared by nanoprecipitation and were then loaded with erythromycin antibiotic agent with the average particle size of ?175 nm. The morphology of gelatin nanoparticles observed by field emission scanning electron microscopy (FE-SEM) was shown to be optimal at the concentration of 1.25 wt % of gelatin in aqueous phase by addition of 20 µL of glutaraldehyde 5% as the crosslinking agent. The nanoparticles were also characterized by dynamic light scattering, zeta potential measurement, and Fourier transform infrared spectroscopy (FTIR). The best bead free morphology for the PVA/chitosan nanofibrous mats were obtained at the solution weight ratio of 96/4. The nanofibrous mats were analyzed by swelling studies, FTIR and antibacterial tests. In vitro dual release profile of the core-sheath nanofibers was also studied within 72 h and showed the release efficiency equal to 84.69 and 75.13% for lidocaine hydrochloride and erythromycin, respectively. According to release exponent n, the release of lidocaine hydrochloride from the sheath part of the matrix is quasi-Fickian diffusion mechanism, while the release of erythromycin is based on anomalous or non-Fickian mechanisms. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3852-3862, 2015. PMID:26112829

  13. Investigation of Size and Morphology of Chitosan Nanoparticles Used in Drug Delivery System Employing Chemometric Technique.

    PubMed

    Khanmohammadi, Mohammadreza; Elmizadeh, Hamideh; Ghasemi, Keyvan

    2015-01-01

    The polymeric nanoparticles are prepared from biocompatible polymers in size between 10-1000 nm. Chitosan is a biocompatible polymer that - can be utilized as drug delivery systems. In this study, chitosan nanoparticles were synthesized using an optimized spontaneous emulsification method. Determining particle size and morphology are two critical parameters in nanotechnology. The aim of this study is to introduce methodology based on relation between particle size and diffuse reflectance infrared fourier transform (DRIFT) spectroscopy technique. Partial least squares (PLS) technique was used to estimate the average particle size based on DRIFT spectra. Forty two different chitosan nanoparticle samples with different particle sizes were analyzed using DRIFT spectrometry and the obtained data were processed by PLS. Results obtained from the real samples were compared to those obtained using field emission scanning electron microscope(FE-SEM) as a reference method. It was observed that PLS could correctly predict the average particle size of synthesized sample. Nanoparticles and their morphological state were determined by FE-SEM. Based on morphological characteristics analyzing with proposed method the samples were separated into two groups of "appropriate" and "inappropriate". Chemometrics methods such as principal component analysis, cluster analysis (CA) and linear discriminate analysis (LDA) were used to classify chitosan nanoparticles in terms of morphology. The percent of correctly classified samples using LDA were 100 %and 90% for training and test sets, respectively. PMID:26330855

  14. Investigation of Size and Morphology of Chitosan Nanoparticles Used in Drug Delivery System Employing Chemometric Technique

    PubMed Central

    Khanmohammadi, Mohammadreza; Elmizadeh, Hamideh; Ghasemi, Keyvan

    2015-01-01

    The polymeric nanoparticles are prepared from biocompatible polymers in size between 10-1000 nm. Chitosan is a biocompatible polymer that - can be utilized as drug delivery systems. In this study, chitosan nanoparticles were synthesized using an optimized spontaneous emulsification method. Determining particle size and morphology are two critical parameters in nanotechnology. The aim of this study is to introduce methodology based on relation between particle size and diffuse reflectance infrared fourier transform (DRIFT) spectroscopy technique. Partial least squares (PLS) technique was used to estimate the average particle size based on DRIFT spectra. Forty two different chitosan nanoparticle samples with different particle sizes were analyzed using DRIFT spectrometry and the obtained data were processed by PLS. Results obtained from the real samples were compared to those obtained using field emission scanning electron microscope(FE-SEM) as a reference method. It was observed that PLS could correctly predict the average particle size of synthesized sample. Nanoparticles and their morphological state were determined by FE-SEM. Based on morphological characteristics analyzing with proposed method the samples were separated into two groups of "appropriate" and "inappropriate". Chemometrics methods such as principal component analysis, cluster analysis (CA) and linear discriminate analysis (LDA) were used to classify chitosan nanoparticles in terms of morphology. The percent of correctly classified samples using LDA were 100 %and 90% for training and test sets, respectively. PMID:26330855

  15. Critical attributes of transdermal drug delivery system (TDDS)--a generic product development review.

    PubMed

    Ruby, P K; Pathak, Shriram M; Aggarwal, Deepika

    2014-11-01

    Bioequivalence testing of transdermal drug delivery systems (TDDS) has always been a subject of high concern for generic companies due to the formulation complexity and the fact that they are subtle to even minor manufacturing differences and hence should be clearly qualified in terms of quality, safety and efficacy. In recent times bioequivalence testing of transdermal patches has gained a global attention and many regulatory authorities worldwide have issued recommendations to set specific framework for demonstrating equivalence between two products. These current regulatory procedures demand a complete characterization of the generic formulation in terms of its physicochemical sameness, pharmacokinetics disposition, residual content and/or skin irritation/sensitization testing with respect to the reference formulation. This paper intends to highlight critical in vitro tests in assessing the therapeutic equivalence of products and also outlines their valuable applications in generic product success. Understanding these critical in vitro parameters can probably help to decode the complex bioequivalence outcomes, directing the generic companies to optimize the formulation design in reduced time intervals. It is difficult to summarize a common platform which covers all possible transdermal products; hence few case studies based on this approach has been presented in this review. PMID:24467407

  16. Communications Drug Delivery

    E-print Network

    Tan, Weihong

    . Zhang,* W. Tan* &&&&--&&&& A Controlled-Release Nanocarrier with Tumor Extracellular pH Value Driven targeting the acidic tumor micro- environment. At low pH values, pHLIPss inserts into the cell membrane A Controlled-Release Nanocarrier with Tumor Extracellular pH Value Driven Targeting and Translocation for Drug

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

    PubMed Central

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

    2012-01-01

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

  18. Functional Cyclodextrin Polyrotaxanes for Drug Delivery

    NASA Astrophysics Data System (ADS)

    Yui, Nobuhiko; Katoono, Ryo; Yamashita, Atsushi

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

  19. Controlled Drug Delivery: Historical perspective for the next generation.

    PubMed

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

    2015-12-10

    The modern day drug delivery technology is only 60years old. During this period numerous drug delivery systems have been developed. The first generation (1950-1980) has been very productive in developing many oral and transdermal controlled release formulations for clinical applications. On the other hand, the second generation (1980-2010) has not been as successful in generating clinical products. This is in large part due to the nature of the problems to overcome. The first generation of drug delivery technologies dealt with physicochemical problems, while the second struggled with biological barriers. Controlled drug delivery systems can be made with controllable physicochemical properties, but they cannot overcome the biological barriers. The third generation (from 2010) drug delivery systems need to overcome both physicochemical and biological barriers. The physicochemical problems stem from poor water solubility of drugs, large molecular weight of peptide and protein drugs, and difficulty of controlling drug release kinetics. The biological barriers to overcome include distribution of drug delivery systems by the body rather than by formulation properties, limiting delivery to a specific target in the body. In addition, the body's reaction to formulations limits their functions in vivo. The prosperous future of drug delivery systems depends on whether new delivery systems can overcome limits set by human physiology, and the development process can be accelerated with new ways of thinking. PMID:26456749

  20. Optimization of self-microemulsifying drug delivery systems (SMEDDS) using a D-optimal design and the desirability function.

    PubMed

    Holm, R; Jensen, I H M; Sonnergaard, J

    2006-10-01

    D-optimal design and the desirability function were applied to optimize a self-microemulsifying drug delivery system (SMEDDS). The optimized key parameters were the following: 1) particle size of the dispersed emulsion, 2) solubility of the drug in the vehicle, and 3) the vehicle compatibility with the hard gelatin capsule. Three formulation variables, PEG200, a surfactant mixture, and an oil mixture, were included in the experimental design. The results of the mathematical analysis of the data demonstrated significant interactions among the formulation variables, and the desirability function was demonstrated to be a powerful tool to predict the optimal formulation for the explored system. PMID:17012115

  1. Drug delivery systems using sandwich configurations of electrospun poly(lactic acid) nanofiber membranes and ibuprofen.

    PubMed

    Immich, Ana Paula Serafini; Arias, Manuel Lis; Carreras, Núria; Boemo, Rafael Luís; Tornero, José Antonio

    2013-10-01

    The primary advantages of electrospun membranes include the ability to obtain very thin fibers that are on the order of magnitude of several nanometers with a considerable superficial area and the possibility for these membranes to be manipulated and processed for many different applications. The purpose of this study is to evaluate and quantify the transport mechanisms that control the release of drugs from polymer-based sandwich membranes produced using the electrospinning processes. These electrospun membranes were composed of poly(lactic acid) (PLA) because it is one of the most promising biodegradable polymers due to its mechanical properties, thermoplastic processability and biological properties, such as its biocompatibility and biodegradability. The transport mechanism that controls the drug delivery was evaluated via the release kinetics of a bioactive agent in physiological serum, which was used as a corporal fluid simulation. To describe the delivery process, mathematical models, such as the Power Law, the classical Higuchi equation and an approach to Fick's Second Law were used. Using the applied mathematical models, it is possible to conclude that control over the release of the drug is significantly dependent on the thickness of the membrane rather than the concentration of the drug. PMID:23910307

  2. Ultrasound-mediated gastrointestinal drug delivery.

    PubMed

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

    2015-10-21

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

  3. Nanoparticles in the ocular drug delivery

    PubMed Central

    Zhou, Hong-Yan; Hao, Ji-Long; Wang, Shuang; Zheng, Yu; Zhang, Wen-Song

    2013-01-01

    Ocular drug transport barriers pose a challenge for drug delivery comprising the ocular surface epithelium, the tear film and internal barriers of the blood-aqueous and blood-retina barriers. Ocular drug delivery efficiency depends on the barriers and the clearance from the choroidal, conjunctival vessels and lymphatic. Traditional drug administration reduces the clinical efficacy especially for poor water soluble molecules and for the posterior segment of the eye. Nanoparticles (NPs) have been designed to overcome the barriers, increase the drug penetration at the target site and prolong the drug levels by few internals of drug administrations in lower doses without any toxicity compared to the conventional eye drops. With the aid of high specificity and multifunctionality, DNA NPs can be resulted in higher transfection efficiency for gene therapy. NPs could target at cornea, retina and choroid by surficial applications and intravitreal injection. This review is concerned with recent findings and applications of NPs drug delivery systems for the treatment of different eye diseases. PMID:23826539

  4. Surfactant-assisted sol-gel synthesis of forsterite nanoparticles as a novel drug delivery system.

    PubMed

    Hassanzadeh-Tabrizi, S A; Bigham, Ashkan; Rafienia, Mohammad

    2016-01-01

    In the present study, forsterite nanoparticles were synthesized via surfactant-assisted sol-gel method using cetyltrimethyl ammonium bromide (CTAB) as a surfactant. The effects of CTAB contents and heat treatment on the textural properties and drug release from nanoparticles were investigated. The synthesized powders were studied by X-ray diffraction, Fourier transform infrared spectra, Brunauer-Emmett-Teller surface area analysis and transmission electron microscope images. Mg2SiO4 materials demonstrated mesoporous characteristics and large specific surface area ranging from 159 to 30m(2)/g. The TEM results showed that forsterite nanorods had diameters about 4nm and lengths ranging from 10 to 60nm. It was found that the samples with 6g CTAB show slower drug release rate than the other specimens, which is due to smaller pore size. This study revealed that the drug delivery of forsterite can be tailored by changing the amount of surfactant. PMID:26478366

  5. Chitosan: a propitious biopolymer for drug delivery.

    PubMed

    Duttagupta, Dibyangana S; Jadhav, Varsha M; Kadam, Vilasrao J

    2015-01-01

    Scientists have always been interested in the use of natural polymers for drug delivery. Chitosan, being a natural cationic polysaccharide has received a great deal of attention in the past few years. It is obtained by deacetylation of chitin and is regarded as the second most ubiquitous polymer subsequent to cellulose on earth. Unlike other natural polymers, the cationic charge possessed by chitosan is accountable for imparting interesting physical and chemical properties. Chitosan has been widely exploited for its mucoadhesive character, permeation enhancing properties and controlled release of drugs. Moreover it's non-toxic, biocompatible and biodegradable properties make it a good candidate for novel drug delivery system. This review provides an insight on various chitosan based formulations for drug delivery. Some of the current applications of chitosan in areas like ophthalmic, nasal, buccal, sublingual, gastro-retentive, pulmonary, transdermal, colon-specific and vaginal drug delivery have been discussed. In addition, active targeting of drugs to tumor cells using chitosan has been described. Lastly a brief section covering the safety aspects of chitosan has also been reviewed. PMID:25761010

  6. Buccal delivery of methimazole as an alternative means for improvement of drug bioavailability: permeation studies and matrix system design.

    PubMed

    De Caro, Viviana; Giandalia, Giulia; Siragusa, Maria Gabriella; Giannola, Libero Italo

    2012-01-01

    The aim of this study was to investigate the potential for systemic administration of Methimazole (MMI) through the buccal mucosa as an alternative route for drug delivery. Considering that the most important restriction in buccal drug delivery could be the low permeability of the mucosa, the ability of MMI to cross the mucosal barrier was assessed. Permeation of MMI through porcine buccal mucosa was investigated ex vivo using Franz type diffusion cells, buffer solution simulating saliva or natural human saliva as donor phase. The collected data suggested that buccal mucosa does not hinder MMI diffusion and the drug crosses the membrane (J(s) = 0.068 mg cm(-2) h(-1) and K(p) = 0.065 cm h(-1)). Matrix tablets, suitable for administration on buccal mucosa, were then designed and prepared by direct compression of MMI loaded matrices (70% w/w) using Eudragit(®) RS 100 as a matrixing, low permeable, pH-independent, mucoadhesive and insoluble agent. The matrix tablets were evaluated in vitro for dissolution; however, the drug was discharged too rapidly from tablets. To obtain drug release rate suitable to maintain constant drug levels in the central compartment the tablets were coated with lipophilic material (glycerol tristearate). In ex vivo permeation experiments, therapeutically MMI plasma levels were obtained when matrix tablets were coated with 0.10 mm thick lipophilic coating film. Coated tablets placed on buccal porcine mucosa provide optimal drug release rate. Coated buccal matrix tablets may represent a potential alternative dosage form for systemic delivery of MMI in hyperthyroidism management. PMID:22632389

  7. Efficient delivery of anticancer drug MTX through MTX-LDH nanohybrid system

    NASA Astrophysics Data System (ADS)

    Oh, Jae-Min; Park, Man; Kim, Sang-Tae; Jung, Jin-Young; Kang, Yong-Gu; Choy, Jin-Ho

    2006-05-01

    We have been successful to intercalate anticancer drug, methotrexate (MTX), into layered double hydroxides (LDHs), Mg2Al(OH)6(NO3)·0.1H2O, through conventional co-precipitation method. Layered double hydroxides (LDHs) are endowed with great potential for delivery vector, since their cationic layers lead to safe reservation of biofunctional molecules such as drug molecules or genes. And their ion exchangeability and solubility in acidic media (pH<4) give rise to the controlled release of drug molecules. Moreover, it has been partly confirmed that LDH itself is non-toxic and facilitate the cellular permeation. To check the toxicity of LDHs, the osteosarcoma cell culture lines (Saos-2 and MG-63) and the normal one (human fibroblast) were used for in vitro test. The anticancer efficacy of MTX intercalated LDHs (MTX-LDH nanohybrids) was also estimated in vitro by the bioassay such as MTT and BrdU (5-bromo-2-deoxyuridine) with the bone cancer cell culture lines (Saos-2 and MG-63). According to the toxicity test results, LDHs do not harm to both the normal and cancer cells upto the concentration of 500 ug/mL. The anticancer efficacy test for the MTX-LDH nanohybrids turn out to be much more effective in cell suppression compared to the MTX itself. According to the cell-line tests, the MTX-LDH shows same drug efficacy to the MTX itself in spite of the low concentration by ˜5000 times. Such a high cancer suppression effect of MTX-LDH hybrid is surely due to the excellent delivery efficiency of inorganic delivery vector, LDHs.

  8. Plasmon resonant liposomes for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Knights-Mitchell, Shellie S.; Romanowski, Marek

    2015-03-01

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

  9. Emergency delivery of Vasopressin from an implantable MEMS rapid drug delivery device

    E-print Network

    Ho Duc, Hong Linh, 1978-

    2009-01-01

    An implantable rapid drug delivery device based on micro-electro-mechanical systems (MEMS) technology was designed, fabricated and validated for the in vivo rapid delivery of vasopressin in a rabbit model. In vitro ...

  10. Polymeric micelles for drug delivery.

    PubMed

    Croy, S R; Kwon, G S

    2006-01-01

    Polymeric micelles are nanoscopic core/shell structures formed by amphiphilic block copolymers. Both the inherent and modifiable properties of polymeric micelles make them particularly well suited for drug delivery purposes. An emphasis of this review has been placed on both the description and characterization techniques of the physical properties of polymeric micelles. Relevant properties discussed include micellar association, morphology, size and stability. These properties and characterization techniques are included to provide context for the known advantages and applications of polymeric micelles for drug delivery. The advantages and applications discussed include solubilization of poorly soluble molecules, sustained release and size advantages, and protection of encapsulated substances from degradation and metabolism. The three most widely studied block copolymer classes are characterized by their hydrophobic blocks, and are poly(propylene oxide), poly(L-amino acid)s and poly(ester)s. These three classes of block copolymers are reviewed with multiple examples of current research in which formulation techniques with polymeric micelles have been applied to some of the most challenging molecules in the pharmaceutical industry. The polymeric micelles used for drug delivery in these examples have shown the abilities to attenuate toxicities, enhance delivery to desired biological sites and improve the therapeutic efficacy of active pharmaceutical ingredients. PMID:17168771

  11. Drug delivery and nanoparticles: Applications and hazards

    PubMed Central

    De Jong, Wim H; Borm, Paul JA

    2008-01-01

    The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed. PMID:18686775

  12. A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery

    E-print Network

    Konofagou, Elisa E.

    A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery Hong Chen1 the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within

  13. Tuberculosis chemotherapy: current drug delivery approaches

    PubMed Central

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

    2006-01-01

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

  14. Microencapsulation: A promising technique for controlled drug delivery

    PubMed Central

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

    2010-01-01

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

  15. Galantamine-loaded PLGA nanoparticles, from nano-emulsion templating, as novel advanced drug delivery systems to treat neurodegenerative diseases

    NASA Astrophysics Data System (ADS)

    Fornaguera, C.; Feiner-Gracia, N.; Calderó, G.; García-Celma, M. J.; Solans, C.

    2015-07-01

    Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from aqueous and micellar solutions. The enzymatic activity of the drug was maintained at 80% after its encapsulation into nanoparticles that were non-cytotoxic at the required therapeutic concentration. Therefore, novel galantamine-loaded polymeric nanoparticles have been designed for the first time using the nano-emulsification approach and showed the appropriate features to become advanced drug delivery systems to treat neurodegenerative diseases.Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from aqueous and micellar solutions. The enzymatic activity of the drug was maintained at 80% after its encapsulation into nanoparticles that were non-cytotoxic at the required therapeutic concentration. Therefore, novel galantamine-loaded polymeric nanoparticles have been designed for the first time using the nano-emulsification approach and showed the appropriate features to become advanced drug delivery systems to treat neurodegenerative diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03474d

  16. Polymeric carriers: role of geometry in drug delivery

    PubMed Central

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

    2009-01-01

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

  17. Development and evaluation of avanafil self-nanoemulsifying drug delivery system with rapid onset of action and enhanced bioavailability.

    PubMed

    Fahmy, Usama A; Ahmed, Osama A A; Hosny, Khaled M

    2015-02-01

    Utilization of lipid-based drug delivery systems has recently gained focus for drugs characterized by poor aqueous solubility. The improved aqueous solubility overcomes one of the main barriers that limit their bioavailability. The objective of this work was to improve the solubility and oral bioavailability of Avanafil (AVA), a recently approved second generation type 5 phospodiesterase inhibitor used for erectile dysfunction.AVA was formulated as self-nanoemulsifying drug delivery system (SNEDDS) utilizing various oils, surfactants, and cosurfactants. The solubility of AVA in various oils, surfactants, and cosurfactants was determined. Ternary phase diagram was constructed to identify stable nanoemulsion region. The prepared AVA loaded SNEDDS were assessed for optical clarity, droplet size, conductivity, and stability studies. In vitro drug release and in vivo pharmacokinetic parameters using animal model were also investigated. Results revealed that stable AVA (SNEDDS) were successfully developed with a droplet size range of 65 to 190 nm. SNEDDS composed of 25% dill oil, 55% Tween 80, and 20% propylene glycol successfully improved solubilization of AVA (over 80% within 30 min) vis-a-vis the powder AVA (35% within 30 min). In vivo pharmacokinetic showed a significant (P?drug. PMID:25168449

  18. A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery

    PubMed Central

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

    2014-01-01

    Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (IN) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+IN) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (IV) drug injection is employed, FUS was also applied after IV injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within the targeted region compared with that achieved by IN only. Despite the fact that the IN route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+IN was not significantly different from that of FUS+IV. As a new drug delivery platform, the FUS+IN technique is potentially useful for treating CNS diseases. PMID:25279463

  19. Synthesis of magnetic and upconversion nanocapsules as multifunctional drug delivery system

    NASA Astrophysics Data System (ADS)

    Huang, Shanshan; Chen, Yinyin; Liu, Bei; He, Fei; Ma, Ping'an; Deng, Xiaoran; Cheng, Ziyong; Lin, Jun

    2015-09-01

    Multifunctional hollow nanocapsules with magnetic and upconversion luminescence properties were synthesized. Hollow Fe3O4@SiO2 was firstly prepared by using rodlike ?-FeOOH as the template followed by silica coating, calcinations and reduction. Then Fe3O4@SiO2@?-NaYF4:Yb3+,Er3+ nanocapsules (FeSiUCNP) were synthesized by the hydrothermal transformation of the Y(Yb3+, Er3+)(OH)CO3 (YOC) deposited onto the surface of nanocapsules through a urea-assisted homogeneous precipitation method. The hollow nanocapsules with porous structure provide space and entrance for the drug molecules. Due to the outside shell of ?-NaYF4:Yb3+, Er3+, the nanomaterial shows upconverting red emission upon 980 nm NIR-light excitation. Moreover, the nanocomposites with hollow magnetite core exhibit a high relaxivity with r2 value of 183 mM-1 s-1, which reveal the potential as T2-weighted contrast agents for magnetic resonance imaging (MRI). The as-prepared nanocapsules can be performed as anti-cancer drug carriers for investigation of drug loading/release properties, which demonstrated a sustained drug release pattern and a comparable cytotoxicity with free doxorubicin (DOX). The multifunctional nanocapsules incorporated upconverting luminescence, T2-weighted MRI imaging and drug targeting delivery modalities have great potential for theranostic applications in cancer treatment.

  20. Optically generated ultrasound for enhanced drug delivery

    DOEpatents

    Visuri, Steven R. (Livermore, CA); Campbell, Heather L. (Baltimore, MD); Da Silva, Luiz (Danville, CA)

    2002-01-01

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

  1. Recent Perspectives in Ocular Drug Delivery

    PubMed Central

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

    2015-01-01

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

  2. Synthesis strategies for disulfide bond-containing polymer-based drug delivery system for reduction-responsive controlled release

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Liu, Peng

    2015-09-01

    Tumor micro-environment responsive drug delivery systems (DDSs) have been developed as a potential approach to reduce the side effects of cancer chemotherapy. Glutathione (GSH) has been supposed to the most significant signal of the difference between the normal tissue and the tumor cells, besides the media pH and temperature. In recent years, the reduction-responsive DDSs have attracted more and more attention for delivery of anti-cancer drugs, based on such physiological signal. Among them, disulfide bond-containing polymers have been designed as the main tool for the purpose. The recent progress in the synthesis strategies for the disulfide bond-containing polymer-based DDS is focused in the present review.

  3. Designing and testing of an effective oil-in-water microemulsion drug delivery system for in vivo application.

    PubMed

    Gupta, S; Moulik, S P; Lala, S; Basu, M K; Sanyal, S K; Datta, S

    2005-01-01

    The phase behavior of a new psedoternary system of clove oil/Tween 20 has been studied. Several compositions from the single-phase region were selected and their stability toward time, temperature, and electrolytes has been examined. A particular composition(clove oil/Tween 20/water as 5/30/65) was chosen as the drug delivery system from the clear oil-in-water zone of the pseudoternary system. The droplet dimension and the polydispersity state of the particular composition was determined by dynamic light scattering. A bioactive compound quarcetin was encapsulated in the vehicle. The efficacy of the drug in the vehicle was examined against leishmaniasis in hamster models. The hepatotoxicity of the vehicle (o/w microemulsion) with and without the drug quarcetin was examined by estimating serum alkaline phosphatase, glutamate pyruvate transaminase, urea, and creatinine. PMID:16188725

  4. Opportunities in respiratory drug delivery.

    PubMed

    Pritchard, John N; Giles, Rachael D

    2014-12-01

    A wide range of asthma and chronic obstructive pulmonary disease products are soon to be released onto the inhaled therapies market and differentiation between these devices will help them to gain market share over their competitors. Current legislation is directing healthcare towards being more efficient and cost-effective in order to continually provide quality care despite the challenges of aging populations and fewer resources. Devices and drugs that can be differentiated by producing improved patient outcomes would, therefore, be likely to win market share. In this perspective article, the current and potential opportunities for the successful delivery and differentiation of new inhaled drug products are discussed. PMID:25531928

  5. A Novel Multifunctional Theranostic Liposome Drug Delivery System: Construction, Characterization, and Multimodality MR, Near-infrared Fluorescent and Nuclear Imaging

    PubMed Central

    Li, Shihong; Goins, Beth; Zhang, Lujun; Bao, Ande

    2012-01-01

    Liposomes are effective lipid nanoparticle drug delivery systems, which can also be functionalized with non-invasive multimodality imaging agents with each modality providing distinct information and having synergistic advantages in diagnosis, monitoring of disease treatment, and evaluation of liposomal drug pharmacokinetics. We designed and constructed a multifunctional theranostic liposomal drug delivery system, which integrated multimodality magnetic resonance (MR), near-infrared (NIR) fluorescent and nuclear imaging of liposomal drug delivery, and therapy monitoring and prediction. The pre-manufactured liposomes were composed of DSPC/cholesterol/Gd-DOTADSPE/DOTA-DSPE with the molar ratio of 39:35:25:1 and having ammonium sulfate/pH gradient. A lipidized NIR fluorescent tracer, IRDye-DSPE, was effectively post-inserted into the pre-manufactured liposomes. Doxorubicin could be effectively post-loaded into the multifunctional liposomes. The multifunctional doxorubicin-liposomes could also be stably radiolabeled with 99mTc or 64Cu for single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging, respectively. MR images displayed the high resolution micro-intratumoral distribution of the liposomes in squamous cell carcinoma of head and neck (SCCHN) tumor xenografts in nude rats after intratumoral injection. NIR fluorescent, SPECT and PET images also clearly showed either the high intratumoral retention or distribution of the multifunctional liposomes. This multifunctional drug carrying liposome system is promising for disease theranostics allowing non-invasive multimodality NIR fluorescent, MR, SPECT and PET imaging of their in vivo behavior and capitalizing on the inherent advantages of each modality. PMID:22577859

  6. Phase transition water-in-oil microemulsions as ocular drug delivery systems: in vitro and in vivo evaluation.

    PubMed

    Chan, Judy; Maghraby, Gamal M M El; Craig, Jennifer P; Alany, Raid G

    2007-01-01

    Microemuslion (ME)-based phase transition systems were evaluated for ocular delivery of pilocarpine hydrochloride (model hydrophilic drug). These used two non-ionic surfactants, sorbitan mono laurate and polyoxyethylene sorbitan mono-oleate with ethyl oleate (oil component) and water. These systems undergo phase change from ME to liquid crystalline (LC) and to coarse emulsion (EM) with a change in viscosity depending on water content. This study selected five formulations containing aqueous phase at 5% (w/w) (ME 5%), 10% (w/w) (ME 10%), 26% (w/w) (LC), 85% (w/w) (O/W EM) and 100% (solution) with the model drug at 1% (w/w). Incorporation of pilocarpine hydrochloride did not affect the phase behaviour. The viscosity was increased initially with dilution from ME 5% to ME 10% then LC, indicating structuring of the system, before being reduced in the EM formulation. Drug release depended on the viscosity with lower release rates obtained from formulations with high viscosity. The miotic response and duration of action were greatest in case of ME and LC formulations indicating high ocular bioavailability. Thus, phase transition ME is promising for ocular drug delivery as it provides the fluidity with its viscosity being increased after application increasing ocular retention while retaining the therapeutic efficiency. PMID:17092668

  7. Strategies for antimicrobial drug delivery to biofilm.

    PubMed

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

    2015-01-01

    Biofilms are formed by the attachment of single or mixed microbial communities to a variety of biological and/or synthetic surfaces. Biofilm micro-organisms benefit from many advantages of the polymicrobial environment including increased resistance against antimicrobials and protection against the host organism's defence mechanisms. These benefits stem from a number of structural and physiological differences between planktonic and biofilm-resident microbes, but two main factors are the presence of extracellular polymeric substances (EPS) and quorum sensing communication. Once formed, biofilms begin to synthesise EPS, a complex viscous matrix composed of a variety of macromolecules including proteins, lipids and polysaccharides. In terms of drug delivery strategies, it is the EPS that presents the greatest barrier to diffusion for drug delivery systems and free antimicrobial agents alike. In addition to EPS synthesis, biofilm-based micro-organisms can also produce small, diffusible signalling molecules involved in cell density-dependent intercellular communication, or quorum sensing. Not only does quorum sensing allow microbes to detect critical cell density numbers, but it also permits co-ordinated behaviour within the biofilm, such as iron chelation and defensive antibiotic activities. Against this backdrop of microbial defence and cell density-specific communication, a variety of drug delivery systems have been developed to deliver antimicrobial agents and antibiotics to extracellular and/or intracellular targets, or more recently, to interfere with the specific mechanisms of quorum sensing. Successful delivery strategies have employed lipidic and polymeric-based formulations such as liposomes and cyclodextrins respectively, in addition to inorganic carriers e.g. metal nanoparticles. This review will examine a range of drug delivery systems and their application to biofilm delivery, as well as pharmaceutical formulations with innate antimicrobial properties such as silver nanoparticles and microemulsions. PMID:25189862

  8. Single non-ionic surfactant based self-nanoemulsifying drug delivery systems: formulation, characterization, cytotoxicity and permeability enhancement study.

    PubMed

    Bandivadekar, Mithun; Pancholi, Shyamsundar; Kaul-Ghanekar, Ruchika; Choudhari, Amit; Koppikar, Soumya

    2013-05-01

    Single non-ionic surfactant based self-nanoemulsifying drug delivery system (SNEDDS) was formulated and characterised for poor water soluble drug, Atorvastatin calcium. Capmul MCM oil showing highest solubility for Atorvastatin calcium was selected as oil phase. Self-nanoemulsifying capacity of Cremophor RH 40, Cremophor EL, Tween 20, Tween 60, Tween 80 and Labrasol were tested for the selected oil. In vitro dissolution studies were performed and were characterized by t85% and dissolution efficiency (DE). Cytotoxicity of the formulations and permeation enhancement of the drug across caco-2 cell monolayer was assessed. Capmul MCM was found to be better nanoemulsified in decreasing order of Cremophor RH 40 > Cremophor EL > Tween 20 > Tween 60 > Tween 80. Values of droplet size (range 11-83 nm), polydispersity index (range 0.07-0.65); zeta potential (range -3.97 to -19.0) and cloud point (60-85°C) before and after drug loading proves the uniformity and stability of the formulations. SNEDDS formulated with Tween 20 surfactant showed enhanced dissolution with t85% and DE values at 10 min and 78.70, respectively. None of the formulation showed cytotoxicity at the concentration tested. Tween 20 based SNEDDS enhanced permeation of the drug as compared with pure drug across cell lines. It can be concluded that SNEDDS can be formulated by using single non-ionic surfactant system for enhance dissolution and absorption of poorly soluble drug, Atorvastatin calcium. PMID:22616839

  9. The Diels-Alder reaction: A powerful tool for the design of drug delivery systems and biomaterials.

    PubMed

    Gregoritza, Manuel; Brandl, Ferdinand P

    2015-11-01

    Click reactions have the potential to greatly facilitate the development of drug delivery systems and biomaterials. These reactions proceed under mild conditions, give high yields, and form only inoffensive by-products. The Diels-Alder cycloaddition is one of the click reactions that do not require any metal catalyst; it is one of the most useful reactions in synthetic organic chemistry and material design. Herein, we highlight possible applications of the Diels-Alder reaction in pharmaceutics and biomedical engineering. Particular focus is placed on the synthesis of polymers and dendrimers for drug delivery, the preparation of functionalized surfaces, bioconjugation techniques, and applications of the Diels-Alder reaction in nanotechnology. Moreover, applications of the reaction for the preparation of hydrogels for drug delivery and tissue engineering are reviewed. A general introduction to the Diels-Alder reaction is presented, along with a discussion of potential pitfalls and challenges. At the end of the article, we provide a set of tools that may facilitate the application of the Diels-Alder reaction to solve important pharmaceutical or biomedical problems. PMID:26614562

  10. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

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

  11. pH- and thermo-responsive microcontainers as potential drug delivery systems: Morphological characteristic, release and cytotoxicity studies.

    PubMed

    Efthimiadou, Eleni K; Tapeinos, Christos; Tziveleka, Leto-Aikaterini; Boukos, Nikos; Kordas, George

    2014-04-01

    Polymeric pH- and thermo-sensitive microcontainers (MCs) were developed as a potential drug delivery system for cancer therapy. It is well known that cancer cells exhibit notable characteristics such as acidic pH due to glycolytic cycle and higher temperature due to their higher proliferation rate. Based on these characteristics, we constructed a dual pH- and thermo-sensitive material for specific drug release on the pathological tissue. The MC's fabrication is based on a two-step procedure, in which, the first step involves the core synthesis and the second one is related to the shell formation. The core consists of poly(methyl methacrylate (PMMA), while the shell consists of PMMA, poly(isopropylacrylamide), poly(acrylic acid) and poly(divinylbenzene). Three different types of MCs were synthesized based on the seed polymerization method. The synthesized MCs were characterized structurally by Fourier transform infrared and morphologically by scanning electron microscopy. Dynamic light scattering was also used to study their behavior in aqueous solution under different pH and temperature conditions. For the loading and release study, the anthracycline drug daunorubicin (DNR) was used as a model drug, and its release properties were evaluated under different pH and thermo-conditions. Cytotoxicity studies were also carried out against MCF-7 breast cancer and 3T3 mouse embryonic fibroblast cells. According to our results, the synthesized microcontainers present desired pH and thermo behavior and can be applied in drug delivery systems. It is worth mentioning that the synthesized microcontainers which incorporated the drug DNR exhibit higher toxicity than the free drug. PMID:24582249

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

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

    Carbon nanotubes (CNTs) have raised great interest in a number of applications, including field emission, energy storage, molecular electronics, sensors, biochips and drug delivery systems. This is due to their remarkable mechanical properties, chemical stability and biofunctionalizability. This nanomaterial is low in weight, has high strength and a high aspect ratio (long length compared to a small diameter). This paper will present a brief overview of drugs adsorbed onto the surface of carbon nanotubes via sonication method. The surface area of carbon nanotubes was measured by methylene blue method, Carbon nanotubes synthesized by catalytic chemical vapor deposition (CCVD) method were purified and functionalized in a mixture of concentrated acids (H2SO4:HNO3 = 3:1) at room temperature (25° C) via sonication in water bath, yielding carboxylic acid group on the CNTs' surface. CNT was successfully loaded with 48 %(w/w) aspirin molecules by suspending CNTs in a solution of aspirin in alcohol. Analysis of loaded CNTs by Field Emission-Scanning Electron Microscope (FESEM), Fourier Transform Infrared Spectrum (FITR) and UV-visible Spectroscopy confirmed the loading of the drug onto the CNTs. The work presented is a prelude to the direction of using carbon nanotubes as a drug delivery system to desired sites in human body.

  13. Is nanotechnology a boon for oral drug delivery?

    PubMed

    Agrawal, Udita; Sharma, Rajeev; Gupta, Madhu; Vyas, Suresh P

    2014-10-01

    The oral route for drug delivery is regarded as the optimal route for achieving therapeutic benefits owing to increased patient compliance. Despite phenomenal advances in injectable, transdermal, nasal and other routes of administration, the reality is that oral drug delivery remains well ahead of the pack as the preferred delivery route. Nanocarriers can overcome the major challenges associated with this route of administration: mainly poor solubility, stability and biocompatibility of drugs. This review focuses on the potential of various polymeric drug delivery systems in oral administration, their pharmacokinetics, in vitro and in vivo models, toxicity and regulatory aspects. PMID:24786464

  14. An aptamer-targeting photoresponsive drug delivery system using ``off-on'' graphene oxide wrapped mesoporous silica nanoparticles

    NASA Astrophysics Data System (ADS)

    Tang, Yuxia; Hu, Hao; Zhang, Molly Gu; Song, Jibin; Nie, Liming; Wang, Shouju; Niu, Gang; Huang, Peng; Lu, Guangming; Chen, Xiaoyuan

    2015-03-01

    We have developed a novel aptamer-targeting photoresponsive drug delivery system by non-covalent assembly of a Cy5.5-AS1411 aptamer conjugate on the surface of graphene oxide wrapped doxorubicin (Dox)-loaded mesoporous silica nanoparticles (MSN-Dox@GO-Apt) for light-mediated drug release and aptamer-targeted cancer therapy. The two ``off-on'' switches of the MSN-Dox@GO-Apt were controlled by aptamer targeting and light triggering, respectively. The Cy5.5-AS1411 ligand provides MSN-Dox@GO-Apt with nucleolin specific targeting and real-time indicator abilities by ``off-on'' Cy5.5 fluorescence recovery. The GO acts as a gatekeeper to prevent the loaded Dox from leaking in the absence of laser irradiation, and to control the Dox release in response to laser irradiation. When the GO wrapping falls off upon laser irradiation, the ``off-on'' photoresponsive drug delivery system is activated, thus inducing chemotherapy. Interestingly, with an increase in laser power, the synergism of chemotherapy and photothermal therapy in a single MSN-Dox@GO-Apt platform led to much more effective cancer cell killing than monotherapies, providing a new approach for treatment against cancer.We have developed a novel aptamer-targeting photoresponsive drug delivery system by non-covalent assembly of a Cy5.5-AS1411 aptamer conjugate on the surface of graphene oxide wrapped doxorubicin (Dox)-loaded mesoporous silica nanoparticles (MSN-Dox@GO-Apt) for light-mediated drug release and aptamer-targeted cancer therapy. The two ``off-on'' switches of the MSN-Dox@GO-Apt were controlled by aptamer targeting and light triggering, respectively. The Cy5.5-AS1411 ligand provides MSN-Dox@GO-Apt with nucleolin specific targeting and real-time indicator abilities by ``off-on'' Cy5.5 fluorescence recovery. The GO acts as a gatekeeper to prevent the loaded Dox from leaking in the absence of laser irradiation, and to control the Dox release in response to laser irradiation. When the GO wrapping falls off upon laser irradiation, the ``off-on'' photoresponsive drug delivery system is activated, thus inducing chemotherapy. Interestingly, with an increase in laser power, the synergism of chemotherapy and photothermal therapy in a single MSN-Dox@GO-Apt platform led to much more effective cancer cell killing than monotherapies, providing a new approach for treatment against cancer. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07493a

  15. Superhydrophobic materials for drug delivery

    NASA Astrophysics Data System (ADS)

    Yohe, Stefan Thomas

    Superhydrophobicity is a property of material surfaces reflecting the ability to maintain air at the solid-liquid interface when in contact with water. These surfaces have characteristically high apparent contact angles, by definition exceeding 150°, as a result of the composite material-air surface formed under an applied water droplet. Superhydrophobic surfaces were first discovered on naturally occurring substrates, and have subsequently been fabricated in the last several decades to harness these favorable surface properties for a number of emerging applications, including their use in biomedical settings. This work describes fabrication and characterization of superhydrophobic 3D materials, as well as their use as drug delivery devices. Superhydrophobic 3D materials are distinct from 2D superhydrophobic surfaces in that air is maintained not just at the surface of the material, but also within the bulk. When the superhydrophobic 3D materials are submerged in water, water infiltrates slowly and continuously as a new water-air-material interface is formed with controlled displacement of air. Electrospinning and electrospraying are used to fabricate superhydrophobic 3D materials utilizing blends of the biocompatible polymers poly(epsilon-caprolactone) and poly(caprolactone-co-glycerol monostearate) (PGC-C18). PGC-C18 is significantly more hydrophobic than PCL (contact angle of 116° versus 83° for flat materials), and further additions of PGC-C18 into electrospun meshes and electrosprayed coatings affords increased stability of the entrapped air layer. For example, PCL meshes alone (500 mum thick) take 10 days to fully wet, and with 10% or 30% PGC-C18 addition wetting rates are dramatically slowed to 60% wetted by 77 days and 4% by 75 days, respectively. Stability of the superhydrophobic materials can be further probed with a variety of physio-chemical techniques, including pressure, surfactant containing solutions, and solvents of varying surface tension. Superhydrophobicity is shown to be enhanced with further increases in PGC-C18 content and surface roughness (a decrease in fiber size). We demonstrate the utility of superhydrophobicity as a method for drug delivery. When the camptothecin derivatives SN-38 and CPT-11 are encapsulated within electrospun meshes, changes in air layer stability (due to changes in PGC-C18 content) dictate the rate of drug release by controlling the rate in which water can permeate into the porous 3D electrospun structure. Drug release can be tuned from 2 weeks to >10 weeks from 300 mum meshes, and meshes effectively kill a variety of cancer cell lines (lung, colon, breast) when utilized in a cytotoxicity assay. After determining that air could be used to control the rate of drug release, superhydrophobic 3D materials are explored for three applications. First, meshes are considered as a potential combination reinforcement-drug delivery device for use in resectable colorectal cancer. Second, removal of the air layer in superhydrophobic meshes is used as a method to trigger drug release. The pressure generated from high-intensity focused ultrasound (0.75-4.25 MPa) can remove the air layer spatially and temporally, allowing drug release to be controlled with application of a sufficient treatment. Third, "connective" electrosprayed coatings are deposited on chemically distinct material surfaces, which are both three-dimensional and mechanically robust. In summary, superhydrophobic 3D materials are fabricated and characterized, and are utilized as drug delivery devices. Controlled air removal from these materials offers an entirely new strategy for drug delivery, and is promising for the applications considered in this work as well as many others.

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

    PubMed

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

    2014-11-01

    The aim of this study was to evaluate the potential of preactivated thiolated pectin (Pec-Cys-MNA) for buccal drug delivery. Therefore, a gel formulation containing this novel polymer and the model drug lidocaine was prepared and investigated in vitro in terms of rheology, mucoadhesion, swelling behavior and drug release in comparison to formulations based on pectin (Pec) and thiolated pectin (Pec-Cys). Both pectin derivatives showed gel formation without addition of any other excipient due to self-crosslinking thiol groups. Under same conditions, pectin did not show gel formation. Viscosity of Pec-Cys-based formulation increased 92-fold and viscosity of Pec-Cys-MNA-based formulations by 4958-fold compared to pectin-based formulation. Gels did not dissolve in aqueous environment during several hours and were able to take up water. Mucoadhesion of pectin on buccal tissue could be improved significantly, value of total work of adhesion increased in the following rank order: Pec-Cys-MNA?>?Pec-Cys?>?Pec. The retention time of a model drug incorporated in gel formulations on buccal mucosa under continuous rinsing with phosphate-buffered saline was prolonged, after 1.5?h 3-fold higher amount of a model drug was to be found on tissue after application of Pec-Cys-MNA-based formulation compared to pectin-based and 2-fold compared to Pec-Cys-based formulation. The Pec-Cys-MNA-based gel showed a more sustained release of lidocaine than Pec-Cys-based gel, whereas pectin solution revealed an immediate release. According to these results, the self-crosslinking pectin-derivative is a promising tool for buccal application. PMID:24025071

  17. Thermo-responsive Layer-by-Layer Assemblies for Nanoparticle-based Drug Delivery 

    E-print Network

    Zhou, Jing

    2013-11-26

    Layer-by-layer (LbL) capsules, known for their versatility and smart response to environmental stimuli, have attracted great interest in drug delivery applications. However, achieving a desired drug delivery system with sustained and tunable drug...

  18. Evaluation of kappa carrageenan as potential carrier for floating drug delivery system: Effect of cross linker.

    PubMed

    Selvakumaran, Suguna; Muhamad, Ida Idayu

    2015-12-30

    Genipin, a natural and non-toxic cross linker, was used to prepare cross linked floating kappa carrageenan/sodium carboxymethyl cellulose hydrogels and the effect of genipin on hydrogels characterization was investigated. Calcium carbonates were employed as gas forming agents. Ranitidine hydrochloride was used as drug. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA) were carried out to study the changes in the characteristics of hydrogels. Furthermore, scanning electron microscope (SEM) was performed to study microstructure of hydrogels. The result showed that all formulated hydrogels had excellent floating behavior. It was discovered that the cross linking reaction showed significant effect on gel strength, porosity and swelling ratio compared to non-cross linked hydrogels. It was found that the drug release was slower and lesser after being cross linked. Microstructure study shows that cross linked hydrogels exhibited hard and rough surface. Therefore, genipin can be an interesting cross linking agent for controlled drug delivery in gastrointestinal tract. PMID:26453788

  19. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    NASA Astrophysics Data System (ADS)

    Stoica-Guzun, Anicuta; Stroescu, Marta; Tache, Florin; Zaharescu, Traian; Grosu, Elena

    2007-12-01

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of ?-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell.

  20. Thermosensitive polymers for drug delivery

    SciTech Connect

    Gutowska, A.; Kim, Sung Wan

    1996-12-31

    Thermosensitive polymers (TSP) demonstrating temperature-dependent temperature-dependent swelling in water have been extensively studied in recent years. Their molecular and physical properties have been tailored for a variety of biomedical and engineering uses. This presentation will discuss TSP based on poly(N-isopropylacrylamide) and its crosslinked networks modified with hydrophobic or hydrophilic components by copolymerization blending and formation of interpenetrating polymer networks (IPNs). TSP designed for three different areas of drug delivery will be presented. First, heparin releasing temperature-sensitive polymers for the prevention of surface induced thrombosis will be presented as an example of a local macromolecular delivery from a surface of a medical device. Second, a new oral delivery device based on a novel mechanical squeezing concept, utilizing specific swelling-deswelling characteristics of temperature- and temperature/pH-sensitive hydrogels will be described. These hydrogels were synthesized to exhibit a controlled swelling-deswelling kinetics, hence a variety of release profiles may be generated: a delayed, a zero-order or an {open_quotes}on-off{close_quotes} release profile. Finally, thermally reversible polymeric gels as an extracellular matrix for the entrapment of pancreatic islet cells in biohybrid artificial pancreas for insulin delivery will be discussed.

  1. ATP-triggered anticancer drug delivery

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  2. Drug Delivery Nanoparticles in Skin Cancers

    PubMed Central

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

    2014-01-01

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

  3. BioMEMS in drug delivery.

    PubMed

    Nuxoll, Eric

    2013-11-01

    The drive to design micro-scale medical devices which can be reliably and uniformly mass produced has prompted many researchers to adapt processing technologies from the semiconductor industry. By operating at a much smaller length scale, the resulting biologically-oriented microelectromechanical systems (BioMEMS) provide many opportunities for improved drug delivery: Low-dose vaccinations and painless transdermal drug delivery are possible through precisely engineered microneedles which pierce the skin's barrier layer without reaching the nerves. Low-power, low-volume BioMEMS pumps and reservoirs can be implanted where conventional pumping systems cannot. Drug formulations with geometrically complex, extremely uniform micro- and nano-particles are formed through micromolding or with microfluidic devices. This review describes these BioMEMS technologies and discusses their current state of implementation. As these technologies continue to develop and capitalize on their simpler integration with other MEMS-based systems such as computer controls and telemetry, BioMEMS' impact on the field of drug delivery will continue to increase. PMID:23856413

  4. Swelling/Floating Capability and Drug Release Characterizations of Gastroretentive Drug Delivery System Based on a Combination of Hydroxyethyl Cellulose and Sodium Carboxymethyl Cellulose

    PubMed Central

    Chen, Ying-Chen; Ho, Hsiu-O; Liu, Der-Zen; Siow, Wen-Shian; Sheu, Ming-Thau

    2015-01-01

    The aim of this study was to characterize the swelling and floating behaviors of gastroretentive drug delivery system (GRDDS) composed of hydroxyethyl cellulose (HEC) and sodium carboxymethyl cellulose (NaCMC) and to optimize HEC/NaCMC GRDDS to incorporate three model drugs with different solubilities (metformin, ciprofloxacin, and esomeprazole). Various ratios of NaCMC to HEC were formulated, and their swelling and floating behaviors were characterized. Influences of media containing various NaCl concentrations on the swelling and floating behaviors and drug solubility were also characterized. Finally, release profiles of the three model drugs from GRDDS formulation (F1-4) and formulation (F1-1) were examined. Results demonstrated when the GRDDS tablets were tested in simulated gastric solution, the degree of swelling at 6 h was decreased for each formulation that contained NaCMC in comparison to those in de-ionized water (DIW). Of note, floating duration was enhanced when in simulated gastric solution compared to DIW. Further, the hydration of tablets was found to be retarded as the NaCl concentration in the medium increased resulting in smaller gel layers and swelling sizes. Dissolution profiles of the three model drugs in media containing various concentrations of NaCl showed that the addition of NaCl to the media affected the solubility of the drugs, and also their gelling behaviors, resulting in different mechanisms for controlling a drug’s release. The release mechanism of the freely water-soluble drug, metformin, was mainly diffusion-controlled, while those of the water-soluble drug, ciprofloxacin, and the slightly water-soluble drug, esomeprazole, were mainly anomalous diffusion. Overall results showed that the developed GRDDS composed of HEC 250HHX and NaCMC of 450 cps possessed proper swelling extents and desired floating periods with sustained-release characteristics. PMID:25617891

  5. Implantable MEMS drug delivery pumps for small animal research.

    PubMed

    Meng, Ellis; Li, Po-Ying; Lo, Ronalee; Sheybani, Roya; Gutierrez, Christian

    2009-01-01

    Advanced devices capable of selective delivery of compounds to targeted tissues are lacking, especially in small animal research. Biomedical microelectromechanical systems (bioMEMS) are uniquely suited to this application through the combination of scalability and precise control of fluid handling. Polymer-based drug delivery components and pumps for acute and chronic delivery in small animals are discussed. PMID:19964178

  6. Nanoparticle mediated non-covalent drug delivery?

    PubMed Central

    Doane, Tennyson; Burda, Clemens

    2013-01-01

    The use of nanoparticles (NPs) for enhanced drug delivery has been heavily explored during the last decade. Within the field, it is has become increasingly apparent that the physical properties of the particles themselves dictate their efficacy, and the relevant non-covalent chemistry at the NP interface also influences how drugs are immobilized and delivered. In this review, we reflect on the physical chemistry of NP mediated drug delivery (and more specifically, non-covalent drug delivery) at the three main experimental stages of drug loading, NP–drug conjugate transport, and the resulting cellular drug delivery. Through a critical evaluation of advances in drug delivery within the last decade, an outlook for biomedical applications of nanoscale transport vectors will be presented. PMID:22664231

  7. Tunable sustained intravitreal drug delivery system for daunorubicin using oxidized porous silicon.

    PubMed

    Hou, Huiyuan; Nieto, Alejandra; Ma, Feiyan; Freeman, William R; Sailor, Michael J; Cheng, Lingyun

    2014-03-28

    Daunorubicin (DNR) is an effective inhibitor of an array of proteins involved in neovascularization, including VEGF and PDGF. These growth factors are directly related to retina scar formation in many devastating retinal diseases. Due to the short vitreous half-life and narrow therapeutic window, ocular application of DNR is limited. It has been shown that a porous silicon (pSi) based delivery system can extend DNR vitreous residence from a few days to 3months. In this study we investigated the feasibility of altering the pore size of the silicon particles to regulate the payload release. Modulation of the etching parameters allowed control of the nano-pore size from 15nm to 95nm. In vitro studies showed that degradation of pSiO2 increased with increasing pore size and the degradation of pSiO2 was approximately constant for a given particle type. The degradation of pSiO2 with 43nm pores was significantly greater than the other two particles with smaller pores, judged by observed and normalized mean Si concentration of the dissolution samples (44.2±8.9 vs 25.7±5.6 or 21.2±4.2?g/mL, p<0.0001). In vitro dynamic DNR release revealed that pSiO2-CO2H:DNR (porous silicon dioxide with covalent loading of daunorubicin) with large pores (43nm) yielded a significantly higher DNR level than particles with 15 or 26nm pores (13.5±6.9ng/mL vs. 2.3±1.6ng/mL and 1.1±0.9ng/mL, p<0.0001). After two months of in vitro dynamic release, 54% of the pSiO2-CO2H:DNR particles still remained in the dissolution chamber by weight. In vivo drug release study demonstrated that free DNR in the vitreous at post-injection day 14 was 66.52ng/mL for 95nm pore size pSiO2-CO2H:DNR, 10.76ng/mL for 43nm pSiO2-CO2H:DNR, and only 1.05ng/mL for 15nm pSiO2-CO2H:DNR. Pore expansion from 15nm to 95nm led to a 63 fold increase of DNR release (p<0.0001) and a direct correlation between the pore size and the drug levels in the living eye vitreous was confirmed. The present study demonstrates the feasibility of regulating DNR release from pSiO2 covalently loaded with DNR by engineering the nano-pore size of pSi. PMID:24424270

  8. Development and Evaluation of a Solid Self-Nanoemulsifying Drug Delivery System for Loratadin by Extrusion-Spheronization

    PubMed Central

    Abbaspour, Mohammadreza; Jalayer, Negar; Sharif Makhmalzadeh, Behzad

    2014-01-01

    Purpose: Recently the liquid nanoemulsifying drug delivery systems (SNEDDS) have shown dramatic effects on improving oral bioavailability of poorly soluble drugs. The main purpose of this study was to prepare a solid form of self-nanoemulsifying drug delivery system of loratadin by extrusion-spheronization. The liquid SNEDDS are generally prepared in a soft or hard gelatin capsules which suffers from several disadvantages. Therefore incorporation of SNEDDS into solid dosage form is desirable to get together the advantages of SNEDDS and solid multiparticualte systems. Methods: The SNEDDS was consisted of liquid paraffin, capriole, span 20, transcutol and loratadin as a poorly soluble drug. A multilevel factorial design was used to formulation of SNEDDS pellets, liquid SNEDDS (20 and 30%) was mixed with lactose, microcrystallin cellulose (40%) and silicon dioxide (0, 5 and 10%), and Na- crosscarmelose (0, 5 and 10%). The resulting wet mass transformed into pellets by extrusion-spheronization. The pellets were dried and characterized for size (sieve analysis), shape (image analysis), mechanical strength (friability test), droplet size (laser light scattering) and drug release rate (dissolution test). Selected SNEDDS pellets were also compared with conventional loratadin pellet or tablet formulation. Results: The resulting SNE pellets exhibited uniform size and shape. Total friability of pellets did not affected by formulation variables. The in vitro release of SNE pellets was higher than the liquid SNE and powder tablets. Conclusion: Our studies demonstrated that extrusion-spheronization is a viable technology to produce self-emulsifying pellets in large scale which can improve in vitro dissolution with better solubility. PMID:24511474

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

    PubMed

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

    2014-12-01

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

  10. VEGF???-conjugated mesoporous silica nanoparticle: a tumor targeted drug delivery system.

    PubMed

    Goel, Shreya; Chen, Feng; Hong, Hao; Valdovinos, Hector F; Hernandez, Reinier; Shi, Sixiang; Barnhart, Todd E; Cai, Weibo

    2014-12-10

    The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling cascade plays a critical role in tumor angiogenesis and metastasis and has been correlated with several poorly prognostic cancers such as malignant gliomas. Although a number of anti-VEGFR therapies have been conceived, inefficient drug administration still limits their therapeutic efficacy and raises concerns of potential side effects. In the present work, we propose the use of uniform mesoporous silica nanoparticles (MSNs) for VEGFR targeted positron emission tomography imaging and delivery of the anti-VEGFR drug (i.e., sunitinib) in human glioblastoma (U87MG) bearing murine models. MSNs were synthesized, characterized and modified with polyethylene glycol, anti-VEGFR ligand VEGF121 and radioisotope (64)Cu, followed by extensive in vitro, in vivo and ex vivo studies. Our results demonstrated that a significantly higher amount of sunitinib could be delivered to the U87MG tumor by targeting VEGFR when compared with the non-targeted counterparts. The as-developed VEGF121-conjugated MSN could become another attractive nanoplatform for the design of future theranostic nanomedicine. PMID:25353068

  11. Multifunctional all-in-one drug delivery systems for tumor targeting and sequential release of three different anti-tumor drugs.

    PubMed

    Fan, Li; Zhang, Yongsheng; Wang, Fuli; Yang, Qian; Tan, Jiali; Renata, Grifantini; Wu, Hong; Song, Chaojun; Jin, Boquan

    2016-01-01

    To achieve active tumor targeting and sequential release of 3 drugs to a tumor site in one nanoparticulate system, self-decomposable SiO2 nanoparticles modified by 3-aminopropyltriethoxysilane (APTS) as their inner structure were used to double load HCPT (in the NP core) and Dox (on the NP surface). Meanwhile, monoclonal antibodies (mAb198.3) against the FAT1 antigen and Bcl-2 siRNA were conjugated onto PEGylated Au-PEG-COOH nanoparticles. The obtained drug-loaded SiO2 nanoparticles were coated with the Au-PEG-mAb.198.3/siRNA nanoparticles through electrostatic interaction to form the SiO2@AuNP sequential drug delivery system, which featured the controlled and sequential release of siRNA, Dox and HCPT step by step to maximize its anticancer efficacy. The results revealed that the SiO2@AuNP sequential drug delivery system specifically targeted tumor cells and was internalize rapidly, followed by endosome escape and sequential drug release. Importantly, the sustainable release characteristics of SiO2 made the Tmax difference between HCPT and Dox approximately 8-12 h, and this enhanced the sensitizing efficiency of HCPT on Dox compared with co-administration. The in vivo antitumor results demonstrated that the tumor size after SiO2@AuNP treatment is 1/400 compared with the saline control group and approximately 1/40 of the HCPT/Dox co-treatment group without any noticeable systemic toxicity. PMID:26561936

  12. Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles.

    PubMed

    Peetla, Chiranjeevi; Vijayaraghavalu, Sivakumar; Labhasetwar, Vinod

    2013-11-01

    In this review, we focus on the biophysics of cell membrane lipids, particularly when cancers develop acquired drug resistance, and how bi