Sample records for drug delivery system

  1. 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

  2. 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.

  3. 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. ...

  4. Peptide and protein delivery using new drug delivery systems.

    PubMed

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

    2013-01-01

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

  5. Physically facilitating drug-delivery systems

    PubMed Central

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

    2012-01-01

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

  6. 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

  7. Nanoparticulate systems for brain delivery of drugs

    Microsoft Academic Search

    Jörg Kreuter

    2001-01-01

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

  8. 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

  9. Nanotechnology-based drug delivery systems

    PubMed Central

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

    2007-01-01

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

  10. [Progression of drug delivery system for glaucoma].

    PubMed

    Xu, Yan; Lyu, Liu

    2014-12-01

    Reduction of intraocular pressure (IOP) by drugs is a major treatment for glaucoma. Clinically, diverse antiglaucoma drugs take effect to decrease the IOP through different mechanisms.However, due to limitations of traditional form of eye drops, the bioavailability of the drug and the patient compliance is lowered, the clinical efficacy is not good and also some toxic and side-effects come out.Otherwise, traditional medication is not suitable for neuroprotective drugs to work on both retina and optic nerve. Drug delivery system has the potential to improve the bioavailability of the drug, prolong the time of drug action, decrease the dosage and frequency of drugs, reduce the side-effects, and improve the patient compliance and efficacy.It is one of the most important studies in glaucoma medication development because it is valuable for patients' neuroprotection.Nowadays, several novel delivery systems have been designed. This review will focus on the progressions of some of the sustained-release antiglaucoma eye drops, polymeric gels, colloidal systems, membrane-controlled drug delivery system, ocular implants, and transscleral drug delivery systems. PMID:25619186

  11. 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

  12. 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

  13. Advances in Biodegradable Ocular Drug Delivery Systems

    Microsoft Academic Search

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

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

  14. 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.

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

    Microsoft Academic Search

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

    2007-01-01

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

  16. Thermosensitive polymeric hydrogels as drug delivery systems.

    PubMed

    Gong, C; Qi, T; Wei, X; Qu, Y; Wu, Q; Luo, F; Qian, Z

    2013-01-01

    Thermosensitive hydrogels are very important biomaterials used in drug delivery systems (DDSs), which gained increasing attention of researchers. Thermosensitive hydrogels have great potential in various applications, such as drug delivery, cell encapsulation, tissue engineering, and etc. Especially, injectable thermosensitive hydrogels with lower sol-gel transition temperature around physiological temperature have been extensively studied. By in vivo injection, the hydrogels formed non-flowing gel at body temperature. Upon incorporation of pharmaceutical agents, the hydrogel systems could act as sustained drug release depot in situ. Injectable thermosensitive hydrogel systems have a number of advantages, including simplicity of drug formulation, protective environment for drugs, prolonged and localized drug delivery, and ease of application. The objective of this review is to summarize fundamentals, applications, and recent advances of injectable thermosensitive hydrogel as DDSs, including chitosan and related derivatives, poly(N-isopropylacrylamide)-based (PNIPAAM) copolymers, poly(ethylene oxide)/poly(propylene oxide) (PEO/PPO) copolymers and its derivatives, and poly(ethylene glycol)/ biodegradable polyester copolymers. PMID:23092130

  17. Ocular drug delivery systems: An overview

    PubMed Central

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

    2014-01-01

    The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also, recent developments with other ocular drug delivery strategies employing in situ gels, implants, contact lens and microneedles have been discussed. PMID:25590022

  18. Pharmaceutical plasticizers for drug delivery systems.

    PubMed

    El-Gendy, Nashwa A

    2012-03-01

    In the field of pharmaceutical science and drug development, there are important and particular challenges related to the selection of suitable and compatible ingredients as well as the design of successful formulations. As plasticization is a phenomenon widely exploited in all formulation fields, plasticizers should be recognized as a critical aspect for drug delivery. The choice of an appropriate plasticizer requires a wide background of information. This is because they are incorporated into drug delivery systems containing an assortment of ingredients which may have different reactions to the presence of plasticizers. Concurrently, there are numerous pharmaceutical plasticizers and various environmental issues dictating favored solutions. To address these encumbrances, an extensive information concerning plasticizers; their types, properties, pharmaceutical roles, etc. is discussed. Additionally, the specific objective of this review is to substantiate the safety and performance of newly discovered plasticizers. PMID:22283652

  19. Provesicles as novel drug delivery systems.

    PubMed

    Bayindir, Zerrin S; Yuksel, Nilufer

    2015-01-01

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

  20. Nanoparticulate systems for brain delivery of drugs.

    PubMed

    Kreuter, J

    2001-03-23

    The blood--brain barrier (BBB) represents an insurmountable obstacle for a large number of drugs, including antibiotics, antineoplastic agents, and a variety of central nervous system (CNS)-active drugs, especially neuropeptides. One of the possibilities to overcome this barrier is a drug delivery to the brain using nanoparticles. Drugs that have successfully been transported into the brain using this carrier include the hexapeptide dalargin, the dipeptide kytorphin, loperamide, tubocurarine, the NMDA receptor antagonist MRZ 2/576, and doxorubicin. The nanoparticles may be especially helpful for the treatment of the disseminated and very aggressive brain tumors. Intravenously injected doxorubicin-loaded polysorbate 80-coated nanoparticles were able to lead to a 40% cure in rats with intracranially transplanted glioblastomas 101/8. The mechanism of the nanoparticle-mediated transport of the drugs across the blood-brain barrier at present is not fully elucidated. The most likely mechanism is endocytosis by the endothelial cells lining the brain blood capillaries. Nanoparticle-mediated drug transport to the brain depends on the overcoating of the particles with polysorbates, especially polysorbate 80. Overcoating with these materials seems to lead to the adsorption of apolipoprotein E from blood plasma onto the nanoparticle surface. The particles then seem to mimic low density lipoprotein (LDL) particles and could interact with the LDL receptor leading to their uptake by the endothelial cells. After this the drug may be released in these cells and diffuse into the brain interior or the particles may be transcytosed. Other processes such as tight junction modulation or P-glycoprotein (Pgp) inhibition also may occur. Moreover, these mechanisms may run in parallel or may be cooperative thus enabling a drug delivery to the brain. PMID:11251246

  1. Development of Controlled Release Drug Delivery Systems

    Microsoft Academic Search

    Ming Li

    2002-01-01

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

  2. Advanced drug delivery systems for antithrombotic agents.

    PubMed

    Greineder, Colin F; Howard, Melissa D; Carnemolla, Ronald; Cines, Douglas B; Muzykantov, Vladimir R

    2013-08-29

    Despite continued achievements in antithrombotic pharmacotherapy, difficulties remain in managing patients at high risk for both thrombosis and hemorrhage. Utility of antithrombotic agents (ATAs) in these settings is restricted by inadequate pharmacokinetics and narrow therapeutic indices. Use of advanced drug delivery systems (ADDSs) may help to circumvent these problems. Various nanocarriers, affinity ligands, and polymer coatings provide ADDSs that have the potential to help optimize ATA pharmacokinetics, target drug delivery to sites of thrombosis, and sense pathologic changes in the vascular microenvironment, such as altered hemodynamic forces, expression of inflammatory markers, and structural differences between mature hemostatic and growing pathological clots. Delivery of ATAs using biomimetic synthetic carriers, host blood cells, and recombinant fusion proteins that are activated preferentially at sites of thrombus development has shown promising outcomes in preclinical models. Further development and translation of ADDSs that spare hemostatic fibrin clots hold promise for extending the utility of ATAs in the management of acute thrombotic disorders through rapid, transient, and targeted thromboprophylaxis. If the potential benefit of this technology is to be realized, a systematic and concerted effort is required to develop clinical trials and translate the use of ADDSs to the clinical arena. PMID:23798715

  3. 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 ...

  4. 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

  5. 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

  6. Importance of novel drug delivery systems in herbal medicines

    PubMed Central

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

    2010-01-01

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

  7. Silk fibroin nanoparticle as a novel drug delivery system.

    PubMed

    Mottaghitalab, Fatemeh; Farokhi, Mehdi; Shokrgozar, Mohammad Ali; Atyabi, Fatemeh; Hosseinkhani, Hossein

    2015-05-28

    Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Nanocarrier-based drug delivery systems, in particular nanoparticles, have generated great excitement in the field of drug delivery since they provide new opportunities to overcome the limitations of conventional delivery methods with regards to the drugs. Silk fibroin (SF) is a naturally occurring protein polymer with several unique properties that make it a suitable material for incorporation into a variety of drug delivery vehicles capable of delivering a range of therapeutic agents. SF matrices have been shown to successfully deliver anticancer drugs, small molecules, and biomolecules. This review will provide an in-depth discussion of the development of SF nanoparticle-based drug delivery systems. PMID:25797561

  8. Design of a Smart Transdermal Insulin Drug Delivery System

    Microsoft Academic Search

    Zhenqing Hou; Chenghong Lin; Qiqing Zhang

    2010-01-01

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

  9. 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

  10. Novel Drug Delivery Systems for Posterior Segment Ocular Disease

    Microsoft Academic Search

    Heather Sheardown; W. Mark Saltzman

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

  11. Application of Plant Viruses as Nano Drug Delivery Systems

    Microsoft Academic Search

    Yupeng Ren; Sek Man Wong; Lee Yong Lim

    2010-01-01

    Nano-sized drug delivery systems based on virus-derived platforms have promising delivery and targeting efficiencies. To date,\\u000a much of our understanding of these systems is obtained from studies of animal viruses. Application of plant viruses for drug\\u000a delivery is in the nascent stage, but it is becoming apparent that plant viral particles can be engineered to possess novel\\u000a properties to meet

  12. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

    PubMed Central

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

    2012-01-01

    This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

  13. Drug Delivery Systems Based On Mucoadhesive Polymers

    Microsoft Academic Search

    Maya Davidovich-Pinhas; Havazelet Bianco-Peled

    \\u000a Transmucosal delivery of therapeutic agents is a non-invasive approach that utilizes human entry paths such as the nasal,\\u000a buccal, rectal and vaginal routs. Mucoadhesive polymers have the ability to adhere to the mucus layer covering those surfaces\\u000a and by that promote drug release, targeting and absorption. Mucoadhesive polymers commonly interact with mucus through non-covalent\\u000a bonds such as hydrogen bonds, ionic

  14. Auto-associative amphiphilic polysaccharides as drug delivery systems.

    PubMed

    Hassani, Leila N; Hendra, Frédéric; Bouchemal, Kawthar

    2012-06-01

    Self-assembly of amphiphilic polysaccharides provides a positive outlook for drug delivery systems without the need for solvents or surfactants. Various polymeric amphiphilic polysaccharides undergo intramolecular or intermolecular associations in water. This type of association, promoted by hydrophobic segments, led to the formation of various drug delivery systems such as micelles, nanoparticles, liposomes and hydrogels. Here, we review a selection of the most important amphiphilic polysaccharides used as drug delivery systems and their pharmaceutical applications. Attention focuses on amphiphilic chitosan owing to its unique properties such as excellent biocompatibility, non-toxicity and antimicrobial and bioadhesive properties. PMID:22305936

  15. 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

  16. Novel Drug Delivery Systems for Retinal Diseases

    Microsoft Academic Search

    Susan S. Lee; Michael R. Robinson

    2009-01-01

    Introduction: Retinal diseases, such as macular edema from diabetic retinopathy and neovascular age-related macular degeneration, are important causes of visual impairment. Pharmacologic intervention has been employed, since laser can have limited success with improving vision. Topical eye drops and systemic therapy deliver low drug levels to the retina and the potential for systemic drug absorption and the accompanying side effects

  17. 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...

  18. Smart-drug delivery system employing molecular motors

    Microsoft Academic Search

    S. K. Vashist; R. Tewari; I. Kaur; R. P. Bajpai; L. M. Bharadwaj

    2005-01-01

    A drug delivery system has been envisioned employing actinmyosin molecular motors, liposomes, microcantilevers and a specific track formed by microfilaments. Molecular motors can pull on giant liposomes enclosing the drug to be delivered at the target site. An array of microcantilevers whose deflection in nanometers would cause the opening of the valves responsible for delivering the drug, would be implanted

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

    PubMed

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

    2014-07-28

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

  20. 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

  1. Dendrimeric Systems and Their Applications in Ocular Drug Delivery

    PubMed Central

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

    2013-01-01

    Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed. PMID:24396306

  2. Dendrimeric systems and their applications in ocular drug delivery.

    PubMed

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

    2013-01-01

    Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed. PMID:24396306

  3. In Vivo Studies Demonstrating Feasibility and Biocompatibilitya of a MEMS Ocular Drug Delivery System

    E-print Network

    Meng, Ellis

    these limitations with a polymer-based MEMS (microelectromechanical systems) intraocular drug delivery deviceIn Vivo Studies Demonstrating Feasibility and Biocompatibilitya of a MEMS Ocular Drug Delivery

  4. Capillary physiology and drug delivery in central nervous system lymphomas

    Microsoft Academic Search

    Peter C. Warnke; Jens Timmer; Christoph B. Ostertag; Klaus Kopitzki

    2005-01-01

    To evaluate whether the chemosensitivity of primary cen- tral nervous system lymphomas to water-soluble drugs could result from improved drug delivery, we quantita- tively assessed pharmacokinetic factors in seven patients. The capillary permeability surface product was found to be significantly increased in central nervous system lym- phomas compared with glioblastoma multiforme, medul- loblastomas, and metastases. Tumoral blood flow was sig-

  5. pH-responsive drug-delivery systems.

    PubMed

    Zhu, Ying-Jie; Chen, Feng

    2015-02-01

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

  6. Therapeutic applications of electrospun nanofibers for drug delivery systems.

    PubMed

    Son, Young Ju; Kim, Woo Jin; Yoo, Hyuk Sang

    2014-01-01

    Electrospun nanofiber drug delivery systems have been studied using various techniques. Herein, we describe the fabrication of a drug-incorporating nanofiber. Drugs, such as proteins, peptide, antibodies, and small molecule drugs, can be loaded within or on the surface of nanofibers according to their properties. Hydrophobic drugs are directly dissolved with a polymer in an organic solvent before electrospinning. However, it is preferred to surface-immobilize bioactive molecules on nanofibers by physical absorption or chemical conjugation. Especially, chemically surface-immobilized proteins on a nanofiber mesh stimulate cell differentiation and proliferation. Using a dual electrospinning nozzle to create nanofiber sheet layers, which are stacked on top of one another, the initial burst release is reduced compared with solid nanofibers because of the layers. Furthermore, hybridization of electrospun nanofibers with nanoparticles, microspheres, and hydrogels is indirect drug loading method into the nanofibers. It is also possible to produce multi-drug delivery systems with timed programmed release. PMID:24234913

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

    PubMed

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

    2011-12-01

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

  8. Drug delivery systems for the treatment of ischemic stroke.

    PubMed

    Rhim, Taiyoun; Lee, Dong Yun; Lee, Minhyung

    2013-10-01

    Stroke is the third leading cause of death in the United States. Reduced cerebral blood flow causes acute damage to the brain due to excitotoxicity, reactive oxygen species (ROS), and ischemia. Currently, the main treatment for stroke is to revive the blood flow by using thrombolytic agents. Reviving blood flow also causes ischemia-reperfusion (I/R) damage. I/R damage results from inflammation and apoptosis and can persist for days to weeks, increasing the infarct size. Drugs can be applied to stroke to intervene in the sub-acute and chronic phases. Chemical, peptide, and genetic therapies have been evaluated to reduce delayed damage to the brain. These drugs have different characteristics, requiring that delivery carriers be developed based on these characteristics. The delivery route is another important factor affecting the efficiency of drug delivery. Various delivery routes have been developed, such as intravenous injection, intranasal administration, and local direct injection to overcome the blood-brain-barrier (BBB). In this review, the delivery carriers and delivery routes for peptide and gene therapies are discussed and examples are provided. Combined with new drugs, drug delivery systems will eventually provide useful treatments for ischemic stroke. PMID:23307348

  9. 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.

  10. 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

  11. 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

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

    PubMed

    Upadhyay, Ravi Kant

    2014-01-01

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

  13. 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

  14. 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.

  15. Programmable nanomedicine: synergistic and sequential drug delivery systems

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  16. 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

  17. 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.

  18. 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

  19. Inhaled formulations and pulmonary drug delivery systems for respiratory infections.

    PubMed

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

    2014-10-24

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

  20. Polymeric Nanoparticles for Drug Delivery to the Central Nervous System

    PubMed Central

    Patel, Toral; Zhou, Jiangbing; Piepmeier, Joseph M.; Saltzman, W. Mark

    2012-01-01

    The central nervous system (CNS) poses a unique challenge for drug delivery. The blood-brain barrier significantly hinders the passage of systemically-delivered therapeutics and the brain extracellular matrix limits the distribution and longevity of locally-delivered agents. Polymeric nanoparticles represent a promising solution to these problems. Over the past 40 years, substantial research efforts have demonstrated that polymeric nanoparticles can be engineered for effective systemic and local delivery of therapeutics to the CNS. Moreover, many of the polymers used in nanoparticle fabrication are both biodegradable and biocompatible, thereby increasing the clinical utility of this strategy. Here, we review the major advances in the development of polymeric nanoparticles for drug delivery to the CNS. PMID:22210134

  1. 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

  2. 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

  3. Acute Myeloid Leukemia: Nanomedicine drug delivery system could improve chemotherapy

    E-print Network

    Pfeifer, Holger

    Acute Myeloid Leukemia: Nanomedicine drug delivery system could improve chemotherapy Chemotherapy is still the backbone of today's cancer treatment. This is exemplified by acute myeloid leukemia (AML generation anti-leukemia treatments. The results have been published in the Journal of Advanced Healthcare

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

    MedlinePLUS

    ... Drug Delivery System Shows Early Promise for Treating Lupus in Mice A drug delivery system using nanoparticle ... cells can potentially improve treatment approaches for systemic lupus erythematosus (SLE), according to research partially funded by ...

  5. Development and characterization of chronomodulated drug delivery system of captopril

    PubMed Central

    Patil, Archana S; Dandagi, Panchaxari M; Masthiholimath, Vinayak S; Gadad, Anand P; Najwade, Basavaraj K

    2011-01-01

    Background: Hypertension shows circadian rhythm that there is a rise in pressure from the time of waking or before (about 4 to 8 a.m.), in most people. Conventional drug delivery system of captopril is inappropriate for the delivery of drug, as they cannot be administered just before the symptoms are worsened, because during this time the patients are asleep, bedtime dosing of captopril will not provide a therapeutic plasma drug concentration at the early hours of morning because of poor pharmacokinetic profile and shorter half-life of 1.9 hours. Thus, this study attempts to design and evaluate a chronomodulated pulsatile drug delivery system of captopril which was aimed to release the drug after a lag time of 6 hours. Materials and Methods: Present delivery system was prepared by rupturable coating method. The core containing captopril as a bioactive compound were prepared by direct compression method and then coated sequentially with an inner swelling layer containing hydrocolloid HPMC E5 and an outer rupturable layer consisted of Eudragit RL/RS (1 : 1). Total 12 formulations with different levels of inner swelling layer and outer polymeric layer were prepared and subjected to various processing and formulative parameters like the effect of core composition, level of swelling layer, and rupturable coating on lag time was investigated. In vitro drug release and rupture tests were performed using United States Pharmacopoeia paddle method at 50 rpm in 0.1N HCl and phosphate buffer of pH 6.8. Results: The results showed that as the amount of inner swelling layer increases, the lag time decreases and as the Eudragit coating level increases, the lag time increases and percent water uptake of time-dependent pulsatile release system decreases. The presence of an osmotic agent and effervescent agent helped in shortening of lag time. Conclusion: The system was found to be satisfactory in terms of release of the drug after the lag time of 6 hours. PMID:23071948

  6. System-based approach for an advanced drug delivery platform

    NASA Astrophysics Data System (ADS)

    Kulinsky, Lawrence; Xu, Han; Tsai, Han-Kuan A.; Madou, Marc

    2006-03-01

    Present study is looking at the problem of integrating drug delivery microcapsule, a bio-sensor, and a control mechanism into a biomedical drug delivery system. A wide range of medical practices from cancer therapy to gastroenterological treatments can benefit from such novel bio-system. Drug release in our drug delivery system is achieved by electrochemically actuating an array of polymeric valves on a set of drug reservoirs. The valves are bi-layer structures, made in the shape of a flap hinged on one side to a valve seat, and consisting of thin films of evaporated gold and electrochemically deposited polypyrrole (PPy). These thin PPy(DBS) bi-layer flaps cover access holes of underlying chambers micromachined in a silicon substrate. Chromium and polyimide layers are applied to implement "differential adhesion" to obtain a voltage induced deflection of the bilayer away from the drug reservoir. The Cr is an adhesion-promoting layer, which is used to strongly bind the gold layer down to the substrate, whereas the gold adheres weakly to polyimide. Drug actives (dry or wet) were pre-stored in the chambers and their release is achieved upon the application of a small bias (~ 1V). Negative voltage causes cation adsorption and volume change in PPy film. This translates into the bending of the PPy/Au bi-layer actuator and release of the drug from reservoirs. This design of the drug delivery module is miniaturized to the dimensions of 200?m valve diameter. Galvanostatic and potentiostatic PPy deposition methods were compared, and potentiostatic deposition method yields film of more uniform thickness. PPy deposition experiments with various pyrrole and NaDBS concentrations were also performed. Glucose biosensor based on glucose oxidase (GOx) embedded in the PPy matrix during elechtrochemical deposition was manufactured and successfully tested. Multiple-drug pulsatile release and continuous linear release patterns can be implemented by controlling the operation of an array of valves. Varying amounts of drugs, together with more complex controlling strategies would allow creation of more complex drug delivery patterns.

  7. Intelligent drug delivery systems obtained by radiation

    NASA Astrophysics Data System (ADS)

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

    1998-06-01

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

  8. Magnetic nanoparticle drug delivery systems for targeting tumor

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  9. Which drug or drug delivery system can change clinical practice for brain tumor therapy?

    PubMed Central

    Siegal, Tali

    2013-01-01

    The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers and active efflux mechanisms lead to drug failure because of inability to reach the desired target at a sufficient concentration. This perspective reviews the leading strategies that aim to improve drug delivery to brain tumors and their likelihood to change clinical practice. The English literature was searched for defined search items. Strategies that use systemic delivery and those that use local delivery are critically reviewed. In addition, challenges posed for drug delivery by combined treatment with anti-angiogenic therapy are outlined. To impact clinical practice and to achieve more than just a limited local control, new drugs and delivery systems must adhere to basic clinical expectations. These include, in addition to an antitumor effect, a verified favorable adverse effects profile, easy introduction into clinical practice, feasibility of repeated or continuous administration, and compatibility of the drug or delivery system with any tumor size and brain location. PMID:23502426

  10. Ocular drug delivery.

    PubMed

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

    2010-09-01

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

  11. 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

  12. Gastrointestinal transit of Oros drug delivery systems in healthy volunteers

    PubMed Central

    John, V. A.; Shotton, P. A.; Moppert, J.; Theobald, W.

    1985-01-01

    1 Transit times for oxprenolol and metoprolol Oros drug delivery systems through the gastrointestinal tract have been measured in 35 individuals in six separate studies. 2 A total of 45 systems were recovered in a median time of 27.4 h; individual transit times varied from 5.1 to 58.3 h. 3 The residual amount of drug in recovered systems was inversely related to transit time and corresponded closely with the amount estimated from in vitro dissolution profiles. PMID:4005123

  13. Polymeric micelles as drug delivery systems: a reactive polymeric micelle carrying aldehyde groups

    Microsoft Academic Search

    Carmen Scholz; Michihiro Iijima; Yukio Nagasaki; Kazunori Kataoka

    1998-01-01

    WWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWW WWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWW WWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWW WWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWW Nanospheric particles as drug delivery systems are gaining increasing interest in the biomedical field. Nanospheres have been proven as efficient drug delivery systems for intravenous administration because of their comparatively long bloodstream circulation. A novel approach in the field of polymeric drug delivery systems was introduced by the formation of polymeric micelles and subsequently by functionalized

  14. Biologically erodable microspheres as potential oral drug delivery systems.

    PubMed

    Mathiowitz, E; Jacob, J S; Jong, Y S; Carino, G P; Chickering, D E; Chaturvedi, P; Santos, C A; Vijayaraghavan, K; Montgomery, S; Bassett, M; Morrell, C

    1997-03-27

    Biologically adhesive delivery systems offer important advantages over conventional drug delivery systems. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium for extended periods of time and actually penetrate it, through and between cells. Thus, once loaded with compounds of pharmacological interest, the microspheres could be developed as delivery systems to transfer biologically active molecules to the circulation. We show that these microspheres increase the absorption of three model substances of widely different molecular size: dicumarol, insulin and plasmid DNA. PMID:9121559

  15. Mathematical modeling and simulation of drug release from microspheres: Implications to drug delivery systems.

    PubMed

    Arifin, Davis Yohanes; Lee, Lai Yeng; Wang, Chi-Hwa

    2006-11-30

    This article aims to provide a comprehensive review of existing mathematical models and simulations of drug release from polymeric microspheres and of drug transport in adjacent tissues. In drug delivery systems, mathematical modeling plays an important role in elucidating the important drug release mechanisms, thus facilitating the development of new pharmaceutical products by a systematic, rather than trial-and-error, approach. The mathematical models correspond to the known release mechanisms, which are classified as diffusion-, swelling-, and erosion-controlled systems. Various practical applications of these models which explain experimental data are illustrated. The effect of gamma-irradiation sterilization on drug release mechanism from erosion-controlled systems will be discussed. The application of existing models to nanoscale drug delivery systems specifically for hydrophobic and hydrophilic molecules is evaluated. The current development of drug transport modeling in tissues utilizing computational fluid dynamics (CFD) will also be described. PMID:17097189

  16. Catheter systems for intrathecal drug delivery.

    PubMed

    Penn, R D; York, M M; Paice, J A

    1995-08-01

    A prospective study of intrathecal catheter reliability was performed at Rush-Presbyterian-St. Luke's Medical Center. All 102 patients who had baclofen administered chronically for spasticity via an implanted drug pump were included. Sixty percent of the patients had no catheter complications; the remaining patients had one to five complications over their course of treatment. Survival analysis demonstrated a steady rate of malfunction up to 80 months, with the mean time to first failure recorded at 20 months. Kinks, holes, breaks, dislodgments, and disconnections were the most common complications. On the basis of their research the authors conclude that the thin-walled silastic catheter does not perform well and that larger, thick-walled catheters should be used. PMID:7616263

  17. Formulation and evaluation of floating drug delivery system of famotidine.

    PubMed

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

    2010-11-01

    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

  18. Programmable Drug Delivery from an Erodible Association Polymer System

    Microsoft Academic Search

    Xin Xu; Ping I. Lee

    1993-01-01

    An erodible association polymer system based on blends of cellulose acetate phthalate (CAP) and Pluronic F127, a block copolymer of poly(ethylene oxide) and poly(propylene oxide), has been investigated for its applicability to rate-programmed drug delivery. The compatibility and thermal properties were characterized by DSC and FTIR. Results from the thermal analysis indicate that the blends are compatible above 50% CAP,

  19. STOMACH SPECIFIC FLOATING DRUG DELIVERY SYSTEM: A REVIEW

    Microsoft Academic Search

    Technological attempts have been made in the research and development of rate-controll ed oral drug delivery systems to overcome physiological adversities, such as short gastric residence times (GRT) and unpredictable gastric emptying times (GET). It is known that differences in gastric physiology, such as, gastric pH, and motility exhibit both intra-as well as inter-subject variability demonstrating significant impact on gastric

  20. CNS Drug Delivery Systems: Novel Approaches

    Microsoft Academic Search

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

    2009-01-01

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

  1. Fundamental study for development magnetic drug delivery system

    NASA Astrophysics Data System (ADS)

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

    2009-10-01

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

  2. Application of Ultrasound Energy as a New Drug Delivery System

    NASA Astrophysics Data System (ADS)

    Tachibana, Katsuro; Tachibana, Shunro

    1999-05-01

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

  3. Bionanocomposites containing magnetic graphite as potential systems for drug delivery.

    PubMed

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

    2014-12-30

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

  4. Synthetic tumor networks for screening drug delivery systems.

    PubMed

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

    2015-03-10

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

  5. Small-scale systems for in vivo drug delivery

    Microsoft Academic Search

    David A LaVan; Terry McGuire; Robert Langer

    2003-01-01

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

  6. Advances in the Applications of Polyhydroxyalkanoate Nanoparticles for Novel Drug Delivery System

    PubMed Central

    Shrivastav, Anupama; Kim, Hae-Yeong; Kim, Young-Rok

    2013-01-01

    Drug delivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drug delivery systems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drug delivery systems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drug delivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drug delivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drug delivery system. PMID:23984383

  7. 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...

  8. Application of artificial neural networks in the design of controlled release drug delivery systems

    Microsoft Academic Search

    Yichun Sun; Yingxu Peng; Yixin Chen; Atul J Shukla

    2003-01-01

    Controlled release drug delivery systems offer great advantages over the conventional dosage forms. However, there are great challenges to efficiently develop controlled release drug delivery systems due to the complexity of these delivery systems. Traditional statistic response surface methodology (RSM) is one of the techniques that has been employed to develop and formulate controlled release dosage forms. However, there are

  9. Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview.

    PubMed

    Mignani, Serge; El Kazzouli, Saïd; Bousmina, Mosto; Majoral, Jean-Pierre

    2013-10-01

    Drugs are introduced into the body by numerous routes such as enteral (oral, sublingual and rectum administration), parenteral (intravascular, intramuscular, subcutaneous and inhalation administration), or topical (skin and mucosal membranes). Each route has specific purposes, advantages and disadvantages. Today, the oral route remains the preferred one for different reasons such as ease and compliance by patients. Several nanoformulated drugs have been already approved by the FDA, such as Abelcet®, Doxil®, Abraxane® or Vivagel®(Starpharma) which is an anionic G4-poly(L-lysine)-type dendrimer showing potent topical vaginal microbicide activity. Numerous biochemical studies, as well as biological and pharmacological applications of both dendrimer based products (dendrimers as therapeutic compounds per se, like Vivagel®) and dendrimers as drug carriers (covalent conjugation or noncovalent encapsulation of drugs) were described. It is widely known that due to their outstanding physical and chemical properties, dendrimers afforded improvement of corresponding carried-drugs as dendrimer-drug complexes or conjugates (versus plain drug) such as biodistribution and pharmacokinetic behaviors. The purpose of this manuscript is to review the recent progresses of dendrimers as nanoscale drug delivery systems for the delivery of drugs using enteral, parenteral and topical routes. In particular, we focus our attention on the emerging and promising routes such as oral, transdermal, ocular and transmucosal routes using dendrimers as delivery systems. PMID:23415951

  10. 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

  11. Liposomal Conjugates for Drug Delivery to the Central Nervous System

    PubMed Central

    Helm, Frieder; Fricker, Gert

    2015-01-01

    Treatments of central nervous system (CNS) diseases often fail due to the blood–brain barrier. Circumvention of this obstacle is crucial for any systemic treatment of such diseases to be effective. One approach to transfer drugs into the brain is the use of colloidal carrier systems—amongst others, liposomes. A prerequisite for successful drug delivery by colloidal carriers to the brain is the modification of their surface, making them invisible to the reticuloendothelial system (RES) and to target them to specific surface epitopes at the blood–brain barrier. This study characterizes liposomes conjugated with cationized bovine serum albumin (cBSA) as transport vectors in vitro in porcine brain capillary endothelial cells (PBCEC) and in vivo in rats using fluorescently labelled liposomes. Experiments with PBCEC showed that sterically stabilized (PEGylated) liposomes without protein as well as liposomes conjugated to native bovine serum albumin (BSA) were not taken up. In contrast, cBSA-liposomes were taken up and appeared to be concentrated in intracellular vesicles. Uptake occurred in a concentration and time dependent manner. Free BSA and free cBSA inhibited uptake. After intravenous application of cBSA-liposomes, confocal fluorescence microscopy of brain cryosections from male Wistar rats showed fluorescence associated with liposomes in brain capillary surrounding tissue after 3, 6 and 24 h, for liposomes with a diameter between 120 and 150 nm, suggesting successful brain delivery of cationized-albumin coupled liposomes. PMID:25835091

  12. Recent patents survey on self emulsifying drug delivery system.

    PubMed

    Jethara, Sahilhusen I; Patel, Alpesh D; Patel, Mukesh R

    2014-01-01

    Self-Emulsifying Drug Delivery System is a unique feasible approach to overcome low oral bioavailability problem which is associated with the hydrophobic drugs due to their unparalleled potential as a drug delivery with the broad range of application. The estimated 40% of active pharmaceuticals are poorly water soluble. Now recently, formulation containing oral SEDDS has received much interest as it solve problems related to oral bioavailability, intra and inter-subject variability and lack of dose proportionality of hydrophobic drugs. Now a days, it is the first way to investigate the development of any kind of innovative dosage forms. Many important in-vitro characteristics such as surfactant concentration, oil/surfactant ratio, emulsion polarity, droplet size and zeta potential play an important role in oral absorption of drug from SEEDS. It can be orally administered in the form of SGC or HGC and also enhances bioavailability of drugs to increase solubility and minimizes the gastric irritation. After administration the drug remains entrapped in the oily droplets (inside the droplet or in the surfactant`s film at the interface) of the emulsion that are formed in the GIT upon self-emulsification process. It is also a bit problematic to say that the drug is being released from SMEDDS, it would be more precise to say that it diffuses out of oily droplets into the GIT media resulting in the formation of an equilibrium between the drug dissolved in oily droplets and the outer dispersed media (e.g. GIT fluids). Many of the application and preparation methods of SEDDS are reported by research articles and patents in different countries. We present an exhaustive and updated account of numerous literature reports and more than 150 patents published on SEDDS in the recent period. This current patent review is useful in knowledge of SEDDS for its preparations and patents in different countries with emphasis on their formulation, characterization and systematic optimization strategies, thus paving the way for accelerated progress into the SEDDS application in pharmaceutical research as well as patents on SEDDS methods. PMID:25146965

  13. Processing of Polymer Nanofibers Through Electrospinning as Drug Delivery Systems

    NASA Astrophysics Data System (ADS)

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

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

  14. Evaluation of metal nanoparticles for drug delivery systems

    PubMed Central

    Adeyemi, Oluyomi S; Sulaiman, Faoziyat A

    2015-01-01

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

  15. 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

  16. Molecular Communication Modeling of Antibody-Mediated Drug Delivery Systems.

    PubMed

    Chahibi, Youssef; Akyildiz, Ian F; Balasubramaniam, Sasitharan; Koucheryavy, Yevgeni

    2015-07-01

    Antibody-mediated Drug Delivery Systems (ADDS) are emerging as one of the most encouraging therapeutic solutions for treating several diseases such as human cancers. ADDS use small molecules (antibodies) that propagate in the body and bind selectively to their corresponding receptors (antigens) expressed at the surface of the diseased cells. In this paper, the Molecular Communication (MC) paradigm, where information is conveyed through the concentration of molecules, is advocated for the engineering of ADDS and modeling their complex behavior, to provide a realistic model without the over-complication of system biology models, and the limitations of experimental approaches. The peculiarities of antibodies, including their anisotropic transport and complex electrochemical structure, are taken into account to develop an analytical model of the ADDS transport and antigen-binding kinetics. The end-to-end response of ADDS, from the drug injection to the drug absorption, is mathematically derived based on the geometry of the antibody molecule, the electrochemical structure of the antibody-antigen complex, and the physiology of the patient. The accuracy of the MC model is validated by finite-element (COMSOL) simulations. The implications of the complex interplay between the transport and kinetics parameters on the performance of ADDS are effectively captured by the proposed MC model. The MC model of ADDS will enable the discovery and optimization of drugs in a versatile, cost-efficient, and reliable manner. PMID:25675450

  17. Oil-filled polymeric ultrasound contrast agent as local drug delivery system for lipophilic drugs

    Microsoft Academic Search

    Klazina Kooiman; Marcel R. Böhmer; Marcia Emmer; Hendrik J. Vos; Ceciel Chlon; William T. Shi; Christopher S. Hall; S. H. P. M. de Winter; K. Schroen; M. Versluis; N. de Jong; A. van Wamel

    2008-01-01

    Novel polymeric microcapsules, filled with a mixture of gas and oil, were produced and their potential as ultrasound contrast agent-based drug delivery system for lipophilic drugs was investigated. Microcapsules were synthesized that contained either no oil, were almost half-filled with oil, or were almost completely filled with oil. Mean number weighted diameters were between 1.22 and 1.31 mum. At a

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

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

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

  19. 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

  20. Advanced drug delivery systems of curcumin for cancer chemoprevention.

    PubMed

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

    2011-08-01

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

  1. 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

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

    Microsoft Academic Search

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

    2007-01-01

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

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

    E-print Network

    Yu, Xiao

    2012-07-16

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

  4. Development and in vitro evaluation of chitosan-based transdermal drug delivery systems for the controlled delivery of propranolol hydrochloride

    Microsoft Academic Search

    D. Thacharodi; K. Panduranga Rao

    1995-01-01

    Membrane permeation-controlled transdermal drug delivery systems were prepared using the natural polymer, chitosan. An adhesive sealing technique was used to construct the devices. Propranolol hydrochloride was selected as the model drug for the present study. Chitosan membranes with different permeability to propranolol hydrochloride obtained by controlled cross-linking with glutaraldehyde were used to regulate the drug release in the devices. Chitosan

  5. Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH-sensitive drug release property

    Microsoft Academic Search

    Cui-Yun Yu; Bo-Cheng Yin; Wei Zhang; Si-Xue Cheng; Xian-Zheng Zhang; Ren-Xi Zhuo

    2009-01-01

    Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH sensitivity were developed for oral delivery of protein drugs, using bovine serum albumin (BSA) as a model drug. The composite drug-loaded microparticles with a mean particle size less than 200?m were prepared by a convenient shredding method. Since the microparticles were formed by tripolyphosphate cross-linking, electrostatic

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

    E-print Network

    Peppas, Nicholas A.

    -controlled drug delivery systems are characterized by a phase erosion of the polymer carrier that is associated swelling of the polymer carrier that is associated with simultaneous or subsequent dissolutionMolecular Analysis of Drug Delivery Systems Controlled by Dissolution of the Polymer Carrier BALAJI

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

    Microsoft Academic Search

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

    2006-01-01

    There is an increasing interest in lipid based drug delivery systems due to factors such as better characterization of lipidic excipients and formulation versatility and the choice of different drug delivery systems. It is important to know the thermal characteristics, crystal habit, texture, and appearance of a new lipid matrix when determining its suitability for use in certain pharmaceutical application.

  8. Bioadhesive polymeric drug delivery systems for tumor targeting and tissue repair

    Microsoft Academic Search

    Zohreh Amoozgar

    2011-01-01

    A drug delivery system refers to a dosage form that is able to control or modify the availability of the active ingredient to the body due to its construction as well as temporal or spatial arrangement. An efficient drug delivery system should localize treatment to diseased cells or the site of injury. This can be achieved by increasing the adhesion

  9. 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

  10. 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

  11. Drug-induced morphology switch in drug delivery systems based on poly(2-oxazoline)s.

    PubMed

    Schulz, Anita; Jaksch, Sebastian; Schubel, Rene; Wegener, Erik; Di, Zhenyu; Han, Yingchao; Meister, Annette; Kressler, Jörg; Kabanov, Alexander V; Luxenhofer, Robert; Papadakis, Christine M; Jordan, Rainer

    2014-03-25

    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

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

    PubMed Central

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

    2013-01-01

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

  13. 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

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

    PubMed Central

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

    2011-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2007-10-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Cukierman, Edna; Khan, David R.

    2010-01-01

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

  19. Heparin-based nanocapsules as potential drug delivery systems.

    PubMed

    Baier, Grit; Winzen, Svenja; Messerschmidt, Claudia; Frank, Daniela; Fichter, Michael; Gehring, Stephan; Mailänder, Volker; Landfester, Katharina

    2015-06-01

    Herein, the synthesis and characterization of heparin-based nanocapsules (NCs) as potential drug delivery systems is described. For the synthesis of the heparin-based NCs, the versatile method of miniemulsion polymerization at the droplets interface was achieved resulting in narrowly distributed NCs with 180?nm in diameter. Scanning and transmission electron microscopy images showed clearly NC morphology. A highly negative charge density for the heparin-based NCs was determined by measuring the electro-kinetic potential. Measuring the activated clotting time demonstrated the biological intactness of the polymeric shell. The ability of heparin-based NCs to bind to antithrombin (AT III) was investigated using isothermal titration calorimetry and dynamic light scattering experiments. The chemical stability of the NCs was studied in physiological protein-containing solutions and also in medically interesting fluids such as sodium chloride 0.9%, Ringer's solution, and phosphate buffer saline using dynamic light scattering and measuring the fluorescence intensity. The impressive uptake of NCs in different cells was confirmed by fluorescence-activated cell sorting, confocal laser scanning microscopy, and transmission electron microscopy. The low toxicity of all types of NCs was demonstrated. PMID:25765603

  20. Nanostructural systems developed with positive charge generation to drug delivery.

    PubMed

    An, Fei-Fei; Cao, Weipeng; Liang, Xing-Jie

    2014-08-01

    The surface charge of a nanostructure plays a critical role in modulating blood circulation time, nanostructure-cell interaction, and intracellular events. It is unfavorable to have positive charges on the nanostructure surface before arriving at the disease site because positively charged nanostructures interact strongly with blood components, resulting in rapid clearance from the blood, and suboptimal targeted accumulation at the tumor site. Once at the tumor site, however, the positive charge on the nanostructure surface accelerates uptake by tumor cells and promotes the release of payloads from the lysosomes to the cytosol or nucleus inside cells. Thus, the ideal nanocarrier systems for drug delivery would maintain a neutral or negatively charged surface during blood circulation but would then generate a positive surface charge after accumulation at the tumor site or inside the cancer cells. This Progress Report focuses on the design and application of various neutral or negatively charged nanostructures that can generate a positive charge in response to the tumor microenvironment or an external stimulus. PMID:24550201

  1. Nanosuspension Technology for Drug Delivery

    Microsoft Academic Search

    Jiraporn CHINGUNPITUK

    The poor water solubility of drugs is major problem for drug formulation. To date, nanoscale systems for drug delivery have gained much interest as a way to improve the solubility problems. The reduction of drug particles into the sub-micron range leads to a significant increase in the dissolution rate and therefore enhances bioavailability. Nanosuspensions are promising candidates that can be

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

    PubMed

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

    2015-01-01

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

  3. Self-emulsifying drug delivery system and the applications in herbal drugs.

    PubMed

    Zhang, Lin; Zhang, Lanying; Zhang, Manhong; Pang, Yue; Li, Zhaoming; Zhao, Aili; Feng, Jing

    2015-06-01

    Herbal drugs have been used for thousands of years in the east and have had a recent resurgence in popularity among consumers in the west. However, most of herbal drug are poorly soluble and have hydrophobic properties and poor distribution, leading to reduced bioavailability and hence decreased treatment efficacy, requiring repeated administration or increased dose. In the past few decades, considerable attention has been focused on the development of self-emulsifying drug delivery system (SEDDS) for herbal drugs. SEDDS is isotropic and thermodynamically stable solutions consisting of oil, surfactant, co-surfactant and drug that can spontaneously form oil-in-water micro/nanoemulsion when mixed with water under gentle stirring. The formulation can be a viable alternative to classical formulations to take advantage of their lipophilic nature and to solve their problems of poor solubility, poor bioavailability, low oral absorption and instability. The mechanism of self-emulsification, solubility studies, construction of phase diagram, optimization and characterization of herbal drugs-loaded SEDDS formulation and in situ absorption evaluation of herbal drugs in rat intestine are presented in our article. PMID:24321014

  4. Organogels in drug delivery.

    PubMed

    Murdan, Sudaxshina

    2005-05-01

    In the last decade, interest in physical organogels has grown rapidly with the discovery and synthesis of a very large number of diverse molecules, which can gel organic solvents at low concentrations. The gelator molecules immobilise large volumes of liquid following their self-assembly into a variety of aggregates such as rods, tubules, fibres and platelets. The many interesting properties of these gels, such as their thermoreversibility, have led to much excitement over their industrial applications. However, only a few organogels are currently being studied as drug/vaccine delivery vehicles as most of the existing organogels are composed of pharmaceutically unacceptable organic liquids and/or unacceptable/untested gelators. In this paper a brief overview of organogels is presented, followed by a more in-depth review of the gels that have been investigated for drug and/or vaccine delivery. These include microemulsion-based gels and lecithin gels (studied for transdermal delivery), sorbitan monostearate organogels and amphiphilogels (studied as vaccine adjuvants and for oral and transdermal drug delivery, respectively), gels composed of alanine derivatives (investigated as in situ forming gels) and Eudragit organogels (studied as a matrix for suppositories). Finally, pluronic lecithin organogels, descendents of lecithin gels but which are not really organogels, are briefly discussed for their interesting history, their root and the wide interest in these systems. PMID:16296770

  5. 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

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

    PubMed

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

    2014-07-11

    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. PMID:24960297

  7. Study on a piezoelectric micropump for the controlled drug delivery system

    Microsoft Academic Search

    Qifeng Cui; Chengliang Liu; Xuan F. Zha

    2007-01-01

    We present the design of a new controlled drug delivery system potential for in vitro injection of diabetics. The system incorporates\\u000a some integrated circuit units and microelectromechanical system devices, such as micropump, microneedle array and microsensor.\\u000a Its goal is to achieve safer and more effective drug delivery. Moreover, a valveless micropump excited by the piezoelectric\\u000a actuator is designed for the

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

    Microsoft Academic Search

    Normaizira Hamidi; Mohd Nasir Taib; Wong Tin Wui

    2008-01-01

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

  9. Development of bioadhesive chitosan superporous hydrogel composite particles based intestinal drug delivery system.

    PubMed

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

    2013-01-01

    Bioadhesive superporous hydrogel composite (SPHC) particles were developed for an intestinal delivery of metoprolol succinate and characterized for density, porosity, swelling, morphology, and bioadhesion studies. Chitosan and HPMC were used as bioadhesive and release retardant polymers, respectively. A 3(2) full factorial design was applied to optimize the concentration of chitosan and HPMC. The drug loaded bioadhesive SPHC particles were filled in capsule, and the capsule was coated with cellulose acetate phthalate and evaluated for drug content, in vitro drug release, and stability studies. To ascertain the drug release kinetics, the drug release profiles were fitted for mathematical models. The prepared system remains bioadhesive up to eight hours in intestine and showed Hixson-Crowell release with anomalous nonfickian type of drug transport. The application of SPHC polymer particles as a biomaterial carrier opens a new insight into bioadhesive drug delivery system and could be a future platform for other molecules for intestinal delivery. PMID:23984380

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

    PubMed Central

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

    2013-01-01

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

  11. Development of a Gas Empowered Drug Delivery system for peptide delivery in the small intestine.

    PubMed

    Sadeghi, A M M; Avadi, M R; Ejtemaimehr, Sh; Abashzadeh, Sh; Partoazar, A; Dorkoosh, F; Faghihi, M; Rafiee-Tehrani, M; Junginger, H E

    2009-02-20

    The aim of this investigation was to design a novel Gas Empowered Drug Delivery (GEDD) system for CO(2) forced transport of peptide drugs together with mucoadhesive polymers to the surface of the small intestine. The GEDD effect of the core tablet was achieved using CO(2) gas to push insulin together with the mucoadhesive excipients poly(ethyleneoxide) (PEO) and the permeation enhancer trimethyl chitosan (TMC) to the surface of the small intestine. The in-vitro insulin release showed that almost 100% of the insulin was released from enterically coated tablets within 30 min at pH 6.8. The designed GEDD system was shown to increase the insulin transport by approximately 7 times in comparison with the free insulin across sheep's intestine ex-vivo. Three different peroral formulations were administered to male rabbits: F1 containing no TMC or PEO, F2 containing PEO but no TMC and F3 containing both PEO and TMC. The administrations of insulin using the formulation F1 resulted in a low FR value of 0.2%+/-0.1%, while the formulations F2 and F3 resulted in a much higher FR values of 0.6+/-0.2% and 1.1%+/-0.4%, respectively. Hence, the insulin permeation achieved by the GEDD system is primarily due to the enhancing effect of TMC and the mucoadhesive properties of PEO both of which synergistically increase the bioavailability of insulin. PMID:19014985

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

    PubMed

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

    2014-06-10

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

  13. 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

  14. 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

  15. Sustained-release ophthalmic drug delivery systems for treatment of macular disorders: present and future applications.

    PubMed

    Booth, Blake A; Vidal Denham, Lori; Bouhanik, Saadallah; Jacob, Jean T; Hill, James M

    2007-01-01

    Macular disease currently poses the greatest threat to vision in aging populations. Historically, most of this pathology could only be dealt with surgically, and then only after much damage to the macula had already occurred. Current pathophysiological insights into macular diseases have allowed the development of effective new pharmacotherapies. The field of drug delivery systems has advanced over the last several years with emphasis placed on controlled release of drug to specific areas of the eye. Its unique location and tendency toward chronic disease make the macula an important and attractive target for drug delivery systems, especially sustained-release systems. This review evaluates the current literature on the research and development of sustained-release posterior segment drug delivery systems that are primarily intended for macular disease with an emphasis on age-related macular degeneration.Current effective therapies include corticosteroids and anti-vascular endothelial growth factor compounds. Recent successes have been reported using anti-angiogenic drugs for therapy of age-related macular degeneration. This review also includes information on implantable devices (biodegradable and non-biodegradable), the use of injected particles (microspheres and liposomes) and future enhanced drug delivery systems, such as ultrasound drug delivery. The devices reviewed show significant drug release over a period of days or weeks. However, macular disorders are chronic diseases requiring years of treatment. Currently, there is no 'gold standard' for therapy and/or drug delivery. Future studies will focus on improving the efficiency and effectiveness of drug delivery to the posterior chamber. If successful, therapeutic modalities will significantly delay loss of vision and improve the quality of life for patients with chronic macular disorders. PMID:17658909

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

    Microsoft Academic Search

    Li Cao; Susan Mantell; Dennis Polla

    2001-01-01

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

  17. Antitumor activity of an epithelial cell adhesion molecule- targeted nanovesicular drug delivery system

    Microsoft Academic Search

    Sajid Hussain; Andreas Pluckthun; Theresa M. Allen; Uwe Zangemeister-Wittke

    2007-01-01

    Site-specific delivery of anticancer agents to tumors represents a promisingtherapeutic strateg y because it increases efficacy and reduces toxicity to normal tissues compared with untargeted drugs. Sterically stabilized immunoliposomes (SIL), guided by antibodies that specif- ically bind to well internalizingantig ens on the tumor cell surface, are effective nanoscale delivery systems capable of accumulating large quantities of anticancer agents at

  18. Innovative Liposomes as a Transfollicular Drug Delivery System: Penetration into Porcine Hair Follicles

    Microsoft Academic Search

    Sascha Jung; Nina Otberg; Gisela Thiede; Heike Richter; Wolfram Sterry; Steffen Panzner; Jürgen Lademann

    2006-01-01

    Liposomes had been widely used for drug delivery in the past. In this study, five different liposomes were used as a follicular delivery system in pig ear skin. The liposomes mainly differed in their sphere diameter, lipid composition, and surface charge. A novel class of liposomes being amphoteric in their charge behavior are compared to established anionic and cationic liposomes.

  19. 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

  20. In vitro assessment of drug delivery through an endotracheal tube using a dry powder inhaler delivery system.

    PubMed Central

    Everard, M. L.; Devadason, S. G.; Le Souëf, P. N.

    1996-01-01

    BACKGROUND: Jet nubulisers and metered dose inhalers are widely used to deliver aerosolised drugs to the lungs of intubated patients in adult intensive care units. Drug delivery using these systems has been shown to be inefficient and both forms of delivery have the potential to induce paradoxical bronchoconstriction in patients with reactive airways disease. METHODS: Experiments were carried out to determine whether it was possible to deliver drug from a dry powder delivery system through an endotracheal tube. A 200 micrograms budesonide Turbohaler was enclosed in a chamber which allowed it to be inserted into a ventilator circuit. Experiments were performed with a multistage liquid impinger in which drug was drawn through the Turbohaler and endotracheal tube at 60 l/min providing an index of the maximum drug delivery achievable via this route. A second series of experiments was performed in which the Turbohaler was placed in a ventilator circuit using a Servo 900C volume cycled ventilator. Drug delivered from the Turbohaler during the inspiratory phase was collected on a filter placed between the end of a 9 mm endotracheal tube and a model lung. A tidal volume of 500 ml and inspiratory time of 0.5 seconds was used. Budesonide was assayed using an ultraviolet spectrophotometric assay. RESULTS: Thirty percent of the nominal dose passed through the endotracheal tube and was collected in the multistage liquid impinger. Mean drug delivery to the filter in the ventilator circuit was 20%. CONCLUSIONS: This in vitro study indicates that drugs from dry powder inhalers (in this case the Turbohaler) can be satisfactorily delivered through endotracheal tubes and that clinical evaluation of this technique is now indicated. Images PMID:8658374

  1. 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

  2. Electrochemical investigation of interaction between mitomycin C and DNA in a novel drug-delivery system

    Microsoft Academic Search

    Hakan Karadeniz; Levent Alparslan; Arzum Erdem; Ercument Karasulu

    2007-01-01

    A novel drug-delivery system was developed by loading the anticancer drug, mitomycin C (MC) into an oil\\/water system with the aim of investigation by electrochemical sensing the interaction between the drug and DNA in microemulsion phase. The physical and physicochemical properties (droplet size, pH, viscosity, conductivity and refractive index) of this microemulsion were examined. The electrochemical detection of the interaction

  3. Development of a polymer stent with shape memory effect as a drug delivery system

    Microsoft Academic Search

    H. M. Wache; D. J. Tartakowska; A. Hentrich; M. H. Wagner

    2003-01-01

    The article presents a new concept for vascular endoprothesis (stent). Almost all commercially available stents are made of metallic materials. A common after effect of stent implantation is restenosis. Several studies on metal stents coated with drug show, that the use of a drug delivery system may reduce restenosis. The purpose of this work is to develop a new stent

  4. 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

  5. Organ-on-a-chip platforms for studying drug delivery systems.

    PubMed

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

    2014-09-28

    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

  6. 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.

  7. 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

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

    PubMed

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

    2012-12-01

    Pharmaceutical research and inventions are increasingly developed for the design of an ideal dosage regimen in drug therapy of many diseases, which attains therapeutic concentration of drug in plasma and maintains it constant for the entire duration of treatment and also minimizes the side effects. Recent trends in pharmaceutical technology indicated that mucoadhesive micro particle and modified alginate beads as drug delivery system especially suitable for achieving delivery of drug in a predetermined rate locally or systemically for a prolonged period of time. The release of drug from microparticle depends on a variety of factors including carrier used to form the micro particle and amount of drug contained in them. The main aim of the present review is to explain the various theories, mechanisms, advanced mucoadhesive polymers, various delivery approaches, methodologies for developing a mucoadhesive micro-particle and modified alginate beads formulation, in vitro, ex vivo and in vivo characterization. Apart from this, an innovative test method that is biacore is highlighted in this review to measure the mucoadhesive strength. This review is also briefly explained about the updated patenting system for the development of micro-particle and modified alginate beads as drug delivery system. PMID:22734868

  9. NOVEL DRUG DELIVERY SYSTEMS: DESIRED FEAT FOR TUBERCULOSIS

    PubMed Central

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

    2010-01-01

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

  10. Functionalized Micellar Systems for Cancer Targeted Drug Delivery

    Microsoft Academic Search

    Damon Sutton; Norased Nasongkla; Elvin Blanco; Jinming Gao

    2007-01-01

    Abstract  Polymer micelles are rapidly becoming a powerful nanomedicine platform for cancer therapeutic applications due to their small\\u000a size (10–100 nm), in vivo stability, ability to solubilize water insoluble anticancer drugs, and prolonged blood circulation times. Recent data from\\u000a clinical trials with three micelle formulations have highlighted these and other pharmacokinetic advantages with reduced systemic\\u000a toxicity and patient morbidity compared to conventional

  11. 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

  12. 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

  13. [Progress of the hydrokinetic chromatography and its application in the characterization of particulate drug delivery systems].

    PubMed

    Liu, Wei; Li, Hai-Yan; Guo, Zhen; Zhang, Ji-Wen; Sun, Li-Xin

    2011-06-01

    In the present paper, the basic principles, the device and the analytical method of the hydrodynamic chromatography (HDC) were summarized, which is most widely used in hydrokinetic chromatography. The application of the hydrodynamic chromatography in the determination of the particle size and size distribution of the particulate drug delivery system was also reviewed. The method can determine the particle size of nano- and micron-scale particulate drug delivery systems rapidly. And this method also has the advantages of economic, convenient and no damage to the samples. In summary, there will be a good prospect for the application of HDC in the determination of particle size distribution features of particulate drug delivery systems. PMID:21882521

  14. 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

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

    PubMed

    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

  16. Drug delivery Combinatorial Drug Conjugation Enables Nanoparticle

    E-print Network

    Zhang, Liangfang

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

  17. Harnessing the capacity of cell-penetrating peptides for drug delivery to the central nervous system.

    PubMed

    Kang, Ting; Gao, Xiaoling; Chen, Jun

    2014-01-01

    The existence of blood-brain barrier (BBB) represents the most formidable challenge for drug delivery to the central nervous system (CNS). Modern breakthrough in biology offers multiple choices for overcoming this barrier but yields modest outcomes for clinical application due to various problems such as safety concerns, insufficient delivery efficiency and poor penetration. Cell penetrating peptides (CPPs) possessing powerful transmembrane capacity have been shown to be effective transport vectors for bioactive molecules and an attractive alternative to traditional active targeting approaches. However, the non-specificity of CPPs has hindered them from targeting a desired site of action. Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with specific targeting property may extricate CPPs from the dilemma. In this review, both the traditional and novel applications of CPPs-based strategies for CNS drug delivery will be discussed. PMID:24938893

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

    PubMed Central

    Chavda, Hitesh; Patel, Chhaganbhai

    2010-01-01

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

  19. 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.

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

    Microsoft Academic Search

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

    2009-01-01

    The main objective of this study was to prepare a solid form of lipid-based self-emulsifying drug delivery system (SEDDS) by spray drying liquid SEDDS with an inert solid carrier Aerosil 200 to improve the oral bioavailability of poorly water-soluble drug dexibuprofen. The liquid SEDDS was a system that consisted of dexibuprofen, Labrasol, Capryol 90 and Labrafil M 1944 CS. The

  1. Experiences with experimental clinical evaluation of a computerized drug delivery system for regulation of mean arterial blood pressure

    Microsoft Academic Search

    K. Ezra Kwok; S. L. Shah; B. A. Finegan; G. K. Kwong

    1999-01-01

    A number of closed-loop control systems have been investigated and developed for the regulation of physiological variables by automatic administration of therapeutic agents. This paper reflects on several years of practical experience, by the authors, in this area including the development of an adaptive computerized drug delivery system. A computerized adaptive drug delivery system has been designed and tested for

  2. 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

  3. 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

  4. 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

  5. Cyclodextrin-containing poly(ethyleneoxide) tablets for the delivery of poorly soluble drugs: potential as buccal delivery system.

    PubMed

    Cappello, Brunella; De Rosa, Giuseppe; Giannini, Lucia; La Rotonda, Maria Immacolata; Mensitieri, Giuseppe; Miro, Agnese; Quaglia, Fabiana; Russo, Roberto

    2006-08-17

    The aim of this work was to develop a tablet for the buccal delivery of the poorly soluble drug carvedilol (CAR), based on poly(ethyleneoxide) (PEO) as bioadhesive sustained-release platform and hydroxypropyl-beta-cyclodextrin (HPbetaCD) as modulator of drug release. As first, PEO tablets loaded with CAR/HPbetaCD binary systems with different dissolution properties were tested for CAR and HPbetaCD release features and compared to PEO tablets containing only CAR. When the drug was incorporated as CAR/HPbetaCD freeze-dried product, all CAR content was released from the tablet in about 10 h, displaying a constant release regimen after a transient. The effect of HPbetaCD incorporation on the release mechanism, was rationalized on the basis of the interplay of different physical phenomena: erosion and swelling of the tablet, drug dissolution, drug counter-diffusion and complex formation. In the second part of the study, the potential of HPbetaCD-containing PEO tablets as buccal delivery system for CAR was tested. It was found that the incorporation of HPbetaCD in the tablet did not alter significantly its good adhesion properties. The feasibility of buccal administration of CAR was assessed by permeation experiments on pig excised mucosa. The amount of CAR permeated from PEO tablet was higher in the case of HPbetaCD-containing tablets, the maximum value being obtained for CAR/HPbetaCD freeze-dried system. Our results demonstrate that, when the tablet is employed as transmucosal system, the role of drug dissolution enhancement in the hydrated tablet is much more relevant than in solution for increasing the delivery rate. PMID:16650700

  6. Heterostructured layered aluminosilicate-itraconazole nanohybrid for drug delivery system.

    PubMed

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

    2013-11-01

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

  7. Development of drug delivery systems based on layered hydroxides for nanomedicine.

    PubMed

    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

  8. 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

  9. 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

  10. A Floating Controlled-Release Drug Delivery System: In Vitro-in Vivo Evaluation

    Microsoft Academic Search

    Subhash Desai; Sanford Bolton

    1993-01-01

    A novel floating controlled-release drug delivery system was formulated in an effort increase the gastric retention time of the dosage form and to control drug release. The buoyancy was attributed to air and oil entrapped in the agar gel network. A floating controlled-release 300-mg theophylline tablet having a density of 0.67 was prepared and compared in vitro and in vivo

  11. Fabrication and characterization of a smart drug delivery system: microsphere in hydrogel

    Microsoft Academic Search

    Xian-Zheng Zhang; Patti Jo Lewis; Chih-Chang Chu

    2005-01-01

    In this contribution, a novel smart drug delivery system (DDS) consisting of hydroxyl-functionalized glycerol poly(?-caprolactone) (PGCL)-based microspheres and poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was developed for prolonged and sustained controlled drug release. Various amounts PGCL-based microspheres were incorporated physically into temperature sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel to form the novel DDSs. Resulting DDSs were characterized by scanning electron microscopy (SEM), differential scanning calorimetry

  12. Phagocytotic Competence of Differentiated U937 Cells for Colloidal Drug Delivery Systems in Immune Cells

    Microsoft Academic Search

    Jacqueline Leßig; Björn Neu; Hans-Jürgen Glander; Jürgen Arnhold; Uta Reibetanz

    2011-01-01

    Drug delivery into immune cells has high potential for the treatment of all kinds of inflammation, allowing a target-oriented\\u000a transport of active agents. The advantage of this local drug release is the prevention of negative effects of systemic applications\\u000a and low-dose application. Thereby, the phagocytotic capability of mature phagocytes is essential. Microparticles can be loaded\\u000a with immune regulatory substances to

  13. Poly(fumaric-co-sebacic) microspheres as oral drug delivery systems.

    PubMed

    Chickering, D; Jacob, J; Mathiowitz, E

    1996-10-01

    The current study focuses on the development of bioadhesive oral delivery systems based on bioerodible polyanhydrides. The polymers were studied and characterized using a novel tensiometer based on a very sensitive electrobalance. The system was designed to mimic in vivo interactions, thus all experiments were conducted with freshly excised tissue immersed in physiological saline at 37 degrees C. Poly(fumaric-co-sebacic) [P(FA:SA)] was found to be the most bioadhesive polymer from a series of different thermoplastic materials evaluated. Correlation with in vivo performance was investigated by determining gastrointestinal (GI) residence time of barium-loaded microspheres. Residence times of 24 to 36 h provided a strong indication that these microspheres were good candidates for bioadhesive drug delivery systems. To evaluate the effect of these materials on bioavailability, the anticoagulant drug, dicumarol, was encapsulated. Systemic blood levels demonstrated increased bioavailability for the encapsulated dicumarol formulation as compared with unencapsulated drug. (c) 1996 John Wiley & Sons, Inc. PMID:18629855

  14. A high-performance silicon micropump for disposable drug delivery systems

    Microsoft Academic Search

    Didier Maillefer; Stephan Gamper; Béatrice Frehner; Patrick Balmer; Harald van Lintel; Philippe Renaud

    2001-01-01

    This paper describes the design, fabrication and experimental results of a new, low cost, high-performance silicon micropump developed for a disposable drug delivery system. The pump chip demonstrates linear and accurate (±5%) pumping characteristics for flow rates up to 2 ml\\/h with intrinsic insensitivity to external conditions. The stroke volume of 160 nl is maintained constant by the implementation of

  15. An observational trial of a computerized drug delivery system on two patients

    Microsoft Academic Search

    K. Ezra Kwok; Sirish L. Shah; Barry A. Finegan; Gary K. Kwong

    1997-01-01

    A computerized drug delivery system has been designed and tested for automatic regulation of mean arterial blood pressure (MAP) of human patients by infusion of a vasodilator (sodium nitroprusside). Its control algorithm belongs to a type of long-range predictive control with a combination of finite-horizon and an infinite horizon optimization terms. The controller operates in an adaptive mode by using

  16. Startup Landscape at GT and in GA Innovative systems for intracellular drug/gene delivery

    E-print Network

    Das, Suman

    #12;Startup Landscape at GT and in GA #12;Innovative systems for intracellular drug/gene delivery with external component manufacturers #12;Generic Startup Process Idea conception Laying the foundation Startup 101: Conception to Commercialization Working with Georgia Tech Technology licensing Conflicts

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

    Microsoft Academic Search

    Hao Zhou; Gursel Alici; Weihua Li; Shaya Ghanbar

    2011-01-01

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

  18. Design of functional dendritic polymers for application as drug and gene delivery systems

    Microsoft Academic Search

    Zili Sideratou; Leto-Aikaterini Tziveleka; Christina Kontoyianni; Dimitris Tsiourvas; Constantinos M. Paleos

    2006-01-01

    Summary The present review deals with the design and preparation of functional and multifunctional dendrimeric and hyperbranched polymers (dendritic polymers), in order to be employed as drug and gene delivery systems. In particular, using as starting materials known and well-characterized basic dendritic polymers, the review discusses the kind of structural modifications that these polymers were subjected for preparing nanocarriers of

  19. Casein-based formulations as promising controlled release drug delivery systems

    Microsoft Academic Search

    Ahmed O. Elzoghby; Wael S. Abo El-Fotoh; Nazik A. Elgindy

    2011-01-01

    Casein, the major milk protein, forms an integral part of the daily diet in many parts of the world. Casein possesses a number of interesting properties that make it a good candidate for conventional and novel drug delivery systems. This article reviews approaches aimed to associate bioactive molecules to casein and analyze the evidence of their efficacy in modifying the

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

    Microsoft Academic Search

    Gesine Winzenburg; Carsten Schmidt; Stefan Fuchs; Thomas Kissel

    2004-01-01

    Biodegradable polymers have been extensively studied for numerous drug delivery systems for human health purposes. The ever-increasing value of animals to human society allows the application of pharmaceutical developments in the veterinary field from those developed in human medicine. Although many similarities between the human and animal health industries exist there are also notable differences. This paper provides an insight

  1. A Bi-Mix Antibacterial Drug-Delivery System for Regenerative Endodontics. Jadesada Palasuk1

    E-print Network

    Zhou, Yaoqi

    A Bi-Mix Antibacterial Drug-Delivery System for Regenerative Endodontics. Jadesada Palasuk1. The antibacterial property of the released media was tested against Enterococcus faecalis (Ef), Porphyromonas to characterize mechanical, chemical and antibacterial properties. One-way ANOVA (only for fiber diameter

  2. Scleroglucan\\/borax: characterization of a novel hydrogel system suitable for drug delivery

    Microsoft Academic Search

    T. Coviello; M. Grassi; R. Lapasin; A. Marino; F. Alhaique

    2003-01-01

    A new hydrogel, with scleroglucan using borax as a crosslinker, has been prepared. The physical gel has been loaded with a model molecule (theophylline) and the release of the drug from the gel was evaluated. The same system was used to prepare tablets and the delivery of theophylline in different environmental conditions (HCl and SIF) was determined. A recent theoretical

  3. Oral lipid based drug delivery system (LBDDS): formulation, characterization and application: a review.

    PubMed

    Rahman, Md Akhlaquer; Harwansh, Ranjit; Mirza, Mohd Aamir; Hussain, Sarfaraj; Hussain, Arshad

    2011-07-01

    The major problem in oral drug formulations is low and erratic bioavailability, which mainly results from poor aqueous solubility. This may lead to high inter- and intra subject variability, lack of dose proportionality and therapeutic failure. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations. Oral lipid based formulations are attracting considerable attention due to their capacity to increase the solubility, facilitating gastrointestinal absorption and reduce or eliminate the effect of food on the absorption of poorly water soluble, lipophilic drug and thus increasing the bioavailability. The present review outlines the recent findings on self-emulsifying drug delivery system (SEDDS), self-micro/nanoemulsifying drug delivery system (SMEDDS/SNEDDS) and evaluation of these formulations published over the past decade. The application of lipid based formulations as a promising system for the oral delivery of many therapeutic agents including traditional medicine (TM) has also been examined in the current review. PMID:21453264

  4. Local drug delivery with a self-contained, programmable, microfluidic system

    PubMed Central

    Fiering, J.; Mescher, M. J.; Swan, E. E. Leary; Holmboe, M. E.; Murphy, B. A.; Chen, Z.; Peppi, M.; Sewell, W. F.; McKenna, M. J.; Kujawa, S. G.; Borenstein, J. T.

    2010-01-01

    The development and optimization of many new drug therapies requires long-term local delivery with controlled, but variable dosage. Current methods for chronic drug delivery have limited utility because they either cannot deliver drugs locally to a specific organ or tissue, do not permit changes in delivery rate in situ, or cannot be used in clinical trials in an untethered, wearable configuration. Here, we describe a small, self-contained system for liquid-phase drug delivery. This system enables studies lasting several months and infusion rates can be programmed and modified remotely. A commercial miniature pump is integrated with microfabricated components to generate ultralow flow rates and stroke volumes. Solutions are delivered in pulses as small as 370 nL, with pulses delivered at any interval of 1 min or longer. A unique feature of the system is the ability to infuse and immediately withdraw liquid, resulting in zero net volume transfer while compounds are exchanged by mixing and diffusion with endogenous fluid. We present in vitro results demonstrating repeatability of the delivered pulse volume for nearly 3 months. Furthermore, we present in vivo results in an otology application, infusing into the cochlea of a guinea pig a glutamate receptor antagonist, which causes localized and reversible changes in auditory sensitivity. PMID:19089621

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

    PubMed

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

    2014-09-28

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

  6. Self-nanoemulsifying drug delivery systems of tamoxifen citrate: design and optimization.

    PubMed

    Elnaggar, Yosra S R; El-Massik, Magda A; Abdallah, Ossama Y

    2009-10-01

    Tamoxifen citrate is an antiestrogen for peroral breast cancer treatment. The drug delivery encounters problems of poor water solubility and vulnerability to enzymatic degradation in both intestine and liver. In the current study, tamoxifen citrate self-nanoemulsifying drug delivery systems (SNEDDS) were prepared in an attempt to circumvent such obstacles. Preliminary screening was carried out to select proper ingredient combinations. All surfactants screened were recognized for their bioactive aspects. Ternary phase diagrams were then constructed and an optimum system was designated. Three tamoxifen SNEDDS were then compared for optimization. The systems were assessed for robustness to dilution, globule size, cloud point, surface morphology and drug release. An optimum system composed of tamoxifen citrate (1.6%), Maisine 35-1 (16.4%), Caproyl 90 (32.8%), Cremophor RH40 (32.8%) and propylene glycol (16.4%) was selected. The system was robust to different dilution volumes and types. It possessed a mean globule size of 150 nm and a cloud point of 80 degrees C. Transmission electron microscopy demonstrated spherical particle morphology. The drug release from the selected formulation was significantly higher than other SNEDDS and drug suspension, as well. Realizing drug incorporation into an optimized nano-sized SNEDD system that encompasses a bioactive surfactant, our results proposed that the prepared system could be promising to improve oral efficacy of the tamoxifen citrate. PMID:19635537

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

    E-print Network

    Gao, Jinming

    nanomedicine platform for cancer therapeutic applications due to their small size (10Y100 nm), in vivo targeting; cancer nanomedicine; micelle pharmacokinetics; polymer micelles; responsive drug release. INTRODUCTION Recently, polymer micelles have gained considerable attention as a versatile nanomedicine platform

  8. Design optimization of a novel pMDI actuator for systemic drug delivery.

    PubMed

    Kakade, Prashant P; Versteeg, Henk K; Hargrave, Graham K; Genova, Perry; Williams Iii, Robert C; Deaton, Daniel

    2007-01-01

    Pressurized metered dose inhalers (pMDIs) are the most widely prescribed and economical respiratory drug delivery systems. Conventional pMDI actuators-those based on "two-orifice-and-sump" designs-produce an aerosol with a reasonable respirable fraction, but with high aerosol velocity. The latter is responsible for high oropharyngeal deposition, and consequently low drug delivery efficiency. Kos' pMDI technology is based on a proprietary vortex nozzle actuator (VNA), an innovative actuator configuration that seeks to reduce aerosol plume velocity, thereby promoting deep lung deposition. Using VNA development as a case study, this paper presents a systematic design optimization process to improve the actuator performance through use of advanced optical characterization tools. The optimization effort mainly relied on laser-based optical diagnostics to provide an improved understanding of the fundamentals of aerosol formation and interplay of various geometrical factors. The performance of the optimized VNA design thus evolved was characterized using phase Doppler anemometry and cascade impaction. The aerosol velocities for both standard and optimized VNA designs were found to be comparable, with both notably less than conventional actuators. The optimized VNA design also significantly reduces drug deposition in the actuator as well as USP throat adapter, which in turn, leads to a significantly higher fine particle fraction than the standard design (78 +/- 3% vs. 63 +/- 2% on an ex valve basis). This improved drug delivery efficiency makes VNA technology a practical proposition as a systemic drug delivery platform. Thus, this paper demonstrates how advanced optical diagnostic and characterization tools can be used in the development of high efficiency aerosol drug delivery devices. PMID:18158718

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

    PubMed Central

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

    2007-01-01

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

  10. Polymers for Colon Targeted Drug Delivery

    PubMed Central

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

    2010-01-01

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

  11. 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

  12. 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

  13. CCMR: Controlled Drug Delivery From New Biomaterials

    NSDL National Science Digital Library

    Rhodes, Steven D.

    2005-08-17

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

  14. Microspheres for controlled release drug delivery.

    PubMed

    Varde, Neelesh K; Pack, Daniel W

    2004-01-01

    Controlled release drug delivery employs drug-encapsulating devices from which therapeutic agents may be released at controlled rates for long periods of time, ranging from days to months. Such systems offer numerous advantages over traditional methods of drug delivery, including tailoring of drug release rates, protection of fragile drugs and increased patient comfort and compliance. Polymeric microspheres are ideal vehicles for many controlled delivery applications due to their ability to encapsulate a variety of drugs, biocompatibility, high bioavailability and sustained drug release characteristics. Research discussed in this review is focused on improving large-scale manufacturing, maintaining drug stability and enhancing control of drug release rates. This paper describes methods of microparticle fabrication and the major factors controlling the release rates of encapsulated drugs. Furthermore, recent advances in the use of polymer microsphere-based systems for delivery of single-shot vaccines, plasmid DNA and therapeutic proteins are discussed, as well as some future directions of microsphere research. PMID:14680467

  15. Nanoscale Drug Delivery Systems for Enhanced Drug Penetration into Solid Tumors: Current Progress and Opportunities

    PubMed Central

    Waite, Carolyn L.; Roth, Charles M.

    2013-01-01

    Poor penetration of anticancer drugs 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 drug 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

  16. 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

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

    PubMed

    Zhang, Xiao-Yu; Lu, Wei-Yue

    2014-12-01

    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

  18. A novel composite drug delivery system: honokiol nanoparticles in thermosensitive hydrogel based on chitosan.

    PubMed

    Li, XingYi; Zheng, XiuLing; Wei, XiaWei; Guo, Gang; Gou, MaLing; Gong, ChangYang; Wang, XianHuo; Dai, Mei; Chen, LiJuan; Wei, YuQuan; Qian, ZhiYong

    2009-08-01

    In this article, a novel composite drug delivery system, honokiol nanoparticles in biodegradable hydrogels based on chitosan (CS) and beta-glycerophosphate (beta-GP), was prepared. CS/beta-GP solution was liquid at room temperature and turned into gel as temperature increased. With increase in beta-GP concentration, the sol-gel transition temperature decreased accordingly. Honokiol nanoparticles with diameter of about 30 nm were prepared by emulsion solvent evaporation method. The sol-gel transition temperature of CS/beta-GP system decreased as F-127 presented in honokiol nanoparticles. In vitro release profiles were studied, the results showed that honokiol could be slowly released from CS/beta-GP gel over at least 2 weeks and the release rate was greatly influenced by initial drug loading. The described injectable hydrogels based on chitosan (CS) and beta-glycerophosphate (beta-GP) might have potential application as local drug delivery for honokiol. PMID:19928122

  19. Development of oral drug delivery system using floating microspheres.

    PubMed

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

    1999-01-01

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

  20. Drug/cyclodextrin solid systems in the design of hydrophilic matrices: a strategy to modulate drug delivery rate.

    PubMed

    Miro, Agnese; Quaglia, Fabiana; Giannini, Lucia; Cappello, Brunella; La Rotonda, Maria Immacolata

    2006-10-01

    The aim of this study was to investigate how the delivery rate of erodible sustained-release hydrophilic matrices intended for the delivery of poorly soluble drugs can be optimized through the incorporation of drug/cyclodextrin binary systems. Carvedilol (CAR), a sparingly water-soluble antihypertensive drug, was selected as a model for the study. As first, we attempted to improve CAR apparent solubility by association with hydroxypropyl-beta-cyclodextrin (HPbetaCD) and then incorporated CAR/HPbetaCD binary systems in sustained-release tablets made of poly(ethyleneoxide) (PEO). Solid CAR/HPbetaCD binary systems were prepared by physical mixing, kneading, co-melting and freeze-drying methods and characterized by DSC and X-ray powder diffractometry. The amount of CAR dissolved from all the HPbetaCD-containing systems was higher than pure CAR, the co-molten and freeze-dried products showing the best dissolution performance. The incorporation of the binary systems in PEO tablets resulted in a CAR release rate much higher than tablets containing only CAR. It was found that the time necessary to achieve complete release from the tablet was linearly related to the dissolution parameters of CAR/HPbetaCD powders. In the case of co-molten and freeze-dried products, all CAR content could be released in about 12 and 10 h, respectively. Our results demonstrate that the incorporation of drug/cyclodextrin solid systems in erodable PEO matrices intended for the delivery of poorly water-soluble drugs is useful to modulate the release rate by controlling the dissolution properties of the drug inside the tablet. PMID:17076639

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

    Microsoft Academic Search

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

    2010-01-01

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

  2. Formulation and evaluation of gastroretentive drug delivery system of propranolol hydrochloride.

    PubMed

    Jagdale, Swati C; Agavekar, Amit J; Pandya, Sudhir V; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

    2009-01-01

    The objective of present study was to develop a gastroretentive drug delivery system of propranolol hydrochloride. The biggest problem in oral drug delivery is low and erratic drug bioavailability. The ability of various polymers to retain the drug when used in different concentrations was investigated. Hydroxypropyl methylcellulose (HPMC) K4 M, HPMC E 15 LV, hydroxypropyl cellulose (HPC; Klucel HF), xanthan gum, and sodium alginate (Keltose) were evaluated for their gel-forming abilities. One of the disadvantages in using propranolol is extensive first pass metabolism of drug and only 25% reaches systemic circulation. The bioavailability of propranolol increases in presence of food. Also, the absorption of various drugs such as propranolol through P-glycoprotein (P-gp) efflux transporter is low and erratic. The density of P-gp increases toward the distal part of the gastrointestinal tract (GIT). Therefore, it was decided to formulate floating tablet of propranolol so that it remains in the upper part of GIT for longer time. They were evaluated for physical properties, in vitro release as well as in vivo behavior. In preliminary trials, tablets formulated with HPC, sodium alginate, and HPMC E 15 LV failed to produce matrix of required strength, whereas formulation containing xanthan gum showed good drug retaining abilities but floating abilities were found to be poor. Finally, floating tablets were formulated with HPMC K4 M and HPC. PMID:19672719

  3. 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

  4. Self emulsifying drug delivery system for enhanced solubility and dissolution of glipizide.

    PubMed

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

    2015-02-01

    The aim of this study was to develop self emulsifying drug delivery systems (SEDDS) of glipizide and to convert it into solid SEDDS (S-SEDDS) using Syloid(®) 244 FP as adsorbent. Solubility study, ternary phase diagram, robustness to dilution, thermodynamic stability study and globule size analysis were adopted to optimize liquid SEDDS. S-SEDDS were evaluated for various studies including in vivo study. The optimized liquid SEDDS formulation consisted of phosphatidylcholine, Tween 80 and Transcutol P as oil, surfactant and cosolvent. In vivo study demonstrated that blood glucose levels were efficiently controlled with S-SEDDS compared with pure drug. The results of this study suggest the potential use of developed S-SEDDS formulation for the delivery of poorly water-soluble drug glipizide. PMID:25576032

  5. Enzymatic characterization of lipid-based drug delivery systems.

    PubMed

    Ljusberg-Wahren, Helena; Seier Nielsen, Flemming; Brogård, Mattias; Troedsson, Emma; Müllertz, Anette

    2005-07-25

    The present work introduces a simple and robust in vitro method for enzymatic characterisation of surface properties of lipid dispersions in aqueous media. The initial lipolysis rate in biorelevant media, using pancreatic lipase and a self-microemulsifying formulation (SMEDDS) containing digestible lipids as substrate, was determined. The impact of incorporating two sparingly water soluble model drugs, probucol and halofantrine, into the SMEDDS was studied. It was found that both model drugs reduced the initial rate of lipolysis compared with the vehicle, probucol having a larger effect than halofantrine. The reduction of initial lipolysis rate indicates that probucol and halofantrine are bound in the water/emulsion interface limiting the substrate availability. PMID:15979260

  6. Recent advances in stealth coating of nanoparticle drug delivery systems

    PubMed Central

    Amoozgar, Zohreh; Yeo, Yoon

    2011-01-01

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

  7. Recent advances in stealth coating of nanoparticle drug delivery systems.

    PubMed

    Amoozgar, Zohreh; Yeo, Yoon

    2012-01-01

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

  8. Use of polylactic acid for the preparation of microparticulate drug delivery systems.

    PubMed

    Conti, B; Pavanetto, F; Genta, I

    1992-01-01

    This report reviews the development of particulate drug delivery systems technology based on polylactic acid (PLA). The following methods used to produce PLA microparticles are considered: emulsion solvent evaporation, emulsion solvent extraction, interfacial phase deposition, spray coating, and the melting method. The different preparation processes and parameters used, the characteristics of microparticles obtained and those parameters affecting the characteristics of these systems, are discussed. PMID:1593398

  9. Development and Characterization of Solid Self-emulsifying Drug Delivery System of Cilnidipine.

    PubMed

    Bakhle, Suparna Sacchit; Avari, Jasmine Gev

    2015-01-01

    The present investigations highlight the development of solid self-emulsifying drug delivery system (solid-SEDDS) for improved oral delivery of the poorly water-soluble drug; cilnidipine. Liquid SEDDS of the drug were formulated using Capryol 90 as the oil phase, Tween 80 as the surfactant, and Transcutol HP as the co-surfactant after screening various vehicles. The prepared systems were characterized for self-emulsification time, robustness to dilution, % transmittance, globule size, drug release, and thermodynamic stability. Ternary phase diagrams were plotted to identify the area of microemulsification. The optimized liquid SEDDS was transformed into a free-flowing powder using Neusilin US2 as the adsorbent. Solid self-emulsifying powder retained the self-emulsifying property of the liquid SEDDS. Differential scanning calorimetric, X-ray powder diffraction studies revealed the possibility of transformation of the crystalline form of the drug to the amorphous form in the SEDDS prepared with the carrier. The morphology of solid-SEDDS from scanning electron microscopy studies demonstrated the presence of spherical, granular particles indicating good flowing ability. Dissolution studies revealed enhanced dissolution of the drug from the solid system compared with the pure drug and its marketed formulation. Similarly, the in vitro absorption profile of the drug from the formulated SEDDS was significantly higher compared with pure drug. Thus it can be concluded that solid-SEDDS, amenable for development of solid dosage form, can be successfully developed using Neusilin US2 with the potential of enhancing the solubility, dissolution rate, and bioavailability of the drug. PMID:26027464

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

    PubMed

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

    2006-12-11

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

  11. 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.

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

    PubMed

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

    2012-01-01

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

  13. 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.

  14. 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.

  15. Pluronic lecithin organogel as a topical drug delivery system.

    PubMed

    Pandey, Mohit; Belgamwar, Veena; Gattani, Surendra; Surana, Sanjay; Tekade, Avinash

    2010-01-01

    The objective of this study was to formulate and evaluate the pluronic lecithin organogel containing flurbiprofen for topical application. Different formulations of pluronic lecithin organogels were prepared by using pluronic F127, lecithin, flurbiprofen, isopropyl palmitate, water, sorbic acid, and potassium sorbate. To study the in vitro potential of these formulations, permeation studies were performed with Keshary-Chien diffusion cells. The results of the in vitro permeation studies found that release of flurbiprofen from dialysis membrane-70 was more than excised dorsal rat skin. Gelation temperature study was carried out to determine the temperature where sol-gel transformation takes place. The viscosities of different formulations were determined by using Brookfield Viscometer at 25°C, the viscosity of formulations increases as the lecithin concentration increases. Also the formulations were tested for appearance and feel psychorheologically, pH, and drug content. Interactions between the components of the gel have been investigated by differential scanning calorimetry and X-ray powder diffractometry. The optimized formulation subjected to differential scanning calorimetry shows no drug-polymer interaction. To investigate the in vivo performance of the formulations, a carrageenan-induced rat paw edema model and skin irritation study was used. The stability studies and freeze-thaw thermal cyclic test were carried out, showing no phase separation of gel, and representing gel stability. Statistical analysis of the data of animal study (anti-inflammatory activity) was done by using one way analysis of variance (ANOVA) followed by Dunnett's test. The formulation shows a statistically significant anti-inflammatory activity and is non-irritant to skin. PMID:22747074

  16. Graphene and graphene oxide as a docking station for modern drug delivery system.

    PubMed

    Muthoosamy, Kasturi; Bai, Renu G; Manickam, Sivakumar

    2014-01-01

    Motivated by the success and exhaustive research on carbon nanotubes (CNTs) based drug delivery, graphene, a two-dimensional; honey-comb crystal lattice has emerged as the rising star in recent years. Graphene is a flat monolayer of carbon atoms that holds many promising properties such as unparalleled thermal conductivity, remarkable electronic properties, and most intriguingly higher planar surface and superlative mechanical strength, which are attractive in biotechnological applications. Delivery of anti-cancer drugs using graphene and its derivatives has sparked major interest in this emerging field. The anti-cancer therapies often pose a limitation of insolubility, administration problems and cell penetration ability. In addition, systemic toxicity caused by lack of selective targeting towards cancer cells and inefficient distribution limits its clinical applications. Graphene nanocomposite is a promising tool to address these drawbacks. This review will focus on various synthesis and functionalization of graphene and graphene oxide for providing better solubility and targeted drug delivery at cancer cells. A more advanced and 'smart' graphene hybrid nanostructures that have several functionalities such as stimulus-response mediated delivery, imaging at release sites as well as transfection into cancer cells are also presented. A brief description on the challenges and perspectives for future research in this field is also discussed. PMID:24909150

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

    Microsoft Academic Search

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

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

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

    NASA Astrophysics Data System (ADS)

    Kelley, Marie-Michelle

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

  19. Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of Zedoary essential oil: formulation and bioavailability studies.

    PubMed

    Zhao, Yi; Wang, Changguang; Chow, Albert H L; Ren, Ke; Gong, Tao; Zhang, Zhirong; Zheng, Ying

    2010-01-01

    The aim of the present study was to develop a self-nanoemulsifying drug delivery system (SNEDDS) for the oral delivery of Zedoary turmeric oil (ZTO), an essential oil extracted from the dry rhizome of Curcuma zedoaria. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification regions. ZTO could serve as a partial oil phase with the aid of the second oil phase to enhance drug loading. Increasing the surfactant concentration reduced the droplet size but increased the emulsification time, while the reverse effect was observed by increasing the co-surfactant concentration. Based on the emulsification time, droplet size and zeta potential after dispersion into aqueous phase, an optimized formulation consisting of ZTO, ethyl oleate, Tween 80, transcutol P (30.8:7.7:40.5:21, w/w) and loaded with 30% drug was prepared. Upon mixing with water, the formulation was rapidly dispersed into fine droplets with a mean size of 68.3+/-1.6 nm and xi-potential of -41.2+/-1.3 mV. The active components remained stable in the optimized SNEDDS stored at 25 degrees C for at least 12 months. Following oral administration of ZTO-SNEDDS in rats, both AUC and C(max) of germacrone (GM), a representative bioactive marker of ZTO, increased by 1.7-fold and 2.5-fold respectively compared with the unformulated ZTO. PMID:19732813

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

    PubMed Central

    Zhang, Jianxiang; Ma, Peter X

    2013-01-01

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

  1. 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).

  2. 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

  3. Design and Simulation of a Piezoelectrically Actuated Micropump for the Drug Delivery System

    Microsoft Academic Search

    Qifeng Cui; Chengliang Liu; X. F. Zha

    2006-01-01

    In this paper, we present a new piezoelectrically actuated valveless micropump for the drug delivery system. A simple fabrication process is based on the deep reactive ion-etching (DRIE), glass etching and the anodical bond. The diffuser\\/nozzle element has the divergence angle of 9.4deg, the width of 0.1 mm for the narrowest part and the length of 1.1 mm. The pressure

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

    PubMed Central

    Muro, Silvia

    2012-01-01

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

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

    PubMed

    Muro, Silvia

    2012-12-10

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

  6. 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

  7. Emulsomes meet S-layer proteins: an emerging targeted drug delivery system.

    PubMed

    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

  8. A targeting drug delivery system for ovarian carcinoma: transferrin modified lipid coated paclitaxel-loaded nanoparticles.

    PubMed

    Li, R; Zhang, Q; Wang, X-y; Chen, X-g; He, Y-x; Yang, W-y; Yang, X

    2014-10-01

    The transferring modified lipid coated PLGA nanoparticles, as a targetable vector, were developed for the targeting delivery of anticancer drugs with paclitaxel (PTX) as a model drug to the ovarian carcinoma, which combines the advantages and avoids disadvantages of polymeric nanoparticles and liposomes in drug delivery. A transmission electron microscopy (TEM) confirmed the lipid coating on the polymeric core. Physicochemical characterizations of TFLPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. In the cellular uptake study, the TFLPs were more efficiently endocytosed by the A2780 cells with high expression of transferrin receptors than HUVEC cells without the transferrin receptors. Furthermore, the anticancer efficacy of TFLPs on the tumor spheroids was stronger than that of lipid coated PLGA nanoparticles (LPs) and PLGA nanoparticles. In the in vivo study, the TFLPs showed the best inhibition effect of the tumor growth for the ovarian carcinoma-bearing mice. In brief, the TFLPs were proved to be an efficient targeting drug delivery system for ovarian carcinoma. PMID:24443309

  9. Liposomal diltiazem HCl as ocular drug delivery system for glaucoma.

    PubMed

    Mokhtar Ibrahim, Mahmoud; Tawfique, Salma A H; Mahdy, Mahmoud M

    2014-06-01

    In this study, unilamellar liposomal vesicles of diltiazem HCl (DH) were prepared using either reversed phase evaporation (REV) or proliposome methods. Soya phosphatidylcholine (SPC) was used for preparing the liposomes, and the vesicles were rigidified using cholesterol (Chol) or cetyl alcohol (CA) in different molarities. The major differences in both the entrapment efficiency percent (EE%) and drug release were evaluated as a function of the method of preparation, Chol or CA contents, and charging lipids. Moreover, the morphology of the vesicles was confirmed by transmission electron microscopy. The effects of Chol or CA incorporation into the liposomes were discussed based on thermal analysis. The in vivo evaluation of liposomal DH was assessed using intra-ocular pressure (IOP), reducing effects in rabbit eyes. Liposomes prepared via REV exhibited higher EE% and lower release rates when compared with those prepared from proliposomes. The incorporation of either Chol or CA in the liposomes enhanced the EE% and decreased the release rates; however, Chol yielded higher results than CA. In addition, both dicetyl phosphate (DCP; negative charge inducer) and stearyl amine (SA, positive charge inducer) decreased the EE% and increased the DH release rate. The in vivo antiglaucoma effects of the liposomes were calculated according to the area above the IOP/Time curve, the maximum response and the time for the maximum response and were compared with effects of the DH solution. The results were in the following order: DH solution?

  10. 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

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

    PubMed Central

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

    2011-01-01

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

  12. 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.

  13. Novel vaginal drug delivery system: deformable propylene glycol liposomes-in-hydrogel.

    PubMed

    Vani?, Željka; Hurler, Julia; Ferderber, Kristina; Golja Gašparovi?, Petra; Škalko-Basnet, Nataša; Filipovi?-Gr?i?, Jelena

    2014-03-01

    Deformable propylene glycol-containing liposomes (DPGLs) incorporating metronidazole or clotrimazole were prepared and evaluated as an efficient drug delivery system to improve the treatment of vaginal microbial infections. The liposome formulations were optimized based on sufficient trapping efficiencies for both drugs and membrane elasticity as a prerequisite for successful permeability and therapy. An appropriate viscosity for vaginal administration was achieved by incorporating the liposomes into Carbopol hydrogel. DPGLs were able to penetrate through the hydrogel network more rapidly than conventional liposomes. In vitro studies of drug release from the liposomal hydrogel under conditions simulating human treatment confirmed sustained and diffusion-based drug release. Characterization of the rheological and textural properties of the DPGL-containing liposomal hydrogels demonstrated that the incorporation of DPGLs alone had no significant influence on mechanical properties of hydrogels compared to controls. These results support the great potential of DPGL-in-hydrogel as an efficient delivery system for the controlled and sustained release of antimicrobial drugs in the vagina. PMID:23931627

  14. 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.

  15. 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±0.76nm, 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

  16. Surface-adsorbed reverse micelle-loaded solid self-nanoemulsifying drug delivery system of talinolol.

    PubMed

    Shakeel, Faiyaz; Haq, Nazrul; Alanazi, Fars K; Alsarra, Ibrahim A

    2014-10-16

    Abstract The aim of present investigation was to develop surface-adsorbed reverse-micelle-loaded solid self-nanoemulsifying drug delivery system (SNEDDS) of talinolol in order to enhance its in vitro dissolution rate, which in turn enhance the bioavailability. SNEDDS were prepared using aqueous phase titration method. Thermodynamically stable formulations were characterized in terms of droplet size, viscosity, % transmittance, drug content and surface morphology. Low cost acid-treated coffee husk was used as an effective biosorbent for preparation of solid SNEDDS. Developed SNEDDS were subjected to in vitro drug release/dissolution studies. In vitro drug release studies showed 99.6% release of talinolol from optimized solid SNEDDS TS3 after 120?min of study. The results of solubility studies showed 4849.5-folds enhancement in solubility of talinolol from optimized SNEDDS as compared to its aqueous solubility. PMID:25318634

  17. 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.

  18. 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.

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

    PubMed

    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

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

    PubMed

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

    2013-12-01

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

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

    Vandghanooni, Somayeh; Eskandani, Morteza

    2011-01-01

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

  3. 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 ...

  4. Evaluation of gliadins nanoparticles as drug delivery systems: a study of three different drugs.

    PubMed

    Duclairoir, C; Orecchioni, A-M; Depraetere, P; Osterstock, F; Nakache, E

    2003-03-01

    In this paper, biopolymer nanoparticles are studied, which unlike many synthetic carriers used for controlled release, are biocompatible and biodegradable systems. Gliadins nanoparticles are obtained by a desolvatation method, also known as drawning-out precipitation. These particles have been shown to be interesting as drug release systems for all-trans-retinoic acid. The aim of this paper was to study the influence of the polarity of different drugs on nanoparticle characteristics such as size and drug loading efficiency. Three drugs of three different polarities were studied: the hydrophobic Vitamin E (VE), the slightly polar mixture of linalool and of linalyl acetate (LLA) and the cationic amphiphilic benzalkonium chloride (BZC). This comparative work shows that the amount of the entrapped VE and LLA is higher than that of the cationic BZC, confirming a strong interaction between gliadins and apolar compounds, due to the apolarity of the proteins. This interaction results in a low diffusion coefficient and a partition coefficient in favour of gliadins, resulting in a low permeability coefficient. The drug release kinetics of two substances, LLA and BZC, are observed, in showing a burst effect, then a diffusion process, which can be modelled assuming that the particles are homogeneous spheres. PMID:12593944

  5. Casein-based formulations as promising controlled release drug delivery systems.

    PubMed

    Elzoghby, Ahmed O; El-Fotoh, Wael S Abo; Elgindy, Nazik A

    2011-08-10

    Casein, the major milk protein, forms an integral part of the daily diet in many parts of the world. Casein possesses a number of interesting properties that make it a good candidate for conventional and novel drug delivery systems. This article reviews approaches aimed to associate bioactive molecules to casein and analyze the evidence of their efficacy in modifying the release and/or improving the bioavailability of the associated molecules. The ability of casein to modify drug dissolution from compacts was reported. The high tensile strength of casein films, favors its use as an acceptable film-coating for tablets. Naturally occurring genipin and a natural tissue enzyme, transglutaminase, were used as crosslinkers to prepare novel casein-based hydrogels for the controlled release of bioactives. Casein floating beads were developed to increase the residence time of drugs in the stomach based on its emulsifying and bubble-forming properties. Casein-based microparticles entrapping bioactive molecules were prepared via emulsification-chemical crosslinking with glutaraldehyde, enzymatic crosslinking by transglutaminase, simple coacervation and electrostatic complexation. Casein nano-formulations were also prepared to deliver nutraceuticals and synthetic drugs via enzymatic crosslinking, graft copolymerization, heat-gelation and polyelectrolyte ionic complexation. It can be concluded that casein-based formulations are promising materials for controlled drug delivery. PMID:21338636

  6. Polymeric micelle-templated synthesis of hydroxyapatite hollow nanoparticles for a drug delivery system.

    PubMed

    Ye, Feng; Guo, Haifeng; Zhang, Haijiao; He, Xiulan

    2010-06-01

    Hydroxyapatite (HA) hollow nanoparticles (HNPs) have great potential in nanoscaled delivery devices due to their small size, excellent biocompatibility and expected high capacity. However, the preparation of HA HNPs for their application in a drug delivery system has rarely been reported because HA has a complicated crystal structure and it is difficult to obtain stable HA HNPs with hollows that are only nanoscaled in size. In the present study, HA HNPs were successfully produced through a novel polymeric micelle-templating method. The micelles were structured with completely insoluble Pluronic P123 molecules at cloud point as the core and Tween-60 molecules as the shell by the hydrophobic interaction of the alkyl chains with the insoluble P123 core. The morphology of the HA HNPs could be transformed from nanospheres to nanotubes by adding citric acid as a cosurfactant. The prepared HA HNPs had a much higher drug payload than traditional nanoparticles, using vancomycin as the model drug. Most importantly, the HA nanotubes were coupled with a layer of citrate molecules on the HA surfaces, which could further improve the drug load efficiency and could form an excellent pH-controlled open/closed gate for drug release with the addition of cationic polyelectrolytes. PMID:20004747

  7. New Methods of Drug Delivery

    Microsoft Academic Search

    Robert Langer

    1990-01-01

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

  8. 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.

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

    PubMed Central

    Ma, Ping; Mumper, Russell J.

    2013-01-01

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

  10. Drug delivery system for poorly water-soluble compounds using lipocalin-type prostaglandin D synthase.

    PubMed

    Fukuhara, Ayano; Nakajima, Hidemitsu; Miyamoto, Yuya; Inoue, Katsuaki; Kume, Satoshi; Lee, Young-Ho; Noda, Masanori; Uchiyama, Susumu; Shimamoto, Shigeru; Nishimura, Shigenori; Ohkubo, Tadayasu; Goto, Yuji; Takeuchi, Tadayoshi; Inui, Takashi

    2012-04-10

    Lipocalin-type prostaglandin D synthase (L-PGDS) is a member of the lipocalin superfamily and a secretory lipid-transporter protein, which binds a wide variety of hydrophobic small molecules. Here we show the feasibility of a novel drug delivery system (DDS), utilizing L-PGDS, for poorly water-soluble compounds such as diazepam (DZP), a major benzodiazepine anxiolytic drug, and 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione (NBQX), an ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist and anticonvulsant. Calorimetric experiments revealed for both compounds that each L-PGDS held three molecules with high binding affinities. By mass spectrometry, the 1:3 complex of L-PGDS and NBQX was observed. L-PGDS of 500?M increased the solubility of DZP and NBQX 7- and 2-fold, respectively, compared to PBS alone. To validate the potential of L-PGDS as a drug delivery vehicle in vivo, we have proved the prospective effects of these compounds via two separate delivery strategies. First, the oral administration of a DZP/L-PGDS complex in mice revealed an increased duration of pentobarbital-induced loss of righting reflex. Second, the intravenous treatment of ischemic gerbils with NBQX/L-PGDS complex showed a protective effect on delayed neuronal cell death at the hippocampal CA1 region. We propose that our novel DDS could facilitate pharmaceutical development and clinical usage of various water-insoluble compounds. PMID:22226778

  11. Colloidal microgels in drug delivery applications

    PubMed Central

    Vinogradov, Serguei V.

    2005-01-01

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

  12. 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

  13. Solubility and dissolution enhancement of tadalafil using self-nanoemulsifying drug delivery system.

    PubMed

    El-Badry, Mahmoud; Haq, Nazrul; Fetih, Gihan; Shakeel, Faiyaz

    2014-01-01

    The aim of this study was to develop and evaluate self-nanoemulsifying drug delivery system (SNEDDS) of tadalafil (TDL) in order to enhance its aqueous solubility and dissolution rate. TDL SNEDDS were developed by aqueous phase titration method via construction of pseudo-ternary phase diagrams. The formulations which passed thermodynamic stability and self-nanoemulsification tests were further characterized in terms of droplet size, viscosity, % transmittance and drug content. Selected SNEDDS and drug suspension were subjected to in vitro drug release studies via dialysis membrane in phosphate buffer (pH 6.8). In vitro drug release studies showed 96.6% release of TDL from optimized SNEDDS F5 as compared to only 12.4% from drug suspension after 24 h of study. The results of solubility studies showed 1434 folds enhancement in TDL solubility from optimized SNEDDS F5 as compared to its aqueous solubility. Overall, these results indicated that developed SNEDDS could be successfully used to enhance solubility and dissolution rate of poorly soluble drugs such as TDL. PMID:24770562

  14. 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) ...

  15. 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.

  16. Optimization of self nanoemulsifying drug delivery system for poorly water-soluble drug using response surface methodology.

    PubMed

    Ren, Shan; Mu, Huiling; Alchaer, Fadi; Chtatou, Azeddine; Müllertz, Anette

    2013-05-01

    There is an increasing interest on self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of poorly water-soluble drugs. However, development of SNEDDS is often driven by empiric, pseudo-ternary diagrams and solubility of drugs, and it is lacking a systematic approach for evaluating impact of excipients on the performance of formulations as well as the fate of drug. The aim of this study was to rationalize the SNEDDS development procedure and to get a better understanding on the role of excipients on the SNEDDS. The formulations consist of soybean oil or rapeseed oil, Cremophor(®) RH40, Maisine™ 35-1 and ethanol. Response surface methodology (RSM) was used in the development of SNEDDS. Significant advantages of RSM were found in reducing the work load and determining the impact of excipients on formulation characteristics. The most significant factor in influencing droplet size was the co-surfactant Maisine™ 35-1, the droplet size increased with increasing concentration of Maisine™ 35-1. It suggests that Maisine™ 35-1 has double functions in the SNEDDS; it functions as co-surfactant to improve the emulsification of oil, meanwhile it also works as the oil phase and results in larger droplets. A significant reduction in droplet size was interestingly observed when fenofibrate was loaded in the vehicles, probably due to the surface activity of fenofibrate, promoting the self-emulsifying process. It was evident that drug precipitation during lipolysis was not affected by the level of co-solvent ethanol in the formulation, while it had pronounced impact on drug solubilization during the initial dispersion stage. PMID:22871082

  17. 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

  18. Metformin hydrochloride-loaded poly(vinyl alcohol) composites as drug delivery systems.

    PubMed

    Cai, Xiaoqing; Shao, Wei; Luan, Yuxia; Pang, Jianmei; Li, Feifei; Li, Zhonghao

    2011-10-01

    A straightforward method is proposed for the preparation of drug-loaded biocompatible polymer composites based on the freeze drying technique. The solution of poly(vinyl alcohol) (PVA) and metformin hydrochloride (MH) is frozen using liquid nitrogen and the ice crystals are removed by sublimation through freeze drying, which results in the formation of MH-loaded PVA composite. By controlling the PVA concentration in the solution, both MH-loaded PVA fibers and porous products can be obtained. The synthesized MH-loaded PVA composites are characterized with scanning electron microscopy (SEM), powder X-ray diffraction (XRD), Fourier-transformed infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The drug release behavior of the as-prepared products is studied to reveal their potential use in drug delivery system. PMID:22400234

  19. 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

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

    PubMed

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

    2003-12-01

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

  1. 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

  2. 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

  3. Effect of radiotherapy and hyperthermia on the tumor accumulation of HPMA copolymer-based drug delivery systems

    Microsoft Academic Search

    Twan Lammers; Peter Peschke; Rainer Kühnlein; Vladimir Subr; Karel Ulbrich; Jürgen Debus; Peter Huber; Wim Hennink; Gert Storm

    2007-01-01

    Copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) are prototypic and well-characterized polymeric drug carriers that have been broadly implemented in the delivery of anticancer therapeutics. In an attempt to improve the tumor accumulation of HPMA copolymer-based drug delivery systems, their in vivo application was combined with radiotherapy and hyperthermia. As the effects of radiotherapy and hyperthermia were considered to depend significantly on the

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

    PubMed Central

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

    2012-01-01

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

  5. Bioresponsive matrices in drug delivery

    Microsoft Academic Search

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

    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

  6. Rheological characterization of bioadhesive binary polymeric systems designed as platforms for drug delivery implants.

    PubMed

    Andrews, Gavin P; Jones, David S

    2006-03-01

    This study describes the formulation and characterization of binary interactive polymeric systems, designed as platforms for improved drug delivery to mucosal sites. Binary interactive systems were manufactured containing hydroxyethylcellulose (HEC; 1-5% w/w) and polycarbophil (PC; 1-5% w/w) at pH 7, and their rheological (flow and dynamic), mechanical, and mucoadhesive properties were characterized, both before and after dilution with phosphate buffered saline (designed to mimic dilution by biological fluids). Physical interactions between HEC and PC were confirmed by the observed rheological synergy. Within the binary interactive systems increasing polymer concentration increased the storage modulus (G'), loss modulus (G' '), dynamic viscosity (eta'), hardness, compressibility, consistency, and mucoadhesion yet decreased the loss tangent. This was attributed to enhanced entanglements and interactions between adjacent polymer chains. Dilution with PBS altered the above properties; however, the binary interactive systems, particularly those containing higher concentrations of HEC, still exhibited predominantly elastic properties (high G', low tan delta). In light of this, it is suggested that the rheological and mucoadhesive properties of binary interactive systems composed of HEC (5% w/w) and PC (1-3% w/w) offered particular promise as platforms for topical mucosal drug delivery systems. PMID:16529429

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  10. 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

  11. Formulation and physicochemical characterization of imwitor 308 based self microemulsifying drug delivery systems.

    PubMed

    Zargar-Shoshtari, Sara; Wen, Jingyuan; Alany, Raid Ghassan

    2010-10-01

    Self Microemulsifying Drug Delivery Systems (SMEDDS) are a novel alternative to the conventional transdermal delivery systems. SMEDDS are water-free systems, made up of oils and surfactants that can readily form a microemulsion upon dilution within an aqueous medium. Before SMEDDS can be used as a drug delivery system it is necessary to investigate the internal microstructure of the resulting microemulsion. Novel Imwitor 308 based SMEDDS were prepared and investigated. Phase behaviour of the comprising components was investigated through the construction of pseudoternary phase diagrams. The formed systems were characterized using visual inspection, measurement of electrical conductivity, viscosity and droplet size. Amongst the pseudoternary systems investigated, IPM/Cremophor EL (50% w/w)/Imwitor (50% w/w) and Myritol 318/Tween 85 (64% w/w)/ Transcutol P (20% w/w)/Imwitor (16% w/w) possessed the largest microemulsion area. Electrical conductivity and viscosity studies depict structural transitions from w/o microemulsion to bicontinuous or o/w microemulsion around 20-35% water. This was further supported by the droplet size and Fourier transform (FT)-IR measurements. The FT-IR data suggests that below the percolation threshold (?(C)) the water molecules are mainly bounded to the surfactant head group (bound water). Above this value, water molecule move to the outer phase of the microemulsion mainly interacting with each other though hydrogen bounding (free water). It was also found that pseudoternary systems with water content of less than 30% were stable at 32°C. Such systems may form stable microemulsion upon contact with the skin. Absorption of water may also result in a supersaturated solution with enhanced transdermal flux. PMID:20930400

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    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

    2010-01-01

    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

  14. 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

  15. Biodegradable polymeric nanoparticles as drug delivery devices

    Microsoft Academic Search

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

    2001-01-01

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

  16. Preparation and in vitro evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) containing clotrimazole.

    PubMed

    Kassem, A A; Marzouk, M A; Ammar, A A; Elosaily, G H

    2010-10-01

    This study sought to formulate and evaluate a self-nanoemulsified drug delivery system (SNEDDS) for clotrimazole (CT), a poorly water-soluble antimycotic drug, used in vaginal delivery. SNEDDS was developed to increase the CT dissolution rate, solubility, and ultimately bioavailability. The solubility of CT in various oils, surfactants, and co-surfactants was determined. Based on solubility studies, oil phase (oleic acid without or with coconut oil), surfactant (Tween 20), and co-surfactants (PEG 200 and n-butanol) were selected and grouped in two combinations for phase studies. Pseudo-ternary phase diagrams were used to evaluate the area of self-nanoemulsification. Essential properties of the prepared systems with regard to emulsion droplet size and turbidity value were determined. In order to investigate the potential for interaction between any of the SNEDDS ingredients used, FTIR spectroscopy was performed. In vitro release studies were performed with SNEDDS formulations in capsules, and the plain drug served as a control. The droplet size of the nanoemulsion was greatly affected by the ratio of the surfactant and co-surfactant. Based on the results with regard to droplet size, turbidity values, and complete drug release after 3 h, three optimized formulations were selected; each contained oleic acid/coconut oil/Tween 20/PEG 200/n-butanol in ratios of 10:0:60:15:15 (%, w/w), 7.5:2.5:53.5:13.3:13.3 (%, w/w), and 6.7:3.3:60:10:10 (%, w/w), respectively. Results suggested that the prepared SNEDDS formulations produced acceptable properties in terms of immediate drug release and could increase the bioavailability of CT. PMID:22491242

  17. Pure and Strontium Doped Nano Hydroxyapatite: New Approach for Bone Implant and Drug Delivery System

    NASA Astrophysics Data System (ADS)

    Tank, Kashmira P.; Vasant, Sonal R.; Chudasama, Kiran S.; Thaker, Vrinda S.; Joshi, Mihir J.

    2011-07-01

    Hydroxyapatite, (Ca10(PO4)6(OH)2-Hap), an excellent inorganic biomaterial, find various applications. The chemical composition of Hap is similar to that of the inorganic matrix of human bone and dental enamel. It is also used in drug delivery system and coating of bone implant. In the present study, pure nano Hap and Strontium doped nano-Hap (Sr-Hap) with different concentrations were synthesized by surfactant mediated approach. The samples were characterized by EDAX, XRD and TEM. The hemolytic properties were also studied and it proved that all the samples were non-hemolytic.

  18. SMART Drug Delivery Systems: Back to the Future vs. Clinical Reality

    PubMed Central

    Lammers, Twan

    2013-01-01

    Recent advances in nanotechology 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

  19. Barium Ions Crosslinked Alginate and Sterculia Gum-Based Gastroretentive Floating Drug Delivery System for Use in Peptic Ulcers

    Microsoft Academic Search

    Baljit Singh; Dimpal Chauhan

    2011-01-01

    The gastro-retentive drug delivery system is required to improve the bioavailability and therapeutic efficacy of the drugs used for the diseases associated with the stomach. Both sterculia gum and alginate enhance the repair of mucosal damage in the GI tract and pantoprazole is a therapeutic agent for GI tract ulcers. Ionotropic gelation of these polysaccharides for the release of pantoprazole

  20. 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

  1. PLGA: a unique polymer for drug delivery.

    PubMed

    Kapoor, Deepak N; Bhatia, Amit; Kaur, Ripandeep; Sharma, Ruchi; Kaur, Gurvinder; Dhawan, Sanju

    2015-01-01

    Biodegradable polymers have played an important role in the delivery of drugs in a controlled and targeted manner. Polylactic-co-glycolic acid (PLGA) is one of the extensively researched synthetic biodegradable polymers due to its favorable properties. It is also known as a 'Smart Polymer' due to its stimuli sensitive behavior. A wide range of PLGA-based drug delivery systems have been reported for the treatment or diagnosis of various diseases and disorders. The present review provides an overview of the chemistry, physicochemical properties, biodegradation behavior, evaluation parameters and applications of PLGA in drug delivery. Different drug-polymer combinations developed into drug delivery or carrier systems are enumerated and discussed. PMID:25565440

  2. Development and characterization of self-nanoemulsifying drug delivery systems (SNEDDS) of atorvastatin calcium.

    PubMed

    Mantri, Shiva Kumar; Pashikanti, Shailaja; Murthy, K V Ramana

    2012-03-01

    The main aim of the present investigation is to develop and characterize the self-nanoemulsifying drug delivery systems (SNEDDS) of atorvastatin calcium (ATV) for improving the dissolution thereby oral bioavailability and to minimize the gastric degradation. Naturally occurring different vegetable oils, various surfactants and co-surfactants were studied for ATV solubility to identify the components of SNEDDS. Ternary phase diagrams comprising surfactant, cosurfactant and oil were plotted. In the ternary phase diagrams the area of self-nanoemulsifying region was marked for the compositions that are giving dispersion with a globule size ? 200 nm. Effect of drug loading on the phase behavior of selected system was studied. A series of SNEDDS were prepared by selecting from the nanoemulsifying area of 2.5% ATV system. Prepared SNEDDS were evaluated for visual observations, turbidity, effect of pH of the dispersion media on globule size and zeta potential, robustness to dilution and in vitro dissolution study and optimized. FT-IR and DSC were studied for interaction between drug and excipients if any. Forced degradation and accelerated stability studies were conducted for optimized SNEDDS. ATVF 04 and 11 were selected as optimized SNEDDS due to their smaller mean globule size (75.2 and 85.8 nm respectively), lower turbidity values, faster drug release and higher DE values among the other SNEDDS. The optimized ATV SNEDDS were not affected by the pH of dissolution medium. FT-IR study revealed no interaction between drug and excipients used. Forced degradation studies indicated the stability of ATV in the gastric environment. Accelerated stability studies showed no significant changes in the mean globule size, zeta potential, drug content and drug release before and after storage of optimized SNEDDS. PMID:22283646

  3. Liposomes for Pulmonary Drug Delivery

    Microsoft Academic Search

    Janani Swaminathan; Carsten Ehrhardt

    \\u000a Liposomes have been widely used in pulmonary drug delivery for ­multiple applications including solubilization, sustained\\u000a release, cellular and intracellular ­targeting, minimization of toxicity, and facilitation of absorption. In this chapter,\\u000a formulation aspects, aerosolization, and an extensive overview of the use of pulmonary drug delivery of liposomes for disease\\u000a and drug classes are provided. Specifically, this chapter examines liposomes from in

  4. Recent advances in ophthalmic drug delivery

    PubMed Central

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

    2011-01-01

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

  5. 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 ...

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

    PubMed

    Joanitti, Graziella A; Silva, Luciano P

    2014-05-01

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

  7. 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.

  8. Self-microemulsifying drug delivery system (SMEDDS) of vinpocetine: formulation development and in vivo assessment.

    PubMed

    Chen, Ying; Li, Gao; Wu, Xianggen; Chen, Zhiyu; Hang, Jiangeng; Qin, Bei; Chen, Song; Wang, Ruihua

    2008-01-01

    A new self-microemulsifying drug delivery system (SMEDDS) has been developed to increase the solubility, dissolution rate and oral bioavailability of vinpocetine (VIP), a poor water-soluble drug. The formulations of VIP-SMEDDS were optimized by solubility assay, compatibility tests, and pseudo-ternary phase diagrams analysis. The optimal ratio in the formulation of SMEDDS was found to be Labrafac : oleic acid : Cremophor EL : Transcutol P=40 : 10 : 40 : 10 (w/w). The average particle diameter of VIP was less than 50 nm. In vitro dissolution study indicated that the dialysis method in reverse was better than the ultrafiltration method and the dialysis method in simulating the drug in vivo environment. Comparing with VIP crude drug power and commercial tablets, (-)VIP-SMEDDS caused a 3.4- and 2.9-fold increase in the percent of accumulated dissolution at 3 h. Further study on the absorption property of VIP-SMEDDS employing in situ intestine of rats demonstrated that VIP in SMEDDS could be well-absorbed in general intestinal tract without specific absorption sites. In addition, the developed SMEDDS formulations significantly improved the oral bioavailability of VIP in rats. Relative bioavailability of (-)VIP-SMEDDS and (+)VIP-SMEDDS increased by 1.85- and 1.91-fold, respectively, in relative of VIP crude powder suspension. The mechanisms of enhanced bioavailability of VIP might contribute to the improved release, enhanced lymphatic transport, and increased intestinal permeability of the drug. PMID:18175953

  9. 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 permeability surface product was found to be significantly increased in central nervous system lym- phomas- and lipid-soluble drugs in primary central nervous system lymphomas. Ann Neurol 2005;57:136­139 Primary

  10. Validated spectrofluorometric method for determination of gemfibrozil in self nanoemulsifying drug delivery systems (SNEDDS)

    NASA Astrophysics Data System (ADS)

    Sierra Villar, Ana M.; Calpena Campmany, Ana C.; Bellowa, Lyda Halbaut; Trenchs, Monserrat Aróztegui; Naveros, Beatriz Clares

    2013-09-01

    A spectrofluorometric method has been developed and validated for the determination of gemfibrozil. The method is based on the excitation and emission capacities of gemfibrozil with excitation and emission wavelengths of 276 and 304 nm respectively. This method allows de determination of the drug in a self-nanoemulsifying drug delivery system (SNEDDS) for improve its intestinal absorption. Results obtained showed linear relationships with good correlation coefficients (r2 > 0.999) and low limits of detection and quantification (LOD of 0.075 ?g mL-1 and LOQ of 0.226 ?g mL-1) in the range of 0.2-5 ?g mL-1, equally this method showed a good robustness and stability. Thus the amounts of gemfibrozil released from SNEDDS contained in gastro resistant hard gelatine capsules were analysed, and release studies could be performed satisfactorily.

  11. Validated spectrofluorometric method for determination of gemfibrozil in self nanoemulsifying drug delivery systems (SNEDDS).

    PubMed

    Sierra Villar, Ana M; Calpena Campmany, Ana C; Bellowa, Lyda Halbaut; Trenchs, Monserrat Aróztegui; Naveros, Beatriz Clares

    2013-09-01

    A spectrofluorometric method has been developed and validated for the determination of gemfibrozil. The method is based on the excitation and emission capacities of gemfibrozil with excitation and emission wavelengths of 276 and 304 nm respectively. This method allows de determination of the drug in a self-nanoemulsifying drug delivery system (SNEDDS) for improve its intestinal absorption. Results obtained showed linear relationships with good correlation coefficients (r(2)>0.999) and low limits of detection and quantification (LOD of 0.075 ?g mL(-1) and LOQ of 0.226 ?g mL(-1)) in the range of 0.2-5 ?g mL(-1), equally this method showed a good robustness and stability. Thus the amounts of gemfibrozil released from SNEDDS contained in gastro resistant hard gelatine capsules were analysed, and release studies could be performed satisfactorily. PMID:23708373

  12. 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

  13. Lipid nanoparticles for dermal drug delivery.

    PubMed

    Kakadia, Pratibha G; Conway, Barbara R

    2015-01-01

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

  14. Microelectronic control of drug delivery.

    PubMed

    Guo, Xin Dong; Prausnitz, Mark R

    2012-07-01

    Microelectronic control of drug delivery devices enables precise management of drug delivery profiles. Iontophoresis patches offer microelectronic control over delivery in a noninvasive manner, but these are limited to the administration of relatively small molecules at small doses. Infusion pumps are widely used for delivery of insulin and other drugs; however, they require an invasive catheter that many patients find inconvenient and can be a site of infection. Implanted pumps avoid these problems, but they require long-term commitment associated with surgical implantation. An alternative is an implanted microchip containing many protected reservoirs filled with drug powder that is selectively released under microelectronic control. This device offers the promise of long-term drug stability in the solid state and precise digital drug dosing. Building on more than 10 years of preclinical studies, this wirelessly controlled microchip technology recently underwent a first-in-human clinical study. The microchip was implanted subcutaneously in the abdomen of eight female patients with osteoporosis. A remote operator was able to establish a wireless link with the microchip to program the schedule of human parathyroid hormone dosing from the device. This study showed that the wireless microchips produced pharmacokinetics similar to those from subcutaneous injections of the drug and produced less variable drug levels in the blood. There were also no toxic or adverse events due to the microchip or drug. This study represents an important step towards more widespread use of microelectronic control of drug delivery to improve pharmaceutical therapies. PMID:22905837

  15. 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

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

    PubMed

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

    2009-08-01

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

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

    PubMed Central

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

    2013-01-01

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

  18. Self-nanoemulsifying drug delivery system of persimmon leaf extract: Optimization and bioavailability studies.

    PubMed

    Li, Wanwen; Yi, Shaoling; Wang, Zhouhua; Chen, Si; Xin, Shuang; Xie, Jingwen; Zhao, Chunshun

    2011-11-25

    In current study, a self-nanoemulsifying drug delivery system (SNEDDS) of persimmon (Diospyros kaki) leaf extract (PLE) was developed and characterized to compare its in vitro dissolution and relative bioavailability with commercially available tablets (Naoxinqing tablets). Pseudo-ternary phase diagrams were constructed by phase diagram by micro plate dilution (PDMPD) method, of which the evaluation method was improved to use Multiskan Ascent for identifying turbidity. The formulation of PLE-loaded SNEDDS was optimized by an extreme vertices experimental design. The optimized nanoemulsion formulation, loading with 44.48 mg/g PLE total flavonoids, consisted of Cremophor EL, Transcutol P, Labrafil M 1944 CS (56:34:10, w/w), and it remained stable after storing at 40°C, 25°C, 4°C for at least 6 months. When diluted with water, the SNEDDS droplet size was 34.85 nm and the zeta potential was -6.18 mV. Compared with the commercial tablets, the AUC of both quercetin and kaempferol, which are representative active flavonoids of PLE, was increased by 1.5-fold and 1.6-fold respectively following oral administration of PLE-loaded SNEDDS in fasting beagle dogs. These results indicate that SNEDDS is a promising drug delivery system for increasing the oral bioavailability of PLE. PMID:21884770

  19. Application of monochromatic keV X-ray source to X-ray drug delivery system

    Microsoft Academic Search

    Mitsuru Uesaka; Hiroki Taguchi; Azusa Mori; Noritaka Yusa; Takamitsu Kato; Ryuichi Okayasu

    2009-01-01

    X-ray Drug Delivery System (DDS) enhances accumulation of anti-cancer drug or contrast agent by surrounding it with polymer and Enhanced Penetration and Retention (EPR) effect. DDS uses advanced nano-scaled polymers that contain and deliver drug or contrast agent to cancers without side effects. Several X-ray DDSs pose high-Z atoms such as gold to absorb X-rays effectively and used as contrast

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

    PubMed

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

    2014-04-14

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

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

    PubMed

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

    2012-02-01

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

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

    PubMed

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

    2005-01-31

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

  3. Self-nanoemulsifying drug delivery system of lutein: physicochemical properties and effect on bioavailability of warfarin.

    PubMed

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

    2013-03-01

    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

  4. 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.

  5. Dissolution and powder flow characterization of solid self-emulsified drug delivery system (SEDDS).

    PubMed

    Agarwal, Vikas; Siddiqui, Akhtar; Ali, Hazem; Nazzal, Sami

    2009-01-21

    In this study, the dynamics of powder flow upon griseofulvin-self-emulsified drug delivery system (SEDDS) addition to silica and silicates and the effect of these adsorbents on drug release were investigated. SEDDS was adsorbed at SEDDS/adsorbent ratios from 0.25:1 to 3:1 on magnesium aluminum silicate [5 and 80 microm], calcium silicate [25 microm], and silicon dioxide [3.6, 20, and 300 microm]. Powder flow was evaluated using the powder rheometer and compared to angle of repose. Release of drug from a 1:1 SEDDS/adsorbent powder was determined by dissolution using USP Type 2 apparatus. Powder rheometer profiles indicated that effect of SEDDS on the flow behavior of the adsorbents could be correlated to stepwise or continuous growing behavior as observed in wet granulation process. However, due to their porous nature, adsorbents exhibited an initial lag phase during which no change in flow was observed. Dissolution of drug from adsorbed-SEDDS was found to be dependent on pore length and nucleation at the lipid/adsorbent interface. Increase in dissolution rate was observed with an increase in surface area and was independent of the chemical nature of the adsorbents. Therefore, in order to manufacture free flowing powder containing liquid SEDDS, special attention should be given to particle size, specific surface area, type and amount of adsorbent. PMID:18832019

  6. 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

  7. Gold nanoparticles decorated by amphiphilic block copolymer as efficient system for drug delivery.

    PubMed

    Wang, Zhifei; Jia, Lin; Li, Min-Hui

    2013-01-01

    A drug delivery system based on gold nanoparticles (Au NPs) stabilized by an thiol-functionalized amphiphilic diblock copolymer was developed. The copolymer, poly(ethylene glycol)-b-poly(n-butyl acrylate) (MPEG-b-PBA), was synthesized by Reversible Addition-Fragmentation Transfer (RAFT) polymerization and the thiocarbonylthio group at the end of the hydrophobic block PBA was further reduced to thiol group. Pyrene, used as a model molecule for the hydrophobic drugs, was loaded in the hydrophobic interior of the shell around Au NPs by physical entrapment. The analysis performed by UV-Vis spectrophotometer show that the obtained Au NPs-pyrene nanocomposites have good stability in the aqueous solution and high drug loading capacity in comparison with Au NPs decorated with small molecular ligands. In addition, both their loading capacity and release behavior were found closely related to the chain length of hydrophobic block. In conclusion, we report here a versatile and simple procedure to fabricate Au NP-polymer hybrids that is applicable to various amphiphilic copolymers synthesized by RAFT polymerization and useful to produce efficient Au NP based drug carriers. PMID:23627068

  8. 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

  9. Enhanced bioavailability of total paeony glycoside by self-microemulsifying drug delivery system.

    PubMed

    Chen, Li-Jiang; Liu, Yang; Liu, Yu; Li, Li; Gao, Fei

    2012-12-01

    Total paeony glycoside (TPG) is extracted and purified from a traditional Chinese herbal medicine. It has many biological and pharmacological activities. However, there are few dosage forms of TPG in the market because of its low bioavailability. Self-microemulsifying drug delivery system (SMEDDS) is a vital tool in solving low bioavailability of poor absorption drugs. So the objective of this study is to develop a new TPG-SMEDDS for the oral delivery of poorly soluble TPG. Through the construction of pseudo-ternary phase diagrams, the optimum prescription was obtained, which consisted of 18.70% TPG, 16.27% ethyl oleate as oil, 43.34% Cremophor RH40 as surfactant and 21.73% Transcutol P as cosurfactant. The characterizations of TPG-SMEDDS including morphological characterization, droplet size, zeta-potential, emulsification time, and dissolution study of TPG-SMEDDS were evaluated. The results showed that TPG-SMEDDS is stable and its release rate is high in four different media (0.1 mol x L(-1) HCl, pH 6.8 PBS, pH 7.4 PBS, and water). The relative bioavailability of SMEDDS was dramatically enhanced in an average of 1.52-fold that of TPG-suspension. It is concluded that the bioavailability of TPG is enhanced greatly by SMEDDS. PMID:23460976

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

    PubMed

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

    2012-10-15

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

  11. A universal level converter towards the realization of energy efficient implantable drug delivery Nano-Electro-Mechanical-Systems

    Microsoft Academic Search

    Saraju P. Mohantyl; Dhruva Ghai; Elias Kougianos; Bharat Joshi

    2009-01-01

    Nano-Electro-Mechanical-Systems (NEMS) are a techno- logical solution for building miniature systems which can be beneficial in terms of safety, efficacy, or convenience. Thus investigation is necessary for their usefulness in drug deliv- ery. In order to be an effective and reliable implantable sys- tem the DDNEMS (Drug Delivery Nano-Electro-Mechanical- System) should have low power dissipation, fault tolerance, and reconfigurability capabilities.

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

    PubMed

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

    2014-03-01

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

  13. Development of a novel osmotically driven drug delivery system for weakly basic drugs.

    PubMed

    Guthmann, C; Lipp, R; Wagner, T; Kranz, H

    2008-06-01

    The drug substance SAG/ZK has a short biological half-life and because of its weakly basic nature a strong pH-dependent solubility was observed. The aim of this study was to develop a controlled release (cr) multiple unit pellet formulation for SAG/ZK with pH-independent drug release. Pellets with a drug load of 60% were prepared by extrusion/spheronization followed by cr-film coating with an extended release polyvinyl acetate/polyvinyl pyrrolidone dispersion (Kollidon SR 30 D). To overcome the problem of pH-dependent drug release the pellets were then coated with a second layer of an enteric methacrylic acid and ethyl acrylate copolymer (Kollicoat MAE 30 DP). To increase the drug release rates from the double layered cr-pellets different osmotically active ionic (sodium and potassium chloride) and nonionic (sucrose) additives were incorporated into the pellet core. Drug release studies were performed in media of different osmotic pressure to clarify the main release mechanism. Extended release coated pellets of SAG/ZK demonstrated pH-dependent drug release. Applying a second enteric coat on top of the extended release film coat failed in order to achieve pH-independent drug release. Already low enteric polymer levels on top of the extended release coated pellets decreased drug release rates at pH 1 drastically, thus resulting in a reversal of the pH-dependency (faster release at pH 6.8 than in 0.1N HCl). The addition of osmotically active ingredients (sodium and potassium chloride, and sucrose) increased the imbibing of aqueous fluids into the pellet cores thus providing a saturated drug solution inside the beads and increasing drug concentration gradients. In addition, for these pellets increased formation of pores and cracks in the polymer coating was observed. Hence drug release rates from double layered beads increased significantly. Therefore, pH-independent osmotically driven SAG/ZK release was achieved from pellets containing osmotically active ingredients and coated with an extended and enteric polymer. In contrast, with increasing osmotic pressure of the dissolution medium the in vitro drug release rates decreased significantly. PMID:18226884

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

    PubMed Central

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

    2011-01-01

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

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

    Microsoft Academic Search

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

    2006-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  17. Nanotechnology and Drug Delivery Part 2: Nanostructures for Drug Delivery

    Microsoft Academic Search

    Nelson A Ochekpe; Patrick O Olorunfemi; Ndidi C

    2009-01-01

    This is the second part of a review on nanotechnology in general and particularly as it pertains to drug deliver. In the earlier paper (Part 1), nanotechnology in nature, its history as well as design and methods were discussed. Its applications, benefits and risks were also outlined. In this paper (Part 2), various nanostructures employed in drug delivery, their methods

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

    PubMed

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

    2013-05-13

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

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

    PubMed

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

    2011-08-01

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

  20. Synthetic micro/nanomotors in drug delivery

    NASA Astrophysics Data System (ADS)

    Gao, Wei; Wang, Joseph

    2014-08-01

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

  1. Synthetic micro/nanomotors in drug delivery.

    PubMed

    Gao, Wei; Wang, Joseph

    2014-09-21

    Nanomachines offer considerable promise for the treatment of diseases. The ability of man-made nanomotors to rapidly deliver therapeutic payloads to their target destination represents a novel nanomedicine approach. Synthetic nanomotors, based on a multitude of propulsion mechanisms, have been developed over the past decade toward diverse biomedical applications. In this review article, we journey from the use of chemically powered drug-delivery nanovehicles to externally actuated (fuel-free) drug-delivery nanomachine platforms, and conclude with future prospects and challenges for such practical propelling drug-delivery systems. As future micro/nanomachines become more powerful and functional, these tiny devices are expected to perform more demanding biomedical tasks and benefit different drug delivery applications. PMID:25096021

  2. Drug release from and sterilization of in situ cubic phase forming monoglyceride drug delivery systems

    Microsoft Academic Search

    Abid Riaz Ahmed; Andrei Dashevsky; Roland Bodmeier

    2010-01-01

    Since a monoglyceride-based cubic phase is too viscous to be injected parenterally, mixtures of monoglyceride, water and water-miscible cosolvents were investigated as low viscosity injectable in situ cubic phase-forming formulations. Upon contact with the release medium, a highly viscous cubic phase formed rapidly and served as an extended release matrix for the oligonucleotide drug. Extended drug release was obtained with

  3. 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.

  4. Preparation and evaluation of self-nanoemulsified drug delivery systems (SNEDDSs) of matrine based on drug-phospholipid complex technique.

    PubMed

    Ruan, Jinghua; Liu, Jie; Zhu, Di; Gong, Tao; Yang, Fumei; Hao, Xiaojiang; Zhang, Zhirong

    2010-02-15

    To enhance oral bioavailability of matrine, a dedicated and newly emerging drug system called self-nanoemulsifying drug delivery system (SNEDDSs) was developed. Phospholipid complex (MPC) was prepared using solvent-evaporation method to improve the liposolubility of matrine. Solubilization test, infrared spectroscopy (IR) and differential scanning calorimetry (DSC) analysis were employed to confirm the formation of MPC. A rational experimental design was adopted to optimize the properties of SNEDDSs. Eight SNEDDSs prototypes were obtained to form nanoemulsion spontaneously based on optimization experiments. Among them, MPC prepared exhibited excellent solubility. SNEDDSs 2 (composition: Lauroglycol FCC, Cremophor EL and Transcutol HP; ratio: 6:4:1) was selected as the optimal formulation, with a mean droplet size in the range of 65-80 nm and 8.34% of the leakage rate, exhibiting instantaneous emulsion formation with only one flask inversion. Media pH and dilution factor showed no effect on the droplet size. The oral absorption of matrine in rats via SNEDDSs delivery was investigated. C(max) was increased dramatically from 4.12 to 6.52 and 7.95 microg/mL in case of matrine, MPC and MPC-SNEDDS. In parallel to C(max), prolonged T(max) from 0.39 to 0.50h, and 3.00 h could be observed. AUC(0-t) of MPC-SNEDDSs was significantly higher than other two counterparts. In conclusion, the absolute bioavailability of matrine drastically increased from 25% to 84.6% by the formation of MPC-SNEDDS, with an outstanding relative bioavailability of 338%, suggesting its great potential for clinical application. PMID:19961910

  5. Raman characterization and chemical imaging of biocolloidal self-assemblies, drug delivery systems, and pulmonary inhalation aerosols: A review

    Microsoft Academic Search

    Heidi M. Mansour; Anthony J. Hickey

    2007-01-01

    This review presents an introduction to Raman scattering and describes the various Raman spectroscopy, Raman microscopy, and\\u000a chemical imaging techniques that have demonstrated utility in biocolloidal self-assemblies, pharmaceutical drug delivery systems,\\u000a and pulmonary research applications. Recent Raman applications to pharmaceutical aerosols in the context of pulmonary inhalation\\u000a aerosol delivery are discussed. The “molecular fingerprint” insight that Raman applications provide includes

  6. Responsive Theranostic Systems: Integration of Diagnostic Imaging Agents and Responsive Controlled Release Drug Delivery Carriers

    PubMed Central

    Caldorera-Moore, Mary E.; Liechty, William B.; Peppas, Nicholas A.

    2011-01-01

    CONSPECTUS The ability to non-invasively monitor and treat physiological conditions within the human body has been an aspiration of researchers and medical professionals for decades. The emergences of nanotechnology opened up new possibilities for effective vehicles that could accomplish non-invasive detection of diseases and localized treatment systems to be developed. In turn, extensive research efforts have been spent on the development of imaging moiety that could be used to seek out specific diseased conditions and can be monitored with convention clinical imaging modalities. Nanoscale detection agents like these have the potential to increase early detection of pathophysiological conditions because they have the capability to detect abnormal cells before they even develop into diseased tissue and/or tumors. Once the diseased cells are detected it would be constructive to just be able to treat them simultaneously. From here, the concept of multifunctional carriers that could target, detect, and treat diseased cells emerged. The term “theranostics” has been created to describe this promising area of research that focuses on the combination of diagnostic detection agents with therapeutic drug delivery carriers. Targeted theranostic nanocarriers offer an attractive improvement to disease treatment because of their ability to simultaneously diagnose, image, and treat at targeted diseased sites. Research efforts in the field of theranostics encompass a broad variety of drug delivery vehicles, detection agents, and targeting modalities for the development of an all-in-one, localized, diagnostic and treatment system. Nanotheranostic systems that utilize metallic or magnetic imaging nanoparticles have the added capability to be used as thermal therapeutic systems. This review aims to explore recent advancements in the field of nanotheranostics and the various fundamental components of an effective theranostic carrier. PMID:21932809

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

    NASA Astrophysics Data System (ADS)

    Patel, Meghavi

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

  8. Template-directed hydrothermal synthesis of hydroxyapatite as a drug delivery system for the poorly water-soluble drug carvedilol

    NASA Astrophysics Data System (ADS)

    Zhao, Qinfu; Wang, Tianyi; Wang, Jing; Zheng, Li; Jiang, Tongying; Cheng, Gang; Wang, Siling

    2011-09-01

    In order to improve the dissolution rate and increase the bioavailability of a poorly water-soluble drug, intended to be administered orally, the biocompatible and bioactive mesoporous hydroxyapatite (HA) was successfully synthesized. In the present study, mesoporous HA nanoparticles were produced using Pluronic block co-polymer F127 and cetyltrimethylammonium bromide (CTAB) as templates by the hydrothermal method. The obtained mesoporous HA was employed as a drug delivery carrier to investigate the drug storage/release properties using carvedilol (CAR) as a model drug. Characterizations of the raw CAR powder, mesoporous HA and CAR-loaded HA were carried out by the scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, N2 adsorption/desorption, thermogravimetric analysis (TGA), and UV-VIS spectrophotometry. The results demonstrated that CAR was successfully incorporated into the mesoporous HA host. In vitro drug release studies showed that mesoporous HA had a high drug load efficiency and provided immediate release of CAR compared with micronized raw drug in simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.8). Consequently, mesoporous HA is a good candidate as a drug carrier for the oral delivery of poorly water-soluble drugs.

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

    E-print Network

    Barthelat, Francois

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

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

    PubMed Central

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  12. 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

  13. Preparation and evaluation of self-microemulsifying drug delivery system containing vinpocetine.

    PubMed

    Cui, Shu-Xia; Nie, Shu-Fang; Li, Li; Wang, Chang-Guang; Pan, Wei-San; Sun, Jian-Ping

    2009-05-01

    The main purpose of current investigation is to prepare a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of vinpocetine, a poorly water-soluble drug. Suitable vehicles were screened by determining the solubility of vinpocetine in them. Certain surfactants were selected according to their emulsifying ability with different oils. Ternary phase diagrams were used to identify the efficient self-microemulsifying region and to screen the effect of surfactant/cosurfactant ratio (K(m)). The optimized formulation for in vitro dissolution and bioavailability assessment was oil (ethyl oleate, 15%), surfactant (Solutol HS 15, 50%), and cosurfactant (Transcutol P, 35%). The release rate of vinpocetine from SMEDDS was significantly higher than that of the commercial tablet. Pharmacokinetics and bioavailability of SMEDDS were evaluated. It was found that the oral bioavailability of vinpocetine of SMEDDS was 1.72-fold higher as compared with that of the commercial tablet. These results obtained demonstrated that vinpocetine absorption was enhanced significantly by employing SMEDDS. Therefore, SMEDDS might provide an efficient way of improving oral bioavailability of poorly water-soluble drugs. PMID:19040178

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

    PubMed

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

    2009-02-15

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

  15. Design and evaluation of self-nanoemulsifying drug delivery system of flutamide.

    PubMed

    Jeevana, Jyothi B; Sreelakshmi, K

    2011-01-01

    Flutamide (FLT) is an antiandrogen drug for the treatment of prostate cancer. It has the drawback of poor water solubility and needs enhancement of its dissolution rate in simulated gastric fluids. Hence, it is prepared as self-nanoemulsifying drug delivery systems (SNEDDS) with an aim to enhance its dissolution rate. The objectives of the study are to develop SNEDDS of FLT and to characterize for particle size, self-nanoemulsification, and dissolution enhancement. Solubility of FLT was determined in various oils, surfactants, and cosurfactants. Sesame oil was selected as an oil phase, Tween 20 as surfactant, and PEG400 as cosurfactant due to their higher solubilization effect. Various formulations were prepared by simple mixing followed by vortexing. From studies, the optimized SNEDDS formulation was composed of FLT (8.04% w/w), sesame oil (24.12% w/w), Tween 20 (53.38% w/w), and PEG400 (14.46% w/w). The selected SNEDDS could be self-emulsified without precipitation upon simple mixing. The mean particle size of the SNEDDS was 148.7 nm and percent drug content was 99.66. The dissolution rate of FLT from SNEDDS was faster and higher in three different dissolution media such as 2% sodium lauryl sulfate (97.85%), simulated gastric fluid (0.1 N HCl containing 0.5% Tween 20) (95.71%), and simulated intestinal fluid (pH 6.8 buffer) (96.21%). PMID:21607048

  16. 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

  17. Novel self-nanoemulsifying drug delivery system for enhanced solubility and dissolution of lutein.

    PubMed

    Yoo, Jeoung Hee; Shanmugam, Srinivasan; Thapa, Pritam; Lee, Eung-Seok; Balakrishnan, Prabagar; Baskaran, Rengarajan; Yoon, Sang-Kwon; Choi, Han-Gon; Yong, Chul Soon; Yoo, Bong Kyu; Han, Kun

    2010-03-01

    Self-nanoemulsifying drug delivery system (SNEDDS) containing oil (Phosal 53 MCT), surfactant (Labrasol), and cosurfactant (Transcutol-HP or Lutrol-E400) was prepared to enhance solubility and dissolution of lutein. Ternary phase diagram of the SNEDDS was constructed to identify the self-emulsifying regions following which the percentage of oil, surfactant, and cosurfactant in the SNEDDS were optimized in terms of emulsification time and mean emulsion droplet size. The optimized SNEDDS consists of 25% oil, 60% surfactant, and 15% cosurfactant. When measured using USP XXIII dissolution apparatus II, the emulsification time of the SNEDDS prepared with Transcutol-HP as cosurfactant was less than 20 sec, and it was 20-30 sec in the SNEDDS prepared with Lutrol-E400. Mean emulsion droplet size was slightly smaller when Transcutol-HP was used as cosurfactant (80 +/- 6 nm), compared to when Lutrol- E400 was used (93 +/- 6 nm). Dissolution of lutein from the solid SNEDDS (physical mixture of the optimized SNEDDS and Aerosil 200) took place immediately (less than 5 min) in distilled water, and, once dissolved, no precipitation or aggregation of the drug were observed. In contrast, no drug was released from lutein powder or from the commercial product (Eyelac(R)) until 3 h of the study duration. PMID:20361307

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

    PubMed Central

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

    2013-01-01

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

  19. 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

  20. 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

  1. Evaluating the mucoadhesive properties of drug delivery systems based on hydrated thiolated alginate.

    PubMed

    Davidovich-Pinhas, Maya; Harari, Offer; Bianco-Peled, Havazelet

    2009-05-21

    Mucoadhesive polymers have been proposed as drug delivery carriers due to their ability to adhere to the mucus layer. A relatively new class of mucoadhesive polymers, termed thiomers, was suggested as an improved carrier capable of creating disulfide covalent bond with the mucus. Since the wet physiological environment is likely to cause any delivery system to adsorb water and arrive hydrated to its target, studying the performance of mucoadhesive systems in their hydrated form is of major importance. Model thiomer, alginate-thiol, were synthesized and characterized the product using Nuclear Magnetic Resonance (NMR), Fourier Transform Infra Red spectroscopy (FTIR). The swelling behavior was determined gravimetrically and found to be affected from the thiolation. Interactions between the alginate-thiol and mucin glycoproteins, which are believed to be an outcome of disulfide bonds, were verified using rheology experiments. Adhesion of hydrated tablets with different cross linking densities to porcine's fresh small intestine tissue were characterized using a Lloyd Tensile Machine. It was shown that the thiolation did not improve the adhesion properties of hydrated tablets. It appears that the benefit achieved by adding thiol group to the polymer in dry tablet form was flawed in hydrated form due to formation of inter-molecular disulfide junctions. PMID:19217920

  2. Formulation and biopharmaceutical issues in the development of drug delivery systems for antiparasitic drugs

    Microsoft Academic Search

    O. Kayser; C. Olbrich; S. L. Croft; A. F. Kiderlen

    2003-01-01

    The development of really new antiparasitic drugs to market level is a very rare event. A large number of lead structures have already been screened and discarded, the market is large but poor, and the administrative barriers are increasingly high and costly. Novel antiparasitics must not only be better, they must also be substantially safer than the existing repertoire. There

  3. Tablets of pre-liposomes govern in situ formation of liposomes: concept and potential of the novel drug delivery system.

    PubMed

    Vani?, Željka; Planinšek, Odon; Škalko-Basnet, Nataša; Tho, Ingunn

    2014-10-01

    The purpose of this study was to develop a novel drug delivery system for challenging drugs with potential for scale-up manufacturing and controlled release of incorporated drug. Pre-liposomes powder containing metronidazole, lecithin and mannitol, prepared by spray-drying, was mixed with different tableting excipients (microcrystalline cellulose, lactose monohydrate, mannitol, dibasic calcium phosphate, pregelatinized starch, pectin or chitosan) and compressed into tablets. The delivery system was characterized with respect to (i) dry powder characteristics, (ii) mechanical tablet properties and drug release, and (iii) liposomal characteristics. The pre-liposomes powder was free-flowing, and tablets of similarly high qualities as tablets made of physical mixtures were prepared with all excipients. Liposomes were formed in situ upon tablet disintegration, dissolution or erosion depending on the type of tablet excipient used. The liposomal characteristics and drug release were found to depend on the tablet excipient. The new delivery system offers a unique synergy between the ability of liposomes to encapsulate and protect drugs and increased stability provided by compressed formulations. It can be adjusted for drug administration via various routes, e.g. oral, buccal and vaginal. PMID:24929211

  4. An intrathecally located broken catheter used for an intrathecal drug delivery system.

    PubMed

    Kim, Jae Hun; Nahm, Francis Sangun; Chang, Jee Eun; Park, Soo Young; Kim, Yong Chul; Lee, Sang Chul

    2012-10-01

    The intrathecal drug delivery system (ITDDS), an effective treatment tool for intractable spasticity and pain, is associated with various complications but breakage of the catheter is rare. We report the case of a 50-yr-old man with ITDDS, in whom an intrathecal catheter was severed, resulting in a 28.6-cm-long intrathecal fragment. The catheter completely retracted into the intrathecal space from the anchor site. The catheter was severed during spine flexion, and the total distal fragment was repositioned in the intrathecal space. Although the outcome of ITDDS was associated with the length or diameter of the broken catheter, no neurologic complications occurred in our patient. Thus, we inserted another catheter instead of removing the old one. Thereafter, the patient has been regularly followed up, and no neurologic complications have developed during the 28 months. PMID:23091331

  5. Helicobacter pylori: an overview on antimicrobials and drug delivery systems for its eradication.

    PubMed

    El-Zahaby, Sally A; Kassem, Abeer A; El-Kamel, Amal H

    2014-01-01

    Since the discovery of Helicobacter pylori (H. pylori) in the early 1980s, its eradication has been one of the most important global challenges in gastroenterology. Various circumstances make the treatment with antimicrobials particularly difficult. One problem has been that antibiotics commonly used were designed for the treatment of infections throughout the body rather than for delivering high concentrations locally within the stomach. Many gastroretentive dosage forms were developed in order to eradicate the infection, yet additional advancements are still needed to eliminate the infection completely and decrease its prevalence worldwide. An overview on different antimicrobials and a literature survey about different drug delivery systems used in eradication of H. pylori infection are presented in this review. PMID:24678600

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

    PubMed

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

    2006-11-01

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

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

    PubMed Central

    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

  8. 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.

  9. Proniosomes in transdermal drug delivery.

    PubMed

    Rahimpour, Yahya; Kouhsoltani, Maryam; Hamishehkar, Hamed

    2015-01-01

    Proniosomes are liquid crystalline-compact niosomal hybrid that can be hydrated to form niosomal dispersion instantly before use. It is a promising drug carrier with better physical and chemical stability than niosomes. Proniosomes have the potential to be scaled up for industrial purposes. They have been remarkably considered for transdermal drug delivery because of their competences, including the penetration enhancing ability of surfactants and their non-toxic characteristics. This review offers current approaches in the research and development of proniosomal formulations for the transdermal delivery of drugs with a focus on therapeutic applications. PMID:25925111

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

    PubMed Central

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

    2013-01-01

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

  11. Transdermal delivery from eutectic systems: enhanced permeation of a model drug, ibuprofen

    Microsoft Academic Search

    Paul W Stott; Adrian C Williams; Brian W Barry

    1998-01-01

    The formation of eutectic systems between ibuprofen (ibu) and seven terpene skin penetration enhancers was studied and, by using the eutectic systems as donors, the effects of melting point depression of the delivery system on transdermal delivery were investigated. A range of ibu:terpene binary mixtures were melted together, cooled, and recrystallised. Composition\\/melting point phase diagrams were determined by DSC and

  12. Synthesis and evaluation of glyco-coated liposomes as drug carriers for active targeting in drug delivery systems.

    PubMed

    Ueki, Akiharu; Un, Keita; Mino, Yuka; Yoshida, Mitsuru; Kawakami, Shigeru; Ando, Hiromune; Ishida, Hideharu; Yamashita, Fumiyoshi; Hashida, Mitsuru; Kiso, Makoto

    2015-03-20

    Novel sugar-conjugated cholesterols, ?-Gal-, ?-Man-, ?-Man-, ?-Fuc-, and ?-Man-6P-S-?-Ala-Chol, were synthesized and incorporated into liposomes. In vitro experiments using the glyco-coated liposomes showed that the glyco-coated liposomes are efficiently taken up by cells expressing carbohydrate-binding receptors selectively. Glyco-coated liposomes are promising candidates for drug delivery vehicles. PMID:25500195

  13. Nanosuspensions in drug delivery

    Microsoft Academic Search

    Barrett E. Rabinow

    2004-01-01

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

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

    PubMed

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

    2012-10-01

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

  15. 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

  16. 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.

  17. Enhanced oral bioavailability of tacrolimus in rats by self-microemulsifying drug delivery systems.

    PubMed

    Wang, Yongjun; Sun, Jin; Zhang, Tianhong; Liu, Hongzhuo; He, Fancui; He, Zhonggui

    2011-10-01

    A new self-microemulsifying drug delivery system (SMEDDS) has been developed to increase the solubility, dissolution rate and oral bioavailability of tacrolimus (TAC). The formulations of TAC-SMEDDS were optimized by solubility assay, compatibility tests, and pseudo-ternary phase diagrams analysis. In order to inhibit the efflux of P-glycoprotein (P-gp) for tacrolimus, which is the substrate of P-gp, the excipients which show the inhibition effect to P-gp, such as tocopheryl polyethylene glycol succinate (TPGS) and Cremophor EL40, were chosen in the SMEDDS formulations. According to particle size and the rate of self-emulsification, two optimized formulations were selected: Miglyol 840 as oil phase, Transcutol P as cosurfactant, TPGS as surfactant (TPGS-SMEDDS) or Cremophor EL40 as surfactant (Crem-SMEDDS), respectively. The ratio of oil phase, surfactant and cosurfactant is 1:7.2:1.8. The mean droplet size distribution of the optimized SMEDDS was less than 20?nm. The in vitro dissolution test indicated a significant improvement in release characteristics of TAC. The prepared SMEDDS was compared with the homemade solution by administering the hard capsule to fasted rats. The absorption of TAC from TPGS-SMEDDS and Crem-SMEDDS form resulted in about sevenfold and eightfold increase in bioavailability compared with the homemade solution. Our study illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as TAC by the oral route. PMID:21615281

  18. Refilling drug delivery depots through the blood

    PubMed Central

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

    2014-01-01

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

  19. Spontaneous emulsification of nifedipine-loaded self-nanoemulsifying drug delivery system.

    PubMed

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

    2015-04-01

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

  20. Recent development of poly(ethylene glycol)-cholesterol conjugates as drug delivery systems.

    PubMed

    He, Zhi-Yao; Chu, Bing-Yang; Wei, Xia-Wei; Li, Jiao; Edwards, Carl K; Song, Xiang-Rong; He, Gu; Xie, Yong-Mei; Wei, Yu-Quan; Qian, Zhi-Yong

    2014-07-20

    Poly(ethylene glycol)-cholesterol (PEG-Chol) conjugates are composed of "hydrophilically-flexible" PEG and "hydrophobically-rigid" Chol molecules. PEG-Chol conjugates are capable of forming micelles through molecular self-assembly and they are also used extensively for the PEGylation of drug delivery systems (DDS). The PEGylated DDS have been shown to display optimized physical stability properties in vitro and longer half-lives in vivo when compared with non-PEGylated DDS. Cell uptake studies have indicated that PEG-Chol conjugates are internalized via clathrin-independent pathways into endosomes and Golgi apparatus. Acid-labile PEG-Chol conjugates are also able to promote the content release of PEGylated DDS when triggered by dePEGylation at acidic conditions. More importantly, biodegradable PEG-Chol molecules have been shown to decrease the "accelerated blood clearance" phenomenon of PEG-DSPE. Ligands, peptides or antibodies which have been modified with PEG-Chols are oftentimes used to formulate active targeting DDS, which have been shown in many systems recently to enhance the efficacy and lower the adverse effects of drugs. Production of PEG-Chol is simple and efficient, and production costs are relatively low. In conclusion, PEG-Chol conjugates appear to be very promising multifunctional biomaterials for many uses in the biomedical sciences and pharmaceutical industries. PMID:24768727

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

    PubMed

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

    2013-02-25

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

  2. Nanoparticles for drug delivery to the lungs.

    PubMed

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

    2007-12-01

    The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. Incorporating therapeutics with polymeric nanoparticles offers additional degrees of manipulation for delivery systems, providing sustained release and the ability to target specific cells and organs. However, nanoparticle delivery to the lungs has many challenges including formulation instability due to particle-particle interactions and poor delivery efficiency due to exhalation of low-inertia nanoparticles. Thus, novel methods formulating nanoparticles into the form of micron-scale dry powders have been developed. These carrier particles exhibit improved handling and delivery, while releasing nanoparticles upon deposition in the lungs. This review covers the development of nanoparticle formulations for pulmonary delivery as both individual nanoparticles and encapsulated within carrier particles. PMID:17997181

  3. Effect of formulation parameters on the preparation of superporous hydrogel self-nanoemulsifying drug delivery system (SNEDDS) of carvedilol.

    PubMed

    Mahmoud, Enas Ahmed; Bendas, Ehab R; Mohamed, Magdy I

    2010-03-01

    The purpose of this study was to formulate a superporous hydrogel (SPH) containing carvedilol self-nanoemulsifying drug delivery system. Effects of formulation parameters (amount of SPH and 0.1 N HCl used during drug loading) were studied in 3(2) factorial design. Response surface plots showed significant effect of the parameters on hydrogel swelling, carvedilol content, and carvedilol in vitro release. Regression equations were generated to calculate the desirable responses. PMID:20127427

  4. Affinity-based drug delivery systems for tissue repair and regeneration.

    PubMed

    Vulic, Katarina; Shoichet, Molly S

    2014-11-10

    Affinity-based release systems use transient interactions to sustain and control the release of a therapeutic from a polymeric matrix. The most common affinity-based systems use heparin-based scaffolds to sustain the release of heparin-binding proteins, such as fibroblast growth factor-2 (FGF2) and vascular endothelial growth factor (VEGF). However, novel affinity-based systems based on, for example, protein-protein or DNA-protein interactions, are emerging to control the release of an expanding repertoire of therapeutics. Mathematical models of affinity-based systems have provided a thorough understanding of which parameters affect release rate from these systems, and how these release rates can be tuned. In this review, recent affinity-based release systems will be described, including an overview of the various types of affinity interactions used to modulate release, the mechanisms by which release from these systems is tuned, and the time scales of sustained release. This advanced drug delivery paradigm provides tunable and predictable release rates and has expanded the scope of deliverable therapeutics for tissue repair and regeneration. PMID:25230248

  5. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2011-10-01

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

  8. Polymethacrylate Microparticles Gel for Topical Drug Delivery

    Microsoft Academic Search

    Hagar Ibrahim Labouta; Labiba K. El-Khordagui

    2010-01-01

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

  9. 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.

  10. Characteristics of Cholesteryl Cetyl Carbonate Liquid Crystals as Drug Delivery Systems

    Microsoft Academic Search

    R. Chuealee; P. Aramwit; T. Srichana

    2007-01-01

    A thermotropic liquid crystals of cholesteryl cetyl carbonate was investigated as a novel nanosystem for delivery of lipophilic drugs. The aims were to synthesize, characterize and develop a formulation for amphotericin B (AmB) in cholesteryl cetyl carbonate liquid crystals. Cholesteryl cetyl carbonate was synthesized and identified by thin layer chromatography (TLC), flash column chromatography, Fourier transformed infrared (FTIR) spectroscopy, mass

  11. 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…

  12. Chimeric advanced drug delivery nano systems (chi-aDDnSs) for shikonin combining dendritic and liposomal technology.

    PubMed

    Kontogiannopoulos, Konstantinos N; Assimopoulou, Andreana N; Hatziantoniou, Sophia; Karatasos, Kostas; Demetzos, Costas; Papageorgiou, Vassilios P

    2012-01-17

    The interest of drug delivery has focused on the creation of new formulations with improved properties, taking much attention to the drug release from the carrier. Liposomes have already been commercialized, while dendrimers and hyperbranched polymers are emerging as potentially ideal drug delivery vehicles. Chimeric advanced drug delivery nano systems (chi-aDDnSs) are mixed nanosystems combining different biomaterials that can offer advantages as drug carriers. Alkannin and shikonin (A/S) are naturally occurring hydroxynaphthoquinones with a well-established spectrum of wound healing, antimicrobial, anti-inflammatory, antioxidant and recently established antitumor activity. In this work three generations of hyperbranched aliphatic polyesters were used for the first time to form complexes with shikonin, as well as liposomal chi-aDDnSs. Characterization of the shikonin-loaded chi-aDDnSs was performed by measuring their particle size distribution, ?-potential, drug encapsulation efficiency and the in vitro release profile. The analysis revealed sufficient drug encapsulation and appropriately featured release profiles. Chi-aDDnSs were also examined for their physical stability at 4°C. The results are considered promising and could be used as a road map for designing in vivo experiments. PMID:21979251

  13. Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system

    PubMed Central

    Aryal, Muna; Arvanitis, Costas D.; Alexander, Phillip M.; McDannold, Nathan

    2014-01-01

    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. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB. PMID:24462453

  14. An implantable closedloop asynchronous drug delivery system for the treatment of refractory epilepsy.

    PubMed

    Salam, Muhammad Tariqus; Mirzaei, Marjan; Ly, My Sandra; Nguyen, Dang Khoa; Sawan, Mohamad

    2012-07-01

    In this paper, we present an implantable device for intra-cerebral electroencephalography (icEEG) data acquisition and real-time epileptic seizure detection with simultaneous focal antiepileptic drug injection feedback. This implantable device includes a neural signal amplifier, an asynchronous seizure detector, a drug delivery system (DDS) including a micropump, and a hybrid subdural electrode (HSE). The asynchronous detection algorithm is based on data-dependent analysis and validated with Matlab tools. The detector and DDS have a power saving mode. The HSE contacts are made of Platinum (Pt) encapsulated with polydimethylsiloxane (PDMS). Given the heterogeneity of electrographic seizure signals and seizure suppression threshold, the implantable device provides tunable parameters facility through an external transmitter to adapt to each individual's neurophysiology prior to clinical deployment. The proposed detector and DDS were assembled in Ø 50 mm and Ø 30 mm circular printed circuit boards, respectively. The detector was validated using icEEG recordings of seven patients who had previously undergone an intracranial investigation for epilepsy surgery. The triggering of the DDS was tested and a predefined seizure suppression dose was delivered ~16 s after electrographical seizure onsets. The device's power consumption was reduced by 12% in active mode and 49% in power saving mode compared to similar seizure detection algorithms implemented with synchronous architecture. PMID:22491131

  15. Single-injection HPLC method for rapid analysis of a combination drug delivery system.

    PubMed

    Tucker, Robert M; Parcher, Benjamin W; Jones, Ella F; Desai, Tejal A

    2012-06-01

    Developing combination drug delivery systems (CDDS) is a challenging but necessary task to meet the needs of complex therapy regimes for patients. As the number of multi-drug regimens being administered increases, so does the difficulty of characterizing the CDDS as a whole. We present a single-step method for quantifying three model therapeutics released from a model hydrogel scaffold using high-performance liquid chromatography (HPLC). Poly(ethylene glycol) dimethacrylate (PEGDMA) hydrogel tablets were fabricated via photoinitiated crosslinking and subsequently loaded with model active pharmaceutical ingredients (APIs), namely, porcine insulin (PI), fluorescein isothiocyanate-labeled bovine serum albumin (FBSA), prednisone (PSE), or a combination of all three. The hydrogel tablets were placed into release chambers and sampled over 21 days, and APIs were quantified using the method described herein. Six compounds were isolated and quantified in total. Release kinetics based on chemical properties of the APIs did not give systematic relationships; however, PSE was found to have improved device loading versus PI and FBSA. Rapid analysis of three model APIs released from a PEGDMA CDDS was achieved with a direct, single-injection HPLC method. Development of CDDS platforms is posited to benefit from such analytical approaches, potentially affording innovative solutions to complex disease states. PMID:22535518

  16. 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.

  17. 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

  18. 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…

  19. Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol transdermal drug delivery systems.

    PubMed

    Yang, Yang; Manda, Prashanth; Pavurala, Naresh; Khan, Mansoor A; Krishnaiah, Yellela S R

    2015-07-28

    The objective of this study was to develop a level A in vitro-in vivo correlation (IVIVC) for drug-in-adhesive (DIA) type estradiol transdermal drug delivery systems (TDDS). In vitro drug permeation studies across human skin were carried out to obtain the percent of estradiol permeation from marketed products. The in vivo time versus plasma concentration data of three estradiol TDDS at drug loadings of 2.0, 3.8 and 7.6mg (delivery rates of 25, 50 and 100?g/day, respectively) was deconvoluted using Wagner-Nelson method to obtain percent of in vivo drug absorption in postmenopausal women. The IVIVC between the in vitro percent of drug permeation (X) and in vivo percent of drug absorption (Y) for these three estradiol TDDS was constructed using GastroPlus® software. There was a high correlation (R(2)=1.0) with a polynomial regression of Y=-0.227X(2)+0.331X-0.001. These three estradiol TDDS were used for internal validation whereas another two products of the same formulation design (with delivery rates of 60 and 100?g/day) were used for external validation. The predicted estradiol serum concentrations (convoluted from in vitro skin permeation data) were compared with the observed serum concentrations for the respective products. The developed IVIVC model passed both the internal and external validations as the prediction errors (%PE) for Cmax and AUC were less than 15%. When another marketed estradiol TDDS with a delivery rate of 100?g/day but with a slight variation in formulation design was chosen, it did not pass external validation indicating the product-specific nature of IVIVC model. Results suggest that the IVIVC model developed in this study can be used to successfully predict the in vivo performance of the same estradiol TDDS with in vivo delivery rates ranging from 25 to 100?g/day. PMID:25979329

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

    PubMed

    Manjanna, K M; Shivakumar, B; Pramod Kumar, T M

    2010-01-01

    Arthritis refers to different medical conditions associated with disorders of the primary structures that determine joint functioning, such as bones, cartilage, and synovial membranes. Drug discovery and delivery to retard the degeneration of joint tissues are challenging. Current treatment of different types of arthritis such as osteoarthritis, rheumatoid arthritis, septic arthritis, juvenile idiopathic arthritis, and ankylosing spondylitis involves the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, diclofenac, aceclofenac, ibuprofen, flurbiprofen, indomethacin piroxicam, dexibuprofen, ketoprofen, nabumetone, nimesulide, and naproxen, mainly by the oral, parenteral, or topical route. However, the frequent dosing that is required with NSAIDs often leads to patient noncompliance, so drug-delivery technologies should be developed to reduce the frequency of dosing and to allow sustained release of medications. Microencapsulation is one of the novel drug-delivery technologies employed to sustain drug release. This method reduces dosing and eliminates gastrointestinal irritation, thus ultimately improving patient compliance in the pharmacotherapy of arthritis. We provide a comprehensive overview of several microencapsulation technologies used in the treatment of arthritis that may reduce the dose-related adverse effects caused by NSAIDs. PMID:21175420

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

    PubMed

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

    2014-12-01

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

  2. 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

  3. 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

  4. Novel multifunctional theranostic liposome drug delivery system: construction, characterization, and multimodality MR, near-infrared fluorescent, and nuclear imaging.

    PubMed

    Li, Shihong; Goins, Beth; Zhang, Lujun; Bao, Ande

    2012-06-20

    Liposomes are effective lipid nanoparticle drug delivery systems, which can also be functionalized with noninvasive 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 premanufactured liposomes were composed of DSPC/cholesterol/Gd-DOTA-DSPE/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 postinserted into the premanufactured liposomes. Doxorubicin could be effectively postloaded into the multifunctional liposomes. The multifunctional doxorubicin-liposomes could also be stably radiolabeled with (99m)Tc or (64)Cu 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 noninvasive multimodality NIR fluorescent, MR, SPECT, and PET imaging of their in vivo behavior and capitalizing on the inherent advantages of each modality. PMID:22577859

  5. Characterization and evaluation of solid self-microemulsifying drug delivery systems with porous carriers as systems for improved carbamazepine release.

    PubMed

    Milovi?, Mladen; Djuriš, Jelena; Djeki?, Ljiljana; Vasiljevi?, Dragana; Ibri?, Svetlana

    2012-10-15

    The purpose of this study was to investigate solid self-microemulsifying drug delivery system (SSMEDDS), as potential delivery system for poorly water soluble drug carbamazepine (CBZ). Self-microemulsifying drug delivery system (SMEDDS) was formulated using the surfactant polyoxyethylene 20 sorbitan monooleate [Polysorbate 80] (S), the cosurfactant PEG-40 hydrogenated castor oil [Cremophor(®) RH40] (C) and the oil caprylic/capric triglycerides [Mygliol(®) 812] (O). Four different adsorbents with high specific surface area were used: Neusilin(®) UFL2, Neusilin(®) FL2 (magnesium aluminometasilicate), Sylysia(®) 320 and Sylysia(®) 350 (porous silica). Microemulsion area at the surfactant to cosurfactant ratio (K(m)) 1:1 was evaluated and for further investigation SMEDDS with SC/O ratio 8:2 was selected. Solubilization capacity of selected SMEDDS for CBZ was 33.771±0.041 mg/ml. Rheological measurements of unloaded and CBZ-loaded SMEDDS at water content varied from 10 to 60% (w/w) were conducted. It has been found that CBZ has great influence on rheological behaviour of investigated system upon water dilution. Photon correlation spectroscopy has shown the ability of CBZ-loaded SMEDDS to produce microemulsion droplet size. SSMEDDS improved release rate of CBZ, but the type of adsorbent significantly affects release rate of CBZ. For SSMEDDS with different magnesium aluminometasilicate adsorbents, release rate of CBZ decreased with increasing specific surface area due to entrapment of liquid SMEDDS inside the pores and its gradual exposure to dissolution medium. With porous silica adsorbents no difference in release rate was found in comparison to physical mixtures. In physical mixtures at 12.5% (w/w) CBZ content, presence of amorphous CBZ led to high dissolution rate. PMID:22721847

  6. Folate-modified pluronic-polyethylenimine and cholic acid polyion complex micelles as targeted drug delivery system for paclitaxel.

    PubMed

    Li, Yimu; Zhou, Yi; De, Bai; Li, Lingbing

    2014-01-01

    The aim of the present study is to construct a type of polyion complex micelles made of PF127-PEI copolymer and cholic acid (CA) and to evaluate the potential of this type of micelles as a targeted drug delivery system for paclitaxel (PTX). To further improve the targeting capability of micelles, folate was also incorporated into micelles. The characteristics and anti-tumour activity in vitro were investigated. Enhanced solubility of PTX was achieved by incorporating into the micelles. The capability of the polyion complex micelles containing rhodamine 123 to increase the level of intracellular delivery was also observed using fluorescence microscopy. The cytotoxicity of PTX-loaded micelles against cancer cell in vitro was remarkably higher than that of free drug and was better when folate was incorporated into the micelles. These properties such as specificity towards the folate receptor and the low toxicity render folate-modified polyion complex micelles promising candidate for targeted PTX delivery. PMID:25090590

  7. Study OF Multiparticulate Floating Drug Delivery System prepared by Emulsion Gelation Technique

    Microsoft Academic Search

    R. A. Fursule; N. Patra; G. B. Patil; S. B. Kosalge

    Gastroretentive systems can remain in the gastric region for several hours and hence significantly prolong the gastric residence time of drugs. Prolonged gastric retention improves bioavailability, reduces drug waste, and improves solubility for drugs that are less soluble in a high pH environment. The present work describes the formulation and evaluation of gastroretentive system of an antibacterial agent, amoxicillin trihydrate,

  8. Multifunctional SMA-based smart inhaler system for improved aerosol drug delivery: design and fabrication

    Microsoft Academic Search

    Matthew E. Pausley; Stefan Seelecke

    2008-01-01

    This paper documents the development of a prototype smart aerosol drug inhaler system using shape memory alloy (SMA) actuators. Unlike conventional dispersed-release inhalers, the smart inhaler system releases the aerosol drug in a very small area within the mouth inlet. Kleinstreuer and Zhang [1] have found that controlled release in the mouth inlet increases drug efficiency and allows targeting of

  9. Correlation study of structural parameters of bioadhesive polymers in designing a tunable drug delivery system.

    PubMed

    Singh, Baljit; Sharma, Vikrant

    2014-07-22

    Keeping in view the importance of network structure in designing tunable drug delivery devices, in the present work, correlation between structural parameters and drug release profile has been determined for polysaccharide gum based polymers. These polymers have been characterized by SEMs, FTIR, (13)C NMR, XRD, TGA/DTA/DTG, DSC, and swelling studies. The mechanical, biocompatible, and mucoadhesive properties of polymers have also been determined. The polymer network parameters such as polymer volume fraction in the swollen state, Flory-Huggins interaction parameter, molecular weight of the polymer chain between two cross-links, cross-link density, and mesh size have been evaluated. Different kinetic models have been applied for the drug release profile of the antifungal drug fluconazole. The swelling and drug release occurred through a non-Fickian diffusion mechanism and a release profile best fitted in the Higuchi square root model. The polymers have been observed as non-thrombogenic, hemo-compatible, and mucoadhesive in nature and may be used in slow drug delivery applications to oral mucosa. PMID:24963826

  10. Optimizing drug delivery to the lung: design of a CFC-free corticosteroid metered-dose aerosol system.

    PubMed

    Donnell, D

    2001-02-01

    The mandatory replacement of chlorofluorocarbons (CFCs) with ozone-friendly propellants, such as hydrofluoroalkanes (HFAs), has provided an opportunity to optimize aerosol design and improve drug delivery to pulmonary tissue. Asthma is an inflammatory disorder of the lungs that appears to affect both small and large airways, so ideally, inhaled corticosteroid should reach both central and peripheral sites. This review considers the development of an aerosol system containing beclomethasone dipropionate in hydrofluoroalkane-134a (HFA) propellant (Qvar, 3M Health Care, Loughborough, UK) designed to target medication delivery throughout the bronchopulmonary tree and to improve the therapeutic ratio (topical efficacy: systemic safety), thereby offering potential clinical benefits to asthma patients. PMID:11266222

  11. Molecular dynamics simulation study of chitosan and gemcitabine as a drug delivery system.

    PubMed

    Razmimanesh, Fariba; Amjad-Iranagh, Sepideh; Modarress, Hamid

    2015-07-01

    By using molecular dynamics (MD) simulation, biodegradable biopolymer chitosan as a carrier for the drug gemcitabine was investigated and the effect of three initial drug concentrations (10, 40, and 80 %) on its loading efficiency was studied. Then water was added to the systems of drug and biopolymer and the effects of water on the interactions of drug and chitosan and on the drug loading efficiency were examined. From the results it was found that the maximum loading of the drug occurred at 40 % of the drug concentration. The radial distribution function calculations indicated that in the absence of water molecules, the drug molecules were located at shorter distance from chitosan and the loading efficiency of the drug in these systems was higher. Graphical Abstract Chitosan and gemcitabine. PMID:26044358

  12. 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. ...

  13. Nanoliposomal minocycline for ocular drug delivery

    PubMed Central

    Kaiser, James M.; Imai, Hisanori; Haakenson, Jeremy K.; Brucklacher, Robert M.; Fox, Todd E.; Shanmugavelandy, Sriram S.; Unrath, Kellee A.; Pedersen, Michelle M.; Dai, Pingqi; Freeman, Willard M.; Bronson, Sarah K.; Gardner, Thomas W.; Kester, Mark

    2012-01-01

    Nanoliposomal technology is a promising drug delivery system that could be employed to improve the pharmacokinetic properties of clearance and distribution in ocular drug delivery to the retina. We developed a nanoscale version of an anionic, cholesterol-fusing liposome that can encapsulate therapeutic levels of minocycline capable of drug delivery. We demonstrate that size extrusion followed by size-exclusion chromatography can form a stable 80-nm liposome that encapsulates minocycline at a concentration of 450 ± 30 ?M, which is 2% to 3% of loading material. More importantly, these nontoxic nanoliposomes can then deliver 40% of encapsulated minocycline to the retina after a subconjunctival injection in the STZ model of diabetes. Efficacy of therapeutic drug delivery was assessed via transcriptomic and proteomic biomarker panels. For both the free minocycline and encapsulated minocycline treatments, proinflammatory markers of diabetes were downregulated at both the messenger RNA and protein levels, validating the utility of biomarker panels for the assessment of ocular drug delivery vehicles. PMID:22465498

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

    PubMed

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

    2014-09-10

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

  15. A fully implanted drug delivery system for peripheral nerve blocks in behaving animals.

    PubMed

    Pohlmeyer, Eric A; Jordon, Luke R; Kim, Peter; Miller, Lee E

    2009-09-15

    Inhibiting peripheral nerve function can be useful for many studies of the nervous system or motor control. Accomplishing this in a temporary fashion in animal models by using peripheral nerve blocks permits studies of the immediate effects of the loss, and/or any resulting short-term changes and adaptations in behavior or motor control, while avoiding the complications commonly associated with permanent lesions, such as sores or self-mutilation. We have developed a method of quickly and repeatedly inducing temporary, controlled motor deficits in rhesus macaque monkeys via a chronically implanted drug delivery system. This assembly consists of a nerve cuff and a subdermal injection dome, and has proved effective for delivering local anesthetics directly to peripheral nerves for many months. Using this assembly for median and ulnar nerve blocks routinely resulted in over 80% losses in hand and wrist strength for rhesus monkeys. The assembly was also effective for inducing ambulatory motor deficits in rabbits through blocks of the sciatic nerve. Interestingly, while standard anesthetics were sufficient for the rabbit nerve blocks, the inclusion of epinephrine was essential for achieving significant motor blockade in the monkeys. PMID:19524613

  16. A biodegradable drug delivery system for the treatment of postoperative inflammation.

    PubMed

    Eperon, S; Bossy-Nobs, L; Petropoulos, I K; Gurny, R; Guex-Crosier, Y

    2008-03-20

    Cataract surgery is often performed in patients suffering from associated pathologies. Our goal is to develop a biodegradable drug delivery system (DDS) combined with the artificial intraocular lens (IOL). DDS were manufactured using poly(D,L-lactide-co-glycolide), or PLGA, and were loaded with triamcinolone acetonide (TA). The loading capacity was approximately 1050 microg of TA per DDS. The higher the molecular weight of PLGA (34,000, 48,000 and 80,000Da), the slower was the release of TA in vitro. Cataract surgery was performed on the right eye of rabbits. IOL was inserted with (i) no DDS, (ii) unloaded DDS PLGA48000, (iii) one loaded DDS PLGA48000, (iv) two loaded DDS. The number of inflammatory cells and the protein concentration were measured in the aqueous humor (AH). Unloaded DDS showed good ocular biocompatibility. One DDS PLGA48000 loaded with TA significantly reduced postoperative ocular inflammation. Two loaded DDS PLGA48000 was even more effective in inhibiting such inflammation. On long-term observation (days 63 and 84), reduction of inflammation could be obtained by insertion of one DDS PLGA48000 and a second DDS PLGA80000. Therefore, our "all in one" system is very promising since it could replace oral treatment and reduce the number of intraocular injections. PMID:18093765

  17. 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.

  18. Hydroxypropyl- ? -cyclodextrin: A Novel Transungual Permeation Enhancer for Development of Topical Drug Delivery System for Onychomycosis.

    PubMed

    Chouhan, Pradeep; Saini, T R

    2014-01-01

    The treatment of onychomycosis is a challenging task because of unique barrier properties of the nail plate which hampers the passage of antifungal drugs in a concentration required to eradicate the deeply seated causative fungi in the nail bed. In present investigation, application of hydroxypropyl-?-cyclodextrin (HP-?-CD) was established as an effective and nail friendly transungual drug permeation enhancer especially for poorly water soluble drugs using terbinafine hydrochloride as a poorly soluble drug. HP-?-CD significantly improves hydration of nail plates and increases solubility of terbinafine hydrochloride in the aqueous environment available therein, which leads to uninterrupted drug permeation through water filled pores of hydrogel-like structure of hydrated nail plates. A nail lacquer formulation was designed with an objective to deliver the drug in an effective concentration across nail plates, using HP-?-CD as a permeation enhancer. The formulations containing HP-?-CD showed higher flux than the control formulation in in vitro drug permeation study. The formulation containing 10%?w/v of HP-?-CD showed maximum flux of 4.586 ± 0.08??g/mL/cm(2) as compared to the control flux of 0.868 ± 0.06??g/mL/cm(2). This finding supports application of HP-?-CD as an effective permeation enhancer for transungual delivery of terbinafine hydrochloride and possibly other poorly water soluble drugs where HP-?-CD can act as a solubilizer. PMID:25177500

  19. CCMR: Drug Delivery Using Nanoparticles

    NSDL National Science Digital Library

    Lin, Joyce

    2005-08-17

    Safe and nontoxic drug delivery is an ongoing area of research. Some current methods of drug delivery include the use of nanoparticles, hydrogels, dendrimers, and micelles. Nanoparticles can be used as vehicles in which to transport certain drugs to cancerous cells. A certain class of nanoparticles called clays is especially useful in synthesizing these drug delivery vehicles. Layered Double Hydroxides (LDHs) are a type of hydrotalcite clay with a structure similar to smectite clays. They have a general structure that consists of layers of metal hydroxides connected to a layer of another metal hydroxide by hydrogen bonding. LDHs are made up of layers of a trivalent and a divalently charged cation coordinated by six oxygen atoms. The resulting structure consists of two-dimensional sheets with positively charged faces and negatively charged edges that are stacked together via hydrogen bonding between hydroxyl groups on adjacent sheets. These sheets generally have a very high aspect ratio, resulting in a large surface area. The positively charged layers are balanced by the presence of anions between them. A wide variety of LDHs can be synthesized depending on the various cations and interlayer anions used. Characterization of the LDHs themselves as well as LDHs intercalated with the drugs was performed using X-ray diffraction and TEM and SEM microscopy.

  20. Ultrasound triggered image-guided drug delivery.

    PubMed

    Böhmer, Marcel R; Klibanov, Alexander L; Tiemann, Klaus; Hall, Christopher S; Gruell, Holger; Steinbach, Oliver C

    2009-05-01

    The integration of therapeutic interventions with diagnostic imaging has been recognized as one of the next technological developments that will have a major impact on medical treatments. Important advances in this field are based on a combination of progress in guiding and monitoring ultrasound energy, novel drug classes becoming available, the development of smart delivery vehicles, and more in depth understanding of the mechanisms of the cellular and molecular basis of diseases. Recent research demonstrates that both pressure sensitive and temperature sensitive delivery systems hold promise for local treatment. The use of ultrasound for the delivery of drugs has been demonstrated in particular the field of cardiology and oncology for a variety of therapeutics ranging from small drug molecules to biologics and nucleic acids. PMID:19272727

  1. pH-responsive drug delivery system based on hollow silicon dioxide micropillars coated with polyelectrolyte multilayers

    PubMed Central

    2014-01-01

    We report on the fabrication of polyelectrolyte multilayer-coated hollow silicon dioxide micropillars as pH-responsive drug delivery systems. Silicon dioxide micropillars are based on macroporous silicon formed by electrochemical etching. Due to their hollow core capable of being loaded with chemically active agents, silicon dioxide micropillars provide additional function such as drug delivery system. The polyelectrolyte multilayer was assembled by the layer-by-layer technique based on the alternative deposition of cationic and anionic polyelectrolytes. The polyelectrolyte pair poly(allylamine hydrochloride) and sodium poly(styrene sulfonate) exhibited pH-responsive properties for the loading and release of a positively charged drug doxorubicin. The drug release rate was observed to be higher at pH 5.2 compared to that at pH 7.4. Furthermore, we assessed the effect of the number of polyelectrolyte bilayers on the drug release loading and release rate. Thus, this hybrid composite could be potentially applicable as a pH-controlled system for localized drug release. PMID:25221455

  2. Gelatin Used for Drug Delivery

    NSDL National Science Digital Library

    University of Southern Mississippi

    2003-01-01

    In this activity, learners discover how gelatin can be used as a medium for drug delivery. Learners create colored gelatin and then cut out pieces of the gelatin to simulate medicine (pills). Learners then put their simulated pills in a pan of hot water. Since gelatin is a thermoreversible or cold-setting polymer, gelatin will convert back to a liquid if put in a hot environment. As the gelatin returns to its liquid form, it releases its embedded dye. The dye eventually diffuses completely out of the gelatin which simulates the slow release of a drug from a pill. From this activity, learners learn more about diffusion and drug delivery. Adult supervision recommended.

  3. Nanocarriers and Drug Delivery

    Microsoft Academic Search

    Svetlana Gelperina

    Nanoparticles may serve, among other techniques, as a useful tool for achieving the main objective of regional cancer therapy:\\u000a they can deliver a higher concentration of the agent to the tumor and expose the tumor to active drug for longer periods than\\u000a safely possible with conventional formulations. These carriers combine many advantages, such as a potential for selective\\u000a targeting and

  4. Spinal drug delivery

    Microsoft Academic Search

    Theodore S. Grabow; David Derdzinski; Peter S. Staats

    2001-01-01

    Clinicians currently base decisions regarding the use of intrathecal drug therapy for chronic pain on reports from uncontrolled\\u000a and retrospective studies that fail to rely on standardized outcome measures. In this article, we summarize what is known\\u000a about currently administered intrathecal therapies, including opioids, gamma-aminobutyric acid agonists, alpha-2 adrenoreceptor\\u000a agonists, local anesthetics (sodium channel antagonists), calcium channel antagonists, miscellaneous agents,

  5. 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

  6. Development and Characterization of Controlled Drug Delivery Using Nanoparticles

    Microsoft Academic Search

    Li Chen

    2004-01-01

    The objective of this project was to develop new controlled drug delivery systems using nanomeric particles and characterize the delivery of drugs into cells in real time by digital fluorescence imaging microscopy techniques. The project is based on the idea that it could be possible to improve efficacy of drug molecules when encapsulated in nanometer-sized particles. Due to their small

  7. Formulation considerations in the design of topical, polymeric film-forming systems for sustained drug delivery to the skin.

    PubMed

    Frederiksen, Kit; Guy, Richard H; Petersson, Karsten

    2015-04-01

    Polymeric film-forming systems (FFSs) are potential drug delivery systems for topical application to the skin. The FFSs form thin and transparent polymeric films in situ upon solvent evaporation. Their application convenience and cosmetic attributes, superior to conventional semi-solids, may offer improved patient compliance. This study represents the first phase of an investigation into the use of FFSs for prolonged dermal drug delivery. FFS formulations were distinguished based on their ability to sustain the release of betamethasone 17-valerate (BMV) in vitro over 72 h. The effect of film-forming polymer (hydrophilic: hydroxypropyl cellulose (Klucel™ LF); hydrophobic: polymethacrylate copolymers (Eudragit® NE and Eudragit® RS), and polyacrylate copolymer (Dermacryl® 79) was first determined, and then the impact of incorporation of plasticisers (triethyl citrate, tributyl citrate, and dibutyl sebacate) was examined. The Klucel film released a significantly higher amount of BMV than the hydrophobic FFS, 42 versus 4 ?g/cm(2), respectively. The release was increased when a plasticiser was incorporated, and with higher enhancement ratios achieved with the more lipophilic plasticisers. In conclusion, the results show that FFSs can sustain drug release (hence representing useful systems for prolonged dermal therapy) and emphasise the importance of the formulation on drug delivery, with the type of polymer being of greatest significance. PMID:25595740

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

    PubMed

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

    2014-03-10

    This work introduces results on a new drug delivery system (DDS) based on the use of chitosan/layered double hydroxide (LDH) biohybrid beads coated with pectin for controlled release in the treatment of colon diseases. Thus, the 5-aminosalicylic acid (5ASA), the most used non-steroid-anti-inflammatory drug (NSAID) in the treatment of ulcerative colitis and Crohn's disease, was chosen as model drug aiming to a controlled and selective delivery in the colon. The pure 5ASA drug and the hybrid material prepared by intercalation in a layered double hydroxide of Mg2Al using the co-precipitation method, were incorporated in a chitosan matrix in order to profit from its mucoadhesiveness. These compounds processed as beads were further treated with the polysaccharide pectin to create a protective coating that ensures the stability of both chitosan and layered double hydroxide at the acid pH of the gastric fluid. The resulting composite beads presenting the pectin coating are stable to water swelling and procure a controlled release of the drug along their passage through the simulated gastrointestinal tract in in vitro experiments, due to their resistance to pH changes. Based on these results, the pectin@chitosan/LDH-5ASA bionanocomposite beads could be proposed as promising candidates for the colon-targeted delivery of 5ASA, with the aim of acting only in the focus of the disease and minimizing side effects. PMID:24374607

  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. 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.

  11. Hybrid drug delivery system for oropharyngeal, cervical and colorectal cancer – in vitro and in vivo evaluation

    PubMed Central

    Pendekal, Mohamed S.; Tegginamat, Pramod K.

    2012-01-01

    The present investigation was designed with the intention to formulate a versatile 5-fluorouracil(5-FU) matrix tablet surpassing issues associated with current conventional chemotherapeutic drug delivery systems. The novel 5-FU matrix tablet fulfills therapeutic needs by engineering matrix tablets utilizing chitosan–sodium alginate interpolyelectrolyte complex (IPEC). IPEC was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The matrix tablets were formulated utilizing IPEC alone and in combination with chitosan, sodium alginate and sodium deoxycholate as permeation enhancer. Pharmaceutical properties, swelling studies, in vitro dissolution and diffusion studies, mucoadhesive studies and in vivo studies were performed for formulated 5-FU. The selected chitosan–sodium alginate IPEC offers pH independent 5-FU release in comparison to alone or physical mixture of chitosan and sodium alginate. Furthermore, novel matrix tablets demonstrated significantly higher bioadhesive properties with controlled 5-FU release without the initial burst effect and also demonstrated a higher permeation of 5-FU. To conclude, the developed novel 5-FU matrix tablets pave way as an excellent alternative for cancer treatment which could potentially minimize the dose dependent side effects and provide better patient compliance. PMID:23960833

  12. Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability.

    PubMed

    Tran, Thanh Huyen; Guo, Yi; Song, Donghui; Bruno, Richard S; Lu, Xiuling

    2014-03-01

    Quercetin is a dietary flavonoid with potential chemoprotective effects, but has low bioavailability because of poor aqueous solubility and low intestinal absorption. A quercetin-containing self-nanoemulsifying drug delivery system (Q-SNEDDS) was developed to form oil-in-water nanoemulsions in situ for improving quercetin oral bioavailability. On the basis of the quercetin solubility, emulsifying ability, and stability after dispersion in an aqueous phase, an optimal SNEDDS consisting of castor oil, Tween® 80, Cremophor® RH 40, and PEG 400 (20:16:34:30, w/w) was identified. Upon mixing with water, Q-SNEDDS formed a nanoemulsion having a droplet size of 208.8 ± 4.5 nm and zeta potential of -26.3 ± 1.2 mV. The presence of Tween® 80 and PEG 400 increased quercetin solubility and maintained supersaturated quercetin concentrations (5 mg/mL) for >1 month. The optimized Q-SNEDDS significantly improved quercetin transport across a human colon carcinoma (Caco-2) cell monolayer. Fluorescence imaging demonstrated rapid absorption of the Q-SNEDDS within 40 min of oral ingestion. Following oral administration of Q-SNEDDS in rats (15 mg/kg), the area under the concentration curve and maximum concentration of plasma quercetin after 24 h increased by approximately twofold and threefold compared with the quercetin control suspension. These data suggest that this Q-SNEDDS formulation can enhance the solubility and oral bioavailability of quercetin for appropriate clinical application. PMID:24464737

  13. Preparation of pH-sensitive anionic liposomes designed for drug delivery system (DDS) application.

    PubMed

    Aoki, Asami; Akaboshi, Hikaru; Ogura, Taku; Aikawa, Tatsuo; Kondo, Takeshi; Tobori, Norio; Yuasa, Makoto

    2015-01-01

    We prepared pH-sensitive anionic liposomes composed solely of anionic bilayer membrane components that were designed to promote efficient release of entrapped agents in response to acidic pH. The pH-sensitive anionic liposomes showed high dispersion stability at neutral pH, but the fluidity of the bilayer membrane was enhanced in an acidic environment. These liposomes were rather simple and were composed of dimyristoylphosphatidylcholine (DMPC), an anionic bilayer membrane component, and polyoxyethylene sorbitan monostearate (Tween 80). In particular, the present pH-sensitive anionic liposomes showed higher temporal stability than those of conventional DMPC/DPPC liposomes. We found that pHsensitive properties strongly depended on the molecular structure, pKa value, and amount of an incorporated anionic bilayer membrane component, such as sodium oleate (SO), dimyristoylphosphatidylserine (DMPS), or sodium ?-sitosterol sulfate (SS). These results provide an opportunity to manipulate liposomal stability in a pH-dependent manner, which could lead to the formulation of a high performance drug delivery system (DDS). PMID:25748383

  14. 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. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2266-2275, 2015. PMID:25980666

  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. Transport of polymeric nanoparticulate drug delivery systems in the proximity of silica and sand.

    PubMed

    Chen, I-Cheng; Zhang, Ming; Teipel, Blake; de Araujo, Isa Silveira; Yegin, Yagmur; Akbulut, Mustafa

    2015-03-17

    The contamination of the environment with traditional therapeutics due to metabolic excretion, improper disposal, and industrial waste has been well-recognized. However, knowledge of the environmental distribution and fate of emerging classes of nanomedicine is scarce. This work investigates the effect of surface chemistry of polymeric nanoparticulate drug delivery systems (PNDDS) on their adsorption dynamics and transport in the vicinity of environmentally relevant surfaces for a concentration comparable with hospital and pharmaceutical manufacturing effluents. To this end, five different types of paclitaxel-based nanomedicine having different polymer stabilizers were employed. Their transport behavior was characterized via quartz crystal microbalance, sand column, spectrofluorometry, and dynamic light scattering techniques. PNDDS having positive zeta-potential displayed strong adsorption onto silica surfaces and no mobility in porous media of quartz sand, even in the presence of humic acid. The mobility of negatively charged PNDDS strongly depended on the amount and type of salt present in the aqueous media: Without any salt, such PNDDS demonstrated no adsorption on silica surfaces and high levels of mobility in sand columns. The presence of CaCl2 and CaSO4, even at low ionic strengths (i.e. 10 mM), induced PNDDS adsorption on silica surfaces and strongly limited the mobility of such PNDSS in sand columns. PMID:25695909

  17. Design and in vitro evaluation of a novel vaginal drug delivery system based on gelucire.

    PubMed

    Geeta, M Patel; Madhabhai, M Patel

    2009-04-01

    Carbamazepine indicated for the control of epilepsy, undergoes extensive hepatic first-pass metabolism after oral administration. A vaginal dosage form of carbamazepine is not commercially available. Conventional suppository having poor retention in the vaginal tract, as they are removed in a short time by the tract's self-cleansing action, having poor patient compliance. To overcome such problems, delivery system with mucoadhesive polymers polyox WSR N-60K and Ucarflock 302 that prolong drug permanence on the vaginal mucosa were developed. In the present study the suitability of gelucires to formulate vaginal pesseries was investigated. The possible modification of carbamazepine release kinetics by using gelucires blends and hydrophilic additives in the pesseries was evaluated. It was observed that among gelucire grades melting point higher than 37 degrees C, the release rate proved to be highly dependant on HLB value and matrix composition. In most of the formulations carbamazepine release occurred by disintegration and erosion of the matrices which is depending upon the vehicle employed. The aging study revealed that the formulations containing G50/13 and G50/13-G44/14 blends undergo some changes during one year of shelf aging. From the results obtained it can be concluded that different gelucire grades and their blends along with hydrophilic polymer could be successesively used to formulate prolong release carbamazepine pesseries. PMID:19450222

  18. Drug delivery Preparation of Monodisperse Biodegradable Polymer

    E-print Network

    Prentiss, Mara

    Drug delivery Preparation of Monodisperse Biodegradable Polymer Microparticles Using a Microfluidic Flow-Focusing Device for Controlled Drug Delivery Qiaobing Xu, Michinao Hashimoto, Tram T. Dang, Todd microparticles have broad utility as vehicles for drug delivery and form the basis of several therapies approved

  19. Preparation and pharmaceutical evaluation of nano-fiber matrix supported drug delivery system using the solvent-based electrospinning method.

    PubMed

    Hamori, Mami; Yoshimatsu, Shiori; Hukuchi, Yuki; Shimizu, Yuki; Fukushima, Keizo; Sugioka, Nobuyuki; Nishimura, Asako; Shibata, Nobuhito

    2014-04-10

    In this study, utilizing the solvent-based electrospinning (ES) method, which is mainly employed in the textile industry, we prepared nanofiber-based capsules including drugs for controlled-release delivery systems using methacrylic acid copolymer (EUDRAGIT(®) S100, MAC) as a polymer, and evaluated their in vitro drug dissolution profiles and in vivo pharmacokinetics in rats. As the model drugs, uranine (UN) was used as a water-soluble drug and nifedipine (NP) as a water-insoluble drug. The mean diameters of drug free nano-fiber and nano-fiber including NP or UN were 751.5 ± 67.2, 703.3 ± 71.2 and 2477.8 ± 206.1 nm, respectively. X-ray diffraction for the nano-fibrotic sheet showed that UN and/or NP were packed in nano-fiber in an amorphous form. The in vitro release of UN or NP from the nano-fiber packed capsules (NFPC) and milled-powder of nano-fiber packed capsules (MPPC) showed controlled release of UN or NP as compared to capsules of a physical mixture of MAC and each drug. An in vivo pharmacokinetic study in rats after intraduodenal administration of NFPC or MPPC including UN and/or NP clearly demonstrated that application of nano-fibrotic technique as a drug delivery system offers drastic changes in pharmacokinetic profiles for both water-soluble and water-insoluble drugs. The ES method is a useful technique to prepare a nano-fiber like solid dispersion for polar or nonpolar drugs, and has wide potential pharmaceutical applications. PMID:24440839

  20. Gelatin-based nanoparticles as drug and gene delivery systems: reviewing three decades of research.

    PubMed

    Elzoghby, Ahmed O

    2013-12-28

    Gelatin is one of the most versatile natural biopolymers widely used in pharmaceutical industries due to its biocompatibility, biodegradability, low cost and numerous available active groups for attaching targeting molecules. These advantages led to its application in the synthesis of nanoparticles for drug and gene delivery during the last thirty years. The current article entails a general review of the different preparation techniques of gelatin nanoparticles (GNPs): desolvation, coacervation-phase separation, emulsification-solvent evaporation, reverse phase microemulsion, nanoprecipitation, self-assembly and layer-by-layer coating, from the point of view of the methodological and mechanistic aspects involved. Various crosslinkers used to improve the physicochemical properties of GNPs includintg aldehydes, genipin, carbodiimide/N-hydroxysuccinimide, and transglutaminase are reported. An analysis is given of the physicochemical behavior of GNPs including drug loading, release, particle size, zeta-potential, cytotoxicity, cellular uptake and stability. This review also attempts to provide an overview of the major applications of GNPs in drug delivery and gene therapy and their in vivo pharmacological performances, as well as site-specific drug targeting using various ligands modifying the surface of GNPs. Finally, nanocomplexes of gelatin with polymers, lipids or inorganic materials are also discussed. PMID:24096021

  1. Nanofibrillar cellulose films for controlled drug delivery.

    PubMed

    Kolakovic, Ruzica; Peltonen, Leena; Laukkanen, Antti; Hirvonen, Jouni; Laaksonen, Timo

    2012-10-01

    Nanofibrillar cellulose (NFC) (also referred to as cellulose nanofibers, nanocellulose, microfibrillated, or nanofibrillated cellulose) has gotten recent and wide attention in various research areas. Here, we report the application of nanofibrillar cellulose as a matrix-former material for long-lasting (up to three months) sustained drug delivery. Film-like matrix systems with drug loadings between 20% and 40% were produced by a filtration method. This simple production method had an entrapment efficacy>90% and offers a possibility for the film thickness adjustment as well as applicability in the incorporation of heat sensitive compounds. The films had excellent mechanical properties suitable for easy handling and shape tailoring of the drug release systems. They were characterized in terms of the internal morphology, and the physical state of the encapsulated drug. The drug release was assessed by dissolution tests, and suitable mathematical models were used to explain the releasing kinetics. The drug release was sustained for a three month period with very close to zero-order kinetics. It is assumed that the nanofibrillar cellulose film sustains the drug release by forming a tight fiber network around the incorporated drug entities. The results indicate that the nanofibrillar cellulose is a highly promising new material for sustained release drug delivery applications. PMID:22750440

  2. Ocular drug delivery in veterinary medicine

    Microsoft Academic Search

    Vincent Baeyens; Christine Percicot; Monia Zignani; Arati A Deshpande; Vassilios Kaltsatos; Robert Gurny

    1997-01-01

    This paper provides a comprehensive overview of the various approaches currently used in the development of ocular drug delivery systems for the treatment of ocular diseases in animals. It is obvious from the literature that most of the products that are currently available are derived from human medicine without consideration given to the differences which exist between the anatomy and

  3. Tuning pharmacokinetics and biodistribution of a targeted drug delivery system through incorporation of a passive targeting component.

    PubMed

    Kudgus, Rachel A; Walden, Chad A; McGovern, Renee M; Reid, Joel M; Robertson, J David; Mukherjee, Priyabrata

    2014-01-01

    Major challenges in the development of drug delivery systems (DDSs) have been the short half-life, poor bioavailability, insufficient accumulation and penetration of the DDSs into the tumor tissue. Understanding the pharmacokinetic (PK) parameters of the DDS is essential to overcome these challenges. Herein we investigate how surface chemistry affects the PK profile and organ distribution of a gold nanoparticle-based DDS containing both a passive and active targeting moiety via two common routes of administration: intravenous and intraperitoneal injections. Using LC/MS/MS, ELISA and INAA we report the half-life, peak plasma concentrations, area under the curve, ability to cross the peritoneal barrier and biodistribution of the nanoconjugates. The results highlight the design criteria for fine-tuning the PK parameters of a targeted drug delivery system that exploits the benefits of both active and passive targeting. PMID:25011609

  4. 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.

  5. 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.

  6. Biodegradable tetra-PEG hydrogels as carriers for a releasable drug delivery system.

    PubMed

    Henise, Jeff; Hearn, Brian R; Ashley, Gary W; Santi, Daniel V

    2015-02-18

    We have developed an approach to prepare drug-releasing Tetra-PEG hydrogels with exactly four cross-links per monomer. The gels contain two cleavable ?-eliminative linkers: one for drug attachment that releases the drug at a predictable rate, and one with a longer half-life placed in each cross-link to control biodegradation. Thus, the system can be optimized to release the drug before significant gel degradation occurs. The synthetic approach involves placing a heterobifunctional connector at each end of a four-arm PEG prepolymer; four unique end-groups of the resultant eight-arm prepolymer are used to tether a linker-drug, and the other four are used for polymerization with a second four-arm PEG. Three different orthogonal reactions that form stable triazoles, diazines, or oximes have been used for tethering the drug to the PEG and for cross-linking the polymer. Three formats for preparing hydrogel-drug conjugates are described that either polymerize preformed PEG-drug conjugates or attach the drug postpolymerization. Degradation of drug-containing hydrogels proceeds as expected for homogeneous Tetra-PEG gels with minimal degradation occurring in early phases and sharp, predictable reverse gelation times. The minimal early degradation allows design of gels that show almost complete drug release before significant gel-drug fragments are released. PMID:25584814

  7. Development of drug delivery systems based on nanostructured porous silicon loaded with the anti-tumoral drug emodin adsorbed on silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Hernández, Margarita; Recio, Gonzalo; Sevilla, Paz; Torres-Costa, Vicente; García-Ramos, José V.; Domingo, Concepción; Martín-Palma, Raúl J. J.

    2012-10-01

    A study of the fluorescence and Raman spectra of a new and complex drug delivery system formed by emodin adsorbed on silver nanoparticles embedded into a matrix of porous silicon is here reported. Several experimental methods of inclusion of the drug-silver set inside the pores, without previous functionalization of porous silicon, have been tested in order to optimize the conditions for the fluorescence detection of emodin. In this sense, we have also added bovine serum albumin to the system, finding that the presence of the protein enhances the fluores-cence signal from emodin.

  8. Liposomes: from a clinically established drug delivery system to a nanoparticle platform for theranostic nanomedicine.

    PubMed

    Al-Jamal, Wafa' T; Kostarelos, Kostas

    2011-10-18

    For decades, clinicians have used liposomes, self-assembled lipid vesicles, as nanoscale systems to deliver encapsulated anthracycline molecules for cancer treatment. The more recent proposition to combine liposomes with nanoparticles remains at the preclinical development stages; however, such hybrid constructs present great opportunities to engineer theranostic nanoscale delivery systems, which can combine simultaneous therapeutic and imaging functions. Many novel nanoparticles of varying chemical compositions are being developed in nanotechnology laboratories, but further chemical modification is often required to make these structures compatible with the biological milieu in vitro and in vivo. Such nanoparticles have shown promise as diagnostic and therapeutic tools and generally offer a large surface area that allows covalent and non-covalent surface functionalization with hydrophilic polymers, therapeutic moieties, and targeting ligands. In most cases, such surface manipulation diminishes the theranostic properties of nanoparticles and makes them less stable. From our perspective, liposomes offer structural features that can make nanoparticles biocompatible and present a clinically proven, versatile platform for further enhancement of the pharmacological and diagnostic efficacy of nanoparticles. In this Account, we describe two examples of liposome-nanoparticle hybrids developed as theranostics: liposome-quantum dot hybrids loaded with a cytotoxic drug (doxorubicin) and artificially enveloped adenoviruses. We incorporated quantum dots into lipid bilayers, which rendered them dispersible in physiological conditions. This overall vesicular structure allowed them to be loaded with doxorubicin molecules. These structures exhibited cytotoxic activity and labeled cells both in vitro and in vivo. In an alternative design, lipid bilayers assembled around non-enveloped viral nanoparticles and altered their infection tropism in vitro and in vivo with no chemical or genetic capsid modifications. Overall, we have attempted to illustrate how alternative strategies to incorporate nanoparticles into liposomal nanostructures can overcome some of the shortcomings of nanoparticles. Such hybrid structures could offer diagnostic and therapeutic combinations suitable for biomedical and even clinical applications. PMID:21812415

  9. Development and characterization of polymeric nanoparticulate delivery system for hydrophillic drug: Gemcitabine

    NASA Astrophysics Data System (ADS)

    Khurana, Jatin

    Gemcitabine is a nucleoside analogue, used in various carcinomas such as non small cell lung cancer, pancreatic cancer, ovarian cancer and breast cancer. The major setbacks to the conventional therapy with gemcitabine include its short half-life and highly hydrophilic nature. The objectives of this investigation were to develop and evaluate the physiochemical properties, drug loading and entrapment efficiency, in vitro release, cytotoxicity, and cellular uptake of polymeric nano-particulate formulations containing gemcitabine hydrochloride. The study also entailed development and validation of a high performance liquid chromatography (HPLC) method for the analysis of gemcitabine hydrochloride. A reverse phase HPLC method using a C18 Luna column was developed and validated. Alginate and Poly lactide co glycolide/Poly-epsilon-caprolactone (PLGA:PCL 80:20) nanoparticles were prepared by multiple emulsion-solvent evaporation methodology. An aqueous solution of low viscosity alginate containing gemcitabine was emulsified into 10% solution of dioctyl-sulfosuccinate in dichloro methane (DCM) by sonication. The primary emulsion was then emulsified in 0.5% (w/v) aqueous solution of polyvinyl alcohol (PVA). Calcium chloride solution (60% w/v) was used to cause cross linking of the polymer. For PLGA:PCL system, the polymer mix was dissolved in dichloromethane (DCM) and an aqueous gemcitabine (with and without sodium chloride) was emulsified under ultrasonic conditions (12-watts; 1-min). This primary emulsion was further emulsified in 2% (w/v) PVA under ultrasonic conditions (24-watts; 3-min) to prepare a multiple-emulsion (w/o/w). In both cases DCM, the organic solvent was evaporated (20- hours, magnetic-stirrer) prior to ultracentrifugation (10000-rpm for PLGA:PCL; 25000-rpm for alginate). The pellet obtained was washed thrice with de-ionized water to remove PVA and any free drug and re-centrifuged. The particles were re-suspended in de-ionized water and then lyophilized to obtain the dried powdered delivery formulation. Particle size and surface charge of the nano-particles were measured using zeta-sizer. The surface morphology and microstructure were evaluated by scanning electron microscopy The drug loading and entrapment efficiencies were evaluated by a HPLC method (Luna C18 column (4.6 X 250 mm), 95/5 (v/v) 0.04M ammonium acetate/acetonitrile mobile phase (pH 5.5), 1.0 ml/min flow rate and 268 nm UV detection). Differential scanning calorimetry (DSC) was used to determine the physical state of gemcitabine in the nanoparticles. The cytotoxicity in pancreatic cancer cells (BxPC-3) was evaluated by MTT assay. The cellular uptake of gemcitabine solution and gemcitabine loaded alginate nano-particle suspension in BxPC-3 cells was determined for 15, 30 and 60 minutes. The particle-size and surface-charge was 564.7+/-56.5nm and -25.65+/-1.94mV for PLGA:PCL and 210.6+/-6.90nm and -33.21+/-1.63mV for alginate. Both the nano-particles were distinctly spherical and non-porous. The drug load was 5.14% for PLGA:PCL and 6.87% for alginate-particles, and the practical entrapment efficiency was found to be 54.1 % and 22.4% respectively. However, in case of PLGA:PCL particles, a two-fold increase in the entrapment efficiency was observed with the addition of sodium-chloride. The absence of endothermic melting peak of the drug in the DSC thermogram was an indication of the non-crystalline state of gemcitabine in the nanoparticles. In addition, there was no cytotoxicity associated with nanoparticle concentrations at-or-below 5 mg/mL. The uptake of nano-particles was around 4 times higher than the solution with treatment for 15 minutes and increased to almost 7 times following treatment for 60 minutes. Gemcitabine hydrochloride could be successfully formulated into a sustained release nano-particulate formulation using calcium cross-linked alginate and dioctyl sulfo succinate system. The nano-particulate delivery system exhibited better cytotoxic activity and also significantly enhanced the accumulation of the drug in BxPC-3 cell monolayers.

  10. 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

  11. Drug delivery across the skin.

    PubMed

    Touitou, Elka

    2002-10-01

    For more than two decades, researchers have attempted to find a way to use the skin as a portal of entry for drugs in order to overcome problems associated with traditional modes of drug administration. This has been a complicated task due to the highly effective barrier properties of the skin. In order to deliver drugs through the skin, most compounds require various degrees of permeation enhancement. Classic enhancement methods focused primarily on chemical enhancement or modulation of interactions between the drug and the vehicle. More recent research makes use of innovative vesicular carriers, electrically assisted delivery and various microinvasive methods, some incorporating technologies from other fields. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This review discusses the different types of permeation enhancement, both classic and innovative, and summarises the current strengths and shortcomings in the field with an emphasis on those that have led to products on the market or in the pipeline. PMID:12387671

  12. Development and effect of different bioactive silicate glass scaffolds: in vitro evaluation for use as a bone drug delivery system.

    PubMed

    Soundrapandian, Chidambaram; Mahato, Arnab; Kundu, Biswanath; Datta, Someswar; Sa, Biswanath; Basu, Debebrata

    2014-12-01

    Local drug delivery systems to bone have attracted appreciable attention due to their efficacy to improve drug delivery, healing and regeneration. In this paper, development and characterization of new formulations of bioactive glass into a porous scaffold has been reported for its suitability to act as a drug delivery system in the management of bone infections, in vitro. Two new glass compositions based on SiO2-Na2O-ZnO-CaO-MgO-P2O5 system (BGZ and MBG) have been developed which after thorough chemical and phase evaluation, studied for acellular static in vitro bioactivity in SBF. Porous scaffolds made of these glasses have been fabricated and characterized thoroughly for bioactivity study, SEM, XRD, in vitro cytotoxicity, MTT assay and wound healing assay using human osteocarcoma cells. Finally, gatifloxacin was loaded into the porous scaffold by vacuum infiltration method and in vitro drug release kinetics have been studied with varying parameters including dissolution medium (PBS and SBF) and with/without impregnation chitosan. Suitable model has also been proposed for the kinetics. 63-66% porous and 5-50?m almost unimodal porous MBG and BGZ bioactive glass scaffolds were capable of releasing drugs successfully for 43 days at concentrations to treat orthopedic infections. In addition, it was also observed that the release of drug followed Peppas-Korsmeyer release pattern based on Fickian diffusion, while 0.5-1% chitosan coating on the scaffolds decreased the burst release and overall release of drug. The results also indicated that MBG based scaffolds were bioactive, biocompatible, noncytotoxic and exhibited excellent wound healing potential while BGZ was mildly cytotoxic with moderate wound healing potential. These results strongly suggest that MBG scaffolds appear to be a suitable bone drug delivery system in orthopedic infections treatment and as bone void fillers, but BGZ should be handled with caution or studied elaborately in detail further to ascertain and confirm the cytotoxic nature and wound healing potential of this glass. PMID:25190432

  13. Design, Development, and Optimization of Polymeric Based-Colonic Drug Delivery System of Naproxen

    PubMed Central

    Sharma, Pooja; Chawla, Anuj; Pawar, Pravin

    2013-01-01

    The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO?:?RLPO mixture and further coated with Eudragit S-100 by dip immerse method. The in vitro drug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highest in vitro drug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting. PMID:24198725

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

    PubMed Central

    Trivedi, Ruchit; Kompella, Uday B

    2010-01-01

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

  15. Idarubicin-loaded folic acid conjugated magnetic nanoparticles as a targetable drug delivery system for breast cancer.

    PubMed

    Gunduz, Ufuk; Keskin, Tugba; Tans?k, Gulistan; Mutlu, Pelin; Yalcin, Serap; Unsoy, Gozde; Yakar, Arzu; Khodadust, Rouhollah; Gunduz, Gungor

    2014-07-01

    Conventional cancer chemotherapies cannot differentiate between healthy and cancer cells, and lead to severe side effects and systemic toxicity. Another major problem is the drug resistance development before or during the treatment. In the last decades, different kinds of controlled drug delivery systems have been developed to overcome these shortcomings. The studies aim targeted drug delivery to tumor site. Magnetic nanoparticles (MNP) are potentially important in cancer treatment since they can be targeted to tumor site by an externally applied magnetic field. In this study, MNPs were synthesized, covered with biocompatible polyethylene glycol (PEG) and conjugated with folic acid. Then, anti-cancer drug idarubicin was loaded onto the nanoparticles. Shape, size, crystal and chemical structures, and magnetic properties of synthesized nanoparticles were characterized. The characterization of synthesized nanoparticles was performed by dynamic light scattering (DLS), Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM) analyses. Internalization and accumulation of MNPs in MCF-7 cells were illustrated by light and confocal microscopy. Empty MNPs did not have any toxicity in the concentration ranges of 0-500?g/mL on MCF-7 cells, while drug-loaded nanoparticles led to significant toxicity in a concentration-dependent manner. Besides, idarubicin-loaded MNPs exhibited higher toxicity compared to free idarubicin. The results are promising for improvement in cancer chemotherapy. PMID:25194441

  16. Mobile Drug-Delivery for Ambient Assisted Living: Implantable and Extracorporeal Devices

    Microsoft Academic Search

    S. Haeberle; R. Gronmaier; T. Goettsche; M Vosseler; A. Kain; M. Reiterer; D. Hradetzky; C. Mueller; S. Messner; R. Zengerle

    Miniaturized smart drug delivery devices pave the way for a personalized treatment of many diseases by un- skilled persons outside the hospital. Many therapies require a repetitive delivery of a defined amount of drug in well defined time slots. Innovative drug delivery systems constitute an important prerequisite for ambient as- sisted living: The reliable delivery of drugs, in time and

  17. Stomach-site specific drug delivery system of clarithromycin for eradication of Helicobacter pylori.

    PubMed

    Rajinikanth, Paruvathanahalli Siddalingam; Mishra, Brahmeshwar

    2009-10-01

    Gellan gum based floating beads containing clarithromycin (FBC) were prepared by iontotropic gelation method for stomach-specific drug delivery against Helicobacter pylori. The scanning electron microscope photograph indicated that prepared beads were spherical in shape with rough outer surface. Formulation variables such as concentrations of gellan, calcium carbonate and drug loading influenced the in vitro drug release characteristics of prepared beads. In vitro release rate of clarithromycin was corrected using first order degradation rate constant which is degraded significantly during the release study in simulated gastric fluid pH 2.0. Further, the absence of interactions between drug and polymer was confirmed by differential scanning calorimetry analysis. Kinetic treatment of the in vitro drug release data with different kinetic equations revealed matrix diffusion mechanism. Prepared beads showed good anti-microbial activity against isolated H. pylori strain. The prepared beads have shown good in vivo floating efficiency in rabbit stomach. The stability studies of beads did not show any significant changes after storage of beads at 40 degrees C/75% relative humidity for 6 months. The preliminary results from this study suggest that floating beads of gellan can be used to incorporate antibiotics like clarithromycin and may be effective when administered locally in the stomach against H. pylori. PMID:19801860

  18. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine for enhanced bioavailability of highly lipophilic bioactive carotenoid lutein

    Microsoft Academic Search

    Srinivasan Shanmugam; Rengarajan Baskaran; Prabagar Balakrishnan; Pritam Thapa; Chul Soon Yong; Bong Kyu Yoo

    2011-01-01

    The objectives of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine (PC), an endogenous phospholipid with excellent in vivo solubilization capacity, as oil phase for the delivery of bioactive carotenoid lutein, by spray drying the SNEDDS (liquid system) containing PC using colloidal silica (Aerosil® 200 VV Pharma) as the inert solid carrier, and to evaluate

  19. ENDOCYTIC MECHANISMS FOR TARGETED DRUG DELIVERY

    PubMed Central

    Bareford, Lisa M.; Swaan, Peter W.

    2007-01-01

    Advances in the delivery of targeted drug systems have evolved to enable highly regulated site specific localization to subcellular organelles. Targeting therapeutics to individual intracellular compartments has resulted in benefits to therapies associated with these unique organelles. Endocytosis, a mechanism common to all cells in the body, internalizes macromolecules and retains them in transport vesicles which traffic along the endolysosomal scaffold. An array of vesicular internalization mechanisms exist, therefore understanding the key players specific to each pathway has allowed researchers to bioengineer macromolecular complexes for highly specialized delivery. Membrane specific receptors most frequently enter the cell through endocytosis following the binding of a high affinity ligand. High affinity ligands interact with membrane receptors, internalize in membrane bound vesicles, and traffic through cells in different manners to allow for accumulation in early endosomal fractions or lysosomally associated fractions. Although most drug delivery complexes aim to avoid lysosomal degradation, more recent studies have shown the clinical utility in directed protein delivery to this environment for the enzymatic release of therapeutics. Targeting nanomedicine complexes to the endolysosomal pathway have serious potential for improving drug delivery for the treatment of lysosomal storage diseases, cancer, and Alzheimer’s disease. Although several issues remain for receptor specific targeting, current work is investigating a synthetic receptor approach for high affinity binding of targeted macromolecules. PMID:17659804

  20. Multifunctional High Drug Loading Nanocarriers for Cancer Drug Delivery

    NASA Astrophysics Data System (ADS)

    Jin, Erlei

    2011-12-01

    Most anticancer drugs have poor water-solubility, rapid blood clearance, low tumor-selectivity and severe systemic toxicity to healthy tissues. Thus, polymeric nanocarriers have been widely explored for anticancer drugs to solve these problems. However, polymer nanocarriers developed to date still suffer drawbacks including low drug loading contents, premature drug release, slow cellular internalization, slow intracellular drug release and thereby low therapeutic efficiency in cancer thermotherapy. Accordingly, in this dissertation, functional nanocapsules and nanoparticles including high drug loading liposome-like nanocapsules, high drug loading phospholipid-mimic nanocapsules with fast intracellular drug release, high drug loading charge-reversal nanocapsules, TAT based long blood circulation nanoparticles and charge-reversal nuclear targeted nanoparticles are designed and synthesized. These functional carriers have advantages such as high drug loading contents without premature drug release, fast cellular internalization and intracellular drug release, nuclear targeted delivery and long blood circulation. As a result, all these drug carriers show much higher in vitro and in vivo anti-cancer activities.

  1. Intracellular antioxidants dissolve man-made antioxidant nanoparticles: using redox vulnerability of nanoceria to develop a responsive drug delivery system.

    PubMed

    Muhammad, Faheem; Wang, Aifei; Qi, Wenxiu; Zhang, Shixing; Zhu, Guangshan

    2014-11-12

    Regeneratable antioxidant property of nanoceria has widely been explored to minimize the deleterious influences of reactive oxygen species. Limited information is, however, available regarding the biological interactions and subsequent fate of nanoceria in body fluids. This study demonstrates a surprising dissolution of stable and ultrasmall (4 nm) cerium oxide nanoparticles (CeO2 NPs) in response to biologically prevalent antioxidant molecules (glutathione, vitamin C). Such a redox sensitive behavior of CeO2 NPs is subsequently exploited to design a redox responsive drug delivery system for transporting anticancer drug (camptothecin). Upon exposing the CeO2 capped and drug loaded nanoconstruct to vitamin c or glutathione, dissolution-accompanied aggregation of CeO2 nanolids unleashes the drug molecules from porous silica to achieve a significant anticancer activity. Besides stimuli responsive drug delivery, immobilization of nanoceria onto the surface of mesoporous silica also facilitates us to gain a basic insight into the biotransformation of CeO2 in physiological mediums. PMID:25312332

  2. 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

  3. Modification of chitosan by using samarium for potential use in drug delivery system.

    PubMed

    Kusrini, Eny; Arbianti, Rita; Sofyan, Nofrijon; Abdullah, Mohd Aidil A; Andriani, Fika

    2014-01-01

    In the presence of hydroxyl and amine groups, chitosan is highly reactive; therefore, it could be used as a carrier in drug delivery. For this study, chitosan-Sm complexes with different concentrations of samarium from 2.5 to 25 wt.% have been successfully synthesized by the impregnation method. Chitosan combined with Sm3+ ions produced a drug carrier material with fluorescence properties; thus, it could also be used as an indicator of drug release with ibuprofen (IBU) as a model drug. We evaluated the spectroscopic and interaction properties of chitosan and Sm3+ ions, the interaction of chitosan-Sm matrices with IBU as a model drug, and the effect of Sm3+ ions addition on the chitosan ability to adsorb the drug. The result showed that the hypersensitive fluorescence intensity of chitosan-Sm (2.5 wt.%) is higher than the others, even though the adsorption efficiency of chitosan-Sm 2.5wt.% is lower (29.75%) than that of chitosan-Sm 25 wt.% (33.04%). Chitosan-Sm 25 wt.% showed the highest efficiency of adsorption of ibuprofen (33.04%). In the release process of ibuprofen from the chitosan-Sm-IBU matrix, the intensity of orange fluorescent properties in the hypersensitive peak of 4G5/2?6H7/2 transition at 590 nm was observed. Fluorescent intensity increased with the cumulative amount of IBU released; therefore, the release of IBU from the Sm-modified chitosan complex can be monitored by the changes in fluorescent intensity. PMID:24177873

  4. In vitro and in vivo performance of novel supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS).

    PubMed

    Thomas, N; Holm, R; Müllertz, A; Rades, T

    2012-05-30

    Novel supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) containing the poorly water-soluble drug halofantrine above equilibrium solubility (150% S(eq)) were compared in vitro and in vivo with conventional SNEDDS containing the drug below equilibrium solubility (75% S(eq)). Pre-concentrates comprising of either medium chain lipids (Captex 300/Capmul MCM) or long chain lipids (soybean oil/Maisine), Cremophor RH40 and ethanol were formulated maintaining the lipid-to-surfactant-to-cosolvent ratio constant (55:35:10, w/w %). The ability of super-SNEDDS to increase the absorption of halofantrine in dogs, as well as the predictivity of the dynamic in vitro lipolysis model was studied. In vitro lipolysis of SNEDDS and super-SNEDDS showed rapid drug precipitation from all formulations while the same drug concentrations in the digestion medium were found during digestion of equal amounts of SNEDDS and super-SNEDDS. Elevated halofantrine solubilisation during in vitro lipolysis was observed only when multiple capsules of conventional SNEDDS were subjected to in vitro digestion. After lipolysis the isolated super-SNEDDS pellets were characterised by XRPD revealing no crystalline halofantrine from any of the investigated formulations. Subsequent dissolution studies of the super-SNEDDS pellet in the lipolysis medium demonstrated enhanced dissolution of halofantrine suggesting that halofantrine in the pellet was amorphous. The enhanced dissolution of the amorphous halofantrine was also reflected in vivo since two capsules of conventional SNEDDS were needed to achieve similar AUC and C(max) as obtained after dosing of a single capsule of super-SNEDDS. The study demonstrated that the absorption of halofantrine was not hampered by drug precipitation. Super-SNEDDS lead to precipitation of halofantrine in an amorphous form, which can be the driving force for enhanced absorption. Since super-SNEDDS were also physically stable for at least 6 months they represent a potential novel oral lipid-based drug delivery system for low aqueous soluble compounds. PMID:22405903

  5. Galantamine-loaded PLGA nanoparticles, from nano-emulsion templating, as novel advanced drug delivery systems to treat neurodegenerative diseases.

    PubMed

    Fornaguera, C; Feiner-Gracia, N; Calderó, G; García-Celma, M J; Solans, C

    2015-07-28

    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. PMID:26118655

  6. Chitosan-based thermosensitive hydrogel as a promising ocular drug delivery system: preparation, characterization, and in vivo evaluation.

    PubMed

    Chen, Xingwei; Li, Xinru; Zhou, Yanxia; Wang, Xiaoning; Zhang, Yanhui; Fan, Yating; Huang, Yanqing; Liu, Yan

    2012-11-01

    The purpose of this study was to evaluate the feasibility of in situ thermosensitive hydrogel based on chitosan in combination with disodium ?-d-Glucose 1-phosphate (DGP) for ocular drug delivery system. Aqueous solution of chitosan/DGP underwent sol-gel transition as temperature increased which was flowing sol at room temperature and then turned into non-flowing hydrogel at physiological temperature. The properties of gels were characterized regarding gelation time, gelation temperature, and morphology. The sol-to-gel phase transition behaviors were affected by the concentrations of chitosan, DGP and the model drug levocetirizine dihydrochloride (LD). The developed hydrogel presented a characteristic of a rapid release at the initial period followed by a sustained release and remarkably enhanced the cornea penetration of LD. The results of ocular irritation demonstrated the excellent ocular tolerance of the hydrogel. The ocular residence time for the hydrogel was significantly prolonged compared with eye drops. The drug-loaded hydrogel produced more effective anti-allergic conjunctivitis effects compared with LD aqueous solution. These results showed that the chitosan/DGP thermosensitive hydrogel could be used as an ideal ocular drug delivery system in terms of the suitable sol-gel transition temperature, mild pH environment in the hydrogel as well as the organic solvent free. PMID:21750179

  7. Microneedle-iontophoresis combinations for enhanced transdermal drug delivery.

    PubMed

    Donnelly, Ryan F; Garland, Martin J; Alkilani, Ahlam Zaid

    2014-01-01

    It has recently been proposed that the combination of skin barrier impairment using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range of drugs suitable for transdermal delivery as well as enabling the rate of delivery to be achieved with precise electronic control. However, few reports exist on the combination of ITP with in situ drug-loaded polymeric MN delivery systems. Our in vitro permeation studies revealed that MN enhances transdermal drug delivery. The combination of dissolving MN and ITP did not further enhance the extent of delivery of the low molecular weight drug ibuprofen sodium after short application periods. However, the extent of peptide/protein delivery was significantly enhanced when ITP was used in combination with hydrogel-forming MN arrays. As such, hydrogel-forming MN arrays show promise for the electrically controlled transdermal delivery of biomacromolecules in a simple, one-step approach, though further technical developments will be necessary before patient benefit is realized. PMID:24567135

  8. Development of a Microfluidics-Based Intracochlear Drug Delivery Device

    Microsoft Academic Search

    William F. Sewell; Jeffrey T. Borenstein; Zhiqiang Chen; Jason Fiering; Ophir Handzel; Maria Holmboe; Ernest S. Kim; Sharon G. Kujawa; Michael J. McKenna; Mark M. Mescher; Brian Murphy; Erin E. Leary Swan; Marcello Peppi; Sarah Tao

    2009-01-01

    Background: Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods: We have taken a microfluidics\\/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the

  9. Drug delivery nanoparticles in skin cancers.

    PubMed

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

    2014-01-01

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

  10. Biodegradable In Situ Gel-Forming Controlled Drug Delivery System Based on Thermosensitive Poly(?-caprolactone)-Poly(ethylene glycol)-Poly(?-caprolactone) Hydrogel.

    PubMed

    Khodaverdi, Elham; Golmohammadian, Ali; Mohajeri, Seyed Ahmad; Zohuri, Gholamhossein; Mirzazadeh Tekie, Farnaz Sadat; Hadizadeh, Farzin

    2012-01-01

    Traditional drug delivery systems which are based on multiple dosing regimens usually pose many disadvantages such as poor compliance of patients and drug plasma level variation. To overcome the obstacles of traditional drug formulations, novel drug delivery system PCL-PEG-PCL hydrogels have been purposed in this study. Copolymers were synthesized by rapid microwave-assisted and conventional synthesis methods. Polymer characterizations were done using gel permeation chromatography and (1)H-NMR. Phase transition behavior was evaluated by inverting tube method and in vitro drug release profile was determined using naltrexone hydrochloride and vitamin B(12) as drug models. The results indicated that loaded drug structure and copolymer concentration play critical roles in release profile of drugs from these hydrogels. This study also confirmed that synthesis of copolymer using microwave is the most effective method for synthesis of this kind of copolymer. PMID:23227366

  11. Biodegradable In Situ Gel-Forming Controlled Drug Delivery System Based on Thermosensitive Poly(?-caprolactone)-Poly(ethylene glycol)-Poly(?-caprolactone) Hydrogel

    PubMed Central

    Khodaverdi, Elham; Golmohammadian, Ali; Mohajeri, Seyed Ahmad; Zohuri, Gholamhossein; Mirzazadeh Tekie, Farnaz Sadat; Hadizadeh, Farzin

    2012-01-01

    Traditional drug delivery systems which are based on multiple dosing regimens usually pose many disadvantages such as poor compliance of patients and drug plasma level variation. To overcome the obstacles of traditional drug formulations, novel drug delivery system PCL-PEG-PCL hydrogels have been purposed in this study. Copolymers were synthesized by rapid microwave-assisted and conventional synthesis methods. Polymer characterizations were done using gel permeation chromatography and 1H-NMR. Phase transition behavior was evaluated by inverting tube method and in vitro drug release profile was determined using naltrexone hydrochloride and vitamin B12 as drug models. The results indicated that loaded drug structure and copolymer concentration play critical roles in release profile of drugs from these hydrogels. This study also confirmed that synthesis of copolymer using microwave is the most effective method for synthesis of this kind of copolymer. PMID:23227366

  12. 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

  13. Polysaccharide-Based Micelles for Drug Delivery

    PubMed Central

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

    2013-01-01

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

  14. The rise and rise of drug delivery

    Microsoft Academic Search

    Howard Rosen; Thierry Abribat

    2005-01-01

    Drug delivery has typically focused on optimizing marketed compounds, improving their effectiveness or tolerability, and simplifying their administration. This role now includes the first biopharmaceuticals as well as more conventional drugs. As drug-delivery technologies come into play earlier in the development cycle, however, they can also enhance the screening and evaluation of new compounds and 'rescue' failed compounds, such as

  15. Biocompatibility and biofouling of MEMS drug delivery devices

    Microsoft Academic Search

    Gabriela Voskerician; Matthew S. Shive; Rebecca S. Shawgo; Horst von Recum; James M. Anderson; Michael J. Cima; Robert Langer

    2003-01-01

    The biocompatibility and biofouling of the microfabrication materials for a MEMS drug delivery device have been evaluated. The in vivo inflammatory and wound healing response of MEMS drug delivery component materials, metallic gold, silicon nitride, silicon dioxide, silicon, and SU-8TM photoresist, were evaluated using the cage implant system. Materials, placed into stainless-steel cages, were implanted subcutaneously in a rodent model.

  16. Physical characterizations of microemulsion systems using tocopheryl polyethylene glycol 1000 succinate (TPGS) as a surfactant for the oral delivery of protein drugs

    Microsoft Academic Search

    Wen-Ting Ke; Shyr-Yi Lin; Hsiu-O Ho; Ming-Thau Sheu

    2005-01-01

    Attempts were to develop microemulsion systems using medium chain triglyceride, deionized water, and TPGS as surfactant for the oral delivery of protein drugs or poorly water-soluble drugs. Phase diagrams were constructed to elucidate the phase behavior of systems composed of Captex 300 and water with d-?-tocopheryl polyethylene glycol 1000 succinate (TPGS) as main surfactant, polysorbates (Tween 20, Tween 40, Tween

  17. Development and evaluation of a novel mucus diffusion test system approved by self-nanoemulsifying drug delivery systems.

    PubMed

    Friedl, Heike; Dünnhaupt, Sarah; Hintzen, Fabian; Waldner, Claudia; Parikh, Shruti; Pearson, Jeffrey P; Wilcox, Matthew D; Bernkop-Schnürch, Andreas

    2013-12-01

    The aim of this study was the development of a novel mucus diffusion model and the approval thereof by self-nanoemulsifying drug delivery systems (SNEDDSs). For diffusion experiments, various SNEDD formulations were developed, spiked with fluorescein diacetate, and evaluated for their mucus diffusion behavior through an intestinal mucus layer within the novel setup. In brief, SNEDD formulations resulting in particle sizes of 12.0 nm produced 70.3% of diffused model drug through the mucus layer. In comparison, SNEDDSs with particle sizes of 455.5 nm led to a permeation of 8.3% only. Apart from this size dependence, two SNEDDS excipients namely Cremophor RH 40 and triacetin were identified to strongly affect the permeation through mucus. Hence, it could be demonstrated that particle size and single excipients can positively influence mucus diffusion of SNEDDSs. Furthermore, it could be shown that the developed mucus diffusion model is a promising tool for pharmaceutical research in comparison with already established systems as it allows an easy handling coupled with the possibility to test different kinds of mucus in parallel within one setup. PMID:24258284

  18. 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

  19. In vitro comparative evaluation of monolayered multipolymeric films embedded with didanosine-loaded solid lipid nanoparticles: a potential buccal drug delivery system for ARV therapy.

    PubMed

    Jones, Elsabé; Ojewole, Elizabeth; Kalhapure, Rahul; Govender, Thirumala

    2014-05-01

    Drug delivery via the buccal route has emerged as a promising alternative to oral drug delivery. Didanosine (DDI) undergoes rapid degradation in the gastrointestinal tract, has a short half-life and low oral bioavailability, making DDI a suitable candidate for buccal delivery. Recent developments in buccal drug delivery show an increased interest toward nano-enabled delivery systems. The advantages of buccal drug delivery can be combined with that of nanoparticulate delivery systems to provide a superior delivery system. The aim of this study was to design and evaluate the preparation of novel nano-enabled films for buccal delivery of DDI. Solid lipid nanoparticles (SLNs) were prepared via hot homogenization followed by ultrasonication and were characterized before being incorporated into nano-enabled monolayered multipolymeric films (MMFs). Glyceryl tripalmitate with Poloxamer 188 was identified as most suitable for the preparation of DDI-loaded SLNs. SLNs with desired particle size (PS) (201?nm), polydispersity index (PDI) (0.168) and zeta potential (-18.8?mV) were incorporated into MMFs and characterized. Conventional and nano-enabled MMFs were prepared via solvent casting/evaporation using Eudragit RS100 and hydroxypropyl methylcellulose. Drug release from the nano-enabled films was found to be faster (56% versus 20% in first hour). Conventional MMFs exhibited higher mucoadhesion and mechanical strength than nano-enabled MMFs. SLNs did not adversely affect the steady state flux (71.63?±?13.54?µg/cm(2)?h versus 74.39?±?15.95?µg/cm(2)?h) thereby confirming the potential transbuccal delivery of DDI using nano-enabled MMFs. Nano-enabled buccal films for delivery of DDI can be successfully prepared, and these physico-mechanical studies serve as a platform for future formulation optimization work in this emerging field. PMID:24576267

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

    PubMed

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

    2014-12-01

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

  1. Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins

    Microsoft Academic Search

    N. Saito; N. Murakami; J. Takahashi; H. Horiuchi; H. Ota; H. Kato; T. Okada; K. Nozaki; K. Takaoka

    2005-01-01

    Bone morphogenetic proteins (BMP) induce bone formation in vivo, and clinical application in repair of bone fractures and defects is expected. However, appropriate systems to deliver BMP for clinical use need to be developed. We synthesized a new synthetic biodegradable polymer, poly-d,l-lactic acid-para-dioxanone-polyethylene glycol block copolymer (PLA-DX-PEG), to serve as a biocompatible, biodegradable polymer for recombinant human (rh) BMP-2 delivery

  2. In situ electrolyte interactions in a disk-compressed configuration system for up-curving and constant drug delivery.

    PubMed

    Pillay, V; Fassihi, R

    2000-06-15

    A new approach in drug delivery system design for meeting the needs that are associated with certain circadian variations is presented. The system is comprised of a pure compressed drug disk, which is encased by a polymeric coat using hydroxypropylmethylcellulose or polyethylene oxide. Within the polymeric coat, a physiologically acceptable binary electrolyte combination such as sodium deoxycholate and adipic acid is disposed. Through this process and upon exposure to dissolution media, ionic interactions occur and a texturally variable matrix is manifested in the form of peripheral stiffening' with self-correcting boundaries as demonstrated by texture analysis studies. The peripheral boundaries erode and progressively shift toward the disk-core, thus constantly reducing the diffusional pathlength with the resultant up-curving kinetics. Utilizing these mechanisms, a lag time is induced and drug is delivered over a 24-h period in one of two ways namely, in an up-curving or constant manner for drug models theophylline and diltiazem hydrochloride with water solubilities of 0.85% and > 50% at 25 degrees C, respectively. It appears that for both sparingly and highly soluble drugs, sum of the dissolution/diffusion rates, dynamics of diffusional pathlength and system erosion rate control the release process. The heterogeneous nature of changes in coat thickness, stiffening dynamics and erosion rate in relation to disk geometry is discussed. The developed technology has potential to provide release patterns, compatible with specific chronophysiological conditions, and overcome the absorption-limited capacity of the distal gastrointestinal tract PMID:10773329

  3. 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

  4. Tunable sustained intravitreal drug delivery system for daunorubicin using oxidized porous silicon

    PubMed Central

    Hou, Huiyuan; Nieto, Alejandra; Ma, Feiyan; Freeman, William R.; Sailor, Michael J.; Cheng, Lingyun

    2014-01-01

    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 3 months. 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 15 nm to 95 nm. In vitro studies showed that degradation of pSi O2 increased with increasing pore size and the degradation of pSi O2 was approximately constant for a given particle type. The degradation of pSi O2 with 43 nm 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 µg/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 (43 nm) yielded a significantly higher DNR level than particles with 15 or 26 nm pores (13.5±6.9 ng/mL vs. 2.3±1.6 ng/mL and 1.1±0.9 ng/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 vitreous at post-injection day 14 was 66.52 ng/mL for 95 nm pore size pSiO2-CO2H:DNR, 10.76 ng/mL for 43 nm pSi O2-CO2 H:DNR, and only 1.05 ng/mL for 15 nm pSi O2-CO2 H:DNR. Pore expansion from 15 nm to 95 nm led to a 63 folds 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 pSi O2 covalently loaded with DNR by engineering the nano-pore size of pSi. PMID:24424270

  5. Interplay of stimuli-responsiveness, drug loading and release for a surface-engineered dendrimer delivery system.

    PubMed

    Liu, Ruihong; Sun, Mingjing; Liu, Xipan; Fan, Aiping; Wang, Zheng; Zhao, Yanjun

    2014-02-28

    The objectives of this study were to generate novel thermo and pH dual responsive poly(amidoamine) (PAMAM) via precise surface engineering, and investigate the interplay of dendrimer stimuli-responsiveness and the loading and release properties of a model agent, vitamin E acetate (VEAc). A higher dendrimer generation and maximized VEAc loading at elevated pH all contributed to a lower cloud point (CP) of the dendrimer-VEAc complex. The drug loading in G3.5 surface-engineered PAMAM was 22 mol/mol (pH 7.0) and 10 mol/mol (pH 5.0), which corresponded to a complex CP value at ca. 13 °C (pH 7.0) and 46 °C (pH 5.0), respectively. At physiological conditions, only less than 40% of VEAc was liberated when reaching the plateau, whilst more than 90% of VEAc was released from such system within 6 h at pH 5.0. This was due to the transition of dendrimer surface from dehydrated state to hydrated state upon pH dropping, enabling rapid drug release for therapeutic action. This smart stimuli-responsive dendritic delivery system holds promise for the efficient drug delivery to tissues with pH abnormality such as tumor. PMID:24374220

  6. An aptamer-targeting photoresponsive drug delivery system using "off-on" graphene oxide wrapped mesoporous silica nanoparticles.

    PubMed

    Tang, Yuxia; Hu, Hao; Zhang, Molly Gu; Song, Jibin; Nie, Liming; Wang, Shouju; Niu, Gang; Huang, Peng; Lu, Guangming; Chen, Xiaoyuan

    2015-04-14

    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. PMID:25782595

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

    PubMed

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

    2015-01-01

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

  8. Oxaliplatin-chitosan nanoparticles induced intrinsic apoptotic signaling pathway: a "smart" drug delivery system to breast cancer cell therapy.

    PubMed

    Vivek, Raju; Thangam, Ramar; Nipunbabu, Varukattu; Ponraj, Thondhi; Kannan, Soundarapandian

    2014-04-01

    This study was to investigate "smart" pH-responsive drug delivery system (DDS) based on chitosan nano-carrier for its potential intelligent controlled release and enhancing chemotherapeutic efficiency of Oxalipaltin. Oxaliplatin was loaded onto chitosan by forming complexes with degradable to construct nano-carrier as a DDS. Oxaliplatin was released from the DDS much more rapidly at pH 4.5 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. Furthermore, the possible intrinsic apoptotic signaling pathway was explored by Western blot. It was found that expression of Bax, Bik, cytochrome C, caspase-9 and -3 was significantly up-regulated while the Bcl-2 and Survivin were inhibited in breast cancer MCF-7 cells. For instance, nanoparticles inducing apoptosis in caspase-dependent manner indicate that chitosan nanoparticles could act as an efficient DDS importing Oxalipaltin to target cancer cells. These approaches suggest that "smart" Oxaliplatin delivery strategy is a promising approach to cancer therapy. PMID:24472507

  9. Comparison of rheological properties, follicular penetration, drug release, and permeation behavior of a novel topical drug delivery system and a conventional cream.

    PubMed

    Lauterbach, Andreas; Müller-Goymann, Christel C

    2014-11-01

    A novel adapalene-loaded solid lipid microparticle (SLMA) dispersion as a topical drug delivery system (TDDS) for follicular penetration has been introduced. The objective of the present study was to investigate the rheological properties, the follicular penetration with differential tape stripping on porcine ear skin, the drug release in sebum and stratum corneum (SC) lipid mixtures, and the permeation behavior across human SC in comparison with a commercially available cream as standard. Physicochemical characterization reveals that adapalene is homogeneously distributed within the SLMA dispersion and chemically stable for at least 24 weeks. The SLMA dispersion shows a lower complex viscosity at 20 °C and a higher one at 32 °C than the cream, while the phase angle of the dispersion is always larger at both temperatures. Both formulations feature an equivalent potential for follicular penetration and deposition. However, the superiority of the SLMA dispersion is based on the preferential drug release in sebum while there is no or just a slight release in SC lipids and no permeation for both formulations. Due to the similarity of the glyceride matrix of the SLMA to sebum components, a targeted drug delivery into sebum and thereby an increased follicular penetration may be facilitated. PMID:25460145

  10. Development of a solid supersaturatable self-emulsifying drug delivery system of docetaxel with improved dissolution and bioavailability.

    PubMed

    Chen, Ying; Chen, Chen; Zheng, Jianling; Chen, Zhiyu; Shi, Qiongzhi; Liu, Hong

    2011-01-01

    The objective of this study was to prepare a solid supersaturatable self-emulsifying drug delivery system (S-sSEDDS) using docetaxel (DTX). Different from conventional self-emulsifying drug delivery systems (SEDDSs), a solid supersaturatable self-emulsifying drug delivery system of docetaxel (DTX-S-sSEDDS) was prepared by spray drying, using lactose as the solid carrier and hydroxypropyl methylcellulose (HPMC) as the supersaturation promoter. Physicochemical properties and in vitro dissolution was observed while taking into account factors such as formulations, supersaturated promoters, solid carriers, and preparation methods. The bioavailability of the DTX-S-sSEDDS(1) compared with other formulations of DTX was evaluated in rats. The results showed that the presence of HPMC effectively sustained the supersaturated state by retarding the precipitation kinetics. Although the total amount of emulsifying excipients in the DTX-S-sSEDDS(1) was only 3/5 as much as that of the conventional SEDDS (DTX-SEDDS(2)), the percent of the accumulated dissolved DTX-S-sSEDDS(1) at 2 h reached 90.96%, which was higher than that of the DTX-SEDDS(2) (76.26%) and approximately 29.8 times as much as that of the DTX crude powder. The in vivo studies indicated that the area under the concentration-time curve (AUC(0-?)) of the DTX-S-sSEDDS(1) increased by nearly 8.77-fold, 1.45-fold more than those of the DTX powder and the conventional SEDDS without the presence of HPMC (DTX-SEDDS(1)) at a dose of 10 mg/kg. In conclusion, the S-sSEDDS provides an effective approach for improving the dissolution and bioavailability of docetaxel with a low level of emulsifying excipients and provides a reference for good stabilization and the safety of SEDDSs. PMID:21415541

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

    PubMed Central

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

    2012-01-01

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

  12. Electrically Controlled Drug Delivery from Graphene Oxide Nanocomposite Films

    PubMed Central

    2015-01-01

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

  13. Targeting strategies for delivery of anti-HIV drugs.

    PubMed

    Ramana, Lakshmi Narashimhan; Anand, Appakkudal R; Sethuraman, Swaminathan; Krishnan, Uma Maheswari

    2014-10-28

    Human Immunodeficiency Virus (HIV) infection remains a significant cause of mortality globally. Though antiretroviral therapy has significantly reduced AIDS-related morbidity and mortality, there are several drawbacks in the current therapy, including toxicity, drug-drug interactions, development of drug resistance, necessity for long-term drug therapy, poor bio-availability and lack of access to tissues and reservoirs. To circumvent these problems, recent anti-HIV therapeutic research has focused on improving drug delivery systems through drug delivery targeted specifically to host cells infected with HIV or could potentially get infected with HIV. In this regard, several surface molecules of both viral and host cell origin have been described in recent years, that would enable targeted drug delivery in HIV infection. In the present review, we provide a comprehensive overview of the need for novel drug delivery systems, and the successes and challenges in the identification of novel viral and host-cell molecules for the targeted drug delivery of anti-HIV drugs. Such targeted anti-retroviral drug delivery approaches could pave the way for effective treatment and eradication of HIV from the body. PMID:25119469

  14. Prilling for the development of multi-particulate colon drug delivery systems: pectin vs. pectin-alginate beads.

    PubMed

    Auriemma, Giulia; Mencherini, Teresa; Russo, Paola; Stigliani, Mariateresa; Aquino, Rita P; Del Gaudio, Pasquale

    2013-01-30

    This paper proposes a multi-particulate drug delivery system produced by prilling technique in combination with an enteric coating. Optimization of process parameters, such as feed viscosity at nozzle, selection of cross-linker, pH of the gelling solution and cross-linking time, allows to obtain beads with strong gelled matrix. Results showed that dextran/piroxicam beads demonstrated high encapsulation efficiency, very narrow dimensional distribution and high sphericity. Coated beads retained shape and narrow size distribution of the uncoated particles. Moreover, the strength of the produced Zn(2+)-pectinate beads allows to reduce Eudragit coating thickness. Piroxicam loaded multi-particulate systems show an interesting prolonged drug release in intestinal fluids. Hence, such platforms could be proposed for the treatment of inflammatory bowel diseases. PMID:23218307

  15. Size and charge characterization of polymeric drug delivery systems by Taylor dispersion analysis and capillary electrophoresis.

    PubMed

    Ibrahim, Amal; Meyrueix, Rémi; Pouliquen, Gauthier; Chan, You Ping; Cottet, Hervé

    2013-06-01

    In this work, Taylor dispersion analysis and capillary electrophoresis were used to characterize the size and charge of polymeric drug delivery nanogels based on polyglutamate chains grafted with hydrophobic groups of vitamin E. The hydrophobic vitamin E groups self-associate in water to form small hydrophobic nanodomains that can incorporate small drugs or therapeutic proteins. Taylor dispersion analysis is well suited to determine the weight average hydrodynamic radius of nanomaterials and to get information on the size polydispersity of polymeric samples. The effective charge was determined either from electrophoretic mobility and hydrodynamic radius using electrophoretic modeling (three different approaches were compared), or by indirect UV detection in capillary electrophoresis. The influence of vitamin E hydrophobicity on the polymer effective charge has been studied. The presence of vitamin E leads to a drastic decrease in polymer effective charge in comparison to non-modified polyglutamate. Finally, the electrophoretic behavior of polyglutamate backbone grafted with hydrophobic vitamin E (pGVE) nanogels according to the ionic strength was investigated using the recently proposed slope plot approach. It was deduced that the pGVE nanogels behave electrophoretically as polyelectrolytes which is in good agreement with the high water content of the nanogels. PMID:23624952

  16. A thermosensitive hydrogel based on quaternized chitosan and poly(ethylene glycol) for nasal drug delivery system.

    PubMed

    Wu, Jie; Wei, Wei; Wang, Lian-Yan; Su, Zhi-Guo; Ma, Guang-Hui

    2007-04-01

    A new thermosensitive hydrogel was designed and prepared by simply mixing N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) and poly(ethylene glycol) (PEG) with a small amount of alpha-beta-glycerophosphate (alpha-beta-GP). The optimum preparative condition was investigated, and the obtained formulation underwent thermal transition from solution below or at room temperature to non-flowing hydrogel around 37 degrees C in several minutes. As a new formulation, its potential use as nasal drug delivery system was studied. It can be dropped or sprayed easily into nasal cavity and spread on the nasal mucosa in solution state. After being administered into nasal cavity, the solution transformed into viscous hydrogel at body temperature, which decreased nasal mucociliary clearance rate and released drug slowly. Morever, quaternized chitosan as absorption enhancer has been studied extensively in several reports and proved its non-toxicity, mucoadhesivity and the capacity to open the tight junctions between epithelial cells. Therefore, in this study insulin as a model drug was entrapped in this formulation and its release behavior in vitro was also investigated. The enhancement of absorption of fluorescein isothiocyanate (FITC)-labeled insulin in rat nasal cavity by this formulation was proved by confocal laser scanning microscopy (CLSM). The cytoxicity and the change of the blood glucose concentration after nasal administration of this hydrogel were also investigated. The hydrogel formulation decreased the blood glucose concentration apparently (40-50% of initial blood glucose concentration) for at least 4-5h after administration, and no apparent cytoxicity was found after application. These results showed that HTCC-PEG-GP formulation can be used as nasal drug delivery system to improve the absorption of hydrophilic macromolecular drugs. PMID:17291582

  17. Hydrogels composed of cyclodextrin inclusion complexes with PLGA-PEG-PLGA triblock copolymers as drug delivery systems.

    PubMed

    Khodaverdi, Elham; Mirzazadeh Tekie, Farnaz Sadat; Hadizadeh, Farzin; Esmaeel, Haydar; Mohajeri, Seyed Ahmad; Sajadi Tabassi, Sayyed A; Zohuri, Gholamhossein

    2014-02-01

    Although conventional pharmaceuticals have many drug dosage forms on the market, the development of new therapeutic molecules and the low efficacy of instant release formulations for the treatment of some chronic diseases and specific conditions encourage scientists to invent different delivery systems. To this purpose, a supramolecular hydrogel consisting of the tri-block copolymer PLGA-PEGPLGA and ?-cyclodextrin was fabricated for the first time and characterised in terms of rheological, morphological, and structural properties. Naltrexone hydrochloride and vitamin B12 were loaded, and their release profiles were determined. PMID:24234803

  18. Co-delivery of natural metabolic inhibitors in a self-microemulsifying drug delivery system for improved oral bioavailability of curcumin.

    PubMed

    Grill, Alex E; Koniar, Brenda; Panyam, Jayanth

    2014-08-01

    In spite of its well-documented anticancer chemopreventive and therapeutic activity, the clinical development of curcumin has been limited by its poor oral bioavailability. Curcumin has low aqueous solubility and undergoes extensive first pass metabolism following oral dosing. We hypothesized that oral bioavailability of curcumin can be enhanced by increasing its absorption and decreasing its metabolic clearance simultaneously. To test this hypothesis, we formulated curcumin with naturally occurring UGT inhibitors (piperine, quercetin, tangeretin, and silibinin) in a self-microemulsifying drug delivery system (SMEDDS). Mouse liver microsome studies showed that silibinin and quercetin inhibited curcumin glucuronidation effectively. When dosed orally in mice, the SMEDDS containing curcumin alone increased curcumin glucuronide concentrations in plasma without significantly affecting parent drug concentration. Of the four inhibitors examined in vivo, silibinin significantly improved the Cmax (0.15 ?M vs. 0.03 ?M for curcumin SMEDDS) and the overall bioavailability (3.5-fold vs. curcumin SMEDDS) of curcumin. Previous studies have shown that silibinin has anticancer activity as well. Thus, co-delivery of silibinin with curcumin in SMEDDS represents a novel and promising approach to improve curcumin bioavailability. PMID:25422796