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Sample records for drug delivery system

  1. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

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

  2. Mucoadhesive drug delivery systems

    PubMed Central

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

    2011-01-01

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

  3. 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.

  4. Polymers for Drug Delivery Systems

    PubMed Central

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

    2012-01-01

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

  5. Novel central nervous system drug delivery systems.

    PubMed

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

    2014-05-01

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

  6. Microfabricated injectable drug delivery system

    DOEpatents

    Krulevitch, Peter A.; Wang, Amy W.

    2002-01-01

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

  7. Collagen macromolecular drug delivery systems

    SciTech Connect

    Gilbert, D.L.

    1988-01-01

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

  8. 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

  9. Heart-targeted nanoscale drug delivery systems.

    PubMed

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

    2014-09-01

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

  10. 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

  11. Radiation sterilization of new drug delivery systems

    PubMed Central

    Abuhanoğlu, Gürhan

    2014-01-01

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

  12. 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

  13. 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

  14. Nanomedicine-nanoscale drugs and delivery systems.

    PubMed

    Singh, Surya

    2010-12-01

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

  15. Brain drug delivery systems for neurodegenerative disorders.

    PubMed

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

    2012-09-01

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

  16. 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.

  17. Recent technologies in pulsatile drug delivery systems

    PubMed Central

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

    2011-01-01

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

  18. Drug delivery system and breast cancer cells

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  19. 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

  20. Kontrollierte therapeutische Systeme (Controlled drug delivery systems)

    NASA Astrophysics Data System (ADS)

    Ha, Suk-Woo; Wintermantel, Erich

    Es gibt eine grosse Anzahl von Arzneistoffen, die nicht mit der höchsten Effizienz eingesetzt werden können, weil das geeignete therapeutische System (drug delivery system) für die optimale Applikation fehlt. Viele Arzneistoffe setzen eine häufige Anwendung voraus und sind oft mit mehr oder weniger starken Nebenwirkungen oder aber mit Beeinträchtigungen von Arbeits- und Lebensrhythmus der Patienten verbunden. Der therapeutische Erfolg einer medikamentösen Behandlung setzt eine korrekte Diagnose, die Wahl der richtigen Wirksubstanz sowie ihr Vorliegen in geeigneter Darreichungsform voraus. Zudem muss ein genauer Verabreichungsplan erstellt werden, dessen Einhaltung seitens der Patienten eine wesentliche Voraussetzung für die optimale Wirkung des Arzneistoffes ist. Das Mass, mit dem eine Wirksubstanz therapeutisch voll genutzt werden kann, korreliert direkt mit der Darreichungsform, in der sie angewandt wird. Da viele hochwirksame Arzneimittel bereits existieren, hat sich, neben Neuentwicklungen, das Interesse im vergangenen Jahrzehnt der Optimierung von Arzneimittelwirkungen durch neue Darreichungsformen zugewandt.

  1. Microemulsions based transdermal drug delivery systems.

    PubMed

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

    2014-01-01

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

  2. 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

  3. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

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

  4. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

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

  5. Silk Electrogel Based Gastroretentive Drug Delivery System

    NASA Astrophysics Data System (ADS)

    Wang, Qianrui

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

  6. Biomedical Imaging in Implantable Drug Delivery Systems

    PubMed Central

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

    2015-01-01

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

  7. Phospholipid nanodisc engineering for drug delivery systems.

    PubMed

    Murakami, Tatsuya

    2012-06-01

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

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

    PubMed

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

    2016-08-20

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

  9. 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

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

    PubMed

    Sutradhar, Kumar Bishwajit; Sumi, Chandra Datta

    2016-01-01

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

  11. Oral Dispersible System: A New Approach in Drug Delivery System

    PubMed Central

    Hannan, P. A.; Khan, J. A.; Khan, A.; Safiullah, S.

    2016-01-01

    Dosage form is a mean used for the delivery of drug to a living body. In order to get the desired effect the drug should be delivered to its site of action at such rate and concentration to achieve the maximum therapeutic effect and minimum adverse effect. Since oral route is still widely accepted route but having a common drawback of difficulty in swallowing of tablets and capsules. Therefore a lot of research has been done on novel drug delivery systems. This review is about oral dispersible tablets a novel approach in drug delivery systems that are now a day's more focused in formulation world, and laid a new path that, helped the patients to build their compliance level with the therapy, also reduced the cost and ease the administration especially in case of pediatrics and geriatrics. Quick absorption, rapid onset of action and reduction in drug loss properties are the basic advantages of this dosage form. PMID:27168675

  12. Oral Dispersible System: A New Approach in Drug Delivery System.

    PubMed

    Hannan, P A; Khan, J A; Khan, A; Safiullah, S

    2016-01-01

    Dosage form is a mean used for the delivery of drug to a living body. In order to get the desired effect the drug should be delivered to its site of action at such rate and concentration to achieve the maximum therapeutic effect and minimum adverse effect. Since oral route is still widely accepted route but having a common drawback of difficulty in swallowing of tablets and capsules. Therefore a lot of research has been done on novel drug delivery systems. This review is about oral dispersible tablets a novel approach in drug delivery systems that are now a day's more focused in formulation world, and laid a new path that, helped the patients to build their compliance level with the therapy, also reduced the cost and ease the administration especially in case of pediatrics and geriatrics. Quick absorption, rapid onset of action and reduction in drug loss properties are the basic advantages of this dosage form.

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

    PubMed

    Tesfamariam, Belay

    2016-09-28

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

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

    PubMed

    Park, Kinam

    2014-09-28

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

  15. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    PubMed

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

    2016-01-01

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

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

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2016-01-01

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

  17. 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

  18. Marine Origin Polysaccharides in Drug Delivery Systems

    PubMed Central

    Cardoso, Matias J.; Costa, Rui R.; Mano, João F.

    2016-01-01

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine. PMID:26861358

  19. 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

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

    PubMed

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

    2002-01-01

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

  1. Colloidal drug delivery systems: current status and future directions.

    PubMed

    Garg, Tarun; Rath, Goutam; Goyal, Amit Kumar

    2015-01-01

    In this paper, we provide an overview an extensive range of colloidal drug delivery systems with special focus on vesicular and particulates systems that are being used in research or might be potentially useful as carriers systems for drug or active biomolecules or as cell carriers with application in the therapeutic field. We present some important examples of commercially available drug delivery systems with applications in research or in clinical fields. This class of systems is widely used due to excellent drug targeting, sustained and controlled release behavior, higher entrapment efficiency of drug molecules, prevention of drug hydrolysis or enzymatic degradation, and improvement of therapeutic efficacy. These characteristics help in the selection of suitable carrier systems for drug, cell, and gene delivery in different fields.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  4. Mucoadhesive and thermogelling systems for vaginal drug delivery.

    PubMed

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

    2015-09-15

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

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

    PubMed Central

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

    2014-01-01

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

  6. Albumin-based nanocomposite spheres for advanced drug delivery systems.

    PubMed

    Misak, Heath E; Asmatulu, Ramazan; Gopu, Janani S; Man, Ka-Poh; Zacharias, Nora M; Wooley, Paul H; Yang, Shang-You

    2014-01-01

    A novel drug delivery system incorporating human serum albumin, poly(lactic-co-glycolic acid, magnetite nanoparticles, and therapeutic agent(s) was developed for potential application in the treatment of diseases such as rheumatoid arthritis and skin cancer. An oil-in-oil emulsion/solvent evaporation (O/OSE) method was modified to produce a drug delivery system with a diameter of 0.5–2 μm. The diameter was mainly controlled by adjusting the viscosity of albumin in the discontinuous phase of the O/OSE method. The drug-release study showed that the release of drug and albumin was mostly dependent on the albumin content of the drug delivery system, which is very similar to the drug occlusion-mesopore model. Cytotoxicity tests indicated that increasing the albumin content in the drug delivery system increased cell viability, possibly due to the improved biocompatibility of the system. Overall, these studies show that the proposed system could be a viable option as a drug delivery system in the treatment of many illnesses, such as rheumatoid arthritis, and skin and breast cancers. PMID:24106002

  7. Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

    PubMed Central

    Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

    2012-01-01

    The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

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

    PubMed

    Szabo, Peter; Zelko, Romana

    2015-01-01

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

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

    PubMed

    Szabo, Peter; Zelko, Romana

    2015-01-01

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

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

    PubMed

    Yavuz, Burçin; Pehlivan, Sibel Bozdağ; Unlü, Nurşen

    2013-01-01

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

  11. Dendrimeric Systems and Their Applications in Ocular Drug Delivery

    PubMed Central

    Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

    2013-01-01

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

  12. Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation

    PubMed Central

    Rajan, Reshmy; Jose, Shoma; Mukund, V. P. Biju; Vasudevan, Deepa T.

    2011-01-01

    Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era. PMID:22171309

  13. Recent advances of cocktail chemotherapy by combination drug delivery systems.

    PubMed

    Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

    2016-03-01

    Combination chemotherapy is widely exploited for enhanced cancer treatment in the clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end.

  14. Functionalized nanofibers as drug-delivery systems for osteochondral regeneration.

    PubMed

    Amler, Evžen; Filová, Eva; Buzgo, Matej; Prosecká, Eva; Rampichová, Michala; Nečas, Alois; Nooeaid, Patcharakamon; Boccaccini, Aldo R

    2014-05-01

    A wide range of drug-delivery systems are currently attracting the attention of researchers. Nanofibers are very interesting carriers for drug delivery. This is because nanofibers are versatile, flexible, nanobiomimetic and similar to extracellular matrix components, possible to be functionalized both on their surface as well as in their core, and also because they can be produced easily and cost effectively. There have been increasing attempts to use nanofibers in the construction of a range of tissues, including cartilage and bone. Nanofibers have also been favorably engaged as a drug-delivery system in cell-free scaffolds. This short overview is devoted to current applications and to further perspectives of nanofibers as drug-delivery devices in the field of cartilage and bone regeneration, and also in osteochondral reconstruction. PMID:24978465

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

    PubMed Central

    2013-01-01

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

  16. [Development of drug delivery systems for targeting to macrophages].

    PubMed

    Chono, Sumio

    2007-09-01

    Drug delivery systems (DDS) using liposomes as drug carriers for targeting to macrophages have been developed for the treatment of diseases that macrophages are related to their progress. Initially, DDS for the treatment of atherosclerosis are described. The influence of particle size on the drug delivery to atherosclerotic lesions that macrophages are richly present and antiatherosclerotic effects following intravenous administration of liposomes containing dexamethasone (DXM-liposomes) was investigated in atherogenic mice. Both the drug delivery efficacy of DXM-liposomes (particle size, 200 nm) to atherosclerotic lesions and their antiatherosclerotic effects were greater than those of 70 and 500 nm. These results indicate that there is an optimal particle size for drug delivery to atherosclerotic lesions. DDS for the treatment of respiratory infections are then described. The influence of particle size and surface mannosylation on the drug delivery to alveolar macrophages (AMs) and antibacterial effects following pulmonary administration of liposomes containing ciprofloxacin (CPFX-liposomes) was investigated in rats. The drug delivery efficacy of CPFX-liposomes to AMs was particle size-dependent over the range 100-1000 nm and then became constant at over 1000 nm. These results indicate that the most effective size is 1000 nm. Both the drug delivery efficacy of mannosylated CPFX-liposomes (particle size, 1000 nm) to AMs and their antibacterial effects were significantly greater than those of unmodified CPFX-liposomes. These results indicate that the surface mannosylation is useful method for drug delivery to AMs. This review provides useful information to help in the development of novel pharmaceutical formulations aimed at drug targeting to macrophages.

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  18. Coacervate delivery systems for proteins and small molecule drugs

    PubMed Central

    Johnson, Noah R; Wang, Yadong

    2015-01-01

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

  19. Coacervate delivery systems for proteins and small molecule drugs.

    PubMed

    Johnson, Noah R; Wang, Yadong

    2014-12-01

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

  20. Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease

    PubMed Central

    Gunay, Mine Silindir; Ozer, A. Yekta; Chalon, Sylvie

    2016-01-01

    Background: Although a variety of therapeutic approaches are available for the treatment of Parkinson’s disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. Methods: This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. Results: It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson’s disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α-synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Conclusion: Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson’s disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson’s Disease therapy and reduce its side effects. PMID:26714584

  1. Coordination polymer particles as potential drug delivery systems.

    PubMed

    Imaz, Inhar; Rubio-Martínez, Marta; García-Fernández, Lorena; García, Francisca; Ruiz-Molina, Daniel; Hernando, Jordi; Puntes, Victor; Maspoch, Daniel

    2010-07-14

    Micro- and nanoscale coordination polymer particles can be used for encapsulating and delivering drugs. In vitro cancer cell cytotoxicity assays showed that these capsules readily release doxorubicin, which shows anticancer efficacy. The results from this work open up new avenues for metal-organic capsules to be used as potential drug delivery systems.

  2. Coordination polymer particles as potential drug delivery systems.

    PubMed

    Imaz, Inhar; Rubio-Martínez, Marta; García-Fernández, Lorena; García, Francisca; Ruiz-Molina, Daniel; Hernando, Jordi; Puntes, Victor; Maspoch, Daniel

    2010-07-14

    Micro- and nanoscale coordination polymer particles can be used for encapsulating and delivering drugs. In vitro cancer cell cytotoxicity assays showed that these capsules readily release doxorubicin, which shows anticancer efficacy. The results from this work open up new avenues for metal-organic capsules to be used as potential drug delivery systems. PMID:20485835

  3. 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

  4. Drug delivery systems improve pharmaceutical profile and facilitate medication adherence.

    PubMed

    Wertheimer, Albert I; Santella, Thomas M; Finestone, Albert J; Levy, Richard A

    2005-01-01

    Innovations in dosage forms and dose delivery systems across a wide range of medications offer substantial clinical advantages, including reduced dosing frequency and improved patient adherence; minimized fluctuation of drug concentrations and maintenance of blood levels within a desired range; localized drug delivery; and the potential for reduced adverse effects and increased safety. The advent of new large-molecule drugs for previously untreatable or only partially treatable diseases is stimulating the development of suitable delivery systems for these agents. Although advanced formulations may be more expensive than conventional dosage forms, they often have a more favorable pharmacologic profile and can be cost-effective. Inclusion of these dosage forms on drug formulary lists may help patients remain on therapy and reduce the economic and social burden of care.

  5. Micro and Nanoparticle Drug Delivery Systems for Preventing Allotransplant Rejection

    PubMed Central

    Fisher, James D.; Acharya, Abhinav P.; Little, Steven R.

    2015-01-01

    Despite decades of advances in transplant immunology, tissue damage caused by acute allograft rejection remains the primary cause of morbidity and mortality in the transplant recipient. Moreover, the long-term sequelae of lifelong immunosuppression leaves patients at risk for developing a host of other deleterious conditions. Controlled drug delivery using micro- and nanoparticles (MNPs) is an effective way to deliver higher local doses of a given drug to specific tissues and cells while mitigating systemic effects. Herein, we review several descriptions of MNP immunotherapies aimed at prolonging allograft survival. We also discuss developments in the field of biomimetic drug delivery that use MNP constructs to induce and recruit our bodies' own suppressive immune cells. Finally, we comment on the regulatory pathway associated with these drug delivery systems. Collectively, it is our hope the studies described in this review will help to usher in a new era of immunotherapy in organ transplantation. PMID:25937032

  6. Smart surface-enhanced Raman scattering traceable drug delivery systems.

    PubMed

    Liu, Lei; Tang, Yonghong; Dai, Sheng; Kleitz, Freddy; Qiao, Shi Zhang

    2016-07-01

    A novel smart nanoparticle-based system has been developed for tracking intracellular drug delivery through surface-enhanced Raman scattering (SERS). This new drug delivery system (DDS) shows targeted cytotoxicity towards cancer cells via pH-cleavable covalent carboxylic hydrazone links and the SERS tracing capability based on gold@silica nanocarriers. Doxorubicin, as a model anticancer drug, was employed to compare SERS with conventional fluorescence tracing approaches. It is evident that SERS demonstrates higher sensitivity and resolution, revealing intracellular details, as the strengths of the original Raman signals can be amplified by SERS. Importantly, non-destructive SERS will provide the designed DDS with great autonomy and potential to study the dynamic procedures of non-fluorescent drug delivery into living cells. PMID:27297745

  7. Intracellular Delivery System for Antibody–Peptide Drug Conjugates

    PubMed Central

    Berguig, Geoffrey Y; Convertine, Anthony J; Frayo, Shani; Kern, Hanna B; Procko, Erik; Roy, Debashish; Srinivasan, Selvi; Margineantu, Daciana H; Booth, Garrett; Palanca-Wessels, Maria Corinna; Baker, David; Hockenbery, David; Press, Oliver W; Stayton, Patrick S

    2015-01-01

    Antibodies armed with biologic drugs could greatly expand the therapeutic potential of antibody–drug conjugates for cancer therapy, broadening their application to disease targets currently limited by intracellular delivery barriers. Additional selectivity and new therapeutic approaches could be realized with intracellular protein drugs that more specifically target dysregulated pathways in hematologic cancers and other malignancies. A multifunctional polymeric delivery system for enhanced cytosolic delivery of protein drugs has been developed that incorporates endosomal-releasing activity, antibody targeting, and a biocompatible long-chain ethylene glycol component for optimized safety, pharmacokinetics, and tumor biodistribution. The pH-responsive polymeric micelle carrier, with an internalizing anti-CD22 monoclonal targeting antibody, effectively delivered a proapoptotic Bcl-2 interacting mediator (BIM) peptide drug that suppressed tumor growth for the duration of treatment and prolonged survival in a xenograft mouse model of human B-cell lymphoma. Antitumor drug activity was correlated with a mechanistic induction of the Bcl-2 pathway biomarker cleaved caspase-3 and a marked decrease in the Ki-67 proliferation biomarker. Broadening the intracellular target space by more effective delivery of protein/peptide drugs could expand the repertoire of antibody–drug conjugates to currently undruggable disease-specific targets and permit tailored drug strategies to stratified subpopulations and personalized medicines. PMID:25669432

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

    PubMed Central

    Upadhyay, Ravi Kant

    2014-01-01

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

  9. 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.

  10. Smart surface-enhanced Raman scattering traceable drug delivery systems

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Tang, Yonghong; Dai, Sheng; Kleitz, Freddy; Qiao, Shi Zhang

    2016-06-01

    A novel smart nanoparticle-based system has been developed for tracking intracellular drug delivery through surface-enhanced Raman scattering (SERS). This new drug delivery system (DDS) shows targeted cytotoxicity towards cancer cells via pH-cleavable covalent carboxylic hydrazone links and the SERS tracing capability based on gold@silica nanocarriers. Doxorubicin, as a model anticancer drug, was employed to compare SERS with conventional fluorescence tracing approaches. It is evident that SERS demonstrates higher sensitivity and resolution, revealing intracellular details, as the strengths of the original Raman signals can be amplified by SERS. Importantly, non-destructive SERS will provide the designed DDS with great autonomy and potential to study the dynamic procedures of non-fluorescent drug delivery into living cells.A novel smart nanoparticle-based system has been developed for tracking intracellular drug delivery through surface-enhanced Raman scattering (SERS). This new drug delivery system (DDS) shows targeted cytotoxicity towards cancer cells via pH-cleavable covalent carboxylic hydrazone links and the SERS tracing capability based on gold@silica nanocarriers. Doxorubicin, as a model anticancer drug, was employed to compare SERS with conventional fluorescence tracing approaches. It is evident that SERS demonstrates higher sensitivity and resolution, revealing intracellular details, as the strengths of the original Raman signals can be amplified by SERS. Importantly, non-destructive SERS will provide the designed DDS with great autonomy and potential to study the dynamic procedures of non-fluorescent drug delivery into living cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr03869g

  11. Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s

    PubMed Central

    Shelate, Pragna; Dave, Divyang

    2016-01-01

    The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients.

  12. Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s

    PubMed Central

    Shelate, Pragna; Dave, Divyang

    2016-01-01

    The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients. PMID:27610247

  13. Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s.

    PubMed

    Patel, Apurv; Dodiya, Hitesh; Shelate, Pragna; Shastri, Divyesh; Dave, Divyang

    2016-01-01

    The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients. PMID:27610247

  14. Nanostructured lipid carriers system: recent advances in drug delivery.

    PubMed

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier. PMID:22931500

  15. The Targeted-liposome Delivery System of Antitumor Drugs.

    PubMed

    Wu, Wei-dang; Yi, Xiu-lin; Jiang, Li-xin; Li, Ya-zhuo; Gao, Jing; Zeng, Yong; Yi, Rong-da; Dai, Li-peng; Li, Wei; Ci, Xiao-yan; Si, Duan-yun; Liu, Chang-xiao

    2015-01-01

    The liposome delivery system has been intensively explored as novel drug delivery system (DDS) for antitumor drugs, due to its safety, selective cytotoxicity, long circulation and slow elimination in blood, which is favorable for cancer therapy. The liposome-based chemotherapeutics are used to treat a variety of cancers to enhance the therapeutic index of antitumor drugs. Here, the author reviewed the important targets for cancer therapy and the pharmacokinetic behavior of liposomal drugs in vivo, as well as the application of the targeting liposomal system in cancer therapy. Considering further application for clinical use, the great challenges of the liposome-based delivery system were also proposed as follows: 1) prepare stealth liposome with steric stabilization and further enhance the therapeutic effects and safety; 2) explore more safe clinical targets and complementary or different types of targeting liposome; 3) thirdly, more investment is needed on the research of pharmacokinetics of the elements such as the ligands (antibody), PEG and lipids of liposome delivery system as well as safety evaluation. Considering the complex process of the liposomal encapsulation drugs in vivo, the author inferred that there are maybe different forms of the encapsulation drug to be internalized by the tumor tissues at the same time and space, although there are little reports on it. PMID:26652257

  16. A look at emerging delivery systems for topical drug products.

    PubMed

    Fireman, Sharon; Toledano, Ofer; Neimann, Karine; Loboda, Natalia; Dayan, Nava

    2011-01-01

    The introduction of new topical drugs based on new chemical entities has become a rare event. Instead, pharmaceutical companies have been focused on reformulating existing drugs resulting in an ever-growing number of topical drug products for every approved drug substance. In light of this trend, soon reformulations may not be as rewarding to their sponsors as they are today unless they offer a substantial improvement over other formulations of the same drug substance and the same indication, namely improved efficacy over existing drugs, reduced side effects, unique drug combinations, or applicability for new indications. This article reviews and compares topical drug delivery systems currently under active research that are designed to offer such advantages in the coming years. The reviewed delivery systems are: liposomes, niosomes, transferosomes, ethosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrin, and sol-gel microcapsules. Among all the topical drug delivery systems currently undergoing active research, only the sol-gel microencapsulation is at clinical stages. PMID:22353154

  17. A clinical perspective on mucoadhesive buccal drug delivery systems

    PubMed Central

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

    2014-01-01

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

  18. Nanoscale drug delivery systems and the blood-brain barrier.

    PubMed

    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.

  19. 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

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

    PubMed

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

    2015-01-01

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

  1. 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.

  2. An emerging platform for drug delivery: aerogel based systems.

    PubMed

    Ulker, Zeynep; Erkey, Can

    2014-03-10

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

  3. Current pharmaceutical design on adhesive based transdermal drug delivery systems.

    PubMed

    Ghosh, Animesh; Banerjee, Subham; Kaity, Santanu; Wong, Tin W

    2015-01-01

    Drug-in-adhesive transdermal drug delivery matrix exploits intimate contact of the carrier with stratum corneum, the principal skin barrier to drug transport, to deliver the actives across the skin and into the systemic circulation. The main application challenges of drug-in-adhesive matrix lie in the physicochemical properties of skin varying with age, gender, ethnicity, health and environmental condition of patients. This in turn poses difficulty to design a universal formulation to meet the intended adhesiveness, drug release and drug permeation performances. This review focuses on pressure-sensitive adhesives, and their adhesiveness and drug release/permeation modulation mechanisms as a function of adhesive molecular structure and formulation attributes. It discusses approaches to modulate adhesive tackiness, strength, elasticity, hydrophilicity, molecular suspension capability and swelling capacity, which contribute to the net effect of adhesive on skin bonding, drug release and drug permeation. PMID:25925119

  4. Current pharmaceutical design on adhesive based transdermal drug delivery systems.

    PubMed

    Ghosh, Animesh; Banerjee, Subham; Kaity, Santanu; Wong, Tin W

    2015-01-01

    Drug-in-adhesive transdermal drug delivery matrix exploits intimate contact of the carrier with stratum corneum, the principal skin barrier to drug transport, to deliver the actives across the skin and into the systemic circulation. The main application challenges of drug-in-adhesive matrix lie in the physicochemical properties of skin varying with age, gender, ethnicity, health and environmental condition of patients. This in turn poses difficulty to design a universal formulation to meet the intended adhesiveness, drug release and drug permeation performances. This review focuses on pressure-sensitive adhesives, and their adhesiveness and drug release/permeation modulation mechanisms as a function of adhesive molecular structure and formulation attributes. It discusses approaches to modulate adhesive tackiness, strength, elasticity, hydrophilicity, molecular suspension capability and swelling capacity, which contribute to the net effect of adhesive on skin bonding, drug release and drug permeation.

  5. 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.

  6. Medicated chewing gum, a novel drug delivery system.

    PubMed

    Aslani, Abolfazl; Rostami, Farnaz

    2015-04-01

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

  7. [Synthesis of nanoparticles for dental drug delivery systems].

    PubMed

    Bakó, József; Szepesi, Márta; Márton, Ildikó; Borbély, János; Hegedûs, Csaba

    2007-06-01

    Modern drug delivery systems are designed for targeted controlled slow drug release. Up to now polymer based hydrogels have been applied in dentistry, which systems can affect the rate of the release due to their structure. Recently, intensive research for other methods is performed all over the world in order to improve the effectiveness of delivery systems. Nanotechnology is one of the most dynamically developing disciplines and is a powerful tool to increase the bioavailability of drugs. The aim of this work is to synthesise biocompatible nanoparticles by free radical initiated copolymerization of the monomers, 2-hydroxyethyl methacrylate (HEMA) and polyethyleneglycol dimethacrylate (PEGDMA) in aqueous solution, which can support the formation of nanoparticles that can be used as a drug delivery system for dental applications. The polymer-based nanoparticles were prepared via micellar polymerisation, which resulted a well dispersible white powder material. The size of particles was determined by Dynamic Laser Light Scattering (DLS) and Scanning Electron Microscopy (SEM). The size of particles is in range of 50-180 nm, measured by SEM. These values are commensurable with the results obtained by DLS experiments, where two size ranges were observed, as 40 +/- 15 nm and 180 +/- 30 nm. The nanoparticles are suitable for incorporation into a hydrogel matrix and to design new drug delivery devices for dental applications.

  8. 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

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

    PubMed

    Torchilin, Vladimir P

    2014-11-01

    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

  10. 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 α-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.

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

    PubMed Central

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

    2015-01-01

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

  12. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

    PubMed Central

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

    2014-01-01

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

  13. Interpenetrating polymer networks as innovative drug delivery systems.

    PubMed

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

    2014-01-01

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

  14. Medicated chewing gum, a novel drug delivery system

    PubMed Central

    Aslani, Abolfazl; Rostami, Farnaz

    2015-01-01

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

  15. 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

    2015-05-01

    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'.

  16. Applications of Magnetic Nanoparticles in Targeted Drug Delivery System.

    PubMed

    Mou, Xianbo; Ali, Zeeshan; Li, Song; He, Nongyue

    2015-01-01

    Magnetic nanoparticles (MNPs) are a special kind of nanomaterials and widely used in biomedical technology applications. Currently they are popularly customized for disease detection and treatment, particularly as drug carriers in drug targeted delivery systems, as a therapeutic in hyperthermia (treating tumors with heat), and as contrast agents in magnetic resonance imaging (MRI). Due to their biocompatibility and superparamagnetic properties, MNPs as next generation drug carriers have great attraction. Although the potential benefits of MNPs are considerable, any potential toxicity associated with these MNPs should be identified distinctly. The drug loading capability and the biomedical properties of MNPs generated by different surface coatings are the most sensitive parameters in toxicity. A lot of organic and inorganic materials are utilized as coating materials for surface functionalization and reducing toxicity of MNPs. pH or temperature sensitivity materials are widely used to manage drug loading and targeted release. In addition, MNPs can be controlled and directed to the desired pathological region by using external magnetic files (EMF). The realization of targeted drug delivery has decreased the dosage and improved the efficiency of drugs, which results in reduced side effects to normal tissues. This review discussed the possible organ toxicities of MNPs and their current advances as a drug delivery vehicle. PMID:26328305

  17. Nanoengineered drug delivery systems for enhancing antibiotic therapy.

    PubMed

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

    2015-03-01

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

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

    PubMed Central

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

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

  19. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs: I. Formulation development.

    PubMed

    Rao, Sripriya Venkata Ramana; Shao, Jun

    2008-10-01

    The global aim of this research project was to develop a self-nanoemulsifying drug delivery system (SNEDDS) for non-invasive delivery of protein drugs. The specific aim of this study was to develop SNEDDS formulations. An experimental design was adopted to develop SNEDDS. Fluorescent labeled beta-lactamase (FITC-BLM), a model protein, was loaded into SNEDDS through solid dispersion technique. The experimental design provided 720 compositions of different oil, surfactant, and co-surfactant at various ratios, of which 33 SNEDDS prototypes were obtained. Solid dispersion of FITC-BLM in SoyPC prepared was able to dissolve in 16 SNEDDS prototypes (approximately 2200 mU BLM in 1g SNEDDS). SNEDDS NE-12-7 (composition: Lauroglycol FCC, Cremophor EL and Transcutol; ratio: 5:4:3) formed O/W nanoemulsion with mean droplet size in the range of 22-50 nm when diluted with various pH media and different dilution factor with PBS (pH 7.4). The phase diagram of NE-12-7 indicated a broad region of nanoemulsion. BLM-loaded SNEDDS (NE-12-7) stored at 4 degrees C for 12 weeks indicated 10% loss of BLM activity. A SNEDDS was developed to load FITC-BLM into the oil phase which can spontaneously form O/W nanoemulsion upon the addition of water.

  20. 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

  1. 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

  2. A multi-drug delivery system with sequential release using titania nanotube arrays.

    PubMed

    Aw, Moom Sinn; Addai-Mensah, Jonas; Losic, Dusan

    2012-04-01

    A multi-drug delivery system with sequential release based on titania nanotube arrays and polymer micelles as drug carriers is presented. Delivery of multiple water insoluble and soluble drugs required for combined local therapy is demonstrated.

  3. 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.

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

    PubMed

    Machida, Y

    1993-05-01

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

  5. Supersaturating drug delivery systems: fast is not necessarily good enough.

    PubMed

    Augustijns, Patrick; Brewster, Marcus E

    2012-01-01

    An emerging technology subtype that has been adopted by formulators to address low-solubility issues is the supersaturating drug delivery system; this system is based on the "spring" and "parachute" design elements, which have been applied to lipid-based formulations, S(M)EDDS, solid dispersions, nano-based systems, and many others. This broad formulation approach attempts to delicately balance the need of creating intraluminal drug concentrations in excess of its thermodynamic solubility while at the same time providing for sufficient solution stability to allow for useful drug absorption. The conundrum created is that the higher the extent of supersaturation, the lower the physical stability of the metastable solution based on an increased tendency for a solubilized drug to precipitate. Traditional dissolution testing is a touchstone of formulation development based on the need for useful dissolution rates and drug availability. Dissolution testing is likewise important in the development and characterization of enabling and supersaturating drug delivery systems; however, their execution and interpretation are distinct from that associated with conventional dosage forms. The nature of the dissolution assay (sink versus nonsink, apparatus type, and rate and extent of supersaturation) can impact the ability to efficiently use the dissolution data in the configuration of these enabling formulations.

  6. Biologically erodable microspheres as potential oral drug delivery systems

    NASA Astrophysics Data System (ADS)

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

    1997-03-01

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

  7. Synthetic Microbes As Drug Delivery Systems

    PubMed Central

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  9. Advancing drug delivery systems for the treatment of multiple sclerosis.

    PubMed

    Tabansky, Inna; Messina, Mark D; Bangeranye, Catherine; Goldstein, Jeffrey; Blitz-Shabbir, Karen M; Machado, Suly; Jeganathan, Venkatesh; Wright, Paul; Najjar, Souhel; Cao, Yonghao; Sands, Warren; Keskin, Derin B; Stern, Joel N H

    2015-12-01

    Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.

  10. 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

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

    PubMed Central

    Youan, Bi-Botti C.

    2010-01-01

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

  12. An implantable thermoresponsive drug delivery system based on Peltier device.

    PubMed

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

    2013-04-15

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

  13. Spatiotemporal drug delivery using laser-generated-focused ultrasound system.

    PubMed

    Di, Jin; Kim, Jinwook; Hu, Quanyin; Jiang, Xiaoning; Gu, Zhen

    2015-12-28

    Laser-generated-focused ultrasound (LGFU) holds promise for the high-precision ultrasound therapy owing to its tight focal spot, broad frequency band, and stable excitation with minimal ultrasound-induced heating. We here report the development of the LGFU as a stimulus for promoted drug release from microgels integrated with drug-loaded polymeric nanoparticles. The pulsed waves of ultrasound, generated by a carbon black/polydimethylsiloxane (PDMS)-photoacoustic lens, were introduced to trigger the drug release from alginate microgels encapsulated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. We demonstrated the antibacterial capability of this drug delivery system against Escherichia coli by the disk diffusion method, and antitumor efficacy toward the HeLa cell-derived tumor spheroids in vitro. This novel LGFU-responsive drug delivery system provides a simple and remote approach to precisely control the release of therapeutics in a spatiotemporal manner and potentially suppress detrimental effects to the surrounding tissue, such as thermal ablation.

  14. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. Unsteady jet in designing innovative drug delivery system

    NASA Astrophysics Data System (ADS)

    Wang, Cong; Mazur, Paul; Cosse, Julia; Rider, Stephanie; Gharib, Morteza

    2014-11-01

    Micro-needle injections, a promising pain-free drug delivery method, is constrained by its limited penetration depth. This deficiency can be overcome by implementing fast unsteady jet that can penetrate sub-dermally. The development of a faster liquid jet would increase the penetration depth and delivery volume of micro-needles. In this preliminary work, the nonlinear transient behavior of an elastic tube balloon in providing fast discharge is analyzed. A physical model that combines the Mooney Rivlin Material model and Young-Lapalce's Law was developed and used to investigate the fast discharging dynamic phenomenon. A proof of concept prototype was constructed to demonstrate the feasibility of a simple thumb-sized delivery system to generate liquid jet with desired speed in the range of 5-10 m/s. This work is supported by ZCUBE Corporation.

  17. Nanotechnology: a focus on nanoparticles as a drug delivery system.

    PubMed

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

    2006-09-01

    This review will provide an in-depth discussion on the previous development of nanoparticle-based drug delivery systems (DDS) and discuss original research data that includes the therapeutic enhancement of antiretroviral therapy. The use of nanoparticle DDS will allow practitioners to use drugs to target specific areas of the body. In the treatment of malignancies, the use of nanoparticles as a DDS is making measurable treatment impact. Medical imaging will also utilize DDS to illuminate tumors, the brain, or other cellular functions in the body. The utility of nanoparticle DDS to improve human health is potentially enormous.

  18. Design of a Multiple Drug Delivery System Directed at Periodontitis

    PubMed Central

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

    2013-01-01

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

  19. [Research progress of the drug delivery system of antitumor platinum drugs with macrocyclic compounds].

    PubMed

    Gao, Chuan-zhu; Zhang, Yan; Chen, Ji; Fei, Fan; Wang, Tian-shuai; Yang, Bo; Dong, Peng; Zhang, Ying-jie

    2015-06-01

    Platinum-based anticancer drugs have been becoming one of the most effective drugs for clinical treatment of malignant tumors for its unique mechanism of action and broad range of anticancer spectrum. But, there are still several problems such as side effects, drug resistance/cross resistance and no-specific targeting, becoming obstacles to restrict its expanding of clinical application. In recent years, supramolecular chemistry drug delivery systems have been gradually concerned for their favorable safety and low toxicity. Supramolecular macrocycles-platinum complexes increased the water solubility, stability and safety of traditional platinum drugs, and have become hot focus of developing novel platinum-based anticancer drugs because of its potential targeting of tumor tissues/organs. This article concentrates in the research progress of the new drug delivery system between platinum-based anticancer drugs with three generations of macrocycles: crown ether, cyclodextrin, cucurbituril and calixarene. PMID:26521433

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. Physical and chemical stimuli-responsive drug delivery systems: targeted delivery and main routes of administration.

    PubMed

    Lopes, Joana R; Santos, Gory; Barata, Pedro; Oliveira, Rita; Lopes, Carla M

    2013-01-01

    In the area of drug delivery, novel tools and technological approaches have captured the attention of researchers in order to improve the performance of conventional therapeutics and patient compliance to pharmacological therapy. Stimuli-responsive drug delivery systems (DDS) appear as a promising approach to control and target drug delivery. When these DDS are administered, the drug release is activated and then modulated through some action or external input and facilitated by the energy supplied externally. The stimuli responsible to activate the drug release can be classified into three types according to their nature or the type of energy applied: physical (e.g. magnetic field, electric field, ultrasound, temperature and osmotic pressure); chemical (e.g. pH, ionic strength and glucose); and biological (enzymes and endogenous receptors). The present review gives an overview of the most significant physical and chemical stimuliresponsive DDS and elucidates about their current and relevant applications in controlled and targeted drug delivery attending different routes of administration.

  5. Green amorphous nanoplex as a new supersaturating drug delivery system.

    PubMed

    Cheow, Wean Sin; Hadinoto, Kunn

    2012-04-17

    The nanoscale formulation of amorphous drugs represents a highly viable supersaturating drug-delivery system for enhancing the bioavailability of poorly soluble drugs. Herein we present a new formulation of a nanoscale amorphous drug in the form of a drug-polyelectrolyte nanoparticle complex (or nanoplex), where the nanoplex is held together by the combination of a drug-polyelectrolyte electrostatic interaction and an interdrug hydrophobic interaction. The nanoplex is prepared by a truly simple, green process that involves the ambient mixing of drug and polyelectrolyte (PE) solutions in the presence of salt. Nanoplexes of poorly soluble acidic (i.e., ibuprofen and curcumin) and basic (i.e., ciprofloxacin) drugs are successfully prepared using biocompatible poly(allylamine hydrochloride) and dextran sulfate as the PE, respectively. The roles of salt, drug, and PE in nanoplex formation are examined from ternary phase diagrams of the drug-PE complex, from which the importance of the drug's charge density and hydrophobicity, as well as the PE ionization at different pH values, is recognized. Under the optimal conditions, the three nanoplexes exhibit high drug loadings of ~80-85% owing to the high drug complexation efficiency (~90-96%), which is achieved by keeping the feed charge ratio of the drug to PE below unity (i.e., excess PE). The nanoplex sizes are ~300-500 nm depending on the drug hydrophobicity. The nanoplex powders remain amorphous after 1 month of storage, indicating the high stability owed to the PE's high glass-transition temperature. FT-IR analysis shows that functional groups of the drug are conserved upon complexation. The nanoplexes are capable of generating prolonged supersaturation upon dissolution with precipitation inhibitors. The supersaturation level depends on the saturation solubility of the native drugs, where the lower the saturation solubility, the higher the supersaturation level. The solubility of curcumin as the least-soluble drug is

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

    PubMed Central

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

    2013-01-01

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

  7. Stealth Engineering for In Vivo Drug Delivery Systems.

    PubMed

    Mohapatra, Ankita; Morshed, Bashir I; Haggard, Warren O; Smith, Richard A

    2015-01-01

    In generic terms, a drug delivery substrate (DDS) can be described as a vehicle to transport drug to the point of interest. A DDS that would ideally have the capability to control drug dosage and achieve target specificity, localization, and higher therapeutic efficacy has been pursued as a holy grail in pharmaceutical research. Over the years, diverse classes, structures, and modifications of DDS have been proposed to achieve this aim. One of its major deterrents, however, is rapid elimination of drug by the immune system before intended functionality. Stealth engineering is broadly defined as a method of designing a drug carrier to minimize or delay opsonization until the encapsulated drug is delivered to the intended target. Stealth-engineered DDS has been successful in extending drug circulation lifetime from a few minutes to several days. Currently, this field of research has made much progress since its initiation in 1960s with liposomes to DNA boxes. Activity has also benefited several areas of medicine, where it has been applied in cancer, gene therapy, bone regrowth, and infection treatment. This review covers the progress of some types of DDS that have been published and indexed in major databases (including ScienceDirect, PubMed, and Google Scholar) in the scientific literature.

  8. Polybutylcyanoacrylate nanocarriers as promising targeted drug delivery systems.

    PubMed

    Gao, Shiya; Xu, Yurui; Asghar, Sajid; Chen, Minglei; Zou, Lang; Eltayeb, Sulieman; Huo, Meirong; Ping, Qineng; Xiao, Yanyu

    2015-01-01

    Among the materials for preparing the polymeric nanocarriers, poly(n-butylcyanoacrylate) (PBCA), a polymer with medium length alkyl side chain, is of lower toxicity and proper degradation time. Therefore, PBCA has recently been regarded as a kind of widely used, biocompatible, biodegradable, low-toxic drug carrier. This review highlights the use of PBCA-based nanocarriers (PBCA-NCs) as targeting drug delivery systems and presents the methods of preparation, the surface modification and the advantages and limitations of PBCA-NCs. The drugs loaded in PBCA-NCs are summarized according to the treatment of diseases, and the different therapeutic applications and the most recent developments of PBCA-NCs are also discussed, which provides useful guidance on the targeting research of PBCA-NCs.

  9. Single-wall carbon nanotubes based anticancer drug delivery system

    NASA Astrophysics Data System (ADS)

    Tripisciano, C.; Kraemer, K.; Taylor, A.; Borowiak-Palen, E.

    2009-08-01

    Conventional administration of chemotherapeutic agents is compromised by their lack of selectivity which is the cause of a lethal effect accomplishment on healthy tissues. Since therapeutic and diagnostic agents could functionalize the structure of carbon nanotubes (CNTs), the development of CNTs as drug containers would pave the way to their employment as nanovectors into the cells. Here a study on cisplatin (Cis-Diamminedichloroplatinum (CDDP) - a platinum-based chemotherapy drug) embedding to single-wall CNTs (SWCNTs) is shown.Being sure that the anticancer drug discharge occurred, in vitro analysis have been performed. The inhibition of prostate cancer cells (PC3 and DU145) viability from tubes encapsulating cisplatin proved the efficiency of the produced delivery system.

  10. Key Considerations in Designing Oral Drug Delivery Systems for Dogs.

    PubMed

    Song, Yunmei; Peressin, Karl; Wong, Pooi Yin; Page, Stephen W; Garg, Sanjay

    2016-05-01

    The present review discusses the pharmaceutical impact of the anatomy and physiology of the canine gastrointestinal tract to provide a comprehensive guide to the theories and challenges associated with the development of oral drug delivery systems for dogs. Novel pharmaceutical technologies applied to veterinary drugs are discussed indicating the advantages and benefits for animals. There are currently immense research and development efforts being funneled into novel canine health products. Such products are being used to overcome limitations of drugs that display site-dependent absorption or possess poor biopharmaceutical properties. Techniques that are employed to increase bioavailability of the Biopharmaceutics Classification System class II drugs are discussed in this article. Furthermore, an overview of palatable oral formulations for dog care is provided as an approach to easy administration. In vitro and in vivo evaluation and correlation of oral drug formulations in dogs are also addressed. This article assesses the outlook of canine oral drug development recognizing substantial growth forecasts of the dog care market. PMID:27056627

  11. Chitosan in nasal delivery systems for therapeutic drugs.

    PubMed

    Casettari, Luca; Illum, Lisbeth

    2014-09-28

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

  12. Chitosan in nasal delivery systems for therapeutic drugs.

    PubMed

    Casettari, Luca; Illum, Lisbeth

    2014-09-28

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

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

    PubMed

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

    2012-06-01

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

  14. 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

  15. The Smart Drug Delivery System and Its Clinical Potential.

    PubMed

    Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

    2016-01-01

    With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications. PMID:27375781

  16. Cubic and hexagonal liquid crystals as drug delivery systems.

    PubMed

    Chen, Yulin; Ma, Ping; Gui, Shuangying

    2014-01-01

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

  17. Cubic and Hexagonal Liquid Crystals as Drug Delivery Systems

    PubMed Central

    Chen, Yulin; Ma, Ping; Gui, Shuangying

    2014-01-01

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

  18. The Smart Drug Delivery System and Its Clinical Potential

    PubMed Central

    Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

    2016-01-01

    With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications. PMID:27375781

  19. Applications of novel drug delivery system for herbal formulations.

    PubMed

    Ajazuddin; Saraf, S

    2010-10-01

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

  20. 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

  1. Matrix embedded microspherules containing indomethacin as controlled drug delivery systems.

    PubMed

    Swamy, K M Lokamatha; Satyanath, B; Shantakumar, S M; Manjula, D; Mohammedi, Hafsa; Farhana, Ayesha

    2008-10-01

    This work is focused on the development of controlled drug delivery systems using different wax/fat embedded indomethacin (IM). Discrete wax/fat embedded microspherules containing indomethacin were prepared by using cetostearyl alcohol, paraffin wax and stearic acid by employing emulsification-phase separation method. These matrices have been used as barrier coatings due to their hydrophobic nature. Chemically inert and tasteless nature of wax/fats promotes their use as taste masking agents for bitter drugs. Various waxes and fats are available having different physicochemical properties to suit the needs of formulation. Methyl cellulose (MC) 1% w/v, sodium alginate (SA) 0.5% w/v and Tween-80 (TW) 1% w/v were used as emulgents. The resulting microspherules were discrete, large, spherical and also free flowing. It is revealed from the literature that natures of wax/fat emulgents were found to influence the rate of drug release. In the present work the drug content in all the batches of microspherules were found to be uniform. The rate of drug release corresponded best to first order kinetics, followed by Higuchi and zero-order equations. The release of the model drug from these wax/fat microspherules was prolonged over an extended period of time and the drug release mechanism followed anomalous (non-Fickian) diffusion controlled as well as Super Case II transport. Among the three matrix materials used, paraffin wax retarded the drug release more than the other two. Surface characteristics of microspherules have been studied by Scanning Electron Microscope (SEM). A fair degree rank of correlation was found to exist between the size and release retardation in all the three-wax/fat emulgent combinations.

  2. Bimodal Gastroretentive Drug Delivery Systems of Lamotrigine: Formulation and Evaluation

    PubMed Central

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

    2014-01-01

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

  3. Evaluation of metal nanoparticles for drug delivery systems.

    PubMed

    Adeyemi, Oluyomi S; Sulaiman, Faoziyat A

    2015-04-01

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

  4. 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

  5. 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.

  6. PLGA-based nanoparticles as cancer drug delivery systems.

    PubMed

    Sadat Tabatabaei Mirakabad, Fatemeh; Nejati-Koshki, Kazem; Akbarzadeh, Abolfazl; Yamchi, Mohammad Rahmati; Milani, Mortaza; Zarghami, Nosratollah; Zeighamian, Vahideh; Rahimzadeh, Amirbahman; Alimohammadi, Somayeh; Hanifehpour, Younes; Joo, Sang Woo

    2014-01-01

    Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug delivery systems due to controlled and sustained- release properties, low toxicity, and biocompatibility with tissue and cells. In the present review, the structure and properties of PLGA copolymers synthesized by ring-opening polymerization of DL-lactide and glicolide were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy and differential scanning calorimetry. Methods of preparation and characterization, various surface modifications, encapsulation of diverse anticancer drugs, active or passive tumor targeting and different release mechanisms of PLGA nanoparticles are discussed. Increasing experience in the application of PLGA nanoparticles has provided a promising future for use of these nanoparticles in cancer treatment, with high efficacy and few side effects. PMID:24568455

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

    PubMed

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

    2014-08-01

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

  8. Nanostructured lipid carriers: Promising drug delivery systems for future clinics.

    PubMed

    Beloqui, Ana; Solinís, María Ángeles; Rodríguez-Gascón, Alicia; Almeida, António J; Préat, Véronique

    2016-01-01

    During the past decade, the number of studies describing nanostructured lipid carriers (NLCs)-based formulations has been dramatically increased. The raise in NLC exploitation is essentially due to defeated barriers within the technological process of lipid-based nanoparticles' formulation and increased knowledge of the underlying mechanisms of transport of NLCs via different routes of administration. This review article aims to give an overview on the current state of the art of NLC as controlled drug delivery systems for future clinics through novel NLC applications providing examples of successfull outcomes. The reported data clearly illustrate the promise of these nanoparticles for novel treatments in the near future. From the Clinical Editor: The understanding of the nanostructured lipid carriers (NLC)-based formulations has improved with continuing research recently. The result has seen an increase in the use of these in the clinical setting. In this comprehensive review, the authors discussed the current state and major challenges in the use of nanostructured lipid carriers as controlled drug delivery systems. PMID:26410277

  9. Gastroretentive drug delivery systems for therapeutic management of peptic ulcer.

    PubMed

    Garg, Tarun; Kumar, Animesh; Rath, Goutam; Goyal, Amit K

    2014-01-01

    A peptic ulcer, stomach ulcer, or gastric ulcer, also known as peptic ulcer disease (PUD), is a very common chronic disorder of the stomach which is mainly caused by damage or impairment of the stomach lining. Various factors such as pepsin, gastric acid, H. pylori, NSAIDs, prostaglandins, mucus, bicarbonate, and blood flow to mucosa play an important role in causing peptic ulcers. In this review article, our main focus is on some important gastroretentive drug delivery systems (GRDDS) (floating, bioadhesive, high density, swellable, raft forming, superporous hydrogel, and magnetic systems) which will be helpful in gastroretention of different dosage forms for treatment of peptic ulcer. GRDDS provides a mean for controlled release of compounds that are absorbed by active transport in the upper intestine. It also enables controlled delivery for paracellularly absorbed drugs without a decrease in bioavailability. The above approaches are specific for targeting and leading to a marked improvement in the quality of life for a large number of patients. In the future, it is expected that they will become of growing significance, finally leading to improved efficiencies of various types of pharmacotherapies.

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Masood, Farha

    2016-03-01

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

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

    PubMed

    Masood, Farha

    2016-03-01

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

  17. An experimental platform for systemic drug delivery to the retina.

    PubMed

    Campbell, Matthew; Nguyen, Anh T H; Kiang, Anna-Sophia; Tam, Lawrence C S; Gobbo, Oliviero L; Kerskens, Christian; Ni Dhubhghaill, Sorcha; Humphries, Marian M; Farrar, G-Jane; Kenna, Paul F; Humphries, Peter

    2009-10-20

    Degenerative retinopathies, including age-related macular degeneration, diabetic retinopathy, and hereditary retinal disorders--major causes of world blindness--are potentially treatable by using low-molecular weight neuroprotective, antiapoptotic, or antineovascular drugs. These agents are, however, not in current systemic use owing to, among other factors, their inability to passively diffuse across the microvasculature of the retina because of the presence of the inner blood-retina barrier (iBRB). Moreover, preclinical assessment of the efficacies of new formulations in the treatment of such conditions is similarly compromised. We describe here an experimental process for RNAi-mediated, size-selective, transient, and reversible modulation of the iBRB in mice to molecules up to 800 Da by suppression of transcripts encoding claudin-5, a protein component of the tight junctions of the inner retinal vasculature. MRI produced no evidence indicative of brain or retinal edema, and the process resulted in minimal disturbance of global transcriptional patterns analyzed in neuronal tissue. We show that visual function can be improved in IMPDH1(-/-) mice, a model of autosomal recessive retinitis pigmentosa, and that the rate of photoreceptor cell death can be reduced in a model of light-induced retinal degeneration by systemic drug delivery after reversible barrier opening. These findings provide a platform for high-throughput drug screening in models of retinal degeneration, and they ultimately could result in the development of a novel "humanized" approach to therapy for conditions with little or no current forms of treatment.

  18. Nanostructured Delivery Systems: Augmenting the Delivery of Antiretroviral Drugs for Better Management of HIV/AIDS.

    PubMed

    Singh, Gurinder; Pai, Roopa S; Mustafa, Sanaul

    2015-01-01

    In the last two decades, HIV-1, the retrovirus associated with acquired immunodeficiency syndrome (AIDS), is globally one of the primary causes of morbidity and mortality. Unfortunately, existing approaches for interventions are not able to suppress the progression of infection due to this virus. Of the many obstacles, viral entry into the mono-nuclear phagocyte system encompassing monocytes/macrophages and dendritic cells is a major concern. Viral infection is also responsible for the subsequent distribution of the virus into various tissues throughout the organism. Tremendous progress has been made during the past few years to diagnose and treat patients with HIV/AIDS infection, yet much remains to be done. Recommended treatment involves long-term and multiple drug therapy that causes severe side effects. With almost 12% of the world population suffering from HIV/AIDS, better management of this global threat is highly desired. Nanostructured delivery systems hold promise for improving the situation. Such systems can facilitate the uptake of antiretroviral drugs, causing a considerable improvement in HIV/AIDS therapy. Nanoscale systems have intriguing potential to drastically improve existing HIV/AIDS diagnosis and treatment platforms. Nanosystems constitute a wide range of systems varying from polymeric nanoparticles, to solid-lipid nanoparticles, liposomes, micro- and nanoemulsions, dendrimers, and self-nanoemulsifying systems. Improved bioavailability, solubility, stability, and biocompatibility make them an ideal choice for delivery of antiretroviral drugs. The present review initially describes an updated bird's-eye view account of the literature. Then, we provide a relatively sententious overview on updated patents of recent nanostructured delivery systems for antiretroviral drugs. Finally, we discuss low-cost therapy (such as antioxidants and immune modulators) for the treatment and prevention of HIV/AIDS. PMID:26559551

  19. 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

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

    PubMed Central

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

    2011-01-01

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

  1. 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

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

    PubMed

    Tashakori-Sabzevar, Faezeh; Mohajeri, Seyed Ahmad

    2015-05-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. 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.

  5. Design strategies and applications of circulating cell-mediated drug delivery systems

    PubMed Central

    Kim, Gloria B.; Dong, Cheng; Yang, Jian

    2015-01-01

    Drug delivery systems, particularly nanomaterial-based drug delivery systems, possess a tremendous amount of potential to improve diagnostic and therapeutic effects of drugs. Controlled drug delivery targeted to a specific disease is designed to significantly improve the pharmaceutical effects of drugs and reduce their side effects. Unfortunately, only a few targeted drug delivery systems can achieve high targeting efficiency after intravenous injection, even with the development of numerous surface markers and targeting modalities. Thus, alternative drug and nanomedicine targeting approaches are desired. Circulating cells, such as erythrocytes, leukocytes, and stem cells, present innate disease sensing and homing properties. Hence, using living cells as drug delivery carriers has gained increasing interest in recent years. This review highlights the recent advances in the design of cell-mediated drug delivery systems and targeting mechanisms. The approaches of drug encapsulation/conjugation to cell-carriers, cell-mediated targeting mechanisms, and the methods of controlled drug release are elaborated here. Cell-based “live” targeting and delivery could be used to facilitate a more specific, robust, and smart payload distribution for the next-generation drug delivery systems. PMID:25984572

  6. NMR characterisation and transdermal drug delivery potential of microemulsion systems.

    PubMed

    Kreilgaard, M; Pedersen, E J; Jaroszewski, J W

    2000-12-01

    The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and to compare the drug delivery potential of microemulsions to conventional vehicles. Self-diffusion coefficients determined by pulsed-gradient spin-echo NMR spectroscopy and T(1) relaxation times were used to characterise the microemulsions. Transdermal flux of lidocaine and prilocaine hydrochloride through rat skin was determined in vitro using Franz-type diffusion cells. The formulation constituents enabled a broad variety of microemulsion compositions, which ranged from water-continuous to oil-continuous aggregates over possible bicontinuous structures, with excellent solubility properties for both lipophilic and hydrophilic compounds. The microemulsions increased transdermal flux of lidocaine up to four times compared to a conventional oil-in-water emulsion, and that of prilocaine hydrochloride almost 10 times compared to a hydrogel. A correlation between self-diffusion of the drugs in the vehicles and transdermal flux was indicated. The increased transdermal drug delivery from microemulsion formulations was found to be due mainly to the increased solubility of drugs and appeared to be dependent on the drug mobility in the individual vehicle. The microemulsions did not perturb the skin barrier, indicating a low skin irritancy.

  7. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs: II. In vitro transport study.

    PubMed

    Rao, Sripriya Venkata Ramana; Agarwal, Payal; Shao, Jun

    2008-10-01

    To develop a self-nanoemulsifying drug delivery system (SNEDDS) for protein drugs, and particularly, to test the in vitro transport of beta-lactamase (BLM) by SNEDDS across the cell monolayer. Fluorescently labeled BLM (FITC-BLM), a model protein, formulated into 16 SNEDDS preparations through a solid dispersion technique were studied for transport across MDCK monolayer. All the SNEDDS nanoemulsions resulted in higher transport rate than the free solution. The transport rate by SNEDDS depends on the SNEDDS composition. SNEDDS NE-12-7 (oil: Lauroglycol FCC, surfactant: Cremophor EL and a cosurfactant: Transcutol HP) at the ratio of 5:4:3, rendered the highest transportation rate, 33% as compared to negligible transport by the free solution. FITC-BLM solution mixed with the surfactant and the cosurfactant of SNEDDS NE-12-7 or with blank SNEDDS NE-12-7 increased the transport only by 3.3 and 1.5 folds, respectively, compared to free solution alone. It was found that the monolayer integrity was not compromised in the presence of SNEDDS NE-12-7 or its surfactant/cosurfactant. The SNEDDS significantly increased the transport of FITC-BLM across MDCK monolayer in vitro. SNEDDS may be a potential effective delivery system for non-invasive protein drug delivery.

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

    PubMed Central

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

    2014-01-01

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

  9. Surfactant-based drug delivery systems for treating drug-resistant lung cancer.

    PubMed

    Kaur, Prabhjot; Garg, Tarun; Rath, Goutam; Murthy, R S R; Goyal, Amit K

    2016-01-01

    Among all cancers, lung cancer is the major cause of deaths. Lung cancer can be categorized into two classes for prognostic and treatment purposes: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Both categories of cancer are resistant to certain drugs. Various mechanisms behind drug resistance are over-expression of superficial membrane proteins [glycoprotein (P-gp)], lung resistance-associated proteins, aberration of the intracellular enzyme system, enhancement of the cell repair system and deregulation of cell apoptosis. Structure-performance relationships and chemical compatibility are consequently major fundamentals in surfactant-based formulations, with the intention that a great deal investigation is committed to this region. With the purpose to understand the potential of P-gp in transportation of anti-tumor drugs to cancer cells with much effectiveness and specificity, several surfactant-based delivery systems have been developed which may include microspheres, nanosized drug carriers (nanoparticles, nanoemulsions, stealth liposomes, nanogels, polymer-drug conjugates), novel powders, hydrogels and mixed micellar systems intended for systemic and/or localized delivery. PMID:25013959

  10. A novel liquid effervescent floating delivery system for sustained drug delivery.

    PubMed

    Ibrahim, H K

    2009-08-01

    An effervescent floating liquid formulation with in situ gelling properties has been assessed for its potential for sustaining drug delivery and targeting. The formulation consisted of sodium alginate and glyceryl monooleate (GMO). The developed formulation met all pre-requisites to become an in situ gelling floating system and it gelled and floated instantaneously in the pH conditions of the stomach. Moreover, the gels formed in situ remained intact for more than 48 h to facilitate sustained release of drugs. Increasing the mannuronic acid ratio of sodium alginate and the GMO concentration significantly retarded the release rate and extent. The in vitro release of both hydrophilic and hydrophobic drugs from the prepared formulations followed root-time kinetics during the sustained release period. Replacing the free drug with drug encapsulated microspheres enabled tailoring of the release profile and achieved zero-order release kinetics. The system retained its appearance and rheological properties for 12 months at ambient conditions. The values of the similarity factor Sd proved the absence of any significant difference in the release profile upon storage.

  11. Single compartment drug delivery

    PubMed Central

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

    2014-01-01

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

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... guidance for industry entitled ``Residual Drug in Transdermal and Related Drug Delivery Systems.'' This... Systems.'' This draft guidance provides recommendations to developers and manufacturers of TDDS, TMDS, and... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Residual Drug in...

  13. 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.

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

    PubMed Central

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

    2015-01-01

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

  15. 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

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

    PubMed

    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.

  17. The effects of irradiation on controlled drug delivery/controlled drug release systems

    NASA Astrophysics Data System (ADS)

    Ražem, Dušan; Katušin-Ražem, Branka

    2008-03-01

    The research of radiation effects on drugs over the past 60 years has mainly dealt with radiation sterilization of individual active pharmaceutical ingredients (APIs) in the form of pure substances or injectable solutions. However, the emergence of novel systems for drug administration and targeting via controlled drug delivery (CDD) and/or controlled drug release (CDR) has extended the use of irradiation with respect to pharmaceuticals: the capacity of radiation to act as an initiator of crosslinking has been used in the manufacturing and modification of a number of polymeric carriers with an added advantage of reducing the microbial load of products at the same time. The application of irradiation to these novel systems requires the understanding of radiation action not only on APIs alone but also on drug carriers and on the functioning of the integral CDD/CDR systems. In this paper, the significance of CDD/CDR systems is considered with a special emphasis on the role of irradiation for sterilization and crosslinking in the developments over the past 15 years. Radiation sterilization, crosslinking and degradation of the principal forms of drug carrier systems and the effects of irradiation on the release kinetics of APIs are discussed in light of radiation chemical principles. Regulatory aspects pertaining to radiation sterilization of drugs are also considered. Relevant results are summarized in tabular form.

  18. 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

  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.

  20. Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of protein drugs: III. In vivo oral absorption study.

    PubMed

    Rao, Sripriya Venkata Ramana; Yajurvedi, Kavya; Shao, Jun

    2008-10-01

    To use self-nanoemulsifying drug delivery system (SNEDDS) to deliver hydrophilic proteins orally. beta-Lactamase (BLM), a 29 kDa protein was used as a model protein, and formulated into the oil phase of a SNEDDS through solid dispersion technique. The oral absorption of BLM in rats when delivered by such a SNEDDS was investigated. Oral delivery of 4500 mU/kg of BLM in SNEDDS nanoemulsion resulted in the relative bioavailability of 6.34%, C(max) of 1.9 mU/ml and mean residence time of 12.12h which was 1.5-, 2.7- and 1.3-fold higher than that by free solution, respectively. Delivery of BLM in the aqueous phase of the nanoemulsion resulted in a PK profile similar to that by the free solution. BLM when loaded in oil phase of SNEDDS, can significantly enhance the oral bioavailability of BLM. SNEDDS has a great potential for oral protein delivery.

  1. 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

  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.

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

    PubMed Central

    Anselmo, Aaron C.; Mitragotri, Samir

    2014-01-01

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

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

    PubMed

    Anselmo, Aaron C; Mitragotri, Samir

    2014-09-28

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

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

    PubMed

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

    2003-02-01

    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 for the drug delivery application. The shape memory properties of thermoplastic polyurethane allow to design a new fully polymeric self-expandable stent. The possibility to use the stent as a drug delivery system is described.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Philip, Anil K.; Philip, Betty

    2010-01-01

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

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

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2015-12-30

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

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

    PubMed

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

    2015-11-10

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

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

    PubMed

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

    2015-01-01

    Galantamine hydrobromide is formulated in tablets and capsules prescribed through oral delivery for the treatment of Alzheimer's disease. However, oral delivery of drugs can cause severe side effects such as nausea, vomiting, and gastrointestinal disturbance. Transdermal delivery of galantamine hydrobromide could avoid these unwanted side effects. In this work, galantamine hydrobromide was formulated in gel drug reservoir which was then fabricated in the transdermal patch. The in vitro drug release studies revealed that the drug release from the donor chamber to receptor chamber of Franz diffusion cell was affected by the amount of polymer, amount of neutralizer, amount of drug, types of permeation enhancer, and amount of permeation enhancer. Visual observations of the gels showed that all formulated gels are translucent, homogeneous, smooth, and stable. These gels have pH in the suitable range for skin. The gel also showed high drug content uniformity. Hence, this formulation can be further used in the preparation of transdermal patch drug delivery system. PMID:25853145

  11. Nanostructured polyelectrolyte multilayer drug delivery systems for bone metastasis prevention.

    PubMed

    Daubiné, Florence; Cortial, Delphine; Ladam, Guy; Atmani, Hassan; Haïkel, Youssef; Voegel, Jean-Claude; Clézardin, Philippe; Benkirane-Jessel, Nadia

    2009-10-01

    Polyelectrolyte multilayers (PEM) are well established nanoarchitectures with numerous potential applications, in particular as biomaterial coatings. They may exhibit specific biological properties in terms of controlled cell activation or local drug delivery. Here, in a new approach for bone metastasis prevention, we employed poly-l-lysine covalently grafted with beta-cyclodextrin as a polycationic vector (PLL-CD) for the antitumor bisphosphonate drug risedronate (RIS). Molar ratio for maximum loading of the PLL-CD vector with RIS was determined by Raman microspectroscopy. The efficacy of RIS at inhibiting cancer cell invasion in vitro was strongly enhanced upon complexation, whatever PLL-CD:RIS complexes were in solution or embedded into PEM nanoarchitectures. Complexes in solution also clearly prevented cancer-induced bone metastasis in animals. Incorporation of the complexes into PEM nanoarchitectures covering bone implants appears of interest for in situ prevention of bone metastasis after ablation.

  12. [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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  14. Emerging Frontiers in Drug Delivery.

    PubMed

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

    2016-01-27

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

  15. 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

  16. Lipid nanoparticles as drug/gene delivery systems to the retina.

    PubMed

    del Pozo-Rodríguez, Ana; Delgado, Diego; Gascón, Alicia R; Solinís, Maria Ángeles

    2013-03-01

    This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patient's vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market. PMID:23286300

  17. Biomedical microelectromechanical systems (BioMEMS): Revolution in drug delivery and analytical techniques.

    PubMed

    Jivani, Rishad R; Lakhtaria, Gaurang J; Patadiya, Dhaval D; Patel, Laxman D; Jivani, Nurrudin P; Jhala, Bhagyesh P

    2016-01-01

    Advancement in microelectromechanical system has facilitated the microfabrication of polymeric substrates and the development of the novel class of controlled drug delivery devices. These vehicles have specifically tailored three dimensional physical and chemical features which together, provide the capacity to target cell, stimulate unidirectional controlled release of therapeutics and augment permeation across the barriers. Apart from drug delivery devices microfabrication technology's offer exciting prospects to generate biomimetic gastrointestinal tract models. BioMEMS are capable of analysing biochemical liquid sample like solution of metabolites, macromolecules, proteins, nucleic acid, cells and viruses. This review summarized multidisciplinary application of biomedical microelectromechanical systems in drug delivery and its potential in analytical procedures. PMID:26903763

  18. Biomedical microelectromechanical systems (BioMEMS): Revolution in drug delivery and analytical techniques

    PubMed Central

    Jivani, Rishad R.; Lakhtaria, Gaurang J.; Patadiya, Dhaval D.; Patel, Laxman D.; Jivani, Nurrudin P.; Jhala, Bhagyesh P.

    2013-01-01

    Advancement in microelectromechanical system has facilitated the microfabrication of polymeric substrates and the development of the novel class of controlled drug delivery devices. These vehicles have specifically tailored three dimensional physical and chemical features which together, provide the capacity to target cell, stimulate unidirectional controlled release of therapeutics and augment permeation across the barriers. Apart from drug delivery devices microfabrication technology’s offer exciting prospects to generate biomimetic gastrointestinal tract models. BioMEMS are capable of analysing biochemical liquid sample like solution of metabolites, macromolecules, proteins, nucleic acid, cells and viruses. This review summarized multidisciplinary application of biomedical microelectromechanical systems in drug delivery and its potential in analytical procedures. PMID:26903763

  19. Enzymatic action of phospholipase A₂ on liposomal drug delivery systems.

    PubMed

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

    2015-08-01

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

  20. Nano-based drug delivery system enhances the oral absorption of lipophilic drugs with extensive presystemic metabolism.

    PubMed

    Zhang, Zhiwen; Gao, Fang; Jiang, Shijun; Ma, Li; Li, Yaping

    2012-10-01

    Oral administration remains the most preferred route for the treatment of many diseases due to its convenience and adaptability. However, the presystemic metabolism may be an important barrier that prevents lipophilic drugs from achieving their pharmacological effects following oral delivery. Nano-based drug delivery system provides an effective strategy to reduce the presystemic metabolism and increase the systemic exposure of lipophilic drugs. In this review, we described the physiological factors affecting the presystemic metabolism of lipophilic drugs, intestinal transport of nanosystems, strategy of nanosystems to avoid the presystemic metabolism, and the current application of various oral nanosystems including lipid and polymeric nanocarriers. The nano-based drug delivery system has a lot of potential for reducing the presystemic metabolism and enhancing the bioavailability of orally administrated lipophilic drugs.

  1. Biophysics and Thermodynamics: The Scientific Building Blocks of Bio-inspired Drug Delivery Nano Systems.

    PubMed

    Demetzos, Costas

    2015-06-01

    Biophysics and thermodynamics are considered as the scientific milestones for investigating the properties of materials. The relationship between the changes of temperature with the biophysical variables of biomaterials is important in the process of the development of drug delivery systems. Biophysics is a challenge sector of physics and should be used complementary with the biochemistry in order to discover new and promising technological platforms (i.e., drug delivery systems) and to disclose the 'silence functionality' of bio-inspired biological and artificial membranes. Thermal analysis and biophysical approaches in pharmaceuticals present reliable and versatile tools for their characterization and for the successful development of pharmaceutical products. The metastable phases of self-assembled nanostructures such as liposomes should be taken into consideration because they represent the thermal events can affect the functionality of advanced drug delivery nano systems. In conclusion, biophysics and thermodynamics are characterized as the building blocks for design and development of bio-inspired drug delivery systems.

  2. Intrathecal Drug Delivery Systems for Noncancer Pain: A Health Technology Assessment

    PubMed Central

    2016-01-01

    Background Intrathecal drug delivery systems can be used to manage refractory or persistent chronic nonmalignant (noncancer) pain. We investigated the benefits, harms, cost-effectiveness, and budget impact of these systems compared with current standards of care for adult patients with chronic pain owing to nonmalignant conditions. Methods We searched Ovid MEDLINE, Ovid Embase, the Cochrane Library, and the National Health Service's Economic Evaluation Database and Tufts Cost-Effectiveness Analysis Registry from January 1994 to April 2014 for evidence of effectiveness, harms, and cost-effectiveness. We used existing systematic reviews that had employed reliable search and screen methods and also searched for studies published after the search date reported in the latest systematic review to identify studies. Two reviewers screened records and assessed study validity. Results We found comparative evidence of effectiveness and harms in one cohort study at high risk of bias (≥ 3-year follow-up, N = 130). Four economic evaluations of low to very low quality were also included. Compared with oral opioid analgesia alone or a program of analgesia plus rehabilitation, intrathecal drug delivery systems significantly reduced pain (27% additional improvement) and morphine consumption. Despite these reductions, intrathecal drug delivery systems were not superior in patient-reported well-being or quality of life. There is no evidence of superiority of intrathecal drug delivery systems over oral opioids in global pain improvement and global treatment satisfaction. Comparative evidence of harms was not found. Cost-effectiveness evidence is of insufficient quality to assess the appropriateness of funding intrathecal drug delivery systems. Evidence comparing intrathecal drug delivery systems with standard care was of very low quality. Conclusions Current evidence does not establish (or rule out) superiority or cost-effectiveness of intrathecal drug delivery systems for managing

  3. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

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

  4. Development of novel drug delivery systems using phage display technology for clinical application of protein drugs

    PubMed Central

    NAGANO, Kazuya; TSUTSUMI, Yasuo

    2016-01-01

    Attempts are being made to develop therapeutic proteins for cancer, hepatitis, and autoimmune conditions, but their clinical applications are limited, except in the cases of drugs based on erythropoietin, granulocyte colony–stimulating factor, interferon-alpha, and antibodies, owing to problems with fundamental technologies for protein drug discovery. It is difficult to identify proteins useful as therapeutic seeds or targets. Another problem in using bioactive proteins is pleiotropic actions through receptors, making it hard to elicit desired effects without side effects. Additionally, bioactive proteins have poor therapeutic effects owing to degradation by proteases and rapid excretion from the circulatory system. Therefore, it is essential to establish a series of novel drug delivery systems (DDS) to overcome these problems. Here, we review original technologies in DDS. First, we introduce antibody proteomics technology for effective selection of proteins useful as therapeutic seeds or targets and identification of various kinds of proteins, such as cancer-specific proteins, cancer metastasis–related proteins, and a cisplatin resistance–related protein. Especially Ephrin receptor A10 is expressed in breast tumor tissues but not in normal tissues and is a promising drug target potentially useful for breast cancer treatment. Moreover, we have developed a system for rapidly creating functional mutant proteins to optimize the seeds for therapeutic applications and used this system to generate various kinds of functional cytokine muteins. Among them, R1antTNF is a TNFR1-selective antagonistic mutant of TNF and is the first mutein converted from agonist to antagonist. We also review a novel polymer-conjugation system to improve the in vivo stability of bioactive proteins. Site-specific PEGylated R1antTNF is uniform at the molecular level, and its bioactivity is similar to that of unmodified R1antTNF. In the future, we hope that many innovative protein drugs will

  5. Cell-Mediated Drugs Delivery

    PubMed Central

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

    2011-01-01

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

  6. Fast disintegrating tablets: Opportunity in drug delivery system

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-02-01

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

  9. Drug-in-cyclodextrin-in-liposomes: A novel drug delivery system for flurbiprofen.

    PubMed

    Zhang, Lina; Zhang, Qi; Wang, Xin; Zhang, Wenji; Lin, Congcong; Chen, Fen; Yang, Xinggang; Pan, Weisan

    2015-08-15

    A novel delivery system based on drug-cyclodextrin (CD) complexation and liposomes has been developed to improve therapeutic effect. Three different means, i.e., co-evaporation (COE), co-ground (GR) and co-lyophilization (COL) and three different CDs (β-CD, HP-β-CD and SBE-β-CD) were contrasted to investigate the characteristics of the end products. FP/FP-CD loaded liposomes were obtained by thin layer evaporation technique. Size, zeta potential and encapsulation efficiency were investigated by light scattering analysis and minicolumn centrifugation. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) showed the amorphous form of complexes and spherical morphology of FP-HP-β-CD COE loaded liposomes. The pH 7.4 phosphate buffer solution (PBS) was selected as the medium for the in vitro release. Wistar rats were put into use to study the pharmacokinetic behavior in vivo. FP-HP-β-CD COE loaded liposomes showed the better physicochemical characters that followed the average particle size, polydispersity index, zeta potential and mean encapsulation efficiency 158±10 nm, 0.19±0.1, -12.4±0.1 mW and 56.1±0.5%, separately. The relative bioavailability of FP-HP-β-CD COE loaded liposomes was 420%, 201% and 402% compared with FP solution, FP-HP-β-CD and FP-liposomes, respectively. In conclusion, the novel delivery system improved the relative bioavailability of FP significantly and provided a perspective way for delivery of insoluble drugs.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  12. 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

  13. Robust and versatile pectin-based drug delivery systems.

    PubMed

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

    2015-02-20

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

  14. Drug delivery to the ear.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2011-01-01

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

  18. Photomechanical drug delivery

    NASA Astrophysics Data System (ADS)

    Doukas, Apostolos G.; Lee, Shun

    2000-05-01

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

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

    PubMed

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

    2013-11-01

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

  20. 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.

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

    PubMed Central

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

    2014-01-01

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

  2. Current perspectives on the US FDA regulatory framework for intelligent drug-delivery systems.

    PubMed

    Sapsford, Kim E; Lauritsen, Kristina; Tyner, Katherine M

    2012-12-01

    The US FDA is the US agency responsible for regulating intelligent drug-delivery systems (IDDS). IDDS can be classified as a device, drug, biologic or combination product. In this perspective, the current regulatory framework for IDDS and future perspectives on how the field is expected to evolve from a regulatory standpoint is discussed.

  3. 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

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

    PubMed Central

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

    2014-01-01

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

  5. Applications of nanoparticle drug delivery systems for the reversal of multidrug resistance in cancer

    PubMed Central

    HUANG, YINGHONG; COLE, SUSAN P.C.; CAI, TIANGE; CAI, YU

    2016-01-01

    Multidrug resistance (MDR) to chemotherapy presents a major obstacle in the treatment of cancer patients, which directly affects the clinical success rate of cancer therapy. Current research aims to improve the efficiency of chemotherapy, whilst reducing toxicity to prolong the lives of cancer patients. As with good biocompatibility, high stability and drug release targeting properties, nanodrug delivery systems alter the mechanism by which drugs function to reverse MDR, via passive or active targeting, increasing drug accumulation in the tumor tissue or reducing drug elimination. Given the potential role of nanodrug delivery systems used in multidrug resistance, the present study summarizes the current knowledge on the properties of liposomes, lipid nanoparticles, polymeric micelles and mesoporous silica nanoparticles, together with their underlying mechanisms. The current review aims to provide a reliable basis and useful information for the development of new treatment strategies of multidrug resistance reversal using nanodrug delivery systems. PMID:27347092

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

    PubMed

    Ali Khan, Arshad; 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

  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

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

    PubMed Central

    Ling, Peixue; Zhang, Tianmin

    2013-01-01

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

  9. Preparation of multiparticulate systems for oral delivery of a micronized or nanosized poorly soluble drug.

    PubMed

    Cerea, Matteo; Pattarino, Franco; Foglio Bonda, Andrea; Palugan, Luca; Segale, Lorena; Vecchio, Carlo

    2016-09-01

    The purpose of the present work was to prepare multiparticulate drug delivery systems for oral administration of a poorly soluble drug such as itraconazole. Multiparticulate systems were prepared by extrusion/spheronization technique using a mix of crospovidone, low viscosity hypromellose, microcrystalline cellulose, micronized drug and water. In order to improve the release performance of the multiparticulate systems, the micronized drug was suspended in water with polysorbate 20 and nanonized by a high-pressure homogenization. The suspension of drug nanoparticles was then spray-dried for enabling an easy handling of the drug and for preventing the over-wetting of the powders during extrusion/spheronization processing. Both multiparticulate units prepared with micronized or nanonized drug showed acceptable disintegrating properties. The nanosizing of micronized drug powder provided a significant improvement of drug dissolution rates of the multiparticulates.

  10. Preparation of multiparticulate systems for oral delivery of a micronized or nanosized poorly soluble drug.

    PubMed

    Cerea, Matteo; Pattarino, Franco; Foglio Bonda, Andrea; Palugan, Luca; Segale, Lorena; Vecchio, Carlo

    2016-09-01

    The purpose of the present work was to prepare multiparticulate drug delivery systems for oral administration of a poorly soluble drug such as itraconazole. Multiparticulate systems were prepared by extrusion/spheronization technique using a mix of crospovidone, low viscosity hypromellose, microcrystalline cellulose, micronized drug and water. In order to improve the release performance of the multiparticulate systems, the micronized drug was suspended in water with polysorbate 20 and nanonized by a high-pressure homogenization. The suspension of drug nanoparticles was then spray-dried for enabling an easy handling of the drug and for preventing the over-wetting of the powders during extrusion/spheronization processing. Both multiparticulate units prepared with micronized or nanonized drug showed acceptable disintegrating properties. The nanosizing of micronized drug powder provided a significant improvement of drug dissolution rates of the multiparticulates. PMID:26786555

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

    PubMed Central

    2011-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Zhang, Wuxu; Zhang, Zhenzhong; Zhang, Yingge

    2011-10-01

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

  13. Design of Drug Delivery Methods for the Brain and Central Nervous System

    NASA Astrophysics Data System (ADS)

    Lueshen, Eric

    Due to the impermeability of the blood-brain barrier (BBB) to macromolecules delivered systemically, drug delivery to the brain and central nervous system (CNS) is quite difficult and has become an area of intense research. Techniques such as convection-enhanced intraparenchymal delivery and intrathecal magnetic drug targeting offer a means of circumventing the blood-brain barrier for targeted delivery of therapeutics. This dissertation focuses on three aspects of drug delivery: pharmacokinetics, convection-enhanced delivery, and intrathecal magnetic drug targeting. Classical pharmacokinetics mainly uses black-box curve fitting techniques without biochemical or biological basis. This dissertation advances the state-of-the-art of pharmacokinetics and pharmacodynamics by incorporating first principles and biochemical/biotransport mechanisms in the prediction of drug fate in vivo. A whole body physiologically-based pharmacokinetics (PBPK) modeling framework is engineered which creates multiscale mathematical models for entire organisms composed of organs, tissues, and a detailed vasculature network to predict drug bioaccumulation and to rigorously determine kinetic parameters. These models can be specialized to account for species, weight, gender, age, and pathology. Systematic individual therapy design using the proposed mechanistic PBPK modeling framework is also a possibility. Biochemical, anatomical, and physiological scaling laws are also developed to accurately project drug kinetics in humans from small animal experiments. Our promising results demonstrate that the whole-body mechanistic PBPK modeling approach not only elucidates drug mechanisms from a biochemical standpoint, but offers better scaling precision. Better models can substantially accelerate the introduction of drug leads to clinical trials and eventually to the market by offering more understanding of the drug mechanisms, aiding in therapy design, and serving as an accurate dosing tool. Convection

  14. Bacterial ghosts as a novel advanced targeting system for drug and DNA delivery.

    PubMed

    Paukner, Susanne; Stiedl, Thomas; Kudela, Pavol; Bizik, Jozef; Al Laham, Firas; Lubitz, Werner

    2006-01-01

    Although there are powerful drugs against infectious diseases and cancer on the market, delivery systems are needed to decrease serious toxic and noncurative side effects. In order to enhance compliance, several delivery systems such as polymeric micro- and nanoparticles, liposomal systems and erythrocyte ghosts have been developed. Bacterial ghosts representing novel advanced delivery and targeting vehicles suitable for the delivery of hydrophobic or water-soluble drugs, are the main focus of this review. They are useful nonliving carriers, as they can carry different active substances in more than one cellular location separately and simultaneously. Bacterial ghosts combine excellent natural or engineered adhesion properties with versatile carrier functions for drugs, proteins and DNA plasmids or DNA minicircles. The simplicity of both bacterial ghost production and packaging of drugs and/or DNA makes them particularly suitable for the use as a delivery system. Further advantages of bacterial ghost delivery vehicles include high bioavailability and a long shelf life without the need of cold-chain storage due to the possibility to freeze-dry the material. PMID:16370937

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

    PubMed

    Lobo, Shabbir; Sachdeva, Sameer; Goswami, Tarun

    2016-01-01

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

  16. 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.

  17. Intrathecal Drug Delivery Systems for Cancer Pain: A Health Technology Assessment

    PubMed Central

    2016-01-01

    Background Intrathecal drug delivery systems can be used to manage refractory or persistent cancer pain. We investigated the benefits, harms, cost-effectiveness, and budget impact of these systems compared with current standards of care for adult patients with chronic pain due owing to cancer. Methods We searched Ovid MEDLINE, Ovid Embase, the Cochrane Library databases, National Health Service's Economic Evaluation Database, and Tufts Cost-Effectiveness Analysis Registry from January 1994 to April 2014 for evidence of effectiveness, harms, and cost-effectiveness. We used existing systematic reviews that had employed reliable search and screen methods and searched for studies published after the search date reported in the latest systematic review to identify studies. Two reviewers screened records and assessed study validity. The cost burden of publicly funding intrathecal drug delivery systems for cancer pain was estimated for a 5-year timeframe using a combination of published literature, information from the device manufacturer, administrative data, and expert opinion for the inputs. Results We included one randomized trial that examined effectiveness and harms, and one case series that reported an eligible economic evaluation. We found very low quality evidence that intrathecal drug delivery systems added to comprehensive pain management reduce overall drug toxicity; no significant reduction in pain scores was observed. Weak conclusions from economic evidence suggested that intrathecal drug delivery systems had the potential to be more cost-effective than high-cost oral therapy if administered for 7 months or longer. The cost burden of publicly funding this therapy is estimated to be $100,000 in the first year, increasing to $500,000 by the fifth year. Conclusions Current evidence could not establish the benefit, harm, or cost-effectiveness of intrathecal drug delivery systems compared with current standards of care for managing refractory cancer pain in

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

    PubMed Central

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

    2015-01-01

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

  19. Use of the "Personal Delivery" System for Assessment of Drug and Alcohol Attitudes and Usage Patterns.

    ERIC Educational Resources Information Center

    Crabtree, J. Michael; Myers, Stanley B.

    Community data concerning drug and alcohol usage patterns was assessed via a unique "personal delivery" system. The system, which can be used for collecting other community data produced a return rate of 45% and was very economical. This system largely overcomes the main drawback of the mailed questionnaire (low return rate) by (1) having…

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

    PubMed

    Mirza, Agha Zeeshan

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Bose, Susmita; Tarafder, Solaiman

    2012-04-01

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

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

    PubMed Central

    Bose, Susmita; Tarafder, Solaiman

    2012-01-01

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

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

    PubMed

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

    2013-01-01

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

  5. 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

  6. [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

  7. Controlled Release of Simvastatin from Biomimetic β-TCP Drug Delivery System

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  10. A thermoresponsive bubble-generating liposomal system for triggering localized extracellular drug delivery.

    PubMed

    Chen, Ko-Jie; Liang, Hsiang-Fa; Chen, Hsin-Lung; Wang, Yucai; Cheng, Po-Yuan; Liu, Hao-Li; Xia, Younan; Sung, Hsing-Wen

    2013-01-22

    The therapeutic effectiveness of chemotherapy is optimal only when tumor cells are subjected to a maximum drug exposure. To increase the intratumoral drug concentration and thus the efficacy of chemotherapy, a thermoresponsive bubble-generating liposomal system is proposed for triggering localized extracellular drug delivery. The key component of this liposomal formulation is the encapsulated ammonium bicarbonate (ABC), which is used to create the transmembrane gradient needed for a highly efficient encapsulation of doxorubicin (DOX). At an elevated temperature (42 °C), decomposition of ABC generates CO(2) bubbles, creating permeable defects in the lipid bilayer that rapidly release DOX and instantly increase the drug concentration locally. Because the generated CO(2) bubbles are hyperechogenic, they also enhance ultrasound imaging. Consequently, this new liposomal system encapsulated with ABC may also provide an ability to monitor a temperature-controlled drug delivery process.

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

    PubMed

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

    2016-01-01

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

  12. Application of mesoporous silicon dioxide and silicate in oral amorphous drug delivery systems.

    PubMed

    Qian, Ken K; Bogner, Robin H

    2012-02-01

    Aqueous solubility of an active pharmaceutical ingredient is an important consideration to ensure successful drug development. Mesoporous materials have been investigated as an amorphous drug delivery system owing to their nanosized capillaries and large surface areas. The complex interactions of crystalline compounds with mesoporous media and their implication in drug delivery are not well understood. Molecules interacting with porous media behave very differently than those in bulk phase. Their altered dynamics and thermodynamics play an important role in the properties and product performance of the amorphous system. In this review, application of mesoporous silicon dioxide and silicates in drug amorphization is the main focus. First, as background, the nature of gas-porous media interactions is summarized. The synthesis of various types of mesoporous silica, which are used by many investigators in this field, is described. Second, the behavior of molecules confined in mesopores is compared with those in bulk, crystalline phase. The molecular dynamics of compounds due to confinement, analyzed using various techniques, and their consequences in drug delivery are discussed. Finally, the preparation and performance of drug delivery systems using mesoporous silica are examined.

  13. Nanotechnology-Based Drug Delivery Systems for Treatment of Tuberculosis--A Review.

    PubMed

    da Silva, Patricia Bento; de Freitas, Eduardo Sinésio; Bernegossi, Jessica; Gonçalez, Maíra Lima; Sato, Mariana Rillo; Leite, Clarice Queico Fujimura; Pavan, Fernando Rogério; Chorilli, Marlus

    2016-02-01

    Tuberculosis (TB) is an infectious and transmissible disease that is caused by Mycobacterium tuberculosis and primarily affects the lungs, although it can affect other organs and systems. The pulmonary presentation of TB, in addition to being more frequent, is also the most relevant to public health because it is primarily responsible for the transmission of the disease. The to their low World Health Organization (WHO) recommends a combined therapeutic regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (ETB). These drugs have low plasma levels after oral administration, due to their low water solubility, poor permeability and ability to be rapidly metabolized by the liver and at high concentrations. Furthermore, they have short t₁/₂ (only 1-4 hours) indicating a short residence in the plasma and the need for multiple high doses, which can result in neurotoxicity and hepatotoxicity. Nanotechnology drug delivery systems have considerable potential for the treatment of TB. The systems can also be designed to allow for the sustained release of drugs from the matrix and drug delivery to a specific target. These properties of the systems enable the improvement of the bioavailability of drugs, can reduce the dosage and frequency of administration, and may solve the problem of non-adherence to prescribed therapy, which is a major obstacle to the control of TB. The purpose of this study was to systematically review nanotechnology-based drug delivery systems for the treatment of TB.

  14. Nanotechnology-Based Drug Delivery Systems for Treatment of Tuberculosis--A Review.

    PubMed

    da Silva, Patricia Bento; de Freitas, Eduardo Sinésio; Bernegossi, Jessica; Gonçalez, Maíra Lima; Sato, Mariana Rillo; Leite, Clarice Queico Fujimura; Pavan, Fernando Rogério; Chorilli, Marlus

    2016-02-01

    Tuberculosis (TB) is an infectious and transmissible disease that is caused by Mycobacterium tuberculosis and primarily affects the lungs, although it can affect other organs and systems. The pulmonary presentation of TB, in addition to being more frequent, is also the most relevant to public health because it is primarily responsible for the transmission of the disease. The to their low World Health Organization (WHO) recommends a combined therapeutic regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (ETB). These drugs have low plasma levels after oral administration, due to their low water solubility, poor permeability and ability to be rapidly metabolized by the liver and at high concentrations. Furthermore, they have short t₁/₂ (only 1-4 hours) indicating a short residence in the plasma and the need for multiple high doses, which can result in neurotoxicity and hepatotoxicity. Nanotechnology drug delivery systems have considerable potential for the treatment of TB. The systems can also be designed to allow for the sustained release of drugs from the matrix and drug delivery to a specific target. These properties of the systems enable the improvement of the bioavailability of drugs, can reduce the dosage and frequency of administration, and may solve the problem of non-adherence to prescribed therapy, which is a major obstacle to the control of TB. The purpose of this study was to systematically review nanotechnology-based drug delivery systems for the treatment of TB. PMID:27305759

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

    PubMed

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

    2014-06-01

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

  16. The XIIth International Symposium on Recent Advances in Drug Delivery Systems.

    PubMed

    Vivès, Eric

    2005-05-01

    The XIIth International Symposium on Recent Advances in Drug Delivery Systems was held from 21-24 February 2005 in Salt Lake City, UT, USA. Approximately 250 people attended this symposium dedicated to a broad variety of topics, ranging from recent advances in drug delivery systems to biomaterials and novel concepts in macromolecular therapeutics. A total of 33 people, all recognised specialists in the aforementioned fields, presented 30-min up-to-date reviews of these topics, as well as discussing recent results. In addition, the symposium included a poster session with approximately 100 displays highlighting various interesting data. PMID:16296778

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

    PubMed Central

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

    2015-01-01

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

  18. Nanotechnology-based drug delivery systems for the treatment of Alzheimer's disease.

    PubMed

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

    2015-01-01

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

  19. Photoresponsive nanoparticles for drug delivery

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. Microfabricated engineered particle systems for respiratory drug delivery and other pharmaceutical applications.

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  3. Pharmaceutical development and regulatory considerations for nanoparticles and nanoparticulate drug delivery systems.

    PubMed

    Narang, Ajit S; Chang, Rong-Kun; Hussain, Munir A

    2013-11-01

    Pharmaceutical nanomaterials (NMs) encompass a wide variety of materials including drug nanoparticles (NPs), which can be amorphous or crystalline; or nanoparticulate drug delivery systems, such as micelles, microemulsions, liposomes, drug-polymer conjugates, and antibody-drug conjugates. These NMs are either transient or persistent-depending on whether the integrity of their structure and size is maintained until reaching the site of drug action. Examples of several approved drug products are included as pharmaceutical nanoparticulate systems along with a commentary on the current development issues and paradigms for various categories of NPs. This commentary discusses the preparation of nanoparticulate systems for commercial development, and the biopharmaceutical and pharmacokinetic advantages of these systems. A criterion of criticality is defined that incorporates the structure, in addition to size requirement of pharmaceutical NPs to identify systems that may require special development and regulatory considerations. PMID:24037829

  4. 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.

  5. Microchip technology in drug delivery.

    PubMed

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

    2000-09-01

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

  6. In-silico simulations of advanced drug delivery systems: what will the future offer?

    PubMed

    Siepmann, Juergen

    2013-09-15

    This commentary enlarges on some of the topics addressed in the Position Paper "Towards more effective advanced drug delivery systems" by Crommelin and Florence (2013). Inter alia, the role of mathematical modeling and computer-assisted device design is briefly addressed in the Position Paper. This emerging and particularly promising field is considered in more depth in this commentary. In fact, in-silico simulations have become of fundamental importance in numerous scientific and related domains, allowing for a better understanding of various phenomena and for facilitated device design. The development of novel prototypes of space shuttles, nuclear power plants and automobiles are just a few examples. In-silico simulations are nowadays also well established in the field of pharmacokinetics/pharmacodynamics (PK/PD) and have become an integral part of the discovery and development process of novel drug products. Since Takeru Higuchi published his seminal equation in 1961 the use of mathematical models for the analysis and optimization of drug delivery systems in vitro has also become more and more popular. However, applying in-silico simulations for facilitated optimization of advanced drug delivery systems is not yet common practice. One of the reasons is the gap between in vitro and in vivo (PK/PD) simulations. In the future it can be expected that this gap will be closed and that computer assisted device design will play a central role in the research on, and development of advanced drug delivery systems.

  7. 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 μL/min on glass substrate and up to 6.8 μL/min on Parylene substrate. The fully integrated system generated a flow rate of 4.72 ± 0.35 μL/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

  8. Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma.

    PubMed

    Li, Cheng-Jun; Liu, Xiao-Zhou; Zhang, Lei; Chen, Long-Bang; Shi, Xin; Wu, Su-Jia; Zhao, Jian-Ning

    2016-05-01

    Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma.

  9. Supramolecular Drug Delivery Systems Based on Water-Soluble Pillar[n]arenes.

    PubMed

    Wu, Xuan; Gao, Lei; Hu, Xiao-Yu; Wang, Leyong

    2016-06-01

    Supramolecular drug delivery systems (SDDSs), including various kinds of nanostructures that are assembled by reversible noncovalent interactions, have attracted considerable attention as ideal drug carriers owing to their fascinating ability to undergo dynamic switching of structure, morphology, and function in response to various external stimuli, which provides a flexible and robust platform for designing and developing functional and smart supramolecular nano-drug carriers. Pillar[n]arenes represent a new generation of macrocyclic hosts, which have unique structures and excellent properties in host-guest chemistry. This account describes recent progress in our group to develop pillararene-based stimuli-responsive supramolecular nanostructures constructed by reversible host-guest interactions for controllable anticancer drug delivery. The potential applications of these supramolecular drug carriers in cancer treatment and the fundamental questions facing SDDSs are also discussed.

  10. Thermoresponsive polymeric gel as an on-demand transdermal drug delivery system for pain management.

    PubMed

    Indulekha, S; Arunkumar, P; Bahadur, D; Srivastava, R

    2016-05-01

    The main aim of this work is to design a heat triggered transdermal drug delivery system (TDDS) using a thermoresponsive polymer, poly (N-vinyl caprolactam) [PNVCL] based gel, where in patients can themselves administer a pulse of drug on mere application of heat pad over the TDDS, whenever pain is experienced. The phase transition temperature of PNVCL was tuned to 35 °C by grafting it onto a pH sensitive biopolymer, Chitosan, to synthesize Chitosan-g-PNVCL (CP) co-polymer which render the gel both thermo- and pH-responsive property. The application of triggered delivery was explored by loading acetamidophenol (a model hydrophilic drug) and etoricoxib (a model hydrophobic drug). In vitro drug release experiments were performed at three different temperatures (25, 32 and 39 °C) at two different pH (5.5 and 7) to study its drug release with response to temperature and pH. Drug release profiles obtained were found to have enhanced release for both the drugs respectively at 39 °C (above LCST) and pH5.5 when compared to other release conditions. In vitro skin permeation of both the drugs performed in rat abdominal skin using Franz diffusion cell showed enhanced drug release when the skin was subjected to higher temperature (39 °C). Moreover, it was also found that skin permeation for hydrophobic drug was better than that of hydrophilic drug. The in vivo biocompatibility studies of the CP gel in rat skin proved that the gel is biocompatible. The results obtained demonstrated the potential use of the thermoresponsive CP gel as an on-demand localized drug delivery system.

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

    PubMed

    Deshmukh, Prashant K; Gattani, Surendra G

    2013-01-01

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

  12. Local Drug Delivery Systems in the Treatment of Periodontitis: A Literature Review.

    PubMed

    Da Rocha, Huberth Alexandre Júnior; Silva, Camila Ferreira; Santiago, Fernanda Lopes; Martins, Ludiele Gonçalves; Dias, Pâmella Coelho; De Magalhães, Denildo

    2015-07-01

    In order to complement non-surgical therapy in periodontitis, there are multiple options of antimicrobials, such as metronidazole, chlorhexidine, minocycline, doxycycline and tetracycline, which can be locally delivered into the mucosa. These drugs are used in periodontal pockets and can inhibit or eliminate periodontopathogenic microorganisms as well as modulate the inflammatory response of tissues. However, limited data are available concerning the relationship between effect, efficacy and clinical status of the periodontium. This review aims to evaluate the effect and the efficacy of five types of local drug delivery systems in clinical parameters of periodontology. Researched papers using MEDLINE via PubMed, and LILACS databases related to five types of local drug delivery systems as chlorhexidine gluconate, doxycycline hyclate, metronidazole gel, minocycline ointment and tetracycline fibers, were reviewed aiming to address the mechanism of action and the evidence of clinical effectiveness of adjunctive use of these antimicrobials following surgical and/or non-surgical therapies. Inclusion criteria defined that articles must be randomized controlled trials performed in humans and published between 1996 and 2014. The adjunctive use of local drug delivery systems with controlled release properties may provide a defined, but limited, beneficial response on periodontal pockets. Furthermore, local drug delivery as an active treatment or maintenance therapy depends on clinical findings, responses to treatment described in the literature, desired clinical outcomes, and patients' dental and medical histories, including their past usage of antimicrobials. PMID:26373225

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

    PubMed

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

    2016-01-01

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

  14. 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

  15. 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

  16. Biomimetic nanowire coatings for next generation adhesive drug delivery systems

    PubMed Central

    Fischer, Kathleen E.; Alemán, Benjamin J.; Tao, Sarah L.; Daniels, R. Hugh; Li, Esther M.; Bünger, Mark D.; Nagaraj, Ganesh; Singh, Parminder; Zettl, Alex; Desai, Tejal A.

    2010-01-01

    Without bioadhesive delivery devices, complex compounds are typically degraded or cleared from mucosal tissues by the mucus layer.1–3 While some chemically-modified, micro-structured surfaces have been studied in aqueous environments,4,5 adhesion due to geometry alone has not been investigated. Silicon nanowire-coated beads show significantly better adhesion than those with targeting agents under shear, and can increase the lift-off force 100-fold. We have shown that nanowire coatings, paired with epithelial physiology, significantly increase adhesion in mucosal conditions. PMID:19199759

  17. Design of attachment type of drug delivery system by complex formation of avidin with biotinyl drug model and biotinyl saccharide.

    PubMed

    Ouchi, Tatsuro; Yamabe, Etsuro; Hara, Kei; Hirai, Mikiko; Ohya, Yuichi

    2004-02-10

    Recent studies have focused on the active targeting of drug delivery by combining a homing device and antitumor drug. For this purpose, synthesis of a well-designed vehicle (such as polymer/drug conjugates or nanoparticles) carrying a drug and a homing device requires many steps. We propose a new type of drug delivery system (DDS) by formation of a complex containing avidin (Av) plus biotinyl drug with a biotinyl homing device, which easily accommodates the combination of various drugs and homing devices. The targetable drug complex can be prepared by selecting an appropriate biotinyl drug derivative and a biotinyl homing device and mixing them with avidin. Fluorescent dye with 5-(and-6)-carboxytetramethylrhodamine (TAMRA) was used as a drug model, and galactose (Gal) recognized by liver parenchymal cells was used as a homing device. TAMRA and galactose were attached to biotin (Bio) through a triethyleneglycol (TEG) spacer group to give Bio-TEG-TAMRA conjugate and Bio-TEG-Gal conjugate, respectively. Confocal laser scanning microscopic studies suggest that the complexes prepared by mixing Bio-TEG-Gal conjugate and fluorescein isothiocyanate (FITC)-labeled Av (feed molar ratio 4:1), and mixing Bio-TEG-Gal conjugate, Bio-TEG-TAMRA conjugate and FITC-labeled Av are internalized into the hepatoma cells through a receptor-mediated endocytosis mechanism.

  18. [Efficacy of a new fenbendazole formulation produced by nanotechnology-based drug delivery system against nematodosis].

    PubMed

    Varlamova, A I; Arkhipov, I A; Odoevskaia, I M; Danilevskaia, N V; Khalikov, S S; Chistiachenko, Iu S; Dushkin, A V

    2014-01-01

    The efficacy of a new fenbendazile formulation produced by nanotechnology-based drug delivery system was investigated in45 sheep naturally infected with gastrointestinal nematodes. The formulation showed 95.6% efficacy against Nematodes spp. at a dose of 1.0 mg/kg dw of its active ingredient and 100% efficacy against other species of gastrointestinal nematodes. Given at a dose of 10 mg/kg dw, the basic drug--fenbendazole (substance) displayed 96.39 and 100% efficacy, respectively.

  19. Pectin/zein microspheres as a sustained drug delivery system

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. Delivery Systems.

    ERIC Educational Resources Information Center

    Hutchison, Betty

    This paper on delivery systems for preparing and training early childhood educators focuses on three main topics: (1) adequacy of delivery systems and access; (2) market influences on delivery systems; and (3) linking preparation and professional development components. Questions addressed include the following: Would the current preparation and…

  1. [Targeting mitochondria: innovation from mitochondrial drug delivery system (DDS) to mitochondrial medicine].

    PubMed

    Yamada, Yuma; Harashima, Hideyoshi

    2012-01-01

    Mitochondrial dysfunction has been implicated in a variety of human diseases, including cancer and neurodegenerative disorders. Effective medical therapies for such diseases will ultimately require the targeted delivery of therapeutic agents to mitochondria. This will likely be achieved through innovations in the areas of the nanotechnology of intracellular trafficking. Mitochondrial delivery systems for a variety of cargoes have been repored to date. However, only a limited number of approaches are available for delivering macromolecules directly to mitochondria. We previously reported on the construction of a MITO-Porter, a liposome-based carrier that introduces macromolecular cargos into mitochondria via membrane fusion. Using the green fluorescence protein as a model macromolecule in conjunction with analysis by confocal laser scanning microscopy, we were able to confirm the mitochondrial delivery of a macromolecule by the MITO-Porter. Moreover, we reported that the Dual Function MITO-Porter (DF-MITO-Porter) could efficiently deliver cargo to mitochondria, through endosomal and mitochondrial membranes via step-wise membrane fusion. Here, We will present our findings on the development of our mitochondrial drug delivery system, and discuss our attempts regarding mitochondrial gene delivery and therapy. Finally, We will discuss the potential use of mitochondrial drug delivery systems in mitochondrial medicine.

  2. A model ternary heparin conjugate by direct covalent bond strategy applied to drug delivery system.

    PubMed

    Wang, Ying; Xin, Dingcheng; Hu, Jiawen; Liu, Kaijian; Pan, Jiangao; Xiang, Jiannan

    2009-01-01

    A model ternary heparin conjugate by direct covalent bond strategy has been developed, in which modified heparin using active mix anhydride as intermediate conjugates with model drug molecule and model specific ligand, respectively. Designed ester bonds between model drug and heparin facilitate hydrolysis kinetics research. The strategy can be extended to design and synthesize a targeted drug delivery system. The key point is to use mixed anhydride groups as activating intermediates to mediate the synthesis of the ternary heparin conjugate. Formation of mixed anhydride is detected by the conductimetry experiment. The ternary heparin conjugate is characterized by (13)C NMR, FT-IR and GPC, respectively. The decreased trend on degree of substitution (DS) is consistent with that of introduced anticancer drug and specific ligand in drug delivery system. Moreover, their anticoagulant activity is evaluated by measuring activated partial thromboplastin time (APTT) and anti-factor Xa activity. The results show that model ternary heparin conjugate with reduced anticoagulant activity may avoid the risk of severe hemorrhagic complication during the administration and is potential to develop a safe and effective drug delivery system on anticancer research.

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

    PubMed

    Gebhardt, B M; Kaufman, H E

    1995-01-01

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

  4. 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

  5. The expanding role of aerosols in systemic drug delivery, gene therapy, and vaccination.

    PubMed

    Laube, Beth L

    2005-09-01

    Aerosolized medications have been used for centuries to treat respiratory diseases. Until recently, inhalation therapy focused primarily on the treatment of asthma and chronic obstructive pulmonary disease, and the pressurized metered-dose inhaler was the delivery device of choice. However, the role of aerosol therapy is clearly expanding beyond that initial focus. This expansion has been driven by the Montreal protocol and the need to eliminate chlorofluorocarbons (CFCs) from traditional metered-dose inhalers, by the need for delivery devices and formulations that can efficiently and reproducibly target the systemic circulation for the delivery of proteins and peptides, and by developments in medicine that have made it possible to consider curing lung diseases with aerosolized gene therapy and preventing epidemics of influenza and measles with aerosolized vaccines. Each of these drivers has contributed to a decade or more of unprecedented research and innovation that has altered how we think about aerosol delivery and has expanded the role of aerosol therapy into the fields of systemic drug delivery, gene therapy, and vaccination. During this decade of innovation, we have witnessed the coming of age of dry powder inhalers, the development of new soft mist inhalers, and improved pressurized metered-dose inhaler delivery as a result of the replacement of CFC propellants with hydrofluoroalkane. The continued expansion of the role of aerosol therapy will probably depend on demonstration of the safety of this route of administration for drugs that have their targets outside the lung and are administered long term (eg, insulin aerosol), on the development of new drugs and drug carriers that can efficiently target hard-to-reach cell populations within the lungs of patients with disease (eg, patients with cystic fibrosis or lung cancer), and on the development of devices that improve aerosol delivery to infants, so that early intervention in disease processes with aerosol

  6. Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review.

    PubMed

    Calixto, Giovana Maria Fioramonti; Bernegossi, Jéssica; de Freitas, Laura Marise; Fontana, Carla Raquel; Chorilli, Marlus

    2016-03-11

    Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

  7. Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review.

    PubMed

    Calixto, Giovana Maria Fioramonti; Bernegossi, Jéssica; de Freitas, Laura Marise; Fontana, Carla Raquel; Chorilli, Marlus

    2016-01-01

    Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer. PMID:26978341

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

    PubMed

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

    2014-06-01

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

  9. Novel self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of cinnarizine: design, optimization, and in-vitro assessment.

    PubMed

    Shahba, Ahmad Abdul-Wahhab; Mohsin, Kazi; Alanazi, Fars Kaed

    2012-09-01

    Due to its extreme lipophilicity, the oral delivery of cinnarizine (CN) encounters several problems such as poor aqueous solubility and pH-dependent dissolution, which result in low and erratic bioavailability. The current study aims to design self-nanoemulsifying drug delivery systems (SNEDDS) of CN that circumvent such obstacles. Equilibrium solubility of CN was determined in a range of anhydrous and diluted lipid-based formulations. Dynamic dispersion tests were carried out to investigate the efficiency of drug release and magnitude of precipitation that could occur upon aqueous dilution. Droplet sizes of selected formulations, upon (1:1,000) aqueous dilution, were presented. The optimal formulations were enrolled in subsequent dissolution studies. The results showed that increasing lipid chain length and surfactant lipophilicity raised the formulation solvent capacity, while adding co-solvents provoked a negative influence. The inclusion of mixed glycerides and/or hydrophilic surfactants improved the drug release efficiency. Generally, no significant precipitation was observed upon aqueous dilution of the formulations. Five formulations were optimal in terms of their superior self-emulsifying efficiency, drug solubility, dispersion characteristics, and lower droplet size. Furthermore, the optimal formulations showed superior dissolution profile compared to the marketed (Stugeron®) tablet. Most importantly, they could resist the intensive precipitation observed with the marketed tablet upon shifting from acidic to alkaline media. However, SNEDDS containing medium-chain mixed glycerides showed the highest drug release rate and provide great potential to enhance the oral CN delivery. Accordingly, the lipid portion seems to be the most vital component in designing CN self-nanoemulsifying systems. PMID:22760454

  10. Application of traditional Chinese medicine preparation in targeting drug delivery system.

    PubMed

    Xu, Wei; Xing, Feng J; Dong, Kai; You, Cuiyu; Yan, Yan; Zhang, Lu; Zhao, Guilan; Chen, Youliang; Wang, Ke

    2015-05-01

    Targeting drug system (TDS) or targeted drug delivery system (TDDS) is a new kind of drug delivery system which could make drug to be directly concentrated on the target site with high curative effects and low side-effects. As the quintessence of Chinese culture, traditional Chinese medicine (TCM) has a large advantage in many disease clinical treatments, especially in cancer, hypertension and many other intractable diseases owing to their low toxicity and side-effects relative to western medicine. This article reviews literatures on development of TCM-targeted preparations which were published in the past 10 years. TDS including active-targeting, passive-targeting and physical-chemical-targeting preparations were introduced through domestic and overseas literatures to reveal the unique advantages of TCM-targeting preparations in drug delivery system. In this article, we have reviewed some kinds of TCM-targeting preparations and indicated that great attention should be paid to the research on the TCM-targeting preparations.

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

    PubMed

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

    2007-09-01

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

  12. Biocompatible drug delivery system for photo-triggered controlled release of 5-Fluorouracil.

    PubMed

    Jin, Qiao; Mitschang, Fabian; Agarwal, Seema

    2011-10-10

    The synthesis of a photo-triggered biocompatible drug delivery system on the basis of coumarin-functionalized block copolymers is reported. The coumarin-functionalized block copolymers poly(ethylene oxide)-b-poly(n-butyl methacrylate-co-4-methyl-[7-(methacryloyl)oxyethyloxy]coumarin)) (PEO-b-P(BMA- co-CMA)) were synthesized via atom transfer radical polymerization (ATRP). The micelle-drug conjugates were made by covalent bonding of anticancer drug 5-fluorouracil (5-FU) to the coumarin under UV irradiation at wavelength >310 nm. These micelle-drug conjugates possessed spherical morphology with diameters of 70 nm from TEM images. In vitro drug release experiments showed the controlled release of anticancer drug 5-FU from the micelle-drug conjugates under UV irradiation (254 nm). These micelle-drug conjugates also showed excellent biocompatibility by the in vitro cytotoxicity experiments. The results suggest that these micelle-drug conjugates could be a promising candidate for the delivery of anticancer agents with low side effects on normal cells and excellent therapeutic efficacy to cancer cells. PMID:21863834

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

    PubMed

    Duncan, Gregg A; Bevan, Michael A

    2015-10-01

    Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ρR, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ρL. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting diseased cells and tissues.

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

    PubMed

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

    2012-04-01

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

  15. PecSys: in situ gelling system for optimised nasal drug delivery.

    PubMed

    Watts, Peter; Smith, Alan

    2009-05-01

    PecSys (PS) is a proprietary pectin-based drug delivery system designed to gel when applied to mucosal surfaces and with potential areas of application for drugs used in local and systemic disease therapy. The current area of focus is intranasal drug delivery where PS is being used to optimise absorption of lipophilic drugs into the systemic circulation. Pectin is described as GRAS (generally regarded as safe) with an excellent regulatory position through its long history of pharmaceutical and food usage. Tests to measure the functional gelling properties of pectin raw material and PS have been devised and validated. The PS-based products at the most advanced stages of development are intranasal formulations containing opioid analgesics intended to provide rapid pain relief with simple and convenient dosing and minimal side effects. The profile of such drugs may not be optimal through current routes of delivery and the ability of PS to modulate their pharmacokinetic profiles, such as attenuation of the peak plasma concentration (Cmax), has been demonstrated in clinical testing. The lead product using PS is a fentanyl nasal spray formulation (NasalFent), which has successfully met the primary objective in a pivotal Phase III clinical study and is scheduled for regulatory filings in the first half of 2009.

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

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

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

  17. Modified titanium implant as a gateway to the human body: the implant mediated drug delivery system.

    PubMed

    Park, Young-Seok; Cho, Joo-Youn; Lee, Shin-Jae; 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.

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

    PubMed Central

    Zhang, Xiao-Yu; Lu, Wei-Yue

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Duncan, Gregg A.; Bevan, Michael A.

    2015-09-01

    Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ρR, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ρL. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting diseased cells and tissues.Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ρR, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ρL. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting

  20. 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.

  1. Spatiotemporally synchronized cancer combination therapy using photo-activated nanoparticle drug delivery systems (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Hasan, Tayyaba

    2016-03-01

    This talk will introduce a new nanotechnology platform for cancer combination therapy that utilizes near infrared light activation not only for photodynamic damage but also as an extrinsic mechanism to initiate release of complimentary drugs to suppress dynamic bursts in molecular signaling networks that promote tumor cell survival and treatment escape. The goal is to achieve co-delivery with concomitant activity of photodynamic, molecular inhibitor and chemotherapeutic agents, selectively within the tumor. This approach overcomes challenges in achieving synergistic interactions using sequential drug delivery. Conventional drug delivery is compromised by the differential pharmacokinetics of individual agents and potentially antagonistic effects—such as vascular shutdown by one agent that limits delivery of the second. Here, photodynamic damage—which efficiently kills drug-resistant cells via damage of common proteins involved in drug-resistance (such as anti-apoptosis factors and drug-efflux transporters)—is synchronized spatially and temporally with the photo-initiated release of complimentary agents—to enable full interaction amongst the individual therapies. This spatiotemporal synchronization offers new prospects for exploiting time-sensitive synergistic interactions. Specific implementations of these concepts will be presented in preclinical models of cancer. Strategies to enable molecular-targeting of cancer cells via site-specific attachment of targeting moieties to the outer lipid shell of these nanovehicles will also be discussed. If successful in humans, this new paradigm for synchronized, tumor-focused combination therapy will ultimately supersede the present use of chronic drug injection by increasing efficacy per cycle whilst reducing systemic exposure to toxic drugs.

  2. Skin delivery of kojic acid-loaded nanotechnology-based drug delivery systems for the treatment of skin aging.

    PubMed

    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

  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. Formulation and Evaluation of a Self-microemulsifying Drug Delivery System Containing Bortezomib.

    PubMed

    Hong, Eon-Pyo; Kim, Ju-Young; Kim, Su-Hyeon; Hwang, Kyu-Mok; Park, Chun-Woong; Lee, Hyo-Jung; Kim, Dong-Wook; Weon, Kwon-Yeon; Jeong, Seo Young; Park, Eun-Seok

    2016-01-01

    The purposes of the present study were to develop a self-microemulsifying drug delivery system (SMEDDS) containing bortezomib, a proteasome inhibitor. The solubility of the drug was evaluated in 15 pharmaceutical excipients. Combinations of oils, surfactants and cosurfactants were screened by drawing pseudo-ternary phase diagrams. The system exhibiting the largest region of microemulsion was considered optimal. Bortezomib SMEDDS spontaneously formed a microemulsion when diluted with an aqueous medium with a median droplet size of approximately 20-30 nm. In vitro release studies showed that the SMEDDS had higher initial release rates for the drug when compared with the raw drug material alone. Measurement of the viscosity, size, and ion conductivity indicated that a phase inversion from water in an oil system to oil in a water system occurred when the weight ratio of the water exceeded 30% of the entire microemulsion system. In a pharmacokinetics study using rats, the bortezomib microemulsion failed to improve the bioavailability of the drug. The reason was assumed to be degradation of the drug in the microemulsion in the gastrointestinal tract. However, bortezomib in Labrasol(®) solution (an aqueous solution containing 0.025% Labrasol(®)) showed significantly increased area under the curve from 0-24 h (AUC0-24 h) and maximum plasma concentration (Cmax) values compared to the drug suspension. The findings of this study imply that oral delivery of a bortezomib and colloidal system containing Labrasol(®) could be an effective strategy for the delivery of bortezomib. PMID:27477648

  5. Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

    PubMed

    Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2016-06-01

    From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB. PMID:26289212

  6. Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

    PubMed

    Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2016-06-01

    From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

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

    PubMed Central

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

    2014-01-01

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

  8. Potential for layered double hydroxides-based, innovative drug delivery systems.

    PubMed

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

    2014-01-01

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

  9. Nanoemulsion-based intranasal drug delivery system of saquinavir mesylate for brain targeting.

    PubMed

    Mahajan, Hitendra S; Mahajan, Milind S; Nerkar, Pankaj P; Agrawal, Anshuman

    2014-03-01

    The central nervous system (CNS) is an immunological privileged sanctuary site-providing reservoir for HIV-1 virus. Current anti-HIV drugs, although effective in reducing plasma viral levels, cannot eradicate the virus completely from the body. The low permeability of anti-HIV drugs across the blood-brain barrier (BBB) leads to insufficient delivery. Therefore, developing a novel approaches enhancing the CNS delivery of anti-HIV drugs are required for the treatment of neuro-AIDS. The aim of this study was to develop intranasal nanoemulsion (NE) for enhanced bioavailability and CNS targeting of saquinavir mesylate (SQVM). SQVM is a protease inhibitor which is a poorly soluble drug widely used as antiretroviral drug, with oral bioavailability is about 4%. The spontaneous emulsification method was used to prepare drug-loaded o/w nanoemulsion, which was characterized by droplet size, zeta potential, pH, drug content. Moreover, ex-vivo permeation studies were performed using sheep nasal mucosa. The optimized NE showed a significant increase in drug permeation rate compared to the plain drug suspension (PDS). Cilia toxicity study on sheep nasal mucosa showed no significant adverse effect of SQVM-loaded NE. Results of in vivo biodistribution studies show higher drug concentration in brain after intranasal administration of NE than intravenous delivered PDS. The higher percentage of drug targeting efficiency (% DTE) and nose-to-brain drug direct transport percentage (% DTP) for optimized NE indicated effective CNS targeting of SQVM via intranasal route. Gamma scintigraphy imaging of the rat brain conclusively demonstrated transport of drug in the CNS at larger extent after intranasal administration as NE.

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

    PubMed Central

    Kaur, Randeep; Badea, Ildiko

    2013-01-01

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

  11. Cryogenic transmission electron microscopy (cryo-TEM) for studying the morphology of colloidal drug delivery systems.

    PubMed

    Kuntsche, Judith; Horst, Jennifer C; Bunjes, Heike

    2011-09-30

    Cryogenic transmission electron microscopy (cryo-TEM) has evolved into an indispensable tool for the characterization of colloidal drug delivery systems. It can be applied to study the size, shape and internal structure of nanoparticulate carrier systems as well as the overall colloidal composition of the corresponding dispersions. This review gives a short overview over the instrumentation used in cryo-TEM experiments and over the sample preparation procedure. Selected examples of cryo-TEM studies on colloidal drug carrier systems, including liposomes, colloidal lipid emulsions, solid lipid nanoparticles, thermotropic and lyotropic liquid crystalline nanoparticles, polymer-based colloids and delivery systems for nucleic acids, are presented in order to illustrate the wealth of information that can be obtained by this technique.

  12. A sustained intravitreal drug delivery system with remote real time monitoring capability

    PubMed Central

    Hou, Huiyuan; Nieto, Alejandra; Belghith, Akram; Nan, Kaihui; Li, Yangyang; Freeman, William R.; Sailor, Michael J.; Cheng, Lingyun

    2015-01-01

    Many chorioretinal diseases are chronic and need sustained drug delivery systems to keep therapeutic drug level at the disease site. Many intravitreal drug delivery systems under developing do not have mechanism incorporated for a non-invasive monitoring of drug release. Current study prepared rugate porous silicon (pSi) particles by electrochemical etching with the currents frequency (K value) of 2.17 and 2.45. Two model drugs (Rapmycin and Dexamethasone) and two drug-loading strategies were tested for the feasibility to monitor drug release from the pSi particles through a color fundus camera. The pSi particles (k=2.45) with infiltration loading of rapamycin demonstrated progressively more violet color reflection which was negatively associated with the rapamycin released into the vitreous (r=−0.4, p<0.001, pairwise). In contrast, pSi with K value of 2.17 demonstrated progressive color change towards green and a weak association between rapmycin released into vitreous and green color abundance was identified (r=−0.23, p=0.002, pairwise). Dexamethasone was covalently loaded on to the fully oxidized pSi particles that appeared in vitreous as yellow color and fading over time. The yellow color decrease over time was strongly associated with the dexamethasone detected from the vitreous samples (r=0.7, p<0.0001, pairwise). These results suggest that engineered porous silicon particles may be used as a self-reporting drug delivery system for a non-invasive real time remote monitoring. PMID:26087110

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Lipka, E; Amidon, G L

    1999-11-01

    The recently proposed Biopharmaceutics Classification System can be used to classify drugs and set standards for scale-up and post-approval changes as well as standards for in vitro/in vivo correlation for immediate and controlled release products. This classification scheme is based on determining the underlying process that is controlling the drug absorption rate and extent, namely, drug solubility and intestinal membrane permeability. Theoretical analysis and experimental results suggest that a permeability/solubility classification scheme can be used to set more rationale drug standards. In particular, high solubility/high permeability, rapidly dissolving drugs may be regulated on the basis of a single point rapid dissolution test while low solubility dissolution rate limited drugs can be regulated based on an in vitro dissolution test that reflects the in vivo dissolution process. This dissolution test may include multiple time points, media change, as well as surfactants in order to reflect the in vivo dissolution process and would be used by the manufacturer for requesting a waiver from a bioequivalence (BE) trial. For controlled release products, the regulation of bioequivalence standards is more complex due to the potential differences in position-dependent permeability/solubility and metabolism of drugs along the gastrointestinal tract. These differences may result in drug absorption rates that are highly transit time dependent. This paper will present the current status of the biopharmaceutic drug classification scheme, the underlying developed data base and its application to optimizing IR and CR products.

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

    PubMed

    Lakkakula, Jaya Raju; Maçedo Krause, Rui Werner

    2014-05-01

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

  16. Nanoencapsulation for drug delivery

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  18. The ideal drug delivery system: a look into the future.

    PubMed

    Aiache, J M

    1991-01-01

    In the very near future, the CFC manufacturers are going to be obliged to stop their production as a result of the "Montreal protocole on substances that deplete the ozone layer". The replacement of these propellants by other fluorinated ones will be possible as soon as their lack of toxicity has been demonstrated. Other substitution substances like haliphatic hydrocarbons (butane, propane) or compressed air generated by the device system itself or the user himself are also under development. The pulverisation can also be obtained by the pressure of a classical propellant onto an aluminum or plastic bag. The dispersion is achieved by means of a regulator which is positioned into the valve. The hand-operated spray pumps with or without compression will also allow the obtention of very small particles though the delivered doses are reduced. However, as few of the new devices have metered valves, they are not yet suitable for pulmonary administration.

  19. 15 years of ATTEMPTS: a macromolecular drug delivery system based on the CPP-mediated intracellular drug delivery and antibody targeting.

    PubMed

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

    2015-05-10

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

  20. 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 μm 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.

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

    PubMed Central

    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

  2. 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.

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

    PubMed

    Osswald, Christian R; Kang-Mieler, Jennifer J

    2015-11-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-05-14

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

  6. Tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems.

    PubMed

    Vazzana, M; Andreani, T; Fangueiro, J; Faggio, C; Silva, C; Santini, A; Garcia, M L; Silva, A M; Souto, E B

    2015-03-01

    Tramadol hydrochloride (TrHC) is a synthetic analgesic drug exhibiting opioid and non-opioid properties, acting mainly on the central nervous system. It has been mostly used to treat pain, although its use to treat anxiety and depression has also been documented. These properties arise from the fact that they inhibit serotonin (5-HT) reuptake augmenting 5-HT concentration on the synaptic cleft. Despite this, TrHC has also been described to have several side effects which are mainly due to its fast metabolization and excretion which in turn requires multiple doses per day. To surpass this limitation, new pharmaceutical formulations are being developed intending the protection, target and sustained delivery as well as a reduction on daily dose aiming a reduction on the side effects. In the present work we have revised the efficacy, safety, biological and adverse effects of TrHC, and the added value of developing a novel drug delivery system for topical administration.

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

    PubMed Central

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

    2016-01-01

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

  8. Evaluation of powder mixtures and hydrophilic gastroretentive drug delivery systems containing zinc acetate and sodium bicarbonate.

    PubMed

    Baki, Gabriella; Bajdik, János; Pintye-Hódi, Klára

    2011-03-25

    The aim of this study was to develop and study floating controlled drug delivery systems consisting of a model drug (zinc acetate dihydrate), different forms of a matrix-forming polymer (Metolose 90 SH) and sodium bicarbonate as an effervescent component. The proportions of Metolose and bicarbonate were varied, and the effects of the different ratios on the properties of the resulting powders and tablets were determined. The water uptakes of different powder mixtures were initially evaluated. These tests indicated the interaction of the active and effervescent agent, this phenomenon leading to an unpredicted increase in the amount of liquid taken up. This interaction was evaluated as concerns the degradation of the hydrophilic matrix system. The disintegration of tablets with different compositions revealed that this interaction increases the time required for the disintegration of these systems. The study demonstrated that the interaction of the components induced significant changes in the parameters of this new sensitive delivery system. In the last steps, the buoyancy and dissolution properties of tablets that appeared appropriate for the formulation of a controlled drug delivery system were investigated. PMID:21109379

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Fu, Yao; Kao, Weiyuan John

    2010-01-01

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

  11. Design of Drug Delivery Methods for the Brain and Central Nervous System

    NASA Astrophysics Data System (ADS)

    Lueshen, Eric

    Due to the impermeability of the blood-brain barrier (BBB) to macromolecules delivered systemically, drug delivery to the brain and central nervous system (CNS) is quite difficult and has become an area of intense research. Techniques such as convection-enhanced intraparenchymal delivery and intrathecal magnetic drug targeting offer a means of circumventing the blood-brain barrier for targeted delivery of therapeutics. This dissertation focuses on three aspects of drug delivery: pharmacokinetics, convection-enhanced delivery, and intrathecal magnetic drug targeting. Classical pharmacokinetics mainly uses black-box curve fitting techniques without biochemical or biological basis. This dissertation advances the state-of-the-art of pharmacokinetics and pharmacodynamics by incorporating first principles and biochemical/biotransport mechanisms in the prediction of drug fate in vivo. A whole body physiologically-based pharmacokinetics (PBPK) modeling framework is engineered which creates multiscale mathematical models for entire organisms composed of organs, tissues, and a detailed vasculature network to predict drug bioaccumulation and to rigorously determine kinetic parameters. These models can be specialized to account for species, weight, gender, age, and pathology. Systematic individual therapy design using the proposed mechanistic PBPK modeling framework is also a possibility. Biochemical, anatomical, and physiological scaling laws are also developed to accurately project drug kinetics in humans from small animal experiments. Our promising results demonstrate that the whole-body mechanistic PBPK modeling approach not only elucidates drug mechanisms from a biochemical standpoint, but offers better scaling precision. Better models can substantially accelerate the introduction of drug leads to clinical trials and eventually to the market by offering more understanding of the drug mechanisms, aiding in therapy design, and serving as an accurate dosing tool. Convection

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

    PubMed

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

    2015-10-12

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

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

    PubMed

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

    2014-10-24

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

  15. PLGA based drug delivery systems: Promising carriers for wound healing activity.

    PubMed

    Chereddy, Kiran Kumar; Vandermeulen, Gaëlle; Préat, Véronique

    2016-03-01

    Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Current treatment options are limited and require repeated administrations which led to the development of new therapeutics to satisfy the unmet clinical needs. Many potent wound healing agents were discovered but most of them are fragile and/or sensitive to in vivo conditions. Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer approved by food and drug administration and European medicines agency as an excipient for parenteral administrations. It is a well-established drug delivery system in various medical applications. The aim of the current review is to elaborate the applications of PLGA based drug delivery systems carrying different wound healing agents and also present PLGA itself as a wound healing promoter. PLGA carriers encapsulating drugs such as antibiotics, anti-inflammatory drugs, proteins/peptides, and nucleic acids targeting various phases/signaling cycles of wound healing, are discussed with examples. The combined therapeutic effects of PLGA and a loaded drug on wound healing are also mentioned.

  16. Formation of controllable hydrophilic/hydrophobic drug delivery systems by electrospinning of vesicles.

    PubMed

    Li, Wei; Luo, Tian; Yang, Yanjuan; Tan, Xiuniang; Liu, Lifei

    2015-05-12

    Novel multifunctional poly(ethylene oxide) (PEO) nanofibrous membrane, which contains vesicles constructed by mixed surfactant cetyltrimethylammonium bromide (CTAB)/sodium dodecylbenzenesulfonate (SDBS), has been designed as dual drug-delivery system and fabricated via the electrospinning process. 5-FU and paeonolum, which are hydrophilic and hydrophobic anticancer model drugs, can be dissolved in vesicle solution's bond water and lipid bilayer membranes, respectively. The physicochemical properties of the electrospun nanofibrous membrane were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). Drug release behaviors of the electrospun nanofibrous membrane fabricated with different molar ratio of CTAB/SDBS vesicle solution were investigated. The result showed that the releasing amount of hydrophilic drug presented an ascending release manner, while the hydrophobic one showed a descending release behavior with increasing of the molar ratio of CTAB/SDBS. Moreover, the release amount of drugs from drug delivery system can be controlled by the molar ratio of CTAB/SDBS in the vesicle solution easily and conveniently. The distinct properties can be utilized to encapsulate environmental demanding and quantificational materials.

  17. 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.

  18. 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

  19. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  2. 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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Waite, Carolyn L; Roth, Charles M

    2012-01-01

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

  5. Development of pH-sensitive self-nanoemulsifying drug delivery systems for acid-labile lipophilic drugs.

    PubMed

    Zhao, Tianjing; Maniglio, Devid; Chen, Jie; Chen, Bin; Migliaresi, Claudio

    2016-03-01

    Oral administration is the most convenient way of all the drug delivery routes. Orally administered bioactive compounds must resist the harsh acidic fluids or enzyme digestion in stomach, to reach their absorbed destination in small intestine. This is the case for silibinin, a drug used to protect liver cells against toxins that has also been demonstrated in vitro to possess anti-cancer effects. However, as many other drugs, silibinin can degrade in the stomach due to the action of the gastric fluid. The use of pH-sensitive self-nanoemulsifying drug delivery systems (pH-SNEDDS) could overcome the drawback due to degradation of the drug in the stomach while enhancing its solubility and dissolution rate. In this paper we have investigated pH-sensitive self-nanoemulsifying formulations containing silibinin as model drug. Pseudo-ternary phase diagrams have been constructed in order to identify the self-emulsification regions under different pH. Solubility of silibinin in selected formulations has been assessed and stability of the pure drug and of the silibinin loaded pH-SNEDDS formulations in simulated gastric fluid had been compared. Droplet size of the optimized pH-SNEDDS has been correlated to pH, volume of dilution medium and silibinin loading amount. TEM (transmission electron microscopy) studies have shown that emulsion droplets had spherical shape and narrow size distribution. In vitro drug release studies of the optimal pH-SNEDDS indicated substantial increase of the drug release and release rate in comparison to pure silibinin and to the commercial silibinin tablet. The results indicated that pH-SNEDDS have potential to improve the biopharmaceutics properties of acid-labile lipophilic drugs.

  6. Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol

    PubMed Central

    Balata, Gehan F; Essa, Ebtessam A; Shamardl, Hanan A; Zaidan, Samira H; Abourehab, Mohammed AS

    2016-01-01

    Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17–99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of −2.24 to −15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic effects of resveratrol in diabetic-induced albino rats and comparing these effects with that of pure resveratrol in different doses. Treatment with the optimized formula, F19, at 10 mg/kg had significant hypoglycemic and hypolipidemic effects in diabetic-induced albino rats which were nearly similar to the high dose (20 mg/kg) of unprocessed resveratrol. From the study, it was concluded that formulation F19 has good emulsification property with uniform globule size, satisfactory in vitro drug release profile, and significant in vivo hypoglycemic effects which identify future

  7. Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol.

    PubMed

    Balata, Gehan F; Essa, Ebtessam A; Shamardl, Hanan A; Zaidan, Samira H; Abourehab, Mohammed As

    2016-01-01

    Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17-99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of -2.24 to -15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic effects of resveratrol in diabetic-induced albino rats and comparing these effects with that of pure resveratrol in different doses. Treatment with the optimized formula, F19, at 10 mg/kg had significant hypoglycemic and hypolipidemic effects in diabetic-induced albino rats which were nearly similar to the high dose (20 mg/kg) of unprocessed resveratrol. From the study, it was concluded that formulation F19 has good emulsification property with uniform globule size, satisfactory in vitro drug release profile, and significant in vivo hypoglycemic effects which identify future opportunities

  8. Transmucosal macromolecular drug delivery.

    PubMed

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

    2005-01-01

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

  9. 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).

  10. Current Trends in Self-Emulsifying Drug Delivery Systems (SEDDSs) to Enhance the Bioavailability of Poorly Water-Soluble Drugs.

    PubMed

    Karwal, Rohit; Garg, Tarun; Rath, Goutam; Markandeywar, Tanmay S

    2016-01-01

    The main object of the self-emulsifying drug-delivery system (SEDDS) is oral bioavailability (BA) enhancement of a poorly water-soluble drug. Low aqueous solubility and low oral BA are major concerns for formulation scientists. As many drugs are lipophilic in nature, their lower solubility and dissolution are major drawbacks for their successful formulation into oral dosage forms. More than 60% of drugs have a lipophilic nature and exhibit poor aqueous solubility. Various strategies are reported in the literature to improve the solubility and enhance BA of lipophilic drugs, including the formation of a cyclodextrin complex, solid dispersions, and micronization. SEDDSs are ideally isotropic mixtures of drug, oil, surfactant, and/or cosurfactant. SEDDSs have gained increasing attention for enhancing oral BA and reducing drug dose. SEDDSs also provide an effective and excellent solution to the various issues related to the formulation of hydrophobic drugs that have limited solubility in gastrointestinal fluid. Our major focus of this review is to highlight the importance of SEDDSs in oral BA enhancement of poorly water-soluble drugs. PMID:27279337

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

    PubMed

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

    2012-01-01

    Zolpidem tartarate is a non-benzodiazepine, sedative-hypnotic, which finds its major use in various types of insomnia. The present work relates to development of multiparticulate floating drug delivery system based on gas generation technique to prolong the gastric residence time and to increase the overall bioavailability. Modified release dosage form of zolpidem tartarate adapted to release over a predetermined time period, according to biphasic profile of dissolution, where the first phase is immediate release phase for inducing the sleep and the second phase is modified release phase for maintaining the sleep up to 10 h. The system consists of zolpidem tartarate layered pellets coated with effervescent layer and polymeric membrane. The floating ability and in vitro drug release of the system were dependent on amount of the effervescent agent (sodium bicarbonate) layered onto the drug layered pellets, and coating level of the polymeric membrane (Eudragit(®) NE 30D). The system could float completely within 5 min and maintain the floating over a period of 10 h. The multiparticulate floating delivery system of zolpidem tartarate with rapid floating and modified drug release was obtained. PMID:21974910

  12. 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.

  13. 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

  14. A New Carbon Nanotube-Based Breast Cancer Drug Delivery System: Preparation and In Vitro Analysis Using Paclitaxel.

    PubMed

    Shao, Wei; Paul, Arghya; Rodes, Laetitia; Prakash, Satya

    2015-04-01

    Paclitaxel (PTX) is one of the most important drugs for breast cancer; however, the drug effects are limited by its systematic toxicity and poor water solubility. Nanoparticles have been applied for delivery of cancer drugs to overcome their limitations. Toward this goal, a novel single-walled carbon nanotube (SWNT)-based drug delivery system was developed by conjugation of human serum albumin (HSA) nanoparticles for loading of antitumor agent PTX. The nanosized macromolecular SWNT-drug carrier (SWNT-HSA) was characterized by TEM, UV-Vis-NIR spectrometry, and TGA. The SWNT-based drug carrier displayed high intracellular delivery efficiency (cell uptake rate of 80%) in breast cancer MCF-7 cells, as examined by fluorescence-labeled drug carriers, suggesting the needle-shaped SWNT-HSA drug carrier was able to transport drugs across cell membrane despite its macromolecular structure. The drug loading on SWNT-based drug carrier was through high binding affinity of PTX to HSA proteins. The PTX formulated with SWNT-HSA showed greater growth inhibition activity in MCF-7 breast cancer cells than PTX formulated with HSA nanoparticle only (cell viability of 63 vs 70% in 48 h and 53 vs 62% in 72 h). The increased drug efficacy could be driven by SWNT-mediated cell internalization. These data suggest that the developed SWNT-based antitumor agent is functional and effective. However, more studies for in vivo drug delivery efficacy and other properties are needed before this delivery system can be fully realized. PMID:27101155

  15. 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

  16. Lyotropic liquid crystalline phases formed from glycerate surfactants as sustained release drug delivery systems.

    PubMed

    Boyd, Ben J; Whittaker, Darryl V; Khoo, Shui-Mei; Davey, Greg

    2006-02-17

    A new class of surfactants with glycerate headgroups, that form viscous lyotropic liquid crystalline phases in excess water, have been investigated for their potential to provide sustained release matrices for depot drug delivery. Oleyl glycerate and phytanyl glycerate were used as representative surfactants of this new class, and their behaviour compared with that of glyceryl monooleate (GMO). The surfactants were found to form reverse hexagonal phase (H(II)) in excess water, and the matrices were loaded with a series of model hydrophobic and hydrophilic drugs, (paclitaxel, irinotecan, glucose, histidine and octreotide), and the release kinetics determined. In all cases, the release behaviour obeyed Higuchi kinetics, with linear drug release versus square root of time. The H(II) phases released model drugs slower than the GMO cubic phase matrix. The oleyl glycerate matrix was found to consistently release drug faster than the phytanyl glycerate matrix, despite both matrices being based on H(II) phase. To further demonstrate the potential utility of these materials as drug depot delivery systems, an injectable precursor formulation for octreotide was also prepared and demonstrated to provide controlled release for the peptide. The stability of the H(II) phase to likely in vivo breakdown products was also assessed.

  17. 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

  18. Self-Microemulsifying Drug Delivery Systems: An Attractive Strategy for Enhanced Therapeutic Profile

    PubMed Central

    Akula, Samatha; Gurram, Aravind Kumar; Devireddy, Srinivas Reddy

    2014-01-01

    Ease of administration and painless approach made oral route the most preferred. Poor oral bioavailability is pronounced with the majority of recent active ingredients because of dissolution rate limited absorption. Failure to attain intended therapeutic effect of the poor water soluble drugs by this route led to development of novel drug delivery systems which will fulfill therapeutic needs with minimum dose. Although many formulation approaches like solid dispersions, complexation, pH modification, and cocrystals exist, lipid based delivery systems finding increased appliance with the apparent increase in absorption of drug. Among lipid based formulations, self-microemulsifying formulations (droplet size < 100 nm) are evident to improve the oral bioavailability of hydrophobic drugs primarily due to their efficiency in facilitating solubilization and in presenting the hydrophobic drug in solubilized form whereby dissolution process can be circumvented. Various components that are used to formulate these dosage forms like surfactants and lipids contribute to the overall improvement in oral bioavailability via promoting the lymphatic transport; thereby hepatic first pass metabolism can be surmounted. The present paper gives exhaustive information on the formulation design and characterization of SMEDDS along with the probable mechanisms by which the bioavailability can be improved with SMEDDS. PMID:27382619

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

    PubMed

    Vanić, Željka; Hurler, Julia; Ferderber, Kristina; Golja Gašparović, Petra; Škalko-Basnet, Nataša; Filipović-Grčić, 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

  20. 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

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

    PubMed Central

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

    2014-01-01

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

  2. Hydrothermal fabrication of porous hollow hydroxyapatite microspheres for a drug delivery system.

    PubMed

    Lai, Wen; Chen, Cen; Ren, Xiaoyuan; Lee, In-Seop; Jiang, Guohua; Kong, Xiangdong

    2016-05-01

    Porous hollow hydroxyapatite microspheres (PHHMs) are the promising biomaterials, owing to their excellent biocompatibility, biodegradability and bioactivity. PHHMs have been used as drug controlled carriers due to their advantages such as large drug loading capacity, nanochannels for drug loading and release and high specific surface area. In this study, PHHMs were prepared successfully in Na2HPO4 solution by an anion-exchange process using vaterite CaCO3 through a hydrothermal method. The previous vaterite CaCO3 was synthesized by a polymer-templated method in the poly(styrene sulfonic acid) sodium salt (PSS) aqueous solutions. The PHHMs have a size distribution from 0.8 to 2.0 μm, with an average pore size of about 24.3 nm. The wall of PHHMs is constructed with building units of hydroxyapatite nanofibers with an average length of 300 nm and an average width of 20 nm. The PHHMs displayed a high drug loading capacity and pH-responsive sustained-controlled drug release behavior when we used doxorubicin hydrochloride (DOX) as a loading drug. Moreover, the controlled drug release system showed a high ability to kill cancer cells and less damage to normal cells. These results indicated that PHHMs are promising for applications in various biomedical fields such as drug delivery system and oncotherapy.

  3. Hydrothermal fabrication of porous hollow hydroxyapatite microspheres for a drug delivery system.

    PubMed

    Lai, Wen; Chen, Cen; Ren, Xiaoyuan; Lee, In-Seop; Jiang, Guohua; Kong, Xiangdong

    2016-05-01

    Porous hollow hydroxyapatite microspheres (PHHMs) are the promising biomaterials, owing to their excellent biocompatibility, biodegradability and bioactivity. PHHMs have been used as drug controlled carriers due to their advantages such as large drug loading capacity, nanochannels for drug loading and release and high specific surface area. In this study, PHHMs were prepared successfully in Na2HPO4 solution by an anion-exchange process using vaterite CaCO3 through a hydrothermal method. The previous vaterite CaCO3 was synthesized by a polymer-templated method in the poly(styrene sulfonic acid) sodium salt (PSS) aqueous solutions. The PHHMs have a size distribution from 0.8 to 2.0 μm, with an average pore size of about 24.3 nm. The wall of PHHMs is constructed with building units of hydroxyapatite nanofibers with an average length of 300 nm and an average width of 20 nm. The PHHMs displayed a high drug loading capacity and pH-responsive sustained-controlled drug release behavior when we used doxorubicin hydrochloride (DOX) as a loading drug. Moreover, the controlled drug release system showed a high ability to kill cancer cells and less damage to normal cells. These results indicated that PHHMs are promising for applications in various biomedical fields such as drug delivery system and oncotherapy. PMID:26952411

  4. Xanthan gum and its derivatives as a potential bio-polymeric carrier for drug delivery system.

    PubMed

    Badwaik, Hemant R; Giri, Tapan Kumar; Nakhate, Kartik T; Kashyap, Pranita; Tripathi, Dulal Krishna

    2013-10-01

    Xanthan gum is a high molecular weight natural polysaccharide produced by fermentation process. It consists of 1, 4-linked β-D-glucose residues, having a trisaccharide side chain attached to alternate D-glucosyl residues. Although the gum has many properties desirable for drug delivery, its practical use is mainly confined to the unmodified forms due to slow dissolution and substantial swelling in biological fluids. Xanthan gum has been chemically modified by conventional chemical methods like carboxymethylation, and grafting such as free radical, microwave-assisted, chemoenzymatic and plasma assisted chemical grafting to alter physicochemical properties for a wide spectrum of biological applications. This article reviews various techniques utilized for modification of xanthan gum and its applications in a range of drug delivery systems.

  5. Generation of tailored aerosols for inhalative drug delivery employing recent vibrating-mesh nebulizer systems.

    PubMed

    Bohr, Adam; Beck-Broichsitter, Moritz

    2015-01-01

    Direct drug delivery to the lungs is considered the gold standard for the treatment of a variety of respiratory diseases, owing to the increased therapeutic selectivity of the inhalative approach. Airborne formulations with defined size characteristics are required to improve the deposition pattern within the airways. In this respect, different nebulizer systems have been conceived, which has enabled the generation of respirable medicament mists. Here, vibrating-mesh technology revealed significant potential to overcome the main shortcomings associated with 'traditional' devices. Tailored orifice dimensions and defined formulation characteristics are of special interest for the generation of suitable aerosol droplets for inhalative purposes. Ongoing developments in device and formulation design will optimize the clinical outcome of inhalative drug delivery under application of vibrating-mesh technology.

  6. 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.

  7. 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

  8. Formulation of avanafil in a solid self-nanoemulsifying drug delivery system for enhanced oral delivery.

    PubMed

    Soliman, Kareem AbuBakr; Ibrahim, Howida Kamal; Ghorab, Mahmoud Mohammed

    2016-10-10

    Avanafil was incorporated into solid self-nanoemulsifying systems with the aim of improving its oral bioavailability. Labrafil, Labrafac, and Miglyol 812 N were investigated as oils, Tween 80 and Cremophor EL as surfactants, and Transcutol HP as a co-surfactant. Nine formulations produced clear solutions of 13.89-38.09nm globules after aqueous dilution. Adsorption of preconcentrate onto Aeroperl 300 Pharma at a 2:1 ratio had no effect on nanoemulsion particle size. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy indicated that avanafil was molecularly dispersed within the solid nanosystems. A formulation containing 10% Labrafil, 60% Tween 80, and 30% Transcutol HP had the highest drug loading (44.48mg/g) and an acceptable in vitro dissolution profile (96.42% within 30min). This formulation was chemically and physically stable for 6months under accelerated storage conditions and it produced a 3.2-fold increase in bioavailability in rabbits, as compared to conventional commercially available avanafil tablets (Spedra(®)). PMID:27590128

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

    PubMed

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

    2011-05-16

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

  10. A self-assembled system for tumor-targeted co-delivery of drug and gene.

    PubMed

    Wang, Cheng; Li, Min; Yang, Tie; Ding, Xuefang; Bao, Xiuli; Ding, Yang; Xiong, Hui; Wu, Ying; Wang, Wei; Zhou, Jianping

    2015-11-01

    A new cationic polymer eprosartan-graft-PEI (ESP) containing eprosartan (ES) and polyethylenimine 1.8K was successfully developed and employed as a safe gene vector to assemble a drug (ES) and gene co-delivery complex (ESP/pDNA). Chondroitin sulfate (CS) was then used as a coating polymer to shield the surface charge of ESP/pDNA complexes, as well as a tumor targeting entity to ensure specific delivery of CS/ESP/pDNA complexes. The CS/ESP/pDNA complexes with desirable particle size and zeta potential, exhibited amidase-responsive drug release and CS-mediated endocytosis in vitro. As compared with ESP/pDNA complexes, in vivo imaging results demonstrated decreased reticuloendothelial system uptake and remarkably increased tumor accumulation of CS/ESP/pDNA complexes. All these findings indicated the potential of CS/ESP/pDNA as a promising tumor-targeted drug and gene co-delivery system. PMID:26249591

  11. 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

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

    NASA Astrophysics Data System (ADS)

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

    2006-03-01

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

  13. Supersaturating drug delivery systems: effect of hydrophilic cyclodextrins and other excipients on the formation and stabilization of supersaturated drug solutions.

    PubMed

    Brewster, M E; Vandecruys, R; Verreck, G; Peeters, J

    2008-03-01

    Supersaturating drug delivery systems (SDDS) utilize two important design elements in their preparation including converting the drug of interest into a high energy state or other rapidly dissolving form to facilitate the formation of supersaturated drug solutions and providing a means for stabilizing the formed supersaturated solution such that significant drug absorption is possible from the gastrointestinal tract. This has been referred to as a "spring" and "parachute" approach. The current effort is designed to assess materials which may affect properties in SDDS. To this end, a series of excipients was tested in a co-solvent/solvent quench method to assess their ability to attain and maintain supersaturation for a group of 14 drug development candidates. The approach focussed on hydrophilic cyclodextrins including hydroxypropyl-beta-cyclodextrin (HPbetaCD) and sulfobutyl-beta-cyclodextrin (SBEbetaCD). Various rheological polymers and surfactants were also included in the study. Consistent with previous investigations, the pharmaceutical polymers, as a class, had minimal effects on the extent of supersaturation but tended to be good stabilizers while the surfactants tended to provide for the greatest degree of supersaturation but the formed systems were poorly stable. This study found that hydrophilic cyclodextrins, especially SBEbetaCD, gave superior results in terms of attaining and maintaining supersaturation. A knowledge of the behavior and performance of excipients in this context can be useful in designing solid oral dosage forms for difficult-to-formulate drugs and drug candidates.

  14. Supersaturating drug delivery systems: effect of hydrophilic cyclodextrins and other excipients on the formation and stabilization of supersaturated drug solutions.

    PubMed

    Brewster, M E; Vandecruys, R; Verreck, G; Peeters, J

    2008-03-01

    Supersaturating drug delivery systems (SDDS) utilize two important design elements in their preparation including converting the drug of interest into a high energy state or other rapidly dissolving form to facilitate the formation of supersaturated drug solutions and providing a means for stabilizing the formed supersaturated solution such that significant drug absorption is possible from the gastrointestinal tract. This has been referred to as a "spring" and "parachute" approach. The current effort is designed to assess materials which may affect properties in SDDS. To this end, a series of excipients was tested in a co-solvent/solvent quench method to assess their ability to attain and maintain supersaturation for a group of 14 drug development candidates. The approach focussed on hydrophilic cyclodextrins including hydroxypropyl-beta-cyclodextrin (HPbetaCD) and sulfobutyl-beta-cyclodextrin (SBEbetaCD). Various rheological polymers and surfactants were also included in the study. Consistent with previous investigations, the pharmaceutical polymers, as a class, had minimal effects on the extent of supersaturation but tended to be good stabilizers while the surfactants tended to provide for the greatest degree of supersaturation but the formed systems were poorly stable. This study found that hydrophilic cyclodextrins, especially SBEbetaCD, gave superior results in terms of attaining and maintaining supersaturation. A knowledge of the behavior and performance of excipients in this context can be useful in designing solid oral dosage forms for difficult-to-formulate drugs and drug candidates. PMID:18444510

  15. Biocompatible medical implant materials with binding sites for a biodegradable drug-delivery system

    PubMed Central

    Al-Dubai, Haifa; Pittner, Gisela; Pittner, Fritz; Gabor, Franz

    2011-01-01

    Feasibility studies have been carried out for development of a biocompatible coating of medical implant materials allowing the binding of biodegradable drug-delivery systems in a way that their reloading might be possible. These novel coatings, able to bind biodegradable nanoparticles, may serve in the long run as drug carriers to mediate local pharmacological activity. After biodegradation of the nanoparticles, the binding sites could be reloaded with fresh drug-delivering particles. As a suitable receptor system for the nanoparticles, antibodies are anchored. The design of the receptor is of great importance as any bio- or chemorecognitive interaction with other components circulating in the blood has to be avoided. Furthermore, the binding between receptor and the particles has to be strong enough to keep them tightly bound during their lifetime, but on the other hand allow reloading after final degradation of the particles. The nanoparticles suggested as a drug-delivery system for medical implants can be loaded with different pharmaceuticals such as antibiotics, growth factors, or immunosuppressives. This concept may enable the changing of medication, even after implantation of the medical device, if afforded by patients’ needs. PMID:24198488

  16. Noninvasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis.

    PubMed

    Kajimoto, Kazuaki; Yamamoto, Masahiko; Watanabe, Misuzu; Kigasawa, Kaoru; Kanamura, Kiyoshi; Harashima, Hideyoshi; Kogure, Kentaro

    2011-01-17

    Iontophoresis is a promising technique for enhancing transdermal administration of charged drugs. However, conventional iontophoresis is not sufficient for effective delivery of large, hydrophilic, or electrically neutral molecules. In this study, we utilized charged liposomes as carriers, focused on a transfollicular route for delivery of the liposomes, and optimized iontophoretic conditions and lipid composition for this method in both in vitro and in vivo conditions. As a result, we identified the optimum condition (lipid composition: DOTAP/EPC/Chol=2:2:1, current supply: 0.45mA/cm(2), duration: 1h) for effective iontophoretic delivery of aqueous solution, which cannot be transferred into the skin without charged liposomes. We also examined the pharmacological effects of iontophoresis of liposomes encapsulating insulin (INS-lipo) using a rat model of type I diabetes. Interestingly, iontophoresis of INS-lipo onto a diabetes rat skin resulted in a gradual decrease in blood glucose levels, with levels reaching 20% of initial values at 18h after administration. These lower blood glucose levels were maintained for up to 24h. Significant amount of insulin were also detected in plasma 18h after iontophoresis of INS-lipo. We succeeded in developing a non-invasive and persistent transfollicular drug delivery system that used a combination of liposomes and iontophoresis.

  17. 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

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

    PubMed

    Ma, Ping; Mumper, Russell J

    2013-06-01

    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.

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

    PubMed

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

    2016-01-01

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

  20. Nanoparticles for Brain Drug Delivery

    PubMed Central

    Masserini, Massimo

    2013-01-01

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

  1. Novel Lipid and Polymeric Materials as Delivery Systems for Nucleic Acid Based Drugs.

    PubMed

    Barba, Anna Angela; Lamberti, Gaetano; Sardo, Carla; Dapas, Barbara; Abrami, Michela; Grassi, Mario; Farra, Rossella; Tonon, Federica; Forte, Giancarlo; Musiani, Francesco; Licciardi, Mariano; Pozzato, Gabriele; Zanconati, Fabrizio; Scaggiante, Bruna; Grassi, Gabriele; Cavallaro, Gennara

    2015-01-01

    Nucleic acid based drugs (NADBs) are short DNA/RNA molecules that include among others, antisense oligonucleotides, aptamers, small interfering RNAs and micro-interfering RNAs. Despite the different mechanisms of actions, NABDs have the ability to combat the effects of pathological gene expression in many experimental systems. Thus, nowadays, NABDs are considered to have a great therapeutic potential, possibly superior to that of available drugs. Unfortunately, however, the lack of effective delivery systems limits the practical use of NABDs. Due to their hydrophilic nature, NABDs cannot efficiently cross cellular membrane; in addition, they are subjected to fast degradation by cellular and extracellular nucleases. Together these aspects make the delivery of NABDs as naked molecules almost un-effective. To optimize NABD delivery, several solutions have been investigated. From the first attempts described in the beginning of the 1980s, a burst in the number of published papers occurred in the beginning of 1990 s reaching a peak in 2012-13. The extensive amount of work performed so far clearly witnesses the interest of the scientific community in this topic. In the present review, we will concentrate on the description of the most interesting advances in the field. Particular emphasis will be put on polymeric and lipid materials used alone or in combination with a promising delivery strategy based on the use of carbon nanotubes. The data presented suggest that, although further improvements are required, we are not far from the identification of effective delivery systems for NABDs thus making the clinical use of these molecules closer to reality.

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

    PubMed

    Werner, Vera; Meinel, Lorenz

    2015-11-01

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

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

    PubMed

    Werner, Vera; Meinel, Lorenz

    2015-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  5. Drug nanocarrier, the future of atopic diseases: Advanced drug delivery systems and smart management of disease.

    PubMed

    Shao, Mei; Hussain, Zahid; Thu, Hnin Ei; Khan, Shahzeb; Katas, Haliza; Ahmed, Tarek A; Tripathy, Minaketan; Leng, Jing; Qin, Hua-Li; Bukhari, Syed Nasir Abbas

    2016-11-01

    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD.

  6. Drug nanocarrier, the future of atopic diseases: Advanced drug delivery systems and smart management of disease.

    PubMed

    Shao, Mei; Hussain, Zahid; Thu, Hnin Ei; Khan, Shahzeb; Katas, Haliza; Ahmed, Tarek A; Tripathy, Minaketan; Leng, Jing; Qin, Hua-Li; Bukhari, Syed Nasir Abbas

    2016-11-01

    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD. PMID:27592075

  7. Modern drug delivery systems for targeting the posterior segment of the eye.

    PubMed

    Peptu, Catalina A; Popa, Marcel; Savin, Corina; Popa, Radu F; Ochiuz, Lacramioara

    2015-01-01

    Some of the most dangerous diseases of the eye are related to the posterior segment. Diseases such as age-related macular degeneration, cytomegalovirus retinitis, diabetic retinopathy, posterior uveitis and retinitis pigmentosa are difficult to treat using classical methods because of the many internal barriers of the eye which affect the drug efficiency. In this review, we will summarize the main research directions in the field of medicamentous treatment of posterior eye disorders belonging to the controlled drug delivery concept. The review is starting with the most important knowledge regarding anatomy and pathology of the posterior segment of the eye and is continuing with the current treatment methods of the eye posterior segment illnesses and drawbacks of these methods, the drugs administration pathways to the posterior segment of the eye. The last three sections present the state of the art regarding the latest discoveries including the commercial products in the modern drug delivery systems; the main classes of materials treated in the present review are implants, hydrogels and nano- microparticulate systems.

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

    PubMed

    Moghassemi, Saeid; Hadjizadeh, Afra

    2014-07-10

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

  9. Development of silymarin self-microemulsifying drug delivery system with enhanced oral bioavailability.

    PubMed

    Li, Xinru; Yuan, Quan; Huang, Yanqing; Zhou, Yanxia; Liu, Yan

    2010-06-01

    The objective of this work was to develop a self-microemulsifying drug delivery system (SMEDDS) for improving oral absorption of poorly water-soluble drug, silymarin. The pseudo-ternary phase diagrams were constructed using ethyl linoleate, Cremophor EL, ethyl alcohol, and normal saline to identify the efficient self-microemulsification region. The particle size and its distribution of the resultant microemulsions were determined using dynamic light scattering. The optimal formulation with the best self-microemulsifying and solubilization ability consisted of 10% (w/w) of ethyl linoleate, 30% of Cremophor EL, and 60% of ethyl alcohol. The release of silymarin from SMEDDS was significantly faster than that from the commercial silymarin preparation hard capsule (Legalon). The bioavailability results indicated that the oral absorption of silymarin SMEDDS was enhanced about 2.2-fold compared with the hard capsule in fasted dogs. It could be concluded that SMEDDS would be a promising drug delivery system for poorly water-soluble drugs by the oral route. PMID:20405254

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

    PubMed

    Moghassemi, Saeid; Hadjizadeh, Afra

    2014-07-10

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

  11. Effect of ca2+ to salicylic acid release in pectin based controlled drug delivery system

    NASA Astrophysics Data System (ADS)

    Kistriyani, L.; Wirawan, S. K.; Sediawan, W. B.

    2016-01-01

    Wastes from orange peel are potentially be utilized to produce pectin, which are currently an import commodity. Pectin can be used in making edible film. Edible films are potentially used as a drug delivery system membrane after a tooth extraction. Drug which is used in the drug delivery system is salicylic acid. It is an antiseptic. In order to control the drug release rate, crosslinking process is added in the manufacturing of membrane with CaCl2.2H2O as crosslinker. Pectin was diluted in water and mixed with a plasticizer and CaCl2.2H2O solution at 66°C to make edible film. Then the mixture was dried in an oven at 50 °C. After edible film was formed, it was coated using plasticizer and CaCl2.2H2O solution with various concentration 0, 0.015, 0.03 and 0.05g/mL. This study showed that the more concentration of crosslinker added, the slower release of salicylic acid would be. This was indicated by the value of diffusivites were getting smaller respectively. The addition of crosslinker also caused smaller gels swelling value,which made the membrane is mechanically stronger

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  13. Comprehensive evaluation of carboxylated nanodiamond as a topical drug delivery system

    PubMed Central

    Lim, Dae Gon; Kim, Ki Hyun; Kang, Eunah; Lim, Sun Hee; Ricci, Jeremy; Sung, Si Kwon; Kwon, Myoung Taek; Jeong, Seong Hoon

    2016-01-01

    The best strategy in the development of topical drug delivery systems may be to facilitate the permeation of drugs without any harmful effects, while staying on the skin surface and maintaining stability of the system. Nanodiamonds (NDs) play a key role with their excellent physicochemical properties, including high biocompatibility, physical adsorption, reactive oxygen species (ROS) scavenging capability, and photostabilizing activity. Z-average sizes of carboxylated ND (ND–COOH) agglutinate decreased significantly as the pH increased. Fluorescein-conjugated ND was observed only on the stratum corneum, and no sample diffused into the dermal layer even after 48 hours. Moreover, ND–COOH and ND–COOH/eugenol complex did not show significant toxic effects on murine macrophage cells. ND improved in vitro skin permeation >50% acting as a “drug reservoir” to maintain a high drug concentration in the donor chamber, which was supported by quartz crystal microbalance results. Moreover, ND–COOH could adsorb a drug amount equivalent to 80% of its own weight. A photostability study showed that ND–COOH increased the photostability ~47% with regard to rate constant of the eugenol itself. A significant decrease in ROS was observed in the ND–COOH and ND–COOH/eugenol complex compared with the negative control during intracellular ROS assay. Moreover, ROS and cupric reducing antioxidant capacity evaluation showed that ND–COOH had synergistic effects of antioxidation with eugenol. Therefore, ND–COOH could be used as an excellent topical drug delivery system with improved permeability, higher stability, and minimized safety issue. PMID:27307736

  14. Novel Strategy to Fabricate Floating Drug Delivery System Based on Sublimation Technique.

    PubMed

    Huanbutta, Kampanart; Limmatvapirat, Sontaya; Sungthongjeen, Srisagul; Sriamornsak, Pornsak

    2016-06-01

    The present study aims to develop floating drug delivery system by sublimation of ammonium carbonate (AMC). The core tablets contain a model drug, hydrochlorothiazide, and various levels (i.e., 0-50% w/w) of AMC. The tablets were then coated with different amounts of the polyacrylate polymers (i.e., Eudragit® RL100, Eudragit® RS100, and the mixture of Eudragit® RL100 and Eudragit® RS100 at 1:1 ratio). The coated tablets were kept at ambient temperature (25°C) or cured at 70°C for 12 h before further investigation. The floating and drug release behaviors of the tablets were performed in simulated gastric fluid USP without pepsin at 37°C. The results showed that high amount of AMC induced the floating of the tablets. The coated tablets containing 40 and 50% AMC floated longer than 8 h with a time-to-float of about 3 min. The sublimation of AMC from the core tablets decreased the density of system, causing floating of the tablets. The tablets coated with Eudragit® RL100 floated at a faster rate than those of Eudragit® RS100. Even the coating level of polymer did not influence the time-to-float and floating time of coated tablets containing the same amount of AMC, the drug release from the tablets coated with higher coating level of polymer showed slower drug release. The results suggested that the sublimation technique using AMC is promising for the development of floating drug delivery system.

  15. Comprehensive evaluation of carboxylated nanodiamond as a topical drug delivery system.

    PubMed

    Lim, Dae Gon; Kim, Ki Hyun; Kang, Eunah; Lim, Sun Hee; Ricci, Jeremy; Sung, Si Kwon; Kwon, Myoung Taek; Jeong, Seong Hoon

    2016-01-01

    The best strategy in the development of topical drug delivery systems may be to facilitate the permeation of drugs without any harmful effects, while staying on the skin surface and maintaining stability of the system. Nanodiamonds (NDs) play a key role with their excellent physicochemical properties, including high biocompatibility, physical adsorption, reactive oxygen species (ROS) scavenging capability, and photostabilizing activity. Z-average sizes of carboxylated ND (ND-COOH) agglutinate decreased significantly as the pH increased. Fluorescein-conjugated ND was observed only on the stratum corneum, and no sample diffused into the dermal layer even after 48 hours. Moreover, ND-COOH and ND-COOH/eugenol complex did not show significant toxic effects on murine macrophage cells. ND improved in vitro skin permeation >50% acting as a "drug reservoir" to maintain a high drug concentration in the donor chamber, which was supported by quartz crystal microbalance results. Moreover, ND-COOH could adsorb a drug amount equivalent to 80% of its own weight. A photostability study showed that ND-COOH increased the photostability ~47% with regard to rate constant of the eugenol itself. A significant decrease in ROS was observed in the ND-COOH and ND-COOH/eugenol complex compared with the negative control during intracellular ROS assay. Moreover, ROS and cupric reducing antioxidant capacity evaluation showed that ND-COOH had synergistic effects of antioxidation with eugenol. Therefore, ND-COOH could be used as an excellent topical drug delivery system with improved permeability, higher stability, and minimized safety issue. PMID:27307736

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

    PubMed

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

    2015-12-10

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

  17. Ethosomes: a novel delivery system for antifungal drugs in the treatment of topical fungal diseases.

    PubMed

    Bhalaria, M K; Naik, Sachin; Misra, A N

    2009-05-01

    Aim of this work was to prepare and characterize fluconazole (FLZ) encapsulated ethosomes, incorporate it in suitable dermatological base, and asses its comparative clinical efficacy in the treatment of Candidiasis patients against liposomal gel, marketed product and hydroethanolic solution of the drug. Drug encapsulated ethosomes and liposomes were prepared and optimized by "Hot" method technique and lipid film hydration technique. Vesicular carriers were characterized for % entrapment efficiency, particle size and shape, in vitro drug diffusion study, mean % reduction in dimension of Candidiasis lesion and stability study by using suitable analytical technique. Vesicle size and drug entrapment efficiency of the optimized ethosomes and liposomes were found to be 144 +/- 6.8 nm and 82.68% and 216 +/- 9.2 nm and 68.22% respectively. Microscopic examinations suggest ethosomes to be multilamellar spherical vesicles with a smooth surface. The differential scanning calorimetry results suggest high fluidity of the ethosomes than liposomes. In vitro drug diffusion studies demonstrated that % drug diffused from ethosomes was nearly twice than liposomes and three times higher than the hydroethanolic solution across rat skin. From the clinical evaluation, the developed novel delivery system demonstrated enhanced antifungal activity compared to liposomal formulation, marketed formulation and hydroethanolic solution of the drug.

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

    SciTech Connect

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

    1998-01-15

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

  19. Sucrose esters as natural surfactants in drug delivery systems--a mini-review.

    PubMed

    Szűts, Angéla; Szabó-Révész, Piroska

    2012-08-20

    Sucrose esters (SEs) are widely used in the food and cosmetic industries and there has recently been great interest in their applicability in different pharmaceutical fields. They are natural and biodegradable excipients with well-known emulsifying and solubilizing behavior. Currently the most common pharmaceutical applications of SEs are for the enhancement of drug dissolution and drug absorption/permeation, and in controlled-release systems. Although the number of articles on SEs is continuously increasing, they have not yet been widely used in the pharmaceutical industry. The aim of this review is to discuss and summarize some of the findings and applications of SEs in different areas of drug delivery. The article highlights the main properties of SEs and focuses on their use in pharmaceutical technology and on their regulatory and toxicological status.

  20. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  2. Coral exoskeletons as a precursor material for the development of a calcium phosphate drug delivery system for bone tissue engineering.

    PubMed

    Chou, Joshua; Hao, Jia; Ben-Nissan, Besim; Milthorpe, Bruce; Otsuka, Makoto

    2013-01-01

    With the global rise in aging of populations, the occurrence of osteoporosis will continue to increase. Biomaterial and pharmaceutical scientists continue to develop innovative strategies and materials to address this disease. In this article, we describe a new perspective and approach into the use of coral exoskeletons as a precursor material to synthesize a calcium phosphate-based drug delivery system. Studies detailing the methodology of the conversion methods and the strategies and approach for the development of these novel drug delivery systems are described. Furthermore, in vivo studies in osteoporotic mice using a drug loaded and chemically modified version of the biomimetic delivery system showed significant cortical and cancellous bone increases. These studies support the notion and the rationale for future research and development of the use of coral exoskeletons as materials for drug delivery applications.

  3. Emerging integrated nanoclay-facilitated drug delivery system for papillary thyroid cancer therapy.

    PubMed

    Zhang, Yi; Long, Mei; Huang, Peng; Yang, Huaming; Chang, Shi; Hu, Yuehua; Tang, Aidong; Mao, Linfeng

    2016-01-01

    Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis.

  4. Emerging integrated nanoclay-facilitated drug delivery system for papillary thyroid cancer therapy

    PubMed Central

    Zhang, Yi; Long, Mei; Huang, Peng; Yang, Huaming; Chang, Shi; Hu, Yuehua; Tang, Aidong; Mao, Linfeng

    2016-01-01

    Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis. PMID:27616592

  5. Emerging integrated nanoclay-facilitated drug delivery system for papillary thyroid cancer therapy.

    PubMed

    Zhang, Yi; Long, Mei; Huang, Peng; Yang, Huaming; Chang, Shi; Hu, Yuehua; Tang, Aidong; Mao, Linfeng

    2016-01-01

    Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis. PMID:27616592

  6. Emerging integrated nanoclay-facilitated drug delivery system for papillary thyroid cancer therapy

    NASA Astrophysics Data System (ADS)

    Zhang, Yi; Long, Mei; Huang, Peng; Yang, Huaming; Chang, Shi; Hu, Yuehua; Tang, Aidong; Mao, Linfeng

    2016-09-01

    Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis.

  7. Recent advances in ocular drug delivery.

    PubMed

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

    2013-11-01

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

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

    PubMed

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

    2015-09-28

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

  9. 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.

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

    PubMed

    Joanitti, Graziella A; Silva, Luciano P

    2013-06-01

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

  11. Gentamicin loaded PLGA nanoparticles as local drug delivery system for the osteomyelitis treatment.

    PubMed

    Posadowska, Urszula; Brzychczy-Włoch, Monika; Pamuła, Elżbieta

    2015-01-01

    Since there are more and more cases of multiresistance among microorganisms, rational use of antibiotics (especially their systemic vs. local application) is of great importance. Here we propose polymeric nanoparticles as locally applied gentamicin delivery system useful in osteomyelitis therapy. Gentamicin sulphate (GS) was encapsulated in the poly(lactide-co-glycolide) (PLGA 85:15) nanoparticles by double emulsification (water/oil/water, W1/O/W2). The nanoparticles were characterized by dynamic light scattering, laser electrophoresis and atomic force microscopy. UV-vis spectroscopy (O-phthaldialdehyde assay, OPA) and Kirby-Bauer tests were used to evaluate drug release and antimicrobial activity, respectively. Physicochemical characterization showed that size, shape and drug solubilization of the nanoparticles mainly depended on GS content and concentration of surface stabilizer (polyvinyl alcohol, PVA). Laser electrophoresis demonstrated negative value of zeta potential of the nanoparticles attributed to PLGA carboxyl end group presence. Drug release studies showed initial burst release followed by prolonged 35-day sustained gentamicin delivery. Agar-diffusion tests performed with pathogens causing osteomyelitis (Staphylococcus aureus and Staphylococcus epidermidis, both reference strains and clinical isolates) showed antibacterial activity of GS loaded nanoparticles (GS-NPs). It can be concluded that GS-NPs are a promising form of biomaterials useful in osteomyelitis therapy. PMID:26687562

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

    PubMed

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

    2016-02-01

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

  13. Integration of Drug, Protein, and Gene Delivery Systems with Regenerative Medicine

    PubMed Central

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

    2013-01-01

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

  14. The role of oral controlled release matrix tablets in drug delivery systems.

    PubMed

    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

  15. Novel drug delivery systems in topical treatment of psoriasis: rigors and vigors.

    PubMed

    Katare, Om Prakash; Raza, Kaisar; Singh, Bhupinder; Dogra, Sunil

    2010-01-01

    Psoriasis is a chronic inflammatory skin disorder that may drastically impair the quality of life of a patient. Among the various modes of treatments for psoriasis, topical therapy is most commonly used in majority of patients. The topical formulations based on conventional excipients could serve the purpose only to a limited extent. With the advent of newer biocompatible and biodegradable materials like phospholipids, and cutting-edge drug delivery technologies like liposomes, solid lipid nanoparticles (SLNs), microemulsions, and nanoemulsions, the possibility to improve the efficacy and safety of the topical products has increased manifold. Improved understanding of the dermal delivery aspects and that of designing and developing diverse carrier systems have brought in further novelty in this approach. Substantial efforts and the consequent publications, patents and product development studies on the subject are the matter of interest and review of this article. However, majority of the work is related to the preclinical studies and demands further clinical assessment in psoriasis patients. PMID:21079304

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

    PubMed

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

    2014-12-30

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

  17. 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

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

    PubMed

    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.

  19. A comparative study on the nanoparticles for improved drug delivery systems.

    PubMed

    Mahmoodi, Nosrat O; Ghavidast, Atefeh; Amirmahani, Najmeh

    2016-09-01

    Nanoparticles have attracted considerable recent interest for diverse biomedical applications because of the unique properties of the nanomaterials. It is already known that one of the major advances in the relative application of nanoparticles is the recognition of the steric stabilization which can increase the particle stability in the biological environment and provide the opportunities of the application of nanoparticles in the development of drug delivery systems (DDSs) for achieving drug targeting and controlled drug release. To facilitate their use in such applications, the appropriate design of surface ligands on these nanoparticles is necessary. In view of these, functionalized nanoparticles through surface modification can be utilized to specifically interact with the target molecules on the cell membrane or intracellular ones. This review briefly presents self-assembled nanoparticles with molecules of therapeutic significance with two strategies. The first strategy attempts to improve the placement of the drugs using conjugating the appropriate ligands or adding targeting moieties to the DDS. The second strategy utilizes trigger-controlled drug-release, which restricts drug release at the targeted site to kill cancer cells by externally controlled mechanisms. Among external stimulations, conveniently light has attracted much interest because it, as an orthogonal external stimulus, gives spatiotemporal control of payload release. PMID:27498233

  20. 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

  1. Microprocessor controlled transdermal drug delivery.

    PubMed

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

    2006-07-01

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

  2. Electrospun Poly(N-isopropylacrylamide)/Ethyl Cellulose Nanofibers as Thermoresponsive Drug Delivery Systems.

    PubMed

    Hu, Juan; Li, He-Yu; Williams, Gareth R; Yang, Hui-Hui; Tao, Lei; Zhu, Li-Min

    2016-03-01

    Fibers of poly(N-isopropylacrylamide) (PNIPAAm), ethyl cellulose (EC), and a blend of both were successfully fabricated by electrospinning. Analogous drug-loaded fibers were prepared loaded with ketoprofen (KET). Scanning and transmission electron microscopy showed that the fibers were largely smooth and cylindrical, with no phase separation observed. The addition of KET to the spinning solutions did not affect the morphology of resultant fibers, and no drug particles could be observed to separate from the polymer matrix. X-ray diffraction demonstrated that the drug was present in the amorphous physical form in the fiber matrix. There are significant intermolecular interactions between KET and polymers, as evidenced by IR spectroscopy and molecular modeling. Water contact angle measurements proved that the PNIPAAm and PNIPAAm/EC fibers switched from being hydrophilic to hydrophobic when the temperature was increased through the lower critical solution temperature of 32°C. In vitro drug release studies found that the PNIPAAm/EC blend nanofibers were able to synergistically combine the properties of the 2 polymers, giving temperature-sensitive systems with sustained release properties. In addition, they were established to be nontoxic and suitable for cell growth. This study demonstrates that electrospun-blend PNIPAAm/EC fibers comprise effective and biocompatible materials for drug delivery systems and tissue engineering. PMID:26886332

  3. PEGylated bile acids for use in drug delivery systems: enhanced solubility and bioavailability of itraconazole.

    PubMed

    Le Dévédec, Frantz; Strandman, Satu; Hildgen, Patrice; Leclair, Grégoire; Zhu, X X

    2013-08-01

    Itraconazole is a drug of choice for the treatment of severe fungal infections and parasitic diseases, but its use is limited by its low water solubility and varying bioavailability. New self-emulsifying drug delivery systems (SEDDS) based on PEGylated bile acids (BA-PEGs) were designed and prepared, where the number and length of PEG arms were varied to optimize the loading of itraconazole in the final drug formulation. The use of both BA-PEGs and oleic acid improved the solubilization and absorption of the drug, which was in a glassy state in the SEDDS prepared with the melting method. High loading efficiencies of itraconazole (up to 20%) and stable liquid formulations were obtained at neutral pH, and full dispersion of itraconazole was reached in 2 h in simulated intestinal fluid (pH 6.8). Aqueous emulsions consisting of spherical micelles with mean hydrodynamic diameters (Dh) of ca. 75-220 nm, as verified by transmission electron microscopy and dynamic light scattering, are expected to improve the intestinal absorption of the drug. The new SEDDS showed good cytocompatibility by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays of BA-PEGs with Caco-2 and RAW 264.2 cells, and a low degree of hemolysis of human erythrocytes. The SEDDS based on PEGylated bile acids provide a controlled release system with significant improvement of the bioavailability of itraconazole in rats, as demonstrated by the pharmacokinetic studies.

  4. Lactobionic acid and carboxymethyl chitosan functionalized graphene oxide nanocomposites as targeted anticancer drug delivery systems.

    PubMed

    Pan, Qixia; Lv, Yao; Williams, Gareth R; Tao, Lei; Yang, Huihui; Li, Heyu; Zhu, Limin

    2016-10-20

    In this work, we report a targeted drug delivery system built by functionalizing graphene oxide (GO) with carboxymethyl chitosan (CMC), fluorescein isothiocyanate and lactobionic acid (LA). Analogous systems without LA were prepared as controls. Doxorubicin (DOX) was loaded onto the composites through adsorption. The release behavior from both the LA-functionalized and the LA-free material is markedly pH sensitive. The modified GOs have high biocompatibility with the liver cancer cell line SMMC-7721, but can induce cell death after 24h incubation if loaded with DOX. Tests with shorter (2h) incubation times were undertaken to investigate the selectivity of the GO composites: under these conditions, neither DOX-loaded system was found to be toxic to the non-cancerous L929 cell line, but the LA-containing composite showed the ability to selectively induce cell death in cancerous (SMMC-7721) cells while the LA-free analogue was inactive here also. These findings show that the modified GO materials are strong potential candidates for targeted anticancer drug delivery systems. PMID:27474628

  5. 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.

  6. Design and evaluation of an innovative floating and bioadhesive multiparticulate drug delivery system based on hollow structure.

    PubMed

    Zhang, Chungang; Tang, Jingya; Liu, Dechun; Li, Xuetao; Cheng, Lan; Tang, Xing

    2016-04-30

    In this study a gastric-retentive delivery system was prepared by a novel method which is reported here for the first time. An innovative floating and bioadhesive drug delivery system with a hollow structure was designed and prepared. The floating and bioadhesive drug delivery system was composed of a hollow spherical shell, a waterproof layer (Stearic acid), a drug layer (Ofloxacin), a release retarding film (the novel blended coating materials) and a bioadhesive layer (Carbomer 934P) prepared by using a liquid multi-layering process. A novel blended coating material was designed and investigated to solve the problem of the initial burst release of the formulation and the release mechanism of the novel material was analyzed in this study. The optimized formulation provided the sustained release characteristic and was able to float for 24h. The SEM cross-section images showed that the particulates were hollow with a spherical shell. X-ray images and pharmacokinetic studies (Frel = 124.1 ± 28.9%) in vivo showed that the gastric-retentive delivery system can be retained in the stomach for more than 6h. The floating and bioadhesive particulate drug delivery system based on a hollow structure with a dual function presented here is a viable alternative to other for gastroretentive drug delivery system. PMID:26943975

  7. 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

  8. Phospholipid-based self-assembled mesophase systems for light-activated drug delivery.

    PubMed

    Du, Joanne D; Fong, Wye-Khay; Salentinig, Stefan; Caliph, Suzanne M; Hawley, Adrian; Boyd, Ben J

    2015-06-01

    The manipulation of the structure of phospholipid-based mesophases to induce a slow to fast drug release profile has potential for use in therapeutic situations where continuous absorption of drug is not desirable and reduce the frequency of injection for short acting or rapidly cleared drugs in treatments for diseases such as macular degeneration. This study had two aims; firstly to confirm the phase behaviour of 20 mol% cholesterol in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), which was previously reported to transition from lamellar (slow release) to bicontinuous cubic (fast release) phase with increasing temperature. Contrary to the literature, no bicontinuous cubic phase was observed but a transition to the inverse hexagonal phase occurred at all POPE : cholesterol ratios investigated. The second aim was to render these mesophases responsive to near-infrared laser (NIR) irradiation by incorporation of gold nanorods (GNR) incorporated into the POPE system to induce photothermal heating. The inclusion of 3 nM GNR in POPE systems induced reversible disruption of lipid packing equivalent to increasing the temperature to 55 °C when irradiated for 30 s. This study confirmed that although the previously published phase behavior was not correct, GNR and NIR can be used to manipulate the self-assembled mesophases in phospholipid-based systems and highlights the potential for a phospholipid-based light-activated drug delivery system.

  9. A new natural angelica polysaccharide based colon-specific drug delivery system.

    PubMed

    Zhou, Siyuan; Zhang, Bangle; Liu, Xinyou; Teng, Zenghui; Huan, Menglei; Yang, Tiehong; Yang, Zhifu; Jia, Min; Mei, Qibing

    2009-12-01

    Colon-specific drug delivery systems are clinically necessary to treat colon diseases locally while minimizing systemic side effects. In this study, we extracted angelica polysaccharide from fresh roots of Angelica sinensis Diels and analyzed the monosaccharide components. With succinate as a cross-linker and angelica polysaccharide as a drug carrier, a dexamethasone-polysaccharide conjugate was synthesized. The amount of dexamethasone (Dex) loaded in the dexamethasone-polysaccharide conjugate was 14.13/100 mg. The newly synthesized dexamethasone-polysaccharide conjugate was found to greatly reduce systemic absorption of Dex and effectively deliver Dex to the large intestine. When dexamethasone-polysaccharide conjugate was used to treat TNBS-induced ulcerative colitis in rats by gavage, the ulcerative area of the colon and the colonic myeloperoxidase (MPO) activity was reduced in a dose-dependent manner. There was no effects on spleen weight, thymus weight, or peripheral blood lymphocyte count (0.25 micromol kg(-1) day(-1)). These results indicate that the dexamethasone-polysaccharide conjugate has a therapeutic effect on TNBS-induced ulcerative colitis in rats, while simultaneously reducing the systemic immunosuppression caused by Dex. Thus, the angelica polysaccharide was a promising colon-specific drug carrier, and the new dexamethasone-polysaccharide conjugate may yield a potential drug for the treatment of human inflammatory bowel disease.

  10. Perispinal Delivery of CNS Drugs.

    PubMed

    Tobinick, Edward Lewis

    2016-06-01

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

  11. Applications of Important Polysaccharides in Drug Delivery.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-04-01

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

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

    PubMed Central

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

    2013-01-01

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

  16. An engineered biocompatible drug delivery system enhances nerve regeneration after delayed repair.

    PubMed

    Tajdaran, Kasra; Gordon, Tessa; Wood, Mathew D; Shoichet, Molly S; Borschel, Gregory H

    2016-02-01

    Localized drug delivery strategies could greatly benefit patients with peripheral nerve injury and could be easy for surgeons to implement. We developed a local drug delivery system (DDS) using drug-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) embedded in a fibrin gel. In an in vitro study, we investigated the biocompatibility of this DDS by performing a toxicity assay in which we incubated PC-12 cells with the medium released from the DDS in vitro. In an in vivo study, this DDS was applied at the rat common peroneal (CP) nerve injury site to deliver exogenous glial cell line-derived neurotrophic factor (GDNF) to the regenerating axons after delayed nerve repair. In vitro, PC-12 cells incubated with released media samples from the DDS had similar viability to control cells cultured with normal media, demonstrating that the DDS was not toxic. In vivo, the numbers of motor and sensory neurons that regenerated their axons with empty MS treatment were the same as when there was no MS treatment. The DDS increased the numbers of regenerating motor- and sensory neurons to levels indistinguishable from those observed with immediate nerve repair. The DDS increased neuron regeneration to levels double those observed with negative control groups. This biocompatible, nontoxic, fibrin gel-based DDS enhances outcomes following severe peripheral nerve injuries.

  17. Preparation and evaluation of self-microemulsifying drug delivery system of baicalein.

    PubMed

    Liu, Wenli; Tian, Rui; Hu, Wenjing; Jia, Yuntao; Jiang, Huiming; Zhang, Jingqing; Zhang, Liangke

    2012-12-01

    The main object of this work is to prepare self-microemulsifying drug delivery system (SMEDDS) for oral bioavailability enhancement of a poorly water-soluble drug, baicalein. SMEDDS is the mixture of surfactants, cosurfactants, and oils, which are emulsified in aqueous media under conditions of gentle agitation or gastrointestinal motility. Solubility of baicalein was determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and droplet size distributions of the resultant microemulsions were determined using a particle size analyzer. Optimized SMEDDS formulations for baicalein were Cremophor RH40 (53.57%) as surfactant, Transcutol P (21.43%) as cosurfactant, and Caprylic capric triglyceride (ODO, 25%) as oil. The drug release rate of SMEDDS was significantly higher than that of the baicalein suspension. Comparison of the pharmacokinetics between baicalein-loaded SMEDDS and baicalein suspension was also performed in rats. The plasma concentrations of baicalein and baicalin, its mainly conjugated metabolite, were determined by HPLC method. The in vivo results showed that the absorption of baicalein from SMEDDS resulted in about 200.7% increase in relative bioavailability compared with that of the baicalein suspension. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as baicalein by the oral route. PMID:22982454

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

    PubMed

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

    2013-01-01

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

  19. Nanopharmaceutics: phytochemical-based controlled or sustained drug-delivery systems for cancer treatment.

    PubMed

    Jeetah, Roubeena; Bhaw-Luximon, Archana; Jhurry, Dhanjay

    2014-09-01

    This review is an attempt to assess the different classes of phytochemicals and some of their members which have been encapsulated into nanocarrier systems for their chemotherapeutic or chemopreventive properties. Given the broad spectrum of nanomedicines currently in clinical trial and clinical use from polymer-protein conjugates, through nanocrystals, nanogels, dendrimers to ethosomes, the focus of this review will be on block copolymer nanomicelles, nanoparticles, polymer-drug conjugates, liposomes and solid lipid nanocarriers (SLNs). The twenty phytochemicals investigated for encapsulation and targeted delivery were selected from a variety of classes intended to encompass the largest possible chemical compositions, namely flavonoids, aromatic acids, xanthones, terpenes, quinones, lignans and alkaloids. To the best of our knowledge, reviews on the nanoencapsulation of these phytochemicals and their delivery are not available. In this review, the issues associated with the limited use of each phytochemical in cancer therapy in humans are reviewed and the advantages of entrapment into nanocarriers are assessed in terms of drug loading efficiency, size of nanocarriers, drug release profiles and in vitro and/or in vivo testing specific to cancer research, e.g., cytotoxicity assay, cell inhibition/viability, scavenging of reactive oxygen species and biodistribution studies (elimination half-life and mean residence time). PMID:25992442

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

    PubMed

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

    2014-05-01

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

  1. Computational and experimental approaches for investigating nanoparticle-based drug delivery systems.

    PubMed

    Ramezanpour, M; Leung, S S W; Delgado-Magnero, K H; Bashe, B Y M; Thewalt, J; Tieleman, D P

    2016-07-01

    Most therapeutic agents suffer from poor solubility, rapid clearance from the blood stream, a lack of targeting, and often poor translocation ability across cell membranes. Drug/gene delivery systems (DDSs) are capable of overcoming some of these barriers to enhance delivery of drugs to their right place of action, e.g. inside cancer cells. In this review, we focus on nanoparticles as DDSs. Complementary experimental and computational studies have enhanced our understanding of the mechanism of action of nanocarriers and their underlying interactions with drugs, biomembranes and other biological molecules. We review key biophysical aspects of DDSs and discuss how computer modeling can assist in rational design of DDSs with improved and optimized properties. We summarize commonly used experimental techniques for the study of DDSs. Then we review computational studies for several major categories of nanocarriers, including dendrimers and dendrons, polymer-, peptide-, nucleic acid-, lipid-, and carbon-based DDSs, and gold nanoparticles. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.

  2. The Role of Drug-Drug Interactions in Hydrogel Delivery Systems: Experimental and Model Study.

    PubMed

    Rossi, Filippo; Castiglione, Franca; Ferro, Monica; Moioli, Marta; Mele, Andrea; Masi, Maurizio

    2016-06-01

    To address the increasing need for improved tissue substitutes, tissue engineering seeks to create synthetic, three-dimensional scaffolds made from polymeric materials able to incorporate cells and drugs. The interpretation of transport phenomena is a key step, but comprehensive theoretical data is still missing and many issues related to these systems are still unsolved. In particular, the contribution of solute-solute interactions is not yet completely understood. Here, we investigate a promising agar-carbomer (AC) hydrogel loaded with sodium fluorescein (SF), a commonly used drug mimetic. The self-diffusion coefficient of SF in AC formulations was measured by using high resolution magic angle spinning NMR spectroscopy (HR-MAS NMR). Starting from experimental data, a complete overview on SF transport properties is provided, in particular a mathematical model that describes and rationalizes the differences between gel and water environments is developed and presented. The hydrogel molecular environment is able to prevent SF aggregation, owing to the adsorption mechanism that reduces the number of monomers available for oligomer formation at low solute concentration. Then, when all adsorption sites are saturated free SF molecules are able to aggregate and form oligomers. The model predictions satisfactorily match with experimental data obtained in water and the gel environment, thus indicating that the model presented here, despite its simplicity, is able to describe the key phenomena governing device behavior and could be used to rationalize experimental activity. PMID:26919298

  3. Roles of dextrans on improving lymphatic drainage for liposomal drug delivery system.

    PubMed

    Feng, Linglin; Zhang, Lei; Liu, Min; Yan, Zhiqiang; Wang, Chenyu; Gu, Bing; Liu, Yu; Wei, Gang; Zhong, Gaoren; Lu, Weiyue

    2010-04-01

    Our aim was to develop a novel liposomal drug delivery system containing dextrans to reduce undesirable retention of antineoplastic agents and thus alleviate local tissue damage. At the cell level, diethylaminoethyl-dextran (DEAE-Dx) showed the strongest inhibiting effect on liposome uptake by macrophages among tested dextrans. The distribution of radiolabeled liposomes mixed with dextrans in injection site and draining lymph node was investigated in rats after subcutaneous injection. DEAE-Dx substantially reduced the undesired local retention and promoted the draining of liposome into lymphatics, which was further confirmed by confocal microscopy images revealing the substantial prevention of rhodamine B-labelled liposome sequestration by macrophages in normal lymph node in rats. Pharmacokinetic data indicated the accelerated drainage of liposome through lymphatics back to systemic circulation by mixing with DEAE-Dx. In the toxicological study in rabbits, DEAE-Dx alleviated the local tissue damage caused by liposomal doxorubicin. In conclusion, dextrans, particularly DEAE-Dx, could efficiently enhanced liposomes drainage into lymphatics, which proves themselves as promising adjuvants for lymphatic-targeted liposomal drug delivery system.

  4. 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.

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

    PubMed

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

    2008-01-01

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

  6. Tumor vascular-targeted co-delivery of anti-angiogenesis and chemotherapeutic agents by mesoporous silica nanoparticle-based drug delivery system for synergetic therapy of tumor.

    PubMed

    Li, Xiaoyu; Wu, Meiying; Pan, Limin; Shi, Jianlin

    2016-01-01

    To overcome the drawback of drug non-selectivity in traditional chemotherapy, the construction of multifunctional targeting drug delivery systems is one of the most effective and prevailing approaches. The intratumoral anti-angiogenesis and the tumor cell-killing are two basic approaches in fighting tumors. Herein we report a novel tumor vascular-targeting multidrug delivery system using mesoporous silica nanoparticles as carrier to co-load an antiangiogenic agent (combretastatin A4) and a chemotherapeutic drug (doxorubicin) and conjugate with targeting molecules (iRGD peptide) for combined anti-angiogenesis and chemotherapy. Such a dual-loaded drug delivery system is capable of delivering the two agents at tumor vasculature and then within tumors through a differentiated drug release strategy, which consequently results in greatly improved antitumor efficacy at a very low doxorubicin dose of 1.5 mg/kg. The fast release of the antiangiogenic agent at tumor vasculatures led to the disruption of vascular structure and had a synergetic effect with the chemotherapeutic drug slowly released in the following delivery of chemotherapeutic drug into tumors.

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2014-09-01

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

  9. Design and evaluation of self-microemulsifying drug delivery system (SMEDDS) of tacrolimus.

    PubMed

    Borhade, Vivek; Nair, Hema; Hegde, Darshana

    2008-01-01

    The objective of present investigation was to formulate self-microemulsifying drug delivery systems (SMEDDS) of tacrolimus (FK 506), a poorly water soluble immunosuppressant that exhibits low and erratic bioavailability. Solubility of FK 506 in various oils, surfactants cosurfactants and buffers was determined. Phase diagrams were constructed at different ratios of surfactant/cosurfactant (K(m)) to determine microemulsion existence region. The effect of oil content, pH of aqueous phase, dilution, and incorporation of drug on mean globule size of resulting microemulsions was studied. The optimized SMEDDS formulation was evaluated for in vitro dissolution profile in comparison to pure drug and marketed formulation (Pangraf capsules). The in vivo immunosuppressant activity of FK 506 SMEDDS was evaluated in comparison to Pangraf capsules. Area of o/w microemulsion region in phase diagram was increased with increase in K(m). The SMEDDS yielded microemulsion with globule size less than 25 nm which was not affected by the pH of dilution medium. The SMEDDS was robust to dilution and did not show any phase separation and drug precipitation even after 24 h. Optimized SMEDDS exhibited superior in vitro dissolution profile as compared to pure drug and Pangraf capsules. Furthermore, FK 506 SMEDDS exhibited significantly higher immunosuppressant activity in mice as compared to Pangraf capsules. PMID:18446456

  10. 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

  11. 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 (λ = 248 nm, τ = 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.

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

    PubMed

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

    2013-04-01

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

  13. Cancer cell spheroids for screening of chemotherapeutics and drug-delivery systems.

    PubMed

    Patel, Niravkumar R; Aryasomayajula, Bhawani; Abouzeid, Abraham H; Torchilin, Vladimir P

    2015-01-01

    Over the last few decades, the most popular platform to perform high-throughput screening for viable anti-neoplastic compounds has been monolayer cell culture. However, cells in monolayer culture lose many of their in vivo characteristics. As a result, this platform provides a limited predictive value in determining the clinical outcome of the compounds of interest. Using a technique known as 3D spheroid culture, may be the answer to this conundrum. Spheroids have been shown to mimic the tissue-like properties of tumors necessary for the proper evaluation of compounds. In this review, production of cancer cell spheroids, utilization of these spheroids in understanding various therapeutic mechanisms and the potential for their use in high-throughput screening of drugs and drug-delivery systems are discussed in detail. PMID:25996047

  14. 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

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

    PubMed Central

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

    2013-01-01

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

  16. 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 μg mL-1 and LOQ of 0.226 μg mL-1) in the range of 0.2-5 μg 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.

  17. 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