Science.gov

Sample records for drug delivery device

  1. Phototriggered multifunctional drug delivery device

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

    Although phototriggered cleavage of chemical bonds induced by single-photon or two-photon-absorption provides attractive tools for controlled drug delivery, the choice of drugs is still limited by the linker system to which the therapeutic molecules need to be bound covalently. The use of a multifunctional linker system suitable for coupling a broad spectrum of drugs to the polymeric carrier will open a new field for drug delivery. We have developed a novel photocleavable multifunctional linker system based on coumarin dimers, whose unique photochemical behavior are well characterized. As a first example, an acrylic polymer-drug conjugate with antimetabolites is explored. The cleavage of the link between the drug and the polymer backbone is triggered by both single- as well as two-photon absorption. The release of the drug is investigated. It is possible to manufacture a polymeric drug delivery device with several drugs in different areas. In particular the two-photon-absorption induced process offers the possibility to address the drug of interest owing to the superior spatial resolution. The key to such devices is a versatile linker-system which can be adopted to work with various drug compounds.

  2. Microfluidic device for drug delivery

    NASA Technical Reports Server (NTRS)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2010-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  3. Implantable Devices for Sustained, Intravesical Drug Delivery

    PubMed Central

    2016-01-01

    In clinical settings, intravesical instillation of a drug bolus is often performed for the treatment of bladder diseases. However, it requires repeated instillations to extend drug efficacy, which may result in poor patient compliance. To alleviate this challenge, implantable devices have been developed for the purpose of sustained, intravesical drug delivery. In this review, we briefly summarize the current trend in the development of intravesical drug-delivery devices. We also introduce the most recently developed devices with strong potential for intravesical drug-delivery applications. PMID:27377941

  4. A pulsed mode electrolytic drug delivery device

    NASA Astrophysics Data System (ADS)

    Yi, Ying; Buttner, Ulrich; Carreno, Armando A. A.; Conchouso, David; Foulds, Ian G.

    2015-10-01

    This paper reports the design of a proof-of-concept drug delivery device that is actuated using the bubbles formed during electrolysis. The device uses a platinum (Pt) coated nickel (Ni) metal foam and a solid drug in reservoir (SDR) approach to improve the device’s performance. This electrochemically-driven pump has many features that are unlike conventional drug delivery devices: it is capable of pumping periodically and being refilled automatically; it features drug release control; and it enables targeted delivery. Pt-coated metal foam is used as a catalytic reforming element, which reduces the period of each delivery cycle. Two methods were used for fabricating the Pt-coated metal: sputtering and electroplating. Of these two methods, the sputtered Pt-coated metal foam has a higher pumping rate; it also has a comparable recombination rate when compared to the electroplated Pt-coated metal foam. The only drawback of this catalytic reformer is that it consumes nickel scaffold. Considering long-term applications, the electroplated Pt metal foam was selected for drug delivery, where a controlled drug release rate of 2.2 μg  ±  0.3 μg per actuation pulse was achieved using 4 mW of power.

  5. Inhalation drug delivery devices: technology update

    PubMed Central

    Ibrahim, Mariam; Verma, Rahul; Garcia-Contreras, Lucila

    2015-01-01

    The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler device, and the patient. However, the biggest single problem that accounts for the lack of desired effect or adverse outcomes is the incorrect use of the device due to lack of training in how to use the device or how to coordinate actuation and aerosol inhalation. This review summarizes the structural and mechanical features of aerosol delivery devices with respect to mechanisms of aerosol generation, their use with different formulations, and their advantages and limitations. A technological update of the current state-of-the-art designs proposed to overcome current challenges of existing devices is also provided. PMID:25709510

  6. Device-assisted transdermal drug delivery.

    PubMed

    Lee, Hyunjae; Song, Changyeong; Baik, Seungmin; Kim, Dokyoon; Hyeon, Taeghwan; Kim, Dae-Hyeong

    2017-09-01

    Transdermal drug delivery is a prospective drug delivery strategy to complement the limitations of conventional drug delivery systems including oral and injectable methods. This delivery route allows both convenient and painless drug delivery and a sustained release profile with reduced side effects. However, physiological barriers in the skin undermine the delivery efficiency of conventional patches, limiting drug candidates to small-molecules and lipophilic drugs. Recently, transdermal drug delivery technology has advanced from unsophisticated methods simply relying on natural diffusion to drug releasing systems that dynamically respond to external stimuli. Furthermore, physical barriers in the skin have been overcome using microneedles, and controlled delivery by wearable biosensors has been enabled ultimately. In this review, we classify the evolution of advanced drug delivery strategies based on generations and provide a comprehensive overview. Finally, the recent progress in advanced diagnosis and therapy through customized drug delivery systems based on real-time analysis of physiological cues is highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Micro-Fluidic Device for Drug Delivery

    NASA Technical Reports Server (NTRS)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2014-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  8. Hydrogel-based biosensors and sensing devices for drug delivery.

    PubMed

    Peppas, Nicholas A; Van Blarcom, Diana Snelling

    2016-10-28

    In the past 15years drug delivery devices have received added attention, not only as passive systems of drug delivery that respond to the needs of the health care provider or the patient but have an added advantage or an added characteristic of being triggered by an external process of recognition of a cause, a disease or an analyte that leads to a triggering mechanism for specific drug delivery. In this review, we will examine some of the pioneering work in this field, and speak on the use of biodegradable, environmentally-responsive hydrogels as sensing components in novel microscale devices. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Polymeric Micro- and Nanofabricatced Devices for Oral Drug Delivery

    NASA Astrophysics Data System (ADS)

    Fox, Cade Brylee

    While oral drug administration is by far the most preferred route, it is accompanied by many barriers that limit drug uptake such as the low pH of the stomach, metabolic and proteolytic enzymes, and limited permeability of the intestinal epithelium. As a result, many drugs ranging from small molecules to biological therapeutics have limited oral bioavailability, precluding them from oral administration. To address this issue, microfabrication has been applied to create planar, asymmetric devices capable of binding to the lining of the gastrointestinal tract and releasing drug at high concentrations, thereby increasing oral drug uptake. While the efficacy of these devices has been validated in vitro and in vivo, modifying their surfaces with nanoscale features has potential to refine their properties for enhanced drug delivery. This dissertation first presents an approach to fabricate polymeric microdevices coated with nanowires in a rapid, high throughput manner. The nanowires demonstrate rapid drug localization onto the surface of these devices via capillary action and increased adhesion to epithelial tissue, suggesting that this fabrication technique can be used to create devices with enhanced properties for oral drug delivery. Also presented are microdevices sealed with nanostraw membranes. The nanostraw membranes provide sustained drug release by limiting drug efflux from the devices, prevent drug degradation by limiting influx of outside biomolecules, and enhance device bioadhesion by penetrating into the mucus layer of the intestinal lining. Finally, an approach that dramatically increases the capacity and efficiency of drug loading into microdevices over previous methods is presented. A picoliter-volume printer is used to print drug directly into device reservoirs in an automated fashion. The technologies presented here expand the capabilities of microdevices for oral drug delivery by incorporating nanoscale structures that enhance device bioadhesion

  10. Molecularly imprinted polymers as the future drug delivery devices.

    PubMed

    Luliński, Piotr

    2013-01-01

    In recent years, the investigations of new drug delivery systems have been directed on the development of some "intelligent" drug delivery devices that are able to directly respond to the patient's individual needs. New drug delivery systems should maximize the efficiency of administrated therapeutic agents and improve the patient's quality of life. Introduction of the new drug delivery devices is an important scientific goal, which could be achieved by combining new technologies and intelligent biomaterials. Molecular imprinting technology has a high potential for the preparation of optimized drug delivery forms. Here, molecularly imprinted polymers (MIPs) are promising new materials for such purposes, but their application in this field is nowadays at a developing stage. In this review, the principles of molecular imprinting and the recognition-release mechanisms of polymeric matrices are discussed. The potential application of molecularly imprinted materials as the future drug delivery systems with various administering routes (transdermal, ocular or oral) are presented, and some future prospects for the imprinted polymers are outlined.

  11. 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.

  12. Development of a Microfluidics-Based Intracochlear Drug Delivery Device

    PubMed Central

    Sewell, William F.; Borenstein, Jeffrey T.; Chen, Zhiqiang; Fiering, Jason; Handzel, Ophir; Holmboe, Maria; Kim, Ernest S.; Kujawa, Sharon G.; McKenna, Michael J.; Mescher, Mark M.; Murphy, Brian; Leary Swan, Erin E.; Peppi, Marcello; Tao, Sarah

    2009-01-01

    Background Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods We have taken a microfluidics/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the cochlea. Iterations of the device were tested in guinea pigs to determine the flow characteristics required for safe and effective delivery. For these tests, we used the glutamate receptor blocker DNQX, which alters auditory nerve responses but not cochlear distortion product otoacoustic emissions. Results We have demonstrated safe and effective delivery of agents into the scala tympani. Equilibration of the drug in the basal turn occurs rapidly (within tens of minutes) and is dependent on reciprocating flow parameters. Conclusion We have described a prototype system for the direct delivery of drugs to the inner ear that has the potential to be a fully implantable means for safe and effective treatment of hearing loss and other diseases. PMID:19923811

  13. Towards soft robotic devices for site-specific drug delivery.

    PubMed

    Alici, Gursel

    2015-01-01

    Considerable research efforts have recently been dedicated to the establishment of various drug delivery systems (DDS) that are mechanical/physical, chemical and biological/molecular DDS. In this paper, we report on the recent advances in site-specific drug delivery (site-specific, controlled, targeted or smart drug delivery are terms used interchangeably in the literature, to mean to transport a drug or a therapeutic agent to a desired location within the body and release it as desired with negligibly small toxicity and side effect compared to classical drug administration means such as peroral, parenteral, transmucosal, topical and inhalation) based on mechanical/physical systems consisting of implantable and robotic drug delivery systems. While we specifically focus on the robotic or autonomous DDS, which can be reprogrammable and provide multiple doses of a drug at a required time and rate, we briefly cover the implanted DDS, which are well-developed relative to the robotic DDS, to highlight the design and performance requirements, and investigate issues associated with the robotic DDS. Critical research issues associated with both DDSs are presented to describe the research challenges ahead of us in order to establish soft robotic devices for clinical and biomedical applications.

  14. Drug delivery from the oral cavity: focus on a novel mechatronic delivery device.

    PubMed

    Scholz, Oliver A; Wolff, Andy; Schumacher, Axel; Giannola, Libero I; Campisi, Giuseppina; Ciach, Tomasz; Velten, Thomas

    2008-03-01

    Dental drug delivery systems have been used for a long time, in particular for the local therapy of diseases affecting the oral cavity. Research today concentrates on the design of formulations to increase their retention time. Even today, however, prosthetic devices incorporating drug delivery are rarely used. Mainly, they are focused on prophylaxis and the release of antibacterial agents. However, as buccal delivery, because of its undeniable advantages, has become popular for systemic drug delivery, and prolonged well-controlled release has been identified as beneficial, especially for chronic diseases, a new class of delivery systems is evolving: highly miniaturized computerized delivery systems, integrated into a dental appliance. Dental delivery systems today are used in two ways: the main application is the local treatment of diseases affecting the oral cavity itself like periodontitis or fungal infections. The second is for systemic drug delivery.

  15. Engineering and evaluating drug delivery particles in microfluidic devices.

    PubMed

    Björnmalm, Mattias; Yan, Yan; Caruso, Frank

    2014-09-28

    The development of new and improved particle-based drug delivery is underpinned by an enhanced ability to engineer particles with high fidelity and integrity, as well as increased knowledge of their biological performance. Microfluidics can facilitate these processes through the engineering of spatiotemporally highly controlled environments using designed microstructures in combination with physical phenomena present at the microscale. In this review, we discuss microfluidics in the context of addressing key challenges in particle-based drug delivery. We provide an overview of how microfluidic devices can: (i) be employed to engineer particles, by providing highly controlled interfaces, and (ii) be used to establish dynamic in vitro models that mimic in vivo environments for studying the biological behavior of engineered particles. Finally, we discuss how the flexible and modular nature of microfluidic devices provides opportunities to create increasingly realistic models of the in vivo milieu (including multi-cell, multi-tissue and even multi-organ devices), and how ongoing developments toward commercialization of microfluidic tools are opening up new opportunities for the engineering and evaluation of drug delivery particles. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Mathematical modelling of the release of drug from porous, nonswelling transdermal drug-delivery devices.

    PubMed

    Lee, A J; King, J R; Hibberd, S

    1998-06-01

    A general model is presented for the release of drug from porous nonswelling, transdermal drug-delivery devices and it is shown to reduce to previously proposed models in suitable limits. The processes which govern the release of drug are considered to be diffusion of dissolved drug and dissolution of dispersed drug, both in the body of the device and in the device pores, and transfer of drug between the two domains. In the classical limit of large dissolution rates, the problem reduces to one of the moving-boundary type, and solution of this problem in the case where the initial drug loading is much greater than the drug solubility in the device yields expressions for the flux of drug to a perfect sink (modelling in vitro conditions). It is shown that behaviour greatly differing from the classical first-order drug delivery (alpha t 1/2) may be exhibited, depending upon the parameter regime. In some situations the dissolution rates may not be so large and solutions of the general model are derived in the case where the dispersed drug is considered to be undepleted and the diffusivity in the solvent-filled pores is much larger than in the body of the delivery device. Numerical studies are undertaken, and the coupling of delivery device and skin-diffusion models (in order to model the complete transdermal drug-delivery process) is also considered.

  17. Silicon based materials for drug delivery devices and implants.

    PubMed

    Bernik, Delia L

    2007-01-01

    This patent review focuses on silicon based materials for drug delivery systems and implant devices devoted to medical applications. The article describes some representative examples of the most depictive silicon based compounds associated with drug release formulations and tissue engineering biomaterials. Ranging from inorganic to organic and hybrid inorganic-organic silicon compounds, the paper referrers to patents describing inventions which make use of the best properties of silicon dioxide, silica aerogel and xerogel, silicon bioactive materials, silicones and ormosils, pointing out the usefulness of each kind of compound within the invention embodiment.

  18. Shock Wave Based Biolistic Device for DNA and Drug Delivery

    NASA Astrophysics Data System (ADS)

    Nakada, Mutsumi; Menezes, Viren; Kanno, Akira; Hosseini, S. Hamid R.; Takayama, Kazuyoshi

    2008-03-01

    A shock wave assisted biolistic (biological ballistic) device has been developed to deliver DNA/drug-coated micro-projectiles into soft living targets. The device consists of an Nd:YAG laser, an optical setup to focus the laser beam and, a thin aluminum (Al) foil (typically 100 µm thick) which is a launch pad for the micro-projectiles. The DNA/drug-coated micro-particles to be delivered are deposited on the anterior surface of the foil and the posterior surface of the foil is ablated using the laser beam with an energy density of about 32×109 W/cm2. The ablation launches a shock wave through the foil that imparts an impulse to the foil surface, due to which the deposited particles accelerate and acquire sufficient momentum to penetrate soft targets. The device has been tested for particle delivery by delivering 1 µm size tungsten particles into liver tissues of experimental rats and in vitro test models made of gelatin. The penetration depths of about 90 and 800 µm have been observed in the liver and gelatin targets, respectively. The device has been tested for in vivo DNA [encoding β-glucuronidase (GUS) gene] transfer by delivering plasmid DNA-coated, 1-µm size gold (Au) particles into onion scale, tobacco leaf and soybean seed cells. The GUS activity was detected in the onion, tobacco and soybean cells after the DNA delivery. The present device is totally non-intrusive in nature and has a potential to get miniaturized to suit the existing medical procedures for DNA and/or drug delivery.

  19. Transdermal Delivery Devices: Fabrication, Mechanics and Drug Release from Silk**

    PubMed Central

    Raja, Waseem K.; MacCorkle, Scott; Diwan, Izzuddin M.; Abdurrob, Abdurrahman; Lu, Jessica; Omenetto, Fiorenzo G.; Kaplan, David L.

    2013-01-01

    Microneedles are a relatively simple, minimally invasive and painless approach to deliver drugs across the skin. However, there remain limitations with this approach because of the materials most commonly utilized for such systems. Silk protein, with tunable and biocompatibility properties, is a useful biomaterial to overcome the current limitations with microneedles. Silk devices preserve drug activity, offer superior mechanical properties and biocompatibility, can be tuned for biodegradability, and can be processed under aqueous, benign conditions. In the present work, we report the fabrication of dense microneedle arrays from silk with different drug release kinetics. The mechanical properties of the microneedle patches are tuned by post-fabrication treatments or by loading the needles with silk microparticles to increase capacity and mechanical strength. Drug release is further enhanced by the encapsulation of the drugs in the silk matrix and coating with a thin dissolvable drug layer. The microneedles are used on human cadaver skin and drugs were delivered successfully. The various attributes demonstrated suggest that silk-based microneedle devices can provide significant benefit as a platform material for transdermal drug delivery. PMID:23653252

  20. Development of nanotoxicology: implications for drug delivery and medical devices.

    PubMed

    Bhattacharjee, Sourav; Brayden, David J

    2015-07-01

    Current nanotoxicology research suffers from suboptimal in vitro models, lack of in vitro-in vivo correlations, variability within in vitro protocols, deficits in both material purity and physicochemical characterization. Reliable nanomaterial toxicity and mechanistic insights are required for health and toxicity risk assessments. Much in vitro toxicological data is inconclusive in designating whether nanomaterials for drug delivery and medical device implants are truly safe. A critique is presented to analyze the interface between toxicology and nanopharmaceuticals. Deficiencies of existing practices in toxicology are reviewed and useful emerging techniques (e.g., lab-on-a-chip, tissue engineering, atomic force microscopy, high-content analysis) are highlighted. Cross-fertilization between disciplines will aid development of biocompatible delivery and implant platforms while improvements are being suggested for better translation of nanotoxicology.

  1. Pulmonary drug delivery. Part II: The role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications

    PubMed Central

    Labiris, N R; Dolovich, M B

    2003-01-01

    Research in the area of pulmonary drug delivery has gathered momentum in the last several years, with increased interest in using the lung as a means of delivering drugs systemically. Advances in device technology have led to the development of more efficient delivery systems capable of delivering larger doses and finer particles into the lung. As more efficient pulmonary delivery devices and sophisticated formulations become available, physicians and health professionals will have a choice of a wide variety of device and formulation combinations that will target specific cells or regions of the lung, avoid the lung's clearance mechanisms and be retained within the lung for longer periods. It is now recognized that it is not enough just to have inhalation therapy available for prescribing; physicians and other healthcare providers need a basic understanding of aerosol science, inhaled formulations, delivery devices, and bioequivalence of products to prescribe these therapies optimally. PMID:14616419

  2. Alginate microparticles as oral colon drug delivery device: A review.

    PubMed

    Agüero, Lissette; Zaldivar-Silva, Dionisio; Peña, Luis; Dias, Marcos L

    2017-07-15

    The increase in the research interest on alginate microparticles in pharmaceutical and biomedical areas confirms its potential use as an effective matrix for drug and cell delivery. Among the well known alginate properties, pH sensitivity remains as an attractive option for targeting of drug in the colon region. This essential aspect is advantageous to enhance therapeutic efficacy of treatment of inflammatory bowel diseases, which require multi-drug administration frequently in a long period. As consequence, severe side effect appears leading to discontinuation of therapy and affecting quality of patient life. This review gives an overview of relevant properties of alginate as oral colon delivery systems and the recent innovative strategies of using alginate with other polymers as well as microencapsulation techniques. At the same time, it describes the several advantages of coating processes involving alginate over microparticles in order to design better material with sustained release characteristic for colon-targeted delivery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Porous silicon in drug delivery devices and materials.

    PubMed

    Anglin, Emily J; Cheng, Lingyun; Freeman, William R; Sailor, Michael J

    2008-08-17

    Porous Si exhibits a number of properties that make it an attractive material for controlled drug delivery applications: The electrochemical synthesis allows construction of tailored pore sizes and volumes that are controllable from the scale of microns to nanometers; a number of convenient chemistries exist for the modification of porous Si surfaces that can be used to control the amount, identity, and in vivo release rate of drug payloads and the resorption rate of the porous host matrix; the material can be used as a template for organic and biopolymers, to prepare composites with a designed nanostructure; and finally, the optical properties of photonic structures prepared from this material provide a self-reporting feature that can be monitored in vivo. This paper reviews the preparation, chemistry, and properties of electrochemically prepared porous Si or SiO2 hosts relevant to drug delivery applications.

  4. Porous silicon in drug delivery devices and materials☆

    PubMed Central

    Anglin, Emily J.; Cheng, Lingyun; Freeman, William R.; Sailor, Michael J.

    2009-01-01

    Porous Si exhibits a number of properties that make it an attractive material for controlled drug delivery applications: The electrochemical synthesis allows construction of tailored pore sizes and volumes that are controllable from the scale of microns to nanometers; a number of convenient chemistries exist for the modification of porous Si surfaces that can be used to control the amount, identity, and in vivo release rate of drug payloads and the resorption rate of the porous host matrix; the material can be used as a template for organic and biopolymers, to prepare composites with a designed nanostructure; and finally, the optical properties of photonic structures prepared from this material provide a self-reporting feature that can be monitored in vivo. This paper reviews the preparation, chemistry, and properties of electrochemically prepared porous Si or SiO2 hosts relevant to drug delivery applications. PMID:18508154

  5. Near-infrared–actuated devices for remotely controlled drug delivery

    PubMed Central

    Timko, Brian P.; Arruebo, Manuel; Shankarappa, Sahadev A.; McAlvin, J. Brian; Okonkwo, Obiajulu S.; Mizrahi, Boaz; Stefanescu, Cristina F.; Gomez, Leyre; Zhu, Jia; Zhu, Angela; Santamaria, Jesus; Langer, Robert; Kohane, Daniel S.

    2014-01-01

    A reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time. Despite the clear clinical need for a device that meets these criteria, none has been reported to date to our knowledge. To address this deficiency, we developed an implantable reservoir capped by a nanocomposite membrane whose permeability was modulated by irradiation with a near-infrared laser. Irradiated devices could exhibit sustained on-state drug release for at least 3 h, and could reproducibly deliver short pulses over at least 10 cycles, with an on/off ratio of 30. Devices containing aspart, a fast-acting insulin analog, could achieve glycemic control after s.c. implantation in diabetic rats, with reproducible dosing controlled by the intensity and timing of irradiation over a 2-wk period. These devices can be loaded with a wide range of drug types, and therefore represent a platform technology that might be used to address a wide variety of clinical indications. PMID:24474759

  6. Devices for stem cell isolation and delivery: current need for drug discovery and cell therapy.

    PubMed

    Reinhardt, Martin; Bader, Augustinus; Giri, Shibashish

    2015-05-01

    Isolation and purification of stem cells and their delivery into diseased or aged tissues or organs need special devices for proper transplantation of stem cells in order to achieve high cell retention at transplant site for repair or regeneration of tissues and organs. The clinical and preclinical importance of special devices such as Celution System, Isolex cell separation device, magnetic surface-enhanced Raman spectroscopic dots, microfluidic devices, immunomagnetic cell separation for stem cell separation and isolation are the main focus in this paper. Further, devices like trans-coronary delivery, trans-endocardial delivery, intracoronary delivery devices for stem cell application to the heart are described. Devices for stem cell application to the brain, the spinal cord and other tissues are also explained. We highlighted scaffolds with incorporated stem cells and other encapsulation devices used to transplant stem cells. Current needs of devices for stem cells isolation, purification and delivery for drug discovery and cell therapy are discussed.

  7. Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

    ERIC Educational Resources Information Center

    Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

    2010-01-01

    A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

  8. Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

    ERIC Educational Resources Information Center

    Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

    2010-01-01

    A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

  9. A novel ingestible electronic drug delivery and monitoring device.

    PubMed

    van der Schaar, Peter J; Dijksman, J Frits; Broekhuizen-de Gast, Henny; Shimizu, Jeff; van Lelyveld, Niels; Zou, Hans; Iordanov, Ventzeslav; Wanke, Christoph; Siersema, Peter D

    2013-09-01

    We developed an ingestible electronic drug delivery and monitoring system. This system includes an electronic capsule comprising a drug reservoir, a pH and temperature sensor, a microprocessor and wireless transceiver, a stepper motor, and batteries. The location of the capsule in the gut derived from pH data can be monitored in real time. The stepper motor can be remotely actuated to expel the contents of the drug reservoir. First human study. Two consecutive observational studies. University medical center. Twenty healthy volunteers. Study I: Ingestion and passage of the capsule. Study II: Ingestion and passage of the capsule, loaded with (99m)technetium-pertechnetate ((99m)Tc); remotely actuated expulsion of (99m)Tc in the gut. Study I: Safety, tolerability, and functionality (wireless pH and temperature recording). Study II: Tracing of the capsule and expulsion and distribution of (99m)Tc from the drug reservoir by scintigraphy. Correlating location pH with scintigraphy. Study I: Ingestion and passage of the capsule was safe and well tolerated. Transmitted pH and temperature data were received by the recorder in 96.5% ± 3%. Study II: pH-determined passage of the esophagogastric, gastroduodenal, and ileocolonic junction correlated well with scintigraphy. Expulsion of (99m)Tc from the capsule was successful in 9 of 10 subjects. Subjects with relatively low body mass index. This electronic drug delivery and monitoring system may be a promising tool for targeted delivery of substances to well-defined areas of the GI tract. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  10. Molecularly imprinted polymers based drug delivery devices: a way to application in modern pharmacotherapy. A review.

    PubMed

    Luliński, Piotr

    2017-07-01

    This review presents the current status of molecularly imprinted polymers (MIPs) for drug delivery, in particular the studies that focus on biocompatibility, cytotoxicity, and in vitro or in vivo behavior of MIPs. It also shows the limitations that hamper the introduction of MIPs to pharmacotherapy and prevent this class of polymers from commercialization. MIPs are promising materials in the construction of drug delivery devices because they can provide improved delivery profiles or longer release times and deliver the drugs in the feedback regulated way, which is extremely important in modern pharmacotherapy. Here, a brief overview of the imprinting process and a concise description of drug release mechanisms from the imprinted materials will be presented followed by the discussion of potential MIP drug delivery devices for ocular, dermal, intravenous and oral routes of administration. Finally, future prospects for imprinted drug delivery forms will be outlined. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Perioperative Management of a Patient With an Intrathecal Drug Delivery Device Infusing Ziconotide: A Case Report.

    PubMed

    Patel, Sephalie; Hafez, Osama; Sexton, Wade J; Edwards, David A

    2017-02-15

    Intrathecal ziconotide is used for the treatment of chronic pain and is delivered by an implanted drug delivery device. Anesthesiologists should be familiar with the perioperative management of the pump as well as the potential adverse events related to continued ziconotide infusion during general anesthesia. A case is presented demonstrating the perioperative management of an intrathecal drug delivery device infusing ziconotide in a patient presenting for radical cystectomy with pelvic lymphadenectomy and ileal conduit diversion.

  12. Perioperative Management of a Patient With an Intrathecal Drug Delivery Device Infusing Ziconotide.

    PubMed

    Patel, Sephalie; Hafez, Osama; Sexton, Wade J; Edwards, David A

    2016-12-09

    Intrathecal ziconotide is used for the treatment of chronic pain and is delivered by an implanted drug delivery device. Anesthesiologists should be familiar with the perioperative management of the pump as well as the potential adverse events related to continued ziconotide infusion during general anesthesia. A case is presented demonstrating the perioperative management of an intrathecal drug delivery device infusing ziconotide in a patient presenting for radical cystectomy with pelvic lymphadenectomy and ileal conduit diversion.

  13. Nanoprecipitation and the "Ouzo effect": Application to drug delivery devices.

    PubMed

    Lepeltier, Elise; Bourgaux, Claudie; Couvreur, Patrick

    2014-05-01

    Biodegradable nanocarriers such as lipid- or polymer-based nanoparticles can be designed to improve the efficacy and reduce the toxic side effects of drugs. Under appropriate conditions, nanoprecipitation of a hydrophobic compound solution in a non-solvent can generate a dispersion of nanoparticles with a narrow distribution of sizes without the use of surfactant ("Ouzo" effect). The aim of this review is to present the main parameters controlling the nucleation and growth of aggregates in a supersaturated solution and the characteristics of the obtained nanoparticles. The importance of the kinetics of mixing of the solution containing the hydrophobic compound and the non-solvent is highlighted. Illustrative examples of polymeric nanoparticles for drug delivery or terpenoid-based nanoprodrugs obtained by nanoprecipitation are reported.

  14. A flexible device for ocular iontophoretic drug delivery

    PubMed Central

    Zhang, Yushi; Chen, Yao; Yu, Xiaoxue; Qi, Yangjia; Chen, Yufeng; Liu, Yuxi; Hu, Yuntao; Li, Zhihong

    2016-01-01

    In this work, a flexible ocular iontophoretic device, which can be fabricated by batch processing, is reported. In vivo experiments were conducted on rabbit eyes, and the results demonstrated this device could realize ocular iontophoresis effectively, simply, and conveniently. Compared to conventional eye cups, it can be placed under the eyelid and can deliver ions through a small area on the eyeball, reducing tissue damage caused by the drug during ion penetration. Owing to the flexibility of the device, the device can be easily seated under the eyelid stably during iontophoresis. Manganese ions as a tracer for detection of optic nerve damage were delivered into rabbit eyes by this iontophoretic device. Under 1 mA for 600 s, the average Mn2+ concentration in the eye ball after iontophoresis was 102 ng/ml, while the one in the control group was 23 ng/ml. Using 2 mA for 600 s, the average concentration was 271 ng/ml, while it was 38 ng/ml in the control group. Thermal injury during iontophoresis was not observed under an applied current of no more than 2 mA for no longer than 10 min, with the local temperature less than 38 °C, measured by an infrared thermal imager. PMID:26958098

  15. An in-vivo evaluation of a MEMS drug delivery device using Kunming mice model.

    PubMed

    Liu, Yaqian; Song, Peiyi; Liu, Jianwei; Tng, Danny Jian Hang; Hu, Rui; Chen, Hongyan; Hu, Yazhuo; Tan, Cher Heng; Wang, Jianhua; Liu, Jing; Ye, Ling; Yong, Ken-Tye

    2015-02-01

    The use of MEMS implantable drug delivery pump device enables one to program the desired drug delivery profile in the device for individualized medicine treatment to patients. In this study, a MEMS drug delivery device is prepared and employed for in vivo applications. 12 devices are implanted subcutaneously into Kunming mice for evaluating their long term biocompatibility and drug-delivery efficiency in vivo. All the mice survived after device implantation surgery procedures. Histological analysis result reveals a normal wound healing progression within the tissues-to-device contact areas. Serum analysis shows that all measured factors are within normal ranges and do not indicate any adverse responses associated with the implanted device. Phenylephrine formulation is chosen and delivered to the abdominal cavity of the mice by using either the implanted MEMS device (experimental group) or the syringe injection method (control group). Both groups show that they are able to precisely control and manipulate the increment rate of blood pressure in the small animals. Our result strongly suggests that the developed refillable implantable MEMS devices will serve as a viable option for future individualized medicine applications such as glaucoma, HIV-dementia and diabetes therapy.

  16. The Respimat Soft Mist Inhaler, a Novel Inhaled Drug Delivery Device.

    PubMed

    Perriello, Emily A; Sobieraj, Diana M

    2016-01-01

    Summary The Respimat SMI offers a novel delivery mechanism for the management of primarily COPD, but asthma as well. Presently, four different medications, as monotherapy or a combination of two active ingredients, are available using the Respimat SMI technology. Multiple studies have demonstrated safety and efficacy of these drugs when delivered via Respimat SMI. Patients tend to prefer the Respimat SMI over traditional inhaler devices, as it overcomes some of the disadvantages posed by traditional delivery devices.

  17. Evaluation of tissue interactions with mechanical elements of a transscleral drug delivery device.

    PubMed

    Cohen, Sarah J; Chan, Robison V Paul; Keegan, Mark; Andreoli, Christopher M; Borenstein, Jeffrey T; Miller, Joan W; Gragoudas, Evangelos S

    2012-03-12

    The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device-one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene) (PTFE) membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion around the device, and inflammation of the conjunctiva. Gear devices encouraged significantly greater inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes prevented tissue invasion through the covered drug ports, though tissue migrated in through other smaller openings. The torque required to turn the mechanical elements increased over 1000 times for gear devices, but only on the order of 100 times for membrane-covered gear devices and less than 100 times for ball bearing devices. Maintaining a lower device profile, minimizing microscale motion on the eye surface and covering drug ports with a porous membrane may minimize inflammation, decreasing the risk of damage to surrounding tissues and minimizing disruption of device operation.

  18. Evaluation of Tissue Interactions with Mechanical Elements of a Transscleral Drug Delivery Device

    PubMed Central

    Cohen, Sarah J.; Chan, Robison V. Paul; Keegan, Mark; Andreoli, Christopher M.; Borenstein, Jeffrey T.; Miller, Joan W.; Gragoudas, Evangelos S.

    2012-01-01

    The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device—one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene) (PTFE) membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion around the device, and inflammation of the conjunctiva. Gear devices encouraged significantly greater inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes prevented tissue invasion through the covered drug ports, though tissue migrated in through other smaller openings. The torque required to turn the mechanical elements increased over 1000 times for gear devices, but only on the order of 100 times for membrane-covered gear devices and less than 100 times for ball bearing devices. Maintaining a lower device profile, minimizing microscale motion on the eye surface and covering drug ports with a porous membrane may minimize inflammation, decreasing the risk of damage to surrounding tissues and minimizing disruption of device operation. PMID:24300189

  19. An Implantable MEMS Drug Delivery Device for Rapid Delivery in Ambulatory Emergency Care

    DTIC Science & Technology

    2009-06-01

    Rabideau for his assistance during the fabrication process. 10. References W. S. Aronow, “Review Article: Treatment of Unstable Angina Pectoris /Non...delivery. Potential pathologies that the device can address with patients at high risk include: cardiac arrest, vasovagal syncope, angina , strokes...pacemaker in this case. Another potential use of this device is for treating angina . The IRD 3 could be implanted in high-risk patients to deliver

  20. An electrochemically actuated MEMS device for individualized drug delivery: an in vitro study.

    PubMed

    Song, Peiyi; Tng, Danny Jian Hang; Hu, Rui; Lin, Guimiao; Meng, Ellis; Yong, Ken-Tye

    2013-08-01

    Individualized disease treatment is a promising branch for future medicine. In this work, we introduce an implantable microelectromechanical system (MEMS) based drug delivery device for programmable drug delivery. An in vitro study on cancer cell treatment has been conducted to demonstrate a proof-of-concept that the engineered device is suitable for individualized disease treatment. This is the first study to demonstrate that MEMS drug delivery devices can influence the outcome of cancer drug treatment through the use of individualized disease treatment regimes, where the strategy for drug dosages is tailored according to different individuals. The presented device is electrochemically actuated through a diaphragm membrane and made of polydimethylsiloxane (PDMS) for biocompatibility using simple and cost-effective microfabrication techniques. Individualized disease treatment was investigated using the in vitro programmed delivery of a chemotherapy drug, doxorubicin, to pancreatic cancer cell cultures. Cultured cell colonies of two pancreatic cancer cell lines (Panc-1 and MiaPaCa-2) were treated with three programmed schedules and monitored for 7 days. The result shows that the colony growth has been successfully inhibited for both cell lines among all the three treatment schedules. Also, the different observations between the two cell lines under different schedules reveal that MiaPaCa-2 cells are more sensitive to the drug applied. These results demonstrate that further development on the device will provide a promising novel platform for individualized disease treatment in future medicine as well as for automatic in vitro assays in drug development industry. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Transdermal power transfer for recharging implanted drug delivery devices via the refill port.

    PubMed

    Evans, Allan T; Chiravuri, Srinivas; Gianchandani, Yogesh B

    2010-04-01

    This paper describes a system for transferring power across a transdermal needle into a smart refill port for recharging implantable drug delivery systems. The device uses a modified 26 gauge (0.46 mm outer diameter) Huber needle with multiple conductive elements designed to couple with mechanical springs in the septum of the refill port of a drug delivery device to form an electrical connection that can sustain the current required to recharge a battery during a reservoir refill session. The needle is fabricated from stainless steel coated with Parylene, and the refill port septum is made from micromachined stainless steel contact springs and polydimethylsiloxane. The device properties were characterized with dry and wet ambient conditions. The needle and port pair had an average contact resistance of less than 2 Omega when mated in either environment. Electrical isolation between the system, the liquid in the needle lumen, and surrounding material has been demonstrated. The device was used to recharge a NiMH battery with currents up to 500 mA with less than 15 degrees C of resistive heating. The system was punctured 100 times to provide preliminary information with regard to device longevity, and exhibited about 1 Omega variation in contact resistance. The results suggest that this needle and refill port system can be used in an implant to enable battery recharging. This allows for smaller batteries to be used and ultimately increases the volume efficiency of an implantable drug delivery device.

  2. On-demand controlled release of docetaxel from a battery-less MEMS drug delivery device.

    PubMed

    Pirmoradi, Fatemeh Nazly; Jackson, John K; Burt, Helen M; Chiao, Mu

    2011-08-21

    We report the development of a magnetically controlled MEMS device capable of on-demand release of defined quantities of an antiproliferative drug, docetaxel (DTX). Controlled release of DTX with a dosage suitable for the treatment of diabetic retinopathy has been achieved for 35 days. The device consists of a drug-loaded microreservoir (Ø6 mm ×∼550 μm), sealed by an elastic magnetic PDMS (polydimethylsiloxane) membrane (Ø6 mm × 40 μm) with a laser-drilled aperture (∼100 × 100 μm(2)). By applying a magnetic field, the magnetic PDMS membrane deforms, causing the discharge of the drug solution from the device. Controlled DTX release at a rate of 171 ± 16.7 ng per actuation interval has been achieved for 35 days using a 255 mT magnetic field. The background leakage of drug solution through the aperture was negligible at 0.053 ± 0.014 ng min(-1). The biological activity of the released drug was investigated using a cytotoxicity assay (cell apoptosis) for two cell lines, HUVEC (human umbilical vein endothelial cells) and PC3 (prostate cancer) cells. Reproducible release rates have been achieved and DTX within the PDMS MEMS reservoir maintains full pharmacological efficacy for more than two months. This device is a proof-of-concept development for targeted delivery of hydrophobic drugs such as DTX and other taxane-based agents that require accurate delivery in nanomolar concentrations.

  3. Perivascular medical devices and drug delivery systems: Making the right choices.

    PubMed

    Mylonaki, Ioanna; Allémann, Éric; Saucy, François; Haefliger, Jacques-Antoine; Delie, Florence; Jordan, Olivier

    2017-02-28

    Perivascular medical devices and perivascular drug delivery systems are conceived for local application around a blood vessel during open vascular surgery. These systems provide mechanical support and/or pharmacological activity for the prevention of intimal hyperplasia following vessel injury. Despite abundant reports in the literature and numerous clinical trials, no efficient perivascular treatment is available. In this review, the existing perivascular medical devices and perivascular drug delivery systems, such as polymeric gels, meshes, sheaths, wraps, matrices, and metal meshes, are jointly evaluated. The key criteria for the design of an ideal perivascular system are identified. Perivascular treatments should have mechanical specifications that ensure system localization, prolonged retention and adequate vascular constriction. From the data gathered, it appears that a drug is necessary to increase the efficacy of these systems. As such, the release kinetics of pharmacological agents should match the development of the pathology. A successful perivascular system must combine these optimized pharmacological and mechanical properties to be efficient.

  4. Multi-pulse drug delivery from a resorbable polymeric microchip device

    NASA Astrophysics Data System (ADS)

    Grayson, Amy C. Richards; Choi, Insung S.; Tyler, Betty M.; Wang, Paul P.; Brem, Henry; Cima, Michael J.; Langer, Robert

    2003-11-01

    Controlled-release drug delivery systems have many applications, including treatments for hormone deficiencies and chronic pain. A biodegradable device that could provide multi-dose drug delivery would be advantageous for long-term treatment of conditions requiring pulsatile drug release. In this work, biodegradable polymeric microchips were fabricated that released four pulses of radiolabelled dextran, human growth hormone or heparin in vitro. Heparin that was released over 142 days retained on average 96 +/- 12% of its bioactivity. The microchips were 1.2 cm in diameter, 480-560 μm thick and had 36 reservoirs that could each be filled with a different chemical. The devices were fabricated from poly(L-lactic acid) and had poly(D,L-lactic-co-glycolic acid) membranes of different molecular masses covering the reservoirs. A drug delivery system can be designed with the potential to release pulses of different drugs at intervals after implantation in a patient by using different molecular masses or materials for the membrane.

  5. Polycaprolactone Thin-Film Drug Delivery Systems: Empirical and Predictive Models for Device Design

    PubMed Central

    Schlesinger, Erica; Ciaccio, Natalie; Desai, Tejal A.

    2015-01-01

    Purpose To define empirical models and parameters based on theoretical equations to describe drug release profiles from two polycaprolactone thin-film drug delivery systems. Additionally, to develop a predictive model for empirical parameters based on drugs’ physicochemical properties. Methods Release profiles from a selection of drugs representing the standard pharmaceutical space in both polycaprolactone matrix and reservoir systems were determined experimentally. The proposed models were used to calculate empirical parameters describing drug diffusion and release. Observed correlations between empirical parameters and drug properties were used to develop equations to predict parameters based on drug properties. Predictive and empirical models were evaluated in the design of three prototype devices: a levonorgestrel matrix system for on-demand locally administered contraception, a timolol-maleate reservoir system for glaucoma treatment, and a primaquine-bisphosphate reservoir system for malaria prophylaxis. Results Proposed empirical equations accurately fit experimental data. Experimentally derived empirical parameters show significant correlations with logP, molecular weight, and solubility. Empirical models based on predicted parameters accurately predict experimental release data for three prototype systems, demonstrating the accuracy and utility of these models. Conclusion The proposed empirical models can be used to design polycaprolactone thin-film devices for target geometries and release rates. Empirical parameters can be predicted based on drug properties. Together, these models provide tools for preliminary evaluation and design of controlled-release delivery systems. PMID:26354259

  6. Application of micro- and nano-electromechanical devices to drug delivery.

    PubMed

    Staples, Mark; Daniel, Karen; Cima, Michael J; Langer, Robert

    2006-05-01

    Micro- and nano-electromechanical systems (MEMS and NEMS)-based drug delivery devices have become commercially-feasible due to converging technologies and regulatory accommodation. The FDA Office of Combination Products coordinates review of innovative medical therapies that join elements from multiple established categories: drugs, devices, and biologics. Combination products constructed using MEMS or NEMS technology offer revolutionary opportunities to address unmet medical needs related to dosing. These products have the potential to completely control drug release, meeting requirements for on-demand pulsatile or adjustable continuous administration for extended periods. MEMS or NEMS technologies, materials science, data management, and biological science have all significantly developed in recent years, providing a multidisciplinary foundation for developing integrated therapeutic systems. If small-scale biosensor and drug reservoir units are combined and implanted, a wireless integrated system can regulate drug release, receive sensor feedback, and transmit updates. For example, an "artificial pancreas" implementation of an integrated therapeutic system would improve diabetes management. The tools of microfabrication technology, information science, and systems biology are being combined to design increasingly sophisticated drug delivery systems that promise to significantly improve medical care.

  7. Physical characterization of polymer electrolytes as novel iontophoretic drug delivery devices.

    PubMed

    Sahota, T S; Latham, R J; Linford, R G; Taylor, P M

    1999-03-01

    Polymer electrolytes are solid-like materials formed by dispersing a salt at the molecular level in a high molecular weight polymer such as poly(ethylene oxide) (PEO). They have been extensively studied for use in electrochemical applications such as batteries and display devices. This paper considers a novel application of polymer electrolytes as the basis of iontophoretic drug delivery systems. Polymer electrolyte films were cast from solutions of PEO and various drug salts using either water or an acetonitrile/ethanol mixture as the solvent. These films were characterized by variable-temperature polarizing microscopy (VTPM), differential scanning calorimetry (DSC), and alternating current (AC) impedance analysis. The films were around 100-micron thick and mechanically strong; the optical and thermal methods provided evidence that the polymer electrolytes had crystalline and amorphous phases, although some drugs may exist in films as nanodispersions. The amorphous phase is important as ions have greater mobility in this phase and therefore allow a current to be passed when the material is incorporated into a device such as one suitable for drug delivery by iontophoresis. The AC impedance analysis showed that the conductivity of the films varied between 10(-6) and 10(-3) S cm-1, depending on the salt, casting solvent, and temperature. Two drugs in particular were shown to be promising candidates in these systems: lidocaine hydrochloride and lithium chloride.

  8. Intracochlear Drug Delivery Systems

    PubMed Central

    Borenstein, Jeffrey T.

    2011-01-01

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

  9. Enhanced intracellular delivery of a model drug using microbubbles produced by a microfluidic device

    PubMed Central

    Dixon, Adam J.; Dhanaliwala, Ali H.; Chen, Johnny L.; Hossack, John A.

    2013-01-01

    Focal drug delivery to a vessel wall facilitated by intravascular ultrasound and microbubbles holds promise as a potential therapy for atherosclerosis. Conventional methods of microbubble administration result in rapid clearance from the blood stream and significant drug loss. To address these limitations, we evaluated whether drug delivery could be achieved with transiently stable microbubbles produced in real-time and in close proximity to the therapeutic site. Rat aortic smooth muscle cells were placed in a flow chamber designed to simulate physiological flow conditions. A flow-focusing microfluidic device (FFMD) produced 8 μm diameter monodisperse microbubbles within the flow chamber, and ultrasound was applied to enhance uptake of a surrogate drug (calcein). Acoustic pressures up to 300 kPa and flow rates up to 18 mL/s were investigated. FFMD generated microbubbles were stabilized with a polyethylene glycol-40 stearate shell and had either a perfluorobutane (PFB) or nitrogen gas core. The gas core composition affected stability, with PFB and nitrogen microbubbles exhibiting half-lives of 40.7 and 18.2 seconds, respectively. Calcein uptake was observed at lower acoustic pressures with nitrogen microbubbles (100 kPa) than with PFB microbubbles (200 kPa) (p < 0.05, n ≥ 3). In addition, delivery was observed at all flow rates, with maximal delivery (> 70% of cells) occurring at a flow rate of 9 mL/s. These results demonstrate the potential of transiently stable microbubbles produced in real-time and in close proximity to the intended therapeutic site for enhancing localized drug delivery. PMID:23643062

  10. Characterization of a poly-epsilon-caprolactone polymeric drug delivery device built by selective laser sintering.

    PubMed

    Leong, K F; Wiria, F E; Chua, C K; Li, S H

    2007-01-01

    Selective Laser Sintering (SLS), an established Rapid Prototyping (RP) process, is investigated for building controlled drug delivery devices (DDD). The drug and its matrix in a powder form were first mixed mechanically before being sintered on the SLS. Each cylindrical DDD is designed with a number of concentric rings separated from each other by a characteristic 'wall' created by the laser of the SLS. These rings act as diffusion obstacles to control the rate of release. Poly-epsilon-caprolactone (PCL) was used as the matrix and Methylene Blue (MB) as the drug model. Samples were built, characterized and tested for homogeneity using Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectrophotometry (FTIR). Experimental results show that the matrices fabricated are not affected by sintering and the polymer and drug model are evenly distributed throughout the matrix. The initial burst effect has been reduced by the increase of the numbers of rings. The linear curve using the Higuchi equation confirmed that the DDD matrix release profile is by diffusion. These results show that the DDD matrix design has promising potential for application in controlled release drug delivery.

  11. Inhaled pulmonary vasodilators for persistent pulmonary hypertension of the newborn: safety issues relating to drug administration and delivery devices

    PubMed Central

    Cosa, Nathan; Costa, Edward

    2016-01-01

    Treatment for persistent pulmonary hypertension of the newborn (PPHN) aims to reduce pulmonary vascular resistance while maintaining systemic vascular resistance. Selective pulmonary vasodilation may be achieved by targeting pulmonary-specific pathways or by delivering vasodilators directly to the lungs. Abrupt withdrawal of a pulmonary vasodilator can cause rebound pulmonary hypertension. Therefore, use of consistent delivery systems that allow for careful monitoring of drug delivery is important. This manuscript reviews published studies of inhaled vasodilators used for treatment of PPHN and provides an overview of safety issues associated with drug delivery and delivery devices as they relate to the risk of rebound pulmonary hypertension. Off-label use of aerosolized prostacyclins and an aerosolized prostaglandin in neonates with PPHN has been reported; however, evidence from large randomized clinical trials is lacking. The amount of a given dose of aerosolized drug that is actually delivered to the lungs is often unknown, and the actual amount of drug deposited in the lungs can be affected by several factors, including patient size, nebulizer used, and placement of the nebulizer within the breathing circuit. Inhaled nitric oxide (iNO) is the only pulmonary vasodilator approved by the US Food and Drug Administration for the treatment of PPHN. The iNO delivery device, INOmax DSIR®IR, is designed to constantly monitor NO, NO2, and O2 deliveries and is equipped with audible and visual alarms to alert providers of abrupt discontinuation and incorrect drug concentration. Other safety features of this device include two independent backup delivery systems, a backup drug cylinder, a battery that provides up to 6 hours of uninterrupted medication delivery, and 27 alarms that monitor delivery, dosage, and system functions. The ability of the drug delivery device to provide safe, consistent dosing is important to consider when selecting a pulmonary vasodilator. PMID

  12. Articulating feedstock delivery device

    DOEpatents

    Jordan, Kevin

    2013-11-05

    A fully articulable feedstock delivery device that is designed to operate at pressure and temperature extremes. The device incorporates an articulating ball assembly which allows for more accurate delivery of the feedstock to a target location. The device is suitable for a variety of applications including, but not limited to, delivery of feedstock to a high-pressure reaction chamber or process zone.

  13. 76 FR 25696 - Guidance for Industry on Dosage Delivery Devices for Orally Ingested OTC Liquid Drug Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-05

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Dosage Delivery Devices for Orally.... SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry... intended to provide guidance to firms that are manufacturing, marketing, or distributing orally...

  14. [Development of the MITO-porter, a nano device for mitochondrial drug delivery via membrane fusion].

    PubMed

    Yamada, Yuma

    2014-01-01

    Many human diseases have been reported to be associated with mitochondrial dysfunction. Therefore, mitochondrial therapy would be expected to be useful and productive in the treatment of various diseases. To achieve such an innovative therapy, it will be necessary to deliver therapeutic agents into mitochondria. However, only a limited number of methods are available for accomplishing this. We previously developed the MITO-Porter, a liposome-based carrier that permits macromolecular cargos to be transported into mitochondria via membrane fusion. Intracellular observations using the green fluorescence protein as a model macromolecule confirmed the mitochondrial delivery of a macromolecule by the MITO-Porter. Moreover, when we attempted the mitochondrial delivery of bongkrekic acid (BKA), an antiapoptosis agent, the MITO-Porter enhanced the antiapoptosis effect compared with naked BKA. To construct a device with enhanced performance, the MITO-Porter was coated with cell membrane-fusogenic outer envelopes to produce the dual function (DF)-MITO-Porter. Intracellular observations indicated that the DF-MITO-Porter was more effective in delivering exogenous macromolecules into mitochondria than the conventional MITO-Porter. Furthermore, when biomacromolecules were delivered using the DF-MITO-Porter to estimate the mitochondrial gene targeting of the carrier, the results confirmed that the MITO-Porter system has the potential for use in therapies aimed at mitochondrial DNA. This paper sumarizes our findings on mitochondrial drug delivery systems that are directed toward mitochondrial medicine development and mitochondrial gene therapy. It is expected that the MITO-Porter system will open new research areas in mitochondrial drug delivery systems and have a significant impact on the medical and life sciences.

  15. Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module

    PubMed Central

    Lee, Hyunjae; Song, Changyeong; Hong, Yong Seok; Kim, Min Sung; Cho, Hye Rim; Kang, Taegyu; Shin, Kwangsoo; Choi, Seung Hong; Hyeon, Taeghwan; Kim, Dae-Hyeong

    2017-01-01

    Electrochemical analysis of sweat using soft bioelectronics on human skin provides a new route for noninvasive glucose monitoring without painful blood collection. However, sweat-based glucose sensing still faces many challenges, such as difficulty in sweat collection, activity variation of glucose oxidase due to lactic acid secretion and ambient temperature changes, and delamination of the enzyme when exposed to mechanical friction and skin deformation. Precise point-of-care therapy in response to the measured glucose levels is still very challenging. We present a wearable/disposable sweat-based glucose monitoring device integrated with a feedback transdermal drug delivery module. Careful multilayer patch design and miniaturization of sensors increase the efficiency of the sweat collection and sensing process. Multimodal glucose sensing, as well as its real-time correction based on pH, temperature, and humidity measurements, maximizes the accuracy of the sensing. The minimal layout design of the same sensors also enables a strip-type disposable device. Drugs for the feedback transdermal therapy are loaded on two different temperature-responsive phase change nanoparticles. These nanoparticles are embedded in hyaluronic acid hydrogel microneedles, which are additionally coated with phase change materials. This enables multistage, spatially patterned, and precisely controlled drug release in response to the patient’s glucose level. The system provides a novel closed-loop solution for the noninvasive sweat-based management of diabetes mellitus. PMID:28345030

  16. Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module.

    PubMed

    Lee, Hyunjae; Song, Changyeong; Hong, Yong Seok; Kim, Min Sung; Cho, Hye Rim; Kang, Taegyu; Shin, Kwangsoo; Choi, Seung Hong; Hyeon, Taeghwan; Kim, Dae-Hyeong

    2017-03-01

    Electrochemical analysis of sweat using soft bioelectronics on human skin provides a new route for noninvasive glucose monitoring without painful blood collection. However, sweat-based glucose sensing still faces many challenges, such as difficulty in sweat collection, activity variation of glucose oxidase due to lactic acid secretion and ambient temperature changes, and delamination of the enzyme when exposed to mechanical friction and skin deformation. Precise point-of-care therapy in response to the measured glucose levels is still very challenging. We present a wearable/disposable sweat-based glucose monitoring device integrated with a feedback transdermal drug delivery module. Careful multilayer patch design and miniaturization of sensors increase the efficiency of the sweat collection and sensing process. Multimodal glucose sensing, as well as its real-time correction based on pH, temperature, and humidity measurements, maximizes the accuracy of the sensing. The minimal layout design of the same sensors also enables a strip-type disposable device. Drugs for the feedback transdermal therapy are loaded on two different temperature-responsive phase change nanoparticles. These nanoparticles are embedded in hyaluronic acid hydrogel microneedles, which are additionally coated with phase change materials. This enables multistage, spatially patterned, and precisely controlled drug release in response to the patient's glucose level. The system provides a novel closed-loop solution for the noninvasive sweat-based management of diabetes mellitus.

  17. Swellable elementary osmotic pump (SEOP): an effective device for delivery of poorly water-soluble drugs.

    PubMed

    Shokri, Javad; Ahmadi, Parinaz; Rashidi, Parisa; Shahsavari, Mahbobeh; Rajabi-Siahboomi, Ali; Nokhodchi, Ali

    2008-02-01

    A new type of elementary osmotic pump (EOP) tablet for efficient delivery of poorly water-soluble/practically insoluble drugs has been designed. Drug release from the system, called swellable elementary osmotic pump (SEOP), is through a delivery orifice in the form of a very fine dispersion ready for dissolution and absorption. SEOP tablets were prepared by compressing the mixture of micronized drug and excipients into convex tablets. Factors affecting the release of drug from the SEOP tablets containing a poorly water-soluble drug, indomethacin, have been explored. The release behaviour of indomethacin from different formulations of this dosage form was studied at pH 6.8 for a period of 24h. The formulations were compared based on four comparative parameters, namely, D(24h) (total release after 24h), t(L) (lag time), RSQ(zero) (R square of zero order equation) and D%(zero) (percentage deviation from zero order kinetics). The drug release profile from osmotic devices showed that the type of polymer in the core formulation can markedly affect the drug release. The results showed that concentration of wetting agent in the core formulation was a very important parameter in D(24h) and release pattern of indomethacin from SEOP system. Increasing the amount of wetting agent to an optimum level (60mg) significantly increased D(24h) and improved zero order release pattern of indomethacin. Increasing concentration of caster oil (hydrophobic) in the semipermeable membrane of the device or hydrophilic plasticizer (glycerin) in coating formulation markedly increased t(L) and decreased D(24h). The results also demonstrated that aperture size is a critical parameter and should be optimized for each SEOP system. Optimum aperture diameter for the formulations studied here was determined to be 650microm for zero order release pattern. t(L) and D%(zero) were dramatically decreased whereas D(24h) and RSQ(zero) increased with increasing the aperture size to optimum level. This study

  18. Isotope-labelled urea to test colon drug delivery devices in vivo: principles, calculations and interpretations.

    PubMed

    Maurer, Marina J M; Schellekens, Reinout C A; Wutzke, Klaus D; Stellaard, Frans

    2013-01-01

    This paper describes various methodological aspects that were encountered during the development of a system to monitor the in vivo behaviour of a newly developed colon delivery device that enables oral drug treatment of inflammatory bowel diseases. [(13)C]urea was chosen as the marker substance. Release of [(13)C]urea in the ileocolonic region is proven by the exhalation of (13)CO2 in breath due to bacterial fermentation of [(13)C]urea. The (13)CO2 exhalation kinetics allows the calculation of a lag time as marker for delay of release, a pulse time as marker for the speed of drug release and the fraction of the dose that is fermented. To determine the total bioavailability, also the fraction of the dose absorbed from the intestine must be quantified. Initially, this was done by calculating the time-dependent [(13)C]urea appearance in the body urea pool via measurement of (13)C abundance and concentration of plasma urea. Thereafter, a new methodology was successfully developed to obtain the bioavailability data by measurement of the urinary excretion rate of [(13)C]urea. These techniques required two experimental days, one to test the coated device, another to test the uncoated device to obtain reference values for the situation that 100 % of [(13)C]urea is absorbed. This is hampered by large day-to-day variations in urea metabolism. Finally, a completely non-invasive, one-day test was worked out based on a dual isotope approach applying a simultaneous administration of [(13)C]urea in a coated device and [(15)N2]urea in an uncoated device. All aspects of isotope-related analytical methodologies and required calculation and correction systems are described.

  19. DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices.

    PubMed

    Linko, Veikko; Ora, Ari; Kostiainen, Mauri A

    2015-10-01

    DNA molecules can be assembled into custom predesigned shapes via hybridization of sequence-complementary domains. The folded structures have high spatial addressability and a tremendous potential to serve as platforms and active components in a plethora of bionanotechnological applications. DNA is a truly programmable material, and its nanoscale engineering thus opens up numerous attractive possibilities to develop novel methods for therapeutics. The tailored molecular devices could be used in targeting cells and triggering the cellular actions in the biological environment. In this review we focus on the DNA-based assemblies - primarily DNA origami nanostructures - that could perform complex tasks in cells and serve as smart drug-delivery vehicles in, for example, cancer therapy, prodrug medication, and enzyme replacement therapy.

  20. A Hydrogel/Carbon-Nanotube Needle-Free Device for Electrostimulated Skin Drug Delivery.

    PubMed

    Guillet, Jean-François; Flahaut, Emmanuel; Golzio, Muriel

    2017-10-06

    The permeability of skin allows passive diffusion across the epidermis to reach blood vessels but this is possible only for small molecules such as nicotine. In order to achieve transdermal delivery of large molecules such as insulin or plasmid DNA, permeability of the skin and mainly the permeability of the stratum corneum skin layer has to be increased. Moreover, alternative routes that avoid the use of needles will improve the quality of life of patients. A method known as electropermeabilisation has been shown to increase skin permeability. Herein, we report the fabrication of an innovative hydrogel made of a nanocomposite material. This nanocomposite device aims to permeabilise the skin and deliver drug molecules at the same time. It includes a biocompatible polymer matrix (hydrogel) and double-walled carbon nanotubes (DWCNTs) in order to bring electrical conductivity and improve mechanical properties. Carbon nanotubes and especially DWCNTs are ideal candidates, combining high electrical conductivity with a very high specific surface area together with a good biocompatibility when included into a material. The preparation and characterization of the nanocomposite hydrogel as well as first results of electrostimulated transdermal delivery using an ex vivo mouse skin model are presented. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Deformable microparticles with multiple functions for drug delivery and device testing

    NASA Astrophysics Data System (ADS)

    Thula, Taili T.

    Since the HIV epidemic of the 1990s, researchers have attempted to develop a red blood cell analog. Even though some of these substitutes are now in Phase III of clinical trials, their use is limited by side effects and short half-life in the human body. As a result, there is still a need for an effective erythrocyte analog with minimum immunogenic and side effects, so that it can be used for multiple applications. Finding new approaches to develop more efficient blood substitutes will not only bring valuable advances in the clinical approach, but also in the area of in vitro testing of medical devices. We examined the feasibility of creating a deformable multi-functional, biodegradable, biocompatible particle for applications in drug delivery and device testing. As a preliminary evaluation, we synthesized different types of microcapsules using natural and synthetic polymers, various cross-linking agents, and diverse manufacturing techniques. After fully characterizing of each system, we determined the most promising red blood cell analog in terms of deformability, stability and toxicity. We also examined the encapsulation and release of bovine serum albumin (BSA) within these deformable particles. After removal of cross-linkers, zinc- and copper-alginate microparticles surrounded by multiple polyelectrolyte layers of chitosan oligosaccharide and alginate were deformable and remained stable under physiological pressures applied by the micropipette technique. In addition, multiple coatings decreased toxicity of heavy-metal crosslinked particles. BSA encapsulation and release from chitosan-alginate microspheres were contingent on the crosslinker and number of polyelectrolyte coatings, respectively. Further rheological studies are needed to determine how closely these particles simulate the behavior of erythrocytes. Also, studies on the encapsulation and release of different proteins, including hemoglobin, are needed to establish the desired controlled release of

  2. Low-energy nanoemulsification to design veterinary controlled drug delivery devices.

    PubMed

    Vandamme, Thierry F; Anton, Nicolas

    2010-10-21

    The unique properties of nanomaterials related to structural stability and quantum-scale reactive properties open up a world of possibilities that could be exploited to design and to target drug delivery or create truly microscale biological sensors for veterinary applications. We developed cost-saving and solvent-free nanoemulsions. Formulated with a low-energy method, these nanoemulsions can find application in the delivery of controlled amounts of drugs into the beverage of breeding animals (such as poultry, cattle, pigs) or be used for the controlled release of injectable poorly water-soluble drugs.

  3. Low-energy nanoemulsification to design veterinary controlled drug delivery devices

    PubMed Central

    Vandamme, Thierry F; Anton, Nicolas

    2010-01-01

    The unique properties of nanomaterials related to structural stability and quantum-scale reactive properties open up a world of possibilities that could be exploited to design and to target drug delivery or create truly microscale biological sensors for veterinary applications. We developed cost-saving and solvent-free nanoemulsions. Formulated with a low-energy method, these nanoemulsions can find application in the delivery of controlled amounts of drugs into the beverage of breeding animals (such as poultry, cattle, pigs) or be used for the controlled release of injectable poorly water-soluble drugs. PMID:21042549

  4. Effects of nasal drug delivery device and its orientation on sprayed particle deposition in a realistic human nasal cavity.

    PubMed

    Tong, Xuwen; Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Tu, Jiyuan

    2016-10-01

    In this study, the effects of nasal drug delivery device and the spray nozzle orientation on sprayed droplets deposition in a realistic human nasal cavity were numerically studied. Prior to performing the numerical investigation, an in-house designed automated actuation system representing mean adults actuation force was developed to produce realistic spray plume. Then, the spray plume development was filmed by high speed photography system, and spray characteristics such as spray cone angle, break-up length, and average droplet velocity were obtained through off-line image analysis. Continuing studies utilizing those experimental data as boundary conditions were applied in the following numerical spray simulations using a commercially available nasal spray device, which was inserted into a realistic adult nasal passage with external facial features. Through varying the particle releasing direction, the deposition fractions of selected particle sizes on the main nasal passage for targeted drug delivery were compared. The results demonstrated that the middle spray direction showed superior spray efficiency compared with upper or lower directions, and the 10µm agents were the most suitable particle size as the majority of sprayed agents can be delivered to the targeted area, the main passage. This study elaborates a comprehensive approach to better understand nasal spray mechanism and evaluate its performance for existing nasal delivery practices. Results of this study can assist the pharmaceutical industry to improve the current design of nasal drug delivery device and ultimately benefit more patients through optimized medications delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Fabrication of porous polymeric matrix drug delivery devices using the selective laser sintering technique.

    PubMed

    Leong, K F; Phua, K K; Chua, C K; Du, Z H; Teo, K O

    2001-01-01

    New techniques in solid freeform fabrication (SFF) have prompted research into methods of manufacturing and controlling porosity. The strategy of this research is to integrate computer aided design (CAD) and the SFF technique of selective laser sintering (SLS) to fabricate porous polymeric matrix drug delivery devices (DDDs). This study focuses on the control of the porosity of a matrix by manipulating the SLS process parameters of laser beam power and scan speed. Methylene blue dye is used as a drug model to infiltrate the matrices via a degassing method; visual inspection of dye penetration into the matrices is carried out. Most notably, the laser power matrices show a two-stage penetration process. The matrices are sectioned along the XZ planes and viewed under scanning electron microscope (SEM). The morphologies of the samples reveal a general increase in channel widths as laser power decreases and scan speed increases. The fractional release profiles of the matrices are determined by allowing the dye to diffuse out in vitro within a controlled environment. The results show that laser power and scan speed matrices deliver the dye for 8-9 days and have an evenly distributed profile. Mercury porosimetry is used to analyse the porosity of the matrices. Laser power matrices show a linear relationship between porosity and variation in parameter values. However, the same relationship for scan speed matrices turns out to be rather inconsistent. Relationships between the SLS parameters and the experimental results are developed using the fractional release rate equation for the infinite slab porous matrix DDD as a basis for correlation.

  6. 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

  7. Poly(amidoamine) dendronized hollow fiber membranes: synthesis, characterization, and preliminary applications as drug delivery devices.

    PubMed

    Zhang, Qian; Wang, Na; Xu, Tongwen; Cheng, Yiyun

    2012-03-01

    Poly(amidoamine) (PAMAM) dendrons were prepared from hollow fiber membranes (HFM) consisting of bromomethylated poly(2,6-dimethyl-1,4-phenylene oxide) (BPPO) in a stepwise manner. The prepared HFM were characterized by Fourier transform infrared spectroscopy, elemental analysis, and scanning electron microscopy. The drug loading efficiency and release behavior of the PAMAM dendronized HFM were evaluated using sodium salicylate, sodium methotrexate, and Congo red as model drugs. The results suggest that PAMAM dendronized HFM can be effectively loaded with a variety of drugs and prolong the release of these drugs. The drug loading and release characteristics of the HFM depend on the generation of PAMAM dendrons grafted on the membranes. The prepared PAMAM dendronized BPPO HFM are promising scaffolds in drug delivery and tissue engineering.

  8. Functionalized bridged silsesquioxane-based nanostructured microspheres: performance as novel drug-delivery devices in bone tissue-related applications.

    PubMed

    Romeo, Hernán Esteban; Fanovich, María Alejandra

    2012-05-01

    Two kinds of functionalized nanostructured hybrid microspheres, based on the bridged silsesquioxane family, were synthesized by employing the sol-gel method via self-assembly of two different organic-inorganic bridged monomers. The architecture reached at molecular level allowed the incorporation of acetylsalicylic acid (ASA) as an anti-inflammatory model drug. The ASA-functionalized microspheres were characterized as delivery devices in simulated body fluid (SBF). The release behaviors of the synthesized microspheres (Fickian or anomalous diffusion mechanisms) were shown to be dependent on the chemical nature of the bridged monomers employed to synthesize the hybrid materials. The functionalized microspheres were proposed as delivery systems into calcium phosphate cements (CPCs), in order to slow down the characteristic drug-delivery kinetics of this kind of bone tissue-related materials. The incorporation of the new functionalized microparticles into the CPCs represented a viable methodology to modify the ASA-release kinetics in comparison to a conventional CPC containing the drug dispersed into the solid phase. The ASA-delivery profiles obtained from the microsphere-loaded CPCs showed that 40-60% of drug can be released after 2 weeks of testing in SBF. The inclusion of the microspheres into the CPC matrices allowed modification of the release profiles through a mechanism that involved two stages: (1) the diffusion of the drug through the organic-inorganic matrix of the microspheres (according to a Fickian or anomalous diffusion, depending on the nanostructuring) and (2) the subsequent diffusion of the drug through the ceramic matrix of the hardened cements. The release behavior of the composite cements was shown to be dependent on the nanostructuring of the hybrid microspheres, which can be selectively tailored by choosing the desired chemical structure of the bridged precursors employed in the sol-gel synthesis. The obtained results demonstrated the ability of

  9. Comparison of drug delivery with autoinjector versus manual prefilled syringe and between three different autoinjector devices administered in pig thigh

    PubMed Central

    Hill, Robert L; Wilmot, John G; Belluscio, Beth A; Cleary, Kevin; Lindisch, David; Tucker, Robin; Wilson, Emmanuel; Shukla, Rajesh B

    2016-01-01

    Parenteral routes of drug administration are often selected to optimize actual dose of drug delivered, assure high bioavailability, bypass first-pass metabolism or harsh gastrointestinal environments, as well as maximize the speed of onset. Intramuscular (IM) delivery can be preferred to intravenous delivery when initiating intravenous access is difficult or impossible. Drugs can be injected intramuscularly using a syringe or an automated delivery device (autoinjector). Investigation into the IM delivery dynamics of these methods may guide further improvements in the performance of injection technologies. Two porcine model studies were conducted to compare differences in dispersion of injectate volume for different methods of IM drug administration. The first study compared the differences in the degree of dispersion and uptake of injectate following the use of a manual syringe and an autoinjector. The second study compared the spatial spread of the injected formulation, or dispersion volume, and uptake of injectate following the use of five different autoinjectors (EpiPen® [0.3 mL], EpiPen® Jr [0.3 mL], Twinject® [0.15 mL, 0.3 mL], and Anapen® 300 [0.3 mL]) with varying needle length, needle gauge, and force applied to the plunger. In the first study, the autoinjector provided higher peak volumes of injectate, indicating a greater degree of dispersion, compared with manual syringe delivery. In the second study, EpiPen autoinjectors resulted in larger dispersion volumes and higher initial dispersion ratios, which decreased rapidly over time, suggesting a greater rate of uptake of injectate than the other autoinjectors. The differences in dispersion and uptake of injectate are likely the result of different functional characteristics of the delivery systems. Both studies demonstrate that the functional characteristics of the method for delivering IM injections impact the dispersion and uptake of the material injected, which could significantly affect the

  10. Degradable Magnetic Composites for Minimally Invasive Interventions: Device Fabrication, Targeted Drug Delivery, and Cytotoxicity Tests.

    PubMed

    Peters, Christian; Hoop, Marcus; Pané, Salvador; Nelson, Bradley J; Hierold, Christofer

    2016-01-20

    Superparamagnetic nanoparticles and a functional, degradable polymer matrix based on poly(ethylene glycol) are combined to enable fully degradable magnetic microdevices for minimally invasive biomedical applications. A bioinspired helical microrobot platform mimicking Escherichia coli bacteria is fabricated and actuated using weak rotating magnetic fields. Locomotion based on corkscrew propulsion, targeted drug delivery, and low-degradation-product cytotoxicity are demonstrated. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Organic-inorganic hybrid anion exchange hollow fiber membranes: a novel device for drug delivery.

    PubMed

    Wang, Na; Wu, Cuiming; Cheng, Yiyun; Xu, Tongwen

    2011-04-15

    The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) (such as sodium salicylate (NaSA)) for the treatment of chronic arthritis is limited due to the adverse effects and patient non-compliance. In order to solve these problems, anion exchange hollow fiber membranes (AEHFMs) are proposed for the first time here as potential drug carriers. Brominated poly(2,6-dimethyl-1,4-phenylene oxide) (BPPO) is used as the starting membrane material. In-situ sol-gel process of γ-methacryloxypropyl trimethoxysilane (γ-MPS) in BPPO matrix is operated so as to enhance the membranes' thermal and dimensional stability. The performances of the membranes in controlled release of the drug (NaSA as the model drug) are improved accordingly. Loading and release experiments illustrate that the hybrid AEHFM can bind salicylate (SA⁻) at a high loading efficiency (28.4%), and the retention of the drug on the membrane matrix is significantly prolonged (drug released in 7 days under physiological condition: 51.9%, neglecting the drug bound by protein). Meanwhile, the membrane is biocompatible and can support the adherence, growth, and survival of human cells. Overall, the prepared AEHFM is a promising scaffolding material for drug delivery and tissue engineering.

  12. A microarray MEMS device for biolistic delivery of vaccine and drug powders

    PubMed Central

    Pirmoradi, Fatemeh Nazly; Pattekar, Ashish V; Linn, Felicia; Recht, Michael I; Volkel, Armin R; Wang, Qian; Anderson, Greg B; Veiseh, Mandana; Kjono, Sandra; Peeters, Eric; Uhland, Scott A; Chow, Eugene M

    2015-01-01

    We report a biolistic technology platform for physical delivery of particle formulations of drugs or vaccines using parallel arrays of microchannels, which generate highly collimated jets of particles with high spatial resolution. Our approach allows for effective delivery of therapeutics sequentially or concurrently (in mixture) at a specified target location or treatment area. We show this new platform enables the delivery of a broad range of particles with various densities and sizes into both in vitro and ex vivo skin models. Penetration depths of ∼1 mm have been achieved following a single ejection of 200 µg high-density gold particles, as well as 13.6 µg low-density polystyrene-based particles into gelatin-based skin simulants at 70 psi inlet gas pressure. Ejection of multiple shots at one treatment site enabled deeper penetration of ∼3 mm in vitro, and delivery of a higher dose of 1 mg gold particles at similar inlet gas pressure. We demonstrate that particle penetration depths can be optimized in vitro by adjusting the inlet pressure of the carrier gas, and dosing is controlled by drug reservoirs that hold precise quantities of the payload, which can be ejected continuously or in pulses. Future investigations include comparison between continuous versus pulsatile payload deliveries. We have successfully delivered plasmid DNA (pDNA)-coated gold particles (1.15 µm diameter) into ex vivo murine and porcine skin at low inlet pressures of ∼30 psi. Integrity analysis of these pDNA-coated gold particles confirmed the preservation of full-length pDNA after each particle preparation and jetting procedures. This technology platform provides distinct capabilities to effectively deliver a broad range of particle formulations into skin with specially designed high-speed microarray ejector nozzles. PMID:26090875

  13. A microarray MEMS device for biolistic delivery of vaccine and drug powders.

    PubMed

    Pirmoradi, Fatemeh Nazly; Pattekar, Ashish V; Linn, Felicia; Recht, Michael I; Volkel, Armin R; Wang, Qian; Anderson, Greg B; Veiseh, Mandana; Kjono, Sandra; Peeters, Eric; Uhland, Scott A; Chow, Eugene M

    2015-01-01

    We report a biolistic technology platform for physical delivery of particle formulations of drugs or vaccines using parallel arrays of microchannels, which generate highly collimated jets of particles with high spatial resolution. Our approach allows for effective delivery of therapeutics sequentially or concurrently (in mixture) at a specified target location or treatment area. We show this new platform enables the delivery of a broad range of particles with various densities and sizes into both in vitro and ex vivo skin models. Penetration depths of ∼1 mm have been achieved following a single ejection of 200 µg high-density gold particles, as well as 13.6 µg low-density polystyrene-based particles into gelatin-based skin simulants at 70 psi inlet gas pressure. Ejection of multiple shots at one treatment site enabled deeper penetration of ∼3 mm in vitro, and delivery of a higher dose of 1 mg gold particles at similar inlet gas pressure. We demonstrate that particle penetration depths can be optimized in vitro by adjusting the inlet pressure of the carrier gas, and dosing is controlled by drug reservoirs that hold precise quantities of the payload, which can be ejected continuously or in pulses. Future investigations include comparison between continuous versus pulsatile payload deliveries. We have successfully delivered plasmid DNA (pDNA)-coated gold particles (1.15 µm diameter) into ex vivo murine and porcine skin at low inlet pressures of ∼30 psi. Integrity analysis of these pDNA-coated gold particles confirmed the preservation of full-length pDNA after each particle preparation and jetting procedures. This technology platform provides distinct capabilities to effectively deliver a broad range of particle formulations into skin with specially designed high-speed microarray ejector nozzles.

  14. Radiation crosslinked polymerization of methacrylamide and psyllium to develop antibiotic drug delivery device.

    PubMed

    Singh, Baljit; Sharma, Vikrant; Kumar, Anil; Kumar, Sanjay

    2009-11-01

    Psyllium is a medicinally important polysaccharide and its modification with methacrylamide through radiation crosslinked polymerization will develop hydrogels meant for drug delivery applications. The present paper deals with the preparation of hydrogels and their characterization by SEMs, FTIR, TGA and swelling studies. The release dynamics of model antibiotic drug rifampicin from the hydrogels has been studied for the evaluation of the release mechanism. The values of the diffusion exponent 'n' have been obtained (0.64, 0.58 and 0.57), respectively, in distilled water, pH 2.2 buffer and pH 7.4 buffer. The release of the drug from the hydrogels occurred through non-Fickian diffusion mechanism.

  15. MRI in ocular drug delivery.

    PubMed

    Li, S Kevin; Lizak, Martin J; Jeong, Eun-Kee

    2008-11-01

    Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed.

  16. MRI in ocular drug delivery

    PubMed Central

    Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

    2008-01-01

    Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

  17. New screening methodology for selection of polymeric materials for transdermal drug delivery devices

    NASA Astrophysics Data System (ADS)

    Falcone, Roberto P.

    As medical advances extend the human lifespan, the level of chronic illnesses will increase and thus straining the needs of the health care system that, as a result, governments will need to balance expenses without upsetting national budgets. Therefore, the selection of a precise and affordable drug delivery technology is seen as the most practical solution for governments, health care professionals, and consumers. Transdermal drug delivery patches (TDDP) are one of the best economical technologies that are favored by pharmaceutical companies and physicians alike because it offers fewer complications when compared to other delivery technologies. TDDP provides increased efficiency, safety and convenience for the patient. The TDDP segment within the US and Global drug delivery markets were valued at 5.6 and 12.7 billion respectively in 2009. TDDP is forecasted to reach $31.5 billion in 2015. The present TDDP technology involves the fabrication of a patch that consists of a drug embedded in a polymeric matrix. The diffusion coefficient is determined from the slope of the cumulative drug release versus time. It is a trial and error method that is time and labor consuming. With all the advantages that TDDPs can offer, the methodology used to achieve the so-called optimum design has resulted in several incidents where the safety and design have been put to question in recent times (e.g. Fentanyl). A more logical screening methodology is needed. This work shows the use of a modified Duda Zielinsky equation (DZE). Experimental release curves from commercial are evaluated. The experimental and theoretical Diffusion Coefficient values are found to be within the limits specified in the patent literature. One interesting finding is that the accuracy of the DZE is closer to experimental values when the type of Molecular Shape and Radius are used. This work shows that the modified DZE could be used as an excellent screening tool to determine the optimal polymeric matrices that

  18. Condensational Growth of Combination Drug-Excipient Submicrometer Particles for Targeted High Efficiency Pulmonary Delivery: Evaluation of Formulation and Delivery Device

    PubMed Central

    Hindle, Michael; Longest, P. Worth

    2012-01-01

    Objectives The objective of this study was to investigate the in vitro particle size growth of combination drug and excipient submicrometer aerosols generated from a series of formulations and two aerosol delivery devices. Methods Submicrometer combination drug and excipient particles were generated experimentally using both the capillary aerosol generator and the Respimat inhaler. Budesonide and albuterol sulfate were used as model drugs and were formulated with sodium chloride, citric acid, and mannitol as excipients in various ratios. Aerosol growth was evaluated in vitro in a coiled tube geometry designed to provide residence times and thermodynamic conditions consistent with the airways. Key Findings Submicrometer combination drug:excipient aerosols when exposed to simulated respiratory conditions increased to micrometer size suitable for pulmonary deposition. It was possible to control the aerosol growth ratio by altering: (1) the hygroscopic excipient, (2) the drug:excipient ratio and (3) the drug. The applicability of this approach was demonstrated using the capillary aerosol generator and the Respimat inhaler. Conclusions The enhanced excipient growth (EEG) approach may enable the delivery of submicrometer aerosol particles that increase in size within the airways and result in high percentages of pulmonary deposition. PMID:22881438

  19. Active packaging for topical cosmetic/drug products: a hot-melt extruded preservative delivery device.

    PubMed

    Zema, L; Sangalli, M E; Maroni, A; Foppoli, A; Bettero, A; Gazzaniga, A

    2010-06-01

    A delivery device intended for the prolonged release of antimicrobial agents, able to enhance the stability profile of liquid/semi-solid cosmetic/pharmaceutical products for topical application, was proposed in the present study. With the aid of a simulation program based on compartment models, the relevant kinetic and formulation parameters were defined using dehydroacetic acid sodium salt (DHA.Na, Prevan) as the model preservative. Indeed, the overall DHA.Na degradation rate is increased in the presence of formaldehyde releasers that are often employed as co-preservatives. Inert matrices (3 g weight and 18 mm diameter) based on high-density polyethylene (HDPE), possibly consistent with the design of an active packaging meant for preservative delivery, were prepared by hot-melt extrusion. Units with satisfactory physical-technological properties could be obtained up to 50%w/w loads of antimicrobial agent. In an attempt to modify the relevant Fickian release profiles by varying the area exposed to the medium, matrix systems coated with an impermeable film except for one base (CMs) or for the inner surface of a central drilled hole (PCMs) were investigated. On the basis of the n exponent of power equation and the outcome of linear fitting, PCMs were proven able to yield the zero-order release behaviour needed to ensure constant DHA.Na levels over a predetermined time period, as indicated by the simulation process.

  20. Mathematical modeling of drug delivery from torus-shaped single-layer devices.

    PubMed

    Helbling, Ignacio M; Luna, Julio A; Cabrera, María I

    2011-02-10

    A mathematical modeling of controlled release of drug from torus-shaped single-layer devices is presented. Analytical solutions based on the pseudo-steady state approximation are derived. The reliability and usefulness of the model are ascertained by comparison of the simulation results with matrix-type vaginal ring experimental release data reported in the literature. A good agreement between the model prediction and the experimental data is observed. An analysis of the effect of the variation in torus design parameters on the solute release is also presented. The model is applicable only to torus-shaped single-layer systems wherein the initial load of drug is higher than its solubility in the polymer.

  1. Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices.

    PubMed

    Genina, Natalja; Holländer, Jenny; Jukarainen, Harri; Mäkilä, Ermei; Salonen, Jarno; Sandler, Niklas

    2016-07-30

    The main purpose of this work was to investigate the printability of different grades of ethylene vinyl acetate (EVA) copolymers as new feedstock material for fused-deposition modeling (FDM™)-based 3D printing technology in fabrication of custom-made T-shaped intrauterine systems (IUS) and subcutaneous rods (SR). The goal was to select an EVA grade with optimal properties, namely vinyl acetate content, melting index, flexural modulus, for 3D printing of implantable prototypes with the drug incorporated within the entire matrix of the medical devices. Indomethacin was used as a model drug in this study. Out of the twelve tested grades of the EVA five were printable. One of them showed superior print quality and was further investigated by printing drug-loaded filaments, containing 5% and 15% indomethacin. The feedstock filaments were fabricated by hot-melt extrusion (HME) below the melting point of the drug substance and the IUS and SR were successfully printed at the temperature above the melting point of the drug. As a result, the drug substance in the printed prototypes showed to be at least partly amorphous, while the drug in the corresponding HME filaments was crystalline. This difference affected the drug release profiles from the filaments and printed prototype products: faster release from the prototypes over 30days in the in vitro tests. To conclude, this study indicates that certain grades of EVA were applicable feedstock material for 3D printing to produce drug-loaded implantable prototypes. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Development of a glucose-sensitive drug delivery device: Microencapsulated liposomes and poly(2-ethylacrylic acid)

    NASA Astrophysics Data System (ADS)

    Kanokpanont, Sorada

    The current study is the development a self-regulated, glucose responsive drug delivery system, using dioleoylphosphatidylcholine (DOPC) liposomes, a pH sensitive polymer, poly (2-ethylacrylic acid)(PEAA), and the feed back reaction of glucose with glucose oxidase enzyme (GO). The thesis investigates the use of PEAR and liposomes to work inside a microcapsule in response to the glucose level of the environment, by following the release of fluorescence probes, 8-aminonapthalene-1,3,6-trisulfonic acid, disodium salt/p-xylene-bis-pyridimuim bromide (ANTS/DPX) and a model protein, myoglobin. The continuing studies of PEAR and liposome interaction indicated an evidence of the previous hypothesis of two-mode release at different pHs. Differential scanning calorimetric studies of DOPC and PEAA complexes revealed the possibility of polymer adsorption to the liposomes in the pH range 5.5--7.0 and insertion in the liposome bilayer at pH < 5.2. The rate and extent of ANTS/DPX release from un-encapsulated liposomes were found to be affected by pH, PEAR concentration, presence of cholesterol in the liposomes, Ca 2+, and the concentration of sodium alginate. We have also shown possibilities of anchoring PEAR on to liposome by covalent conjugation although this led to inactivation of the polymer. It is also possible to entrap small molecular weight PEAA in liposomes. The evidence of the pH-induced protein release by the interaction of PEAA and liposomes was first demonstrated in this thesis. Kinetic parameters of GO were estimated to use as a basis for determination optimal concentration in the capsules. The pH reduction inside the capsule due to GO reaction showed positive results for the use of GO in a non-buffered system. The procedure of liquid-core alginate capsules was modified to facilitate the pH-responsive release of ANTS/DPX and myoglobin. The capsules responded to high blood glucose concentration by releasing myoglobin within 30 minutes. Although more studies are

  3. Buccal drug delivery.

    PubMed

    Smart, John D

    2005-05-01

    Buccal formulations have been developed to allow prolonged localised therapy and enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for biopharmaceutical products (proteins and oligonucleotides) arising from the recent advances in genomics and proteomics. The buccal route is typically used for extended drug delivery, so formulations that can be attached to the buccal mucosa are favoured. The bioadhesive polymers used in buccal drug delivery to retain a formulation are typically hydrophilic macro-molecules containing numerous hydrogen bonding groups. Newer second-generation bioadhesives have been developed and these include modified or new polymers that allow enhanced adhesion and/or drug delivery, in addition to site-specific ligands such as lectins. Over the last 20 years a wide range of formulations has been developed for buccal drug delivery (tablet, patch, liquids and semisolids) but comparatively few have found their way onto the market. Currently, this route is restricted to the delivery of a limited number of small lipophilic molecules that readily cross the buccal mucosa. However, this route could become a significant means for the delivery of a range of active agents in the coming years, if the barriers to buccal drug delivery are overcome. In particular, patient acceptability and the successful systemic delivery of large molecules (proteins, oligonucleotides and polysaccharides) via this route remains both a significant opportunity and challenge, and new/improved technologies may be required to address these.

  4. Electrospun PVP-indomethacin constituents for transdermal dressings and drug delivery devices.

    PubMed

    Rasekh, Manoochehr; Karavasili, Christina; Soong, Yi Ling; Bouropoulos, Nikolaos; Morris, Mhairi; Armitage, David; Li, Xiang; Fatouros, Dimitrios G; Ahmad, Zeeshan

    2014-10-01

    A method in layering dressings with a superficial active layer of sub-micrometer scaled fibrous structures is demonstrated. For this, polyvinylpyrolidone (PVP)-indomethacin (INDO) fibres (5% w/v PVP, 5% w/w indomethacin, using a 50:50 ethanol-methanol solvent system) were produced at different flow rates (50 μL/min and 100 μL/min) via a modified electrospinning device head (applied voltage varied between 15 ± 2 kV). We further assessed these structures for their morphological, physical and chemical properties using SEM, AFM, DSC, XRD, FTIR and HPLC-UV. The average diameter of the resulting 3D (ca. 500 nm in height) PVP-INDO fibres produced at 50 μL/min flow rate was 2.58 ± 0.30 μm, while an almost two-fold increase in the diameter was observed (5.22 ± 0.83 μm) when the flow rate was doubled. However, both of these diameters were appreciably smaller than the existing dressing fibres (ca. 30 μm), which were visible even when layered with the active spun fibres. Indomethacin was incorporated in the amorphous state. The encapsulation efficiency was 75% w/w, with complete drug release in 45 min. The advantages are the ease of fabrication and deposition onto any existing normal or functionalised dressing (retaining the original fabric functionality), elimination of topical product issues (application, storage and transport), rapid release of active and controlled loading of drug content (fibre layer).

  5. Challenges to Value-Enhancing Innovation in Health Care Delivery: Commonalities and Contrasts with Innovation in Drugs and Devices.

    PubMed

    Garber, Steven; Gates, Susan M; Blume-Kohout, Margaret E; Burgdorf, James R; Wu, Helen

    2012-01-01

    Limiting the growth of health care costs while improving population health is perhaps the most important and difficult challenge facing U.S. health policymakers. The role of innovation in advancing these social goals is controversial, with many seeing innovation as a major cause of cost growth and many others viewing innovation as crucial for improving the quality of care and health outcomes. The authors argue that mitigating the tension between improving health and controlling costs requires more-nuanced perspectives on innovation. More specifically, they argue that policymakers should carefully distinguish between innovative activities that are worth their social costs and activities that are not worth their social costs and try to encourage the former and discourage the latter. The article considers innovation in drugs, devices, and methods of delivering health care, with particular attention to delivery.

  6. Structured Biodegradable Polymeric Microparticles for Drug Delivery Produced Using Flow Focusing Glass Microfluidic Devices.

    PubMed

    Ekanem, Ekanem E; Nabavi, Seyed Ali; Vladisavljević, Goran T; Gu, Sai

    2015-10-21

    Biodegradable poly(DL-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microparticles with tunable size, shape, internal structure and surface morphology were produced by counter-current flow focusing in axisymmetric (3D) glass capillary devices. The dispersed phase was composed of 0.5-2 wt % polymer solution in a volatile organic solvent (ethyl acetate or dichloromethane) and the continuous phase was 5 wt % aqueous poly(vinyl alcohol) solution. The droplets with a coefficient of variation in dripping regime below 2.5% were evaporated to form polymeric particles with uniform sizes ranging between 4 and 30 μm. The particle microstructure and surface roughness were modified by adding nanofiller (montmorillonite nanoclay) or porogen (2-methylpentane) in the dispersed phase to form less porous polymer matrix or porous particles with golf-ball-like dimpled surface, respectively. The presence of 2-4 wt % nanoclay in the host polymer significantly reduced the release rate of paracetamol and prevented the early burst release, as a result of reduced polymer porosity and tortuous path for the diffusing drug molecules. Numerical modeling results using the volume of fluid-continuum surface force model agreed well with experimental behavior and revealed trapping of nanoclay particles in the dispersed phase upstream of the orifice at low dispersed phase flow rates and for 4 wt % nanoclay content, due to vortex formation. Janus PLA/PCL (polycaprolactone) particles were produced by solvent evaporation-induced phase separation within organic phase droplets containing 3% (v/v) PLA/PCL (30/70 or 70/30) mixture in dichloromethane. A strong preferential adsorption of Rhodamine 6G dye onto PLA was utilized to identify PLA portions of the Janus particles by confocal laser scanning microscopy (CLSM). Uniform hemispherical PCL particles were produced by dissolution of PLA domes with acetone.

  7. 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

  8. Sublingual drug delivery.

    PubMed

    Goswami, Tarun; Jasti, Bhaskara; Li, Xiaoling

    2008-01-01

    The sublingual route is one of the early modes of administration for systemic drug delivery. This route avoids first-pass metabolism and affords quick drug entry into the systemic circulation. Attempts have been made to deliver various pharmacologically active agents, such as cardiovascular drugs, analgesics, and peptides, across the sublingual mucosa. In this review, the anatomical structure, blood supply, biochemical composition, transport pathways, permeation enhancement strategies, in vitro/in vivo models, and clinical investigations for the sublingual route of drug delivery is discussed.

  9. The role of community pharmacies in counseling of personal medical devices and drug-delivery products in Estonia.

    PubMed

    Volmer, Daisy; Ratassepp, Tagne; Shagandina, Alina; Turunen, Juha; Ahonen, Riitta; Heinämäki, Jyrki

    2015-07-01

    To evaluate the current situation on medical technology at community pharmacies in Estonia, looking into the availability, dispensing and counseling of personal medical devices/drug-delivery products (PMDs/DDPs) and related professional knowledge of community pharmacists. A descriptive cross-sectional questionnaire-based study using an internet-based eFormular study platform. In total, 137 community pharmacies responded to the study. Of the pharmacies, 51.8% dispensed and 32.1% counseled PMDs/DDPs several times a day. 55.4% of the respondents assessed their professional knowledge on PMDs/DDPs as good to medium and 44.6% as satisfactory to poor. Of the respondents, 79.6% reported a need for systematic education about named devices. Community pharmacies are a frequent source for the dispensing and counseling of PMDs/DDPs in Estonia. However, community pharmacists admitted a strong need for continuing education about general and practical aspects related to the use of PMDs/DDPs for the provision of more professional services in the future.

  10. Development of a Poly-ε-Lysine Contact Lens as a Drug Delivery Device for the Treatment of Fungal Keratitis.

    PubMed

    Gallagher, Andrew G; McLean, Keri; Stewart, Rosalind M K; Wellings, Don A; Allison, Heather E; Williams, Rachel L

    2017-09-01

    The purpose of this study was to develop a more efficient drug delivery device to overcome the limitations of current drop therapy for the treatment of fungal keratitis. Amphotericin B (AmpB), 0 to 30 μg/mL, was associated with a poly-ε-lysine (pεK) hydrogel. Fungicidal effect against Candida albicans was assessed at 18 and 42 hours by optical density (OD600) and growth on agar. Tear film dilution effect was mimicked by storage of AmpB pεK gels in 3.4 mL sterile PBS for 24 hours prior to fungal incubation. Drug elution over 96 hours was evaluated by HPLC, and drug stability was tested while associated with the gel by OD600 up to 48 hours. Lack of cytotoxicity toward the HCE-T corneal epithelial cell line was assessed over 7 days. AmpB pεK gels show fungicidal activity in normal conditions (0.057 OD600, SD 0.003, P < 0.005) and in the presence of horse serum (0.048 OD600, SD 0.028 P < 0.005) at 18 hours. The drug release profile was above therapeutic levels (0.188 μg/mL) for up to 72 hours. Tear dilution had no significant effect at higher concentrations of AmpB (3 to 10 μg/mL). AmpB pεK gels were not cytotoxic to the HCE-T cell line. We demonstrated that AmpB pεK gels confer sustained therapeutic antifungal activity for at least 48 hours without corneal epithelial cell line cytotoxicity, suggesting their potential for in vivo use as an antifungal bandage contact lens. This could avoid the need for intensive topical medication in the treatment of fungal keratitis.

  11. Microfabrication for Drug Delivery

    PubMed Central

    Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

    2016-01-01

    This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

  12. Integrated microsystems for controlled drug delivery.

    PubMed

    Razzacki, S Zafar; Thwar, Prasanna K; Yang, Ming; Ugaz, Victor M; Burns, Mark A

    2004-02-10

    Efficient drug delivery and administration are needed to realize the full potential of molecular therapeutics. Integrated microsystems that incorporate extremely fast sensory and actuation capabilities can fulfill this need for efficient drug delivery tools. Photolithographic technologies borrowed from the semiconductor industry enable mass production of such microsystems. Rapid prototyping allows for the quick development of customized devices that would accommodate for diverse therapeutic requirements. This paper reviews the capabilities of existing microfabrication and their applications in controlled drug delivery microsystems. The next generation of drug delivery systems--fully integrated and self-regulating--would not only improve drug administration, but also revolutionize the health-care industry.

  13. 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.

  14. Metrology for drug delivery.

    PubMed

    Lucas, Peter; Klein, Stephan

    2015-08-01

    In various recently published studies, it is argued that there are underestimated risks with infusion technology, i.e., adverse incidents believed to be caused by inadequate administration of the drugs. This is particularly the case for applications involving very low-flow rates, i.e., <1 ml/h and applications involving drug delivery by means of multiple pumps. The risks in infusing are caused by a lack of awareness, incompletely understood properties of the complete drug delivery system and a lack of a proper metrological infrastructure for low-flow rates. Technical challenges such as these were the reason a European research project "Metrology for Drug Delivery" was started in 2011. In this special issue of Biomedical Engineering, the results of that project are discussed.

  15. A novel drug delivery of 5-fluorouracil device based on TiO2/ZnS nanotubes.

    PubMed

    Faria, Henrique Antonio Mendonça; de Queiroz, Alvaro Antonio Alencar

    2015-11-01

    The structural and electronic properties of titanium oxide nanotubes (TiO2) have attracted considerable attention for the development of therapeutic devices and imaging probes for nanomedicine. However, the fluorescence response of TiO2 has typically been within ultraviolet spectrum. In this study, the surface modification of TiO2 nanotubes with ZnS quantum dots was found to produce a red shift in the ultra violet emission band. The TiO2 nanotubes used in this work were obtained by sol-gel template synthesis. The ZnS quantum dots were deposited onto TiO2 nanotube surface by a micelle-template inducing reaction. The structure and morphology of the resulting hybrid TiO2/ZnS nanotubes were investigated by scanning electron microscopy, transmission electron microscopy and X-ray diffraction techniques. According to the results of fluorescence spectroscopy, pure TiO2 nanotubes exhibited a high emission at 380nm (3.26eV), whereas TiO2/ZnS exhibited an emission at 410nm (3.02eV). The TiO2/ZnS nanotubes demonstrated good bio-imaging ability on sycamore cultured plant cells. The biocompatibility against mammalian cells (Chinese Hamster Ovarian Cells-CHO) suggesting that TiO2/ZnS may also have suitable optical properties for use as biological markers in diagnostic medicine. The drug release characteristic of TiO2/ZnS nanotubes was explored using 5-fluorouracil (5-FU), an anticancer drug used in photodynamic therapy. The results show that the TiO2/ZnS nanotubes are a promising candidate for anticancer drug delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Drug delivery systems from nose to brain.

    PubMed

    Misra, Ambikanandan; Kher, Gitanjali

    2012-09-01

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

  17. Polymer-based Drug Delivery Systems Applied to Insects Repellents Devices: A Review.

    PubMed

    Barradas, Thaís Nogueira; Senna, Juliana Perdiz; Ricci, Eduardo; Mansur, Claudia Regina Elias

    2016-01-01

    Insects-borne diseases constitute a public health concern. Since there is no vaccine or curative treatment for many of these diseases, individual protection is the main approach to prevent them. Nowadays, the search for replacing synthetic molecules for insect repellents from natural sources, such as essential oils, is increasing. However, most of them present low efficiency compared to synthetic repellents. Therefore, decreasing skin permeation of synthetic repellents or yet, increasing effectiveness of natural repellents are challenges that must be overcome during the development of novel insect repellent formulations. In this context, polymer-based formulations allow entrapping active ingredients and provide release control. Encapsulation into polymeric micro/nanocapsules, cyclodextrins, polymeric micelles or hydrogels constitutes an approach to modify physicochemical properties of encapsulated molecules. Such techniques, applied in topical formulations, fabrics modification for personal protection, or food packaging have proved to be more effective in increasing repellency time and also in reducing drug dermal absorption, improving safety profiles of these products. In this work, the main synthetic and natural insect repellents are described as well as their polymeric carrier systems and their potential applications.

  18. 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

  19. Acceptability of a non-woven device for vaginal drug delivery of microbicides or other active agents.

    PubMed

    Joanis, Carol L; Hart, Catherine W

    2010-06-01

    Vaginal microbicides could reduce incidence of HIV. However, the current method of delivering gel formulations (standard applicator) can result in acceptability concerns/issues. This study evaluated the concept of using a non-woven textile material (modified tampon) for vaginal drug delivery. The study was nested within a Phase I randomized safety trial of lime juice concentrations used intra-vaginally. Of 47 women completing the safety trial, 16 were interviewed about their experiences. Overall, women found the concept of non-woven materials for vaginal drug delivery acceptable for use in delivering yeast medications (13 of 16) and STI/HIV preventives (10 of 16).

  20. Breathable Medicine: Pulmonary Mode of Drug Delivery.

    PubMed

    Gandhimathi, Chinnasamy; Venugopal, Jayarama Reddy; Sundarrajan, Subramanian; Sridhar, Radhakrishnan; Tay, Samuel Sam Wah; Ramakrishna, Seeram; Kumar, Srinivasan Dinesh

    2015-04-01

    Pharmaceutically active compounds require different modes of drug delivery systems to accomplish therapeutic activity without loss of its activity and lead to exhibit no adverse effects. Originating from ancient days, pulmonary mode of drug delivery is gaining much importance compared to other modes of drug delivery systems with respect to specific diseases. Pulmonary drug delivery is a non-invasive route for local and systemic therapies together with more patient convenience, compliance and is a needleless system. In this review, we addressed the vaccine delivery via non- or minimally invasive routes. Polymeric nanoparticles are preferred for use in the pulmonary delivery devices owing to a prolonged retention in lungs. Small site for absorption, mucociliary clearance, short residence time and low bioavailability are some of the limitations in pulmonary drug delivery have been resolved by generating micro- and nano-sized aerosol particles. We have classified the breathable medicine on the basis of available devices for inhalation and also prominent diseases treated through pulmonary mode of drug delivery. Owing to increasing toxicity of pharmacological drugs, the use of natural medicines has been rapidly gaining importance recently. The review article describes breathability of medicines or the pulmonary mode of drug delivery system and their drug release profile, absorption, distribution and efficacy to cure asthma and diabetes.

  1. 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.

  2. Mechanisms Underlying Drug Delivery to Peripheral Arteries.

    PubMed

    Li, Jun; Tzafriri, Rami; Patel, Sandeep M; Parikh, Sahil A

    2017-04-01

    Delivery of drugs onto arterial targets via endovascular devices commands several principles: dissolution, diffusion, convection, drug binding, barriers to absorption, and interaction between the drug, delivery vehicle, and accepting arterial wall. The understanding of drug delivery in the coronary vasculature is vast; there is ongoing work needed in the peripheral arteries. There are differences that account for some failures of application of coronary technology into the peripheral vascular space. Breakthroughs in peripheral vascular interventional techniques building on current technologies require investigators willing to acknowledge the similarities and differences between these different vascular territories, while developing technologies adapted for peripheral arteries.

  3. Thermosensitive polymers for drug delivery

    SciTech Connect

    Gutowska, A.; Kim, Sung Wan

    1996-12-31

    Thermosensitive polymers (TSP) demonstrating temperature-dependent temperature-dependent swelling in water have been extensively studied in recent years. Their molecular and physical properties have been tailored for a variety of biomedical and engineering uses. This presentation will discuss TSP based on poly(N-isopropylacrylamide) and its crosslinked networks modified with hydrophobic or hydrophilic components by copolymerization blending and formation of interpenetrating polymer networks (IPNs). TSP designed for three different areas of drug delivery will be presented. First, heparin releasing temperature-sensitive polymers for the prevention of surface induced thrombosis will be presented as an example of a local macromolecular delivery from a surface of a medical device. Second, a new oral delivery device based on a novel mechanical squeezing concept, utilizing specific swelling-deswelling characteristics of temperature- and temperature/pH-sensitive hydrogels will be described. These hydrogels were synthesized to exhibit a controlled swelling-deswelling kinetics, hence a variety of release profiles may be generated: a delayed, a zero-order or an {open_quotes}on-off{close_quotes} release profile. Finally, thermally reversible polymeric gels as an extracellular matrix for the entrapment of pancreatic islet cells in biohybrid artificial pancreas for insulin delivery will be discussed.

  4. Providers' payment and delivery system reforms hold both threats and opportunities for the drug and device industries.

    PubMed

    Robinson, James C

    2012-09-01

    For decades, medical device and specialty drug makers have produced a steady stream of breakthroughs and incremental improvements, from cancer therapies to orthopedic joint replacements, drug-eluting stents, and cardiac pacemakers. The advances were financed by a fragmented health care system that paid for whichever clinical technologies were favored by physicians without strong concern for cost. But now hospitals, health systems, insurers, and policy makers are embracing payment reforms that seek to control costs and foster uniformity in the adoption of new drugs and devices. This article explores payment reforms that will have an impact on the medical technology industry and describes opportunities for the industry to flourish in this new, more financially constrained landscape.

  5. Nanomaterials for Drugs Delivery

    SciTech Connect

    Márquez, Francisco; Morant, Carmen

    2014-07-01

    Nanotechnology has revolutionized engineering, biology, chemistry, physics and medicine of today. These disciplines are evolving thanks to the ongoing development of new materials and applications. Nanomedicine, as application of nanotechnology in the field of health care, has undergone unprecedented development. Some of these changes have real applications as, for example, the use of nanoparticles in MRI imaging, in hyperthermia, in immunotherapy, or to improve the bioavailability of drugs, among others. Furthermore, when a drug is administered to a patient, the blood distributes it throughout the body. In the case of very localized diseases (i.e. tumors), only a small fraction of the drug reaches the target. Chemotherapy is one of the most aggressive treatment options used in some types of cancer, and is usually administered intravenously. The drug circulates throughout the body, reaching and destroying healthy and cancerous tissues, producing side effects throughout the body, sometimes with serious consequences for the health of the patient (nephrotoxicity, cardiotoxicity, peripheral neuropathy, anemia, etc.) in this type of therapy. Among the many applications of nanotechnology, the fabrication of nanostructures capable of safely transporting these drugs is seen as a strategy for reducing these side effects. Nanoparticles are able to carry and release the drug in the right place and with the required dose, greatly reducing the problems associated with direct treatment with these drugs. In recent years, there have been continuous improvements in the design and development of new tailor-made drug delivery systems, including hollow magnetic nanoparticles, liposomal structures, dendrimers, nanoporous silicon, etc. These structures can be obtained with different molecular weights (in the case of polymers), structures, shapes, and even with the appropriate functional groups for interaction at the desired positions. But, a great effort is still required to solve many

  6. Nanomaterials for Drugs Delivery

    DOE PAGES

    Márquez, Francisco; Morant, Carmen

    2014-07-01

    Nanotechnology has revolutionized engineering, biology, chemistry, physics and medicine of today. These disciplines are evolving thanks to the ongoing development of new materials and applications. Nanomedicine, as application of nanotechnology in the field of health care, has undergone unprecedented development. Some of these changes have real applications as, for example, the use of nanoparticles in MRI imaging, in hyperthermia, in immunotherapy, or to improve the bioavailability of drugs, among others. Furthermore, when a drug is administered to a patient, the blood distributes it throughout the body. In the case of very localized diseases (i.e. tumors), only a small fraction ofmore » the drug reaches the target. Chemotherapy is one of the most aggressive treatment options used in some types of cancer, and is usually administered intravenously. The drug circulates throughout the body, reaching and destroying healthy and cancerous tissues, producing side effects throughout the body, sometimes with serious consequences for the health of the patient (nephrotoxicity, cardiotoxicity, peripheral neuropathy, anemia, etc.) in this type of therapy. Among the many applications of nanotechnology, the fabrication of nanostructures capable of safely transporting these drugs is seen as a strategy for reducing these side effects. Nanoparticles are able to carry and release the drug in the right place and with the required dose, greatly reducing the problems associated with direct treatment with these drugs. In recent years, there have been continuous improvements in the design and development of new tailor-made drug delivery systems, including hollow magnetic nanoparticles, liposomal structures, dendrimers, nanoporous silicon, etc. These structures can be obtained with different molecular weights (in the case of polymers), structures, shapes, and even with the appropriate functional groups for interaction at the desired positions. But, a great effort is still required to

  7. Assessment of surface concentrations in resorbable ocular implants: controlled drug delivery devices for 5-fluorouracil (5-FU)

    NASA Astrophysics Data System (ADS)

    Milne, Peter J.; Gautier, Sandrine; Parel, Jean-Marie A.; Jallet, Valerie

    1997-05-01

    The antineoplastic drug 5-fluorouracil (5-fluoro- 2,4,(1H,3H)-pyrimidinedione; 5-FU) has been used to control proliferation of penetrating fibroblasts and to prevent channel closure following glaucoma filtration surgery (trabeculectomy) or laser sclerectomy. Because of the toxicity of the drug, administration of low dosages slowly over time, at the site of the desired treatment, is indicated for optimum efficacy. Repeated injections of low dosages of the drug represent an undesirable intervention and may also result in unwanted toxicity to the corneal epithelium. A suitable biocompatible and resorbable polymer matrix composed of a poly (D,L-lactic-co-glycolic acid: PLGA) has been admixed with varying amounts of 5-FU and cast as shapes suitable for intracorneal implantation. Slow biodegradation of this polymer over a one to two week period has been shown to result in an acceptably slow drug release mechanism. An issue arising during the clinical evaluation of the efficacy of this drug delivery system was how best to quantify the concentration of 5-FU and its distribution spatially in the solid implant. FT-IR and FT-Raman spectroscopies distinguishes between the drug and the polymer matrix and were used to differentiate and quantitate the 5-FU concentration of the implants.

  8. Superhydrophobic materials for drug delivery

    NASA Astrophysics Data System (ADS)

    Yohe, Stefan Thomas

    Superhydrophobicity is a property of material surfaces reflecting the ability to maintain air at the solid-liquid interface when in contact with water. These surfaces have characteristically high apparent contact angles, by definition exceeding 150°, as a result of the composite material-air surface formed under an applied water droplet. Superhydrophobic surfaces were first discovered on naturally occurring substrates, and have subsequently been fabricated in the last several decades to harness these favorable surface properties for a number of emerging applications, including their use in biomedical settings. This work describes fabrication and characterization of superhydrophobic 3D materials, as well as their use as drug delivery devices. Superhydrophobic 3D materials are distinct from 2D superhydrophobic surfaces in that air is maintained not just at the surface of the material, but also within the bulk. When the superhydrophobic 3D materials are submerged in water, water infiltrates slowly and continuously as a new water-air-material interface is formed with controlled displacement of air. Electrospinning and electrospraying are used to fabricate superhydrophobic 3D materials utilizing blends of the biocompatible polymers poly(epsilon-caprolactone) and poly(caprolactone-co-glycerol monostearate) (PGC-C18). PGC-C18 is significantly more hydrophobic than PCL (contact angle of 116° versus 83° for flat materials), and further additions of PGC-C18 into electrospun meshes and electrosprayed coatings affords increased stability of the entrapped air layer. For example, PCL meshes alone (500 mum thick) take 10 days to fully wet, and with 10% or 30% PGC-C18 addition wetting rates are dramatically slowed to 60% wetted by 77 days and 4% by 75 days, respectively. Stability of the superhydrophobic materials can be further probed with a variety of physio-chemical techniques, including pressure, surfactant containing solutions, and solvents of varying surface tension

  9. 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

  10. Improvement in sodium cromoglycate delivery from a spacer device by use of an antistatic lining, immediate inhalation, and avoiding multiple actuations of drug.

    PubMed Central

    O'Callaghan, C; Lynch, J; Cant, M; Robertson, C

    1993-01-01

    BACKGROUND--Aerosols generated from metered dose inhalers may be highly charged. The aim of this study was to determine whether lining the walls of a polycarbonate spacer device with an antistatic agent would result in an increase in drug output. The effects of multiple actuations of drug into the spacer device and increasing residence time of drug within the spacer were also determined. METHODS--The amount of sodium cromoglycate contained in particles of various size available for inhalation (per 5 mg actuation) from a 750 ml polycarbonate spacer was determined by impinger measurement and spectrophotometric assay. RESULTS--Lining the spacer with an antistatic agent increased the mean (SD) amount of sodium cromoglycate in particles < 5 microns available for inhalation (per 5 mg actuation) by 244% from (0.59 (0.03) to 1.44 (0.2) mg). When there was a 20 second interval between actuation into the spacer device and inhalation, sodium cromoglycate available for inhalation in particles < 5 micrograms decreased by 67% (from 0.59 (0.03) mg to 0.2 (0.01) mg). Use of the spacer device increased sodium cromoglycate available for inhalation in respirable particles (< 5 microns) by 18% compared with direct delivery by metered dose inhaler. Multiple actuations into the spacer decreased the amount of sodium cromoglycate available for inhalation in particles < 5 microns by 31% after two actuations and 56% after three acutations. CONCLUSIONS--Multiple actuations of sodium cromoglycate into a spacer device before inhalation should be avoided, and inhalation from spacer devices should take place immediately after actuation to ensure maximum dose. Lining of a standard spacer device with an antistatic agent significantly increased output of sodium cromoglycate. This may have implications for improved therapeutic response and drug cost. Images PMID:8346488

  11. Optimizing drugs for local delivery.

    PubMed

    Collingwood, S; Lock, R; Searcey, M

    2009-12-01

    An international panel of speakers together with approximately 70 delegates were brought together by The Society for Medicines Research's symposium on Optimising Drugs for Local Delivery, held on June 11, 2009 at the Novartis Institutes for Biomedical Research, Horsham, UK. The focus of the conference was on the delivery of drugs direct to the site of action and the consequences of this delivery route on delivery technologies, formulation science and molecular design.

  12. Microprocessor controlled transdermal drug delivery.

    PubMed

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

    2006-07-06

    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.

  13. Controlled Drug Delivery Using Microdevices

    PubMed Central

    Sanjay, Sharma T.; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

    2016-01-01

    Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems. PMID:26813304

  14. Thiolated polymers as mucoadhesive drug delivery systems.

    PubMed

    Duggan, Sarah; Cummins, Wayne; O' Donovan, Orla; Hughes, Helen; Owens, Eleanor

    2017-03-30

    Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug. This review explores the concept of mucoadhesion and the recent advances in both the polymers and the methods of thiolation used in the synthesis of mucoadhesive drug delivery devices.

  15. Sonophoresis in transdermal drug deliverys.

    PubMed

    Park, Donghee; Park, Hyunjin; Seo, Jongbum; Lee, Seunghun

    2014-01-01

    Transdermal drug delivery (TDD) has several significant advantages compared to oral drug delivery, including elimination of pain and sustained drug release. However, the use of TDD is limited by low skin permeability due to the stratum corneum (SC), the outermost layer of the skin. Sonophoresis is a technique that temporarily increases skin permeability such that various medications can be delivered noninvasively. For the past several decades, various studies of sonophoresis in TDD have been performed focusing on parameter optimization, delivery mechanism, transport pathway, or delivery of several drug categories including hydrophilic and high molecular weight compounds. Based on these various studies, several possible mechanisms of sonophoresis have been suggested. For example, cavitation is believed to be the predominant mechanism responsible for drug delivery in sonophoresis. This review presents details of various studies on sonophoresis including the latest trends, delivery of various therapeutic drugs, sonophoresis pathways and mechanisms, and outlook of future studies.

  16. Intraocular tissue distribution of betamethasone after intrascleral administration using a non-biodegradable sustained drug delivery device.

    PubMed

    Okabe, Komei; Kimura, Hideya; Okabe, Junko; Kato, Aki; Kunou, Noriyuki; Ogura, Yuichiro

    2003-06-01

    To evaluate the tissue distribution of betamethasone (BM) after implantation of a nonbiodegradable intrascleral implant as a new, controlled intraocular delivery system. Nonbiodegradable intrascleral implants designed to release BM for at least 1 month were placed in the sclera of pigmented rabbits. The BM concentrations in the aqueous humor, vitreous, and retina-choroid were determined by high-performance liquid chromatography (HPLC) at 3, 7, 14, and 28 days after implantation. The BM concentrations in three sections of retina-choroid were also investigated. Retinal toxicity was evaluated by electroretinography and histology. The BM released from the intrascleral implant in vitro and in vivo showed zero-ordered release profiles for 4 weeks. The BM concentrations in the retina-choroid after placement of the intrascleral implants remained higher than effective concentrations for suppressing various inflammatory processes for at least 28 days. The BM concentrations in the retina-choroid around the implantation site were more than 10 times higher than in the opposite side throughout the study. No substantial toxic reactions were observed by electroretinography or histology. These findings suggested that the nonbiodegradable intrascleral implant could be a useful drug carrier for intraocular delivery of BM without producing severe retinal toxicity. The intrascleral site may be considered for effective intraocular drug distribution after implantation.

  17. 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

  18. Ultrasound mediated transdermal drug delivery.

    PubMed

    Azagury, Aharon; Khoury, Luai; Enden, Giora; Kost, Joseph

    2014-06-01

    Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injections. However, the stratum corneum serves as a barrier that limits the penetration of substances to the skin. Application of ultrasound (US) irradiation to the skin increases its permeability (sonophoresis) and enables the delivery of various substances into and through the skin. This review presents the main findings in the field of sonophoresis in transdermal drug delivery as well as transdermal monitoring and the mathematical models associated with this field. Particular attention is paid to the proposed enhancement mechanisms and future trends in the fields of cutaneous vaccination and gene therapy.

  19. Nanotech approaches to drug delivery and imaging.

    PubMed

    Sahoo, Sanjeeb K; Labhasetwar, Vinod

    2003-12-15

    Nanotechnology, a multidisciplinary scientific undertaking, involves creation and utilization of materials, devices or systems on the nanometer scale. The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to create innovations and play a critical role in various biomedical applications, not only in drug delivery, but also in molecular imaging, biomarkers and biosensors. Target-specific drug therapy and methods for early diagnosis of pathologies are the priority research areas where nanotechnology would play a vital role. This review considers different nanotechnology-based drug delivery and imaging approaches, and their economic impact on pharmaceutical and biomedical industries.

  20. Microfabrication Technologies for Oral Drug Delivery

    PubMed Central

    Sant, Shilpa; Tao, Sarah L.; Fisher, Omar; Xu, Qiaobing; Peppas, Nicholas A.; Khademhosseini, Ali

    2012-01-01

    Micro-/nanoscale technologies such as lithographic techniques and microfluidics offer promising avenues to revolutionalize the fields of tissue engineering, drug discovery, diagnostics and personalized medicine. Microfabrication techniques are being explored for drug delivery applications due to their ability to combine several features such as precise shape and size into a single drug delivery vehicle. They also offer to create unique asymmetrical features incorporated into single or multiple reservoir systems maximizing contact area with the intestinal lining. Combined with intelligent materials, such microfabricated platforms can be designed to be bioadhesive and stimuli-responsive. Apart from drug delivery devices, microfabrication technologies offer exciting opportunities to create biomimetic gastrointestinal tract models incorporating physiological cell types, flow patterns and brush-border like structures. Here we review the recent developments in this field with a focus on the applications of microfabrication in the development of oral drug delivery devices and biomimetic gastrointestinal tract models that can be used to evaluate the drug delivery efficacy. PMID:22166590

  1. 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.

  2. 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.

  3. Transmucosal macromolecular drug delivery.

    PubMed

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

    2005-01-03

    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

  4. Drug Delivery for Peripheral Nerve Regeneration

    DTIC Science & Technology

    2015-11-01

    Gale)(months 0-1) b. Optimize nanoporous membrane dimensions ......................(Gale...kinetics of NGF in vitro using our novel drug delivery conduit Material Fabrication The proposed device consists of two concentric tubes, a reservoir...suctioning of material into the conduits, any excess PLGA was allowed to drip out of the molds. The conduits were then placed vertically into a water

  5. A Mobile Device App to Reduce Medication Errors and Time to Drug Delivery During Pediatric Cardiopulmonary Resuscitation: Study Protocol of a Multicenter Randomized Controlled Crossover Trial.

    PubMed

    Siebert, Johan N; Ehrler, Frederic; Lovis, Christian; Combescure, Christophe; Haddad, Kevin; Gervaix, Alain; Manzano, Sergio

    2017-08-22

    During pediatric cardiopulmonary resuscitation (CPR), vasoactive drug preparation for continuous infusions is complex and time-consuming. The need for individual specific weight-based drug dose calculation and preparation places children at higher risk than adults for medication errors. Following an evidence-based and ergonomic driven approach, we developed a mobile device app called Pediatric Accurate Medication in Emergency Situations (PedAMINES), intended to guide caregivers step-by-step from preparation to delivery of drugs requiring continuous infusion. In a prior single center randomized controlled trial, medication errors were reduced from 70% to 0% by using PedAMINES when compared with conventional preparation methods. The purpose of this study is to determine whether the use of PedAMINES in both university and smaller hospitals reduces medication dosage errors (primary outcome), time to drug preparation (TDP), and time to drug delivery (TDD) (secondary outcomes) during pediatric CPR when compared with conventional preparation methods. This is a multicenter, prospective, randomized controlled crossover trial with 2 parallel groups comparing PedAMINES with a conventional and internationally used drug infusion rate table in the preparation of continuous drug infusion. The evaluation setting uses a simulation-based pediatric CPR cardiac arrest scenario with a high-fidelity manikin. The study involving 120 certified nurses (sample size) will take place in the resuscitation rooms of 3 tertiary pediatric emergency departments and 3 smaller hospitals. After epinephrine-induced return of spontaneous circulation, nurses will be asked to prepare a continuous infusion of dopamine using either PedAMINES (intervention group) or the infusion table (control group) and then prepare a continuous infusion of norepinephrine by crossing the procedure. The primary outcome is the medication dosage error rate. The secondary outcome is the time in seconds elapsed since the oral

  6. Intranasal delivery of antipsychotic drugs.

    PubMed

    Katare, Yogesh K; Piazza, Justin E; Bhandari, Jayant; Daya, Ritesh P; Akilan, Kosalan; Simpson, Madeline J; Hoare, Todd; Mishra, Ram K

    2016-11-29

    Antipsychotic drugs are used to treat psychotic disorders that afflict millions globally and cause tremendous emotional, economic and healthcare burdens. However, the potential of intranasal delivery to improve brain-specific targeting remains unrealized. In this article, we review the mechanisms and methods used for brain targeting via the intranasal (IN) route as well as the potential advantages of improving this type of delivery. We extensively review experimental studies relevant to intranasal delivery of therapeutic agents for the treatment of psychosis and mental illnesses. We also review clinical studies in which intranasal delivery of peptides, like oxytocin (7 studies) and desmopressin (1), were used as an adjuvant to antipsychotic treatment with promising results. Experimental animal studies (17) investigating intranasal delivery of mainstream antipsychotic drugs have revealed successful targeting to the brain as suggested by pharmacokinetic parameters and behavioral effects. To improve delivery to the brain, nanotechnology-based carriers like nanoparticles and nanoemulsions have been used in several studies. However, human studies assessing intranasal delivery of mainstream antipsychotic drugs are lacking, and the potential toxicity of nanoformulations used in animal studies has not been explored. A brief discussion of future directions anticipates that if limitations of low aqueous solubility of antipsychotic drugs can be overcome and non-toxic formulations used, IN delivery (particularly targeting specific tissues within the brain) will gain more importance moving forward given the inherent benefits of IN delivery in comparison to other methods.

  7. Microneedles for drug and vaccine delivery

    PubMed Central

    Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R.

    2012-01-01

    Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990’s when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. PMID:22575858

  8. 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

  9. A Mobile Device App to Reduce Time to Drug Delivery and Medication Errors During Simulated Pediatric Cardiopulmonary Resuscitation: A Randomized Controlled Trial

    PubMed Central

    Combescure, Christophe; Lacroix, Laurence; Haddad, Kevin; Sanchez, Oliver; Gervaix, Alain; Lovis, Christian; Manzano, Sergio

    2017-01-01

    Background During pediatric cardiopulmonary resuscitation (CPR), vasoactive drug preparation for continuous infusion is both complex and time-consuming, placing children at higher risk than adults for medication errors. Following an evidence-based ergonomic-driven approach, we developed a mobile device app called Pediatric Accurate Medication in Emergency Situations (PedAMINES), intended to guide caregivers step-by-step from preparation to delivery of drugs requiring continuous infusion. Objective The aim of our study was to determine whether the use of PedAMINES reduces drug preparation time (TDP) and time to delivery (TDD; primary outcome), as well as medication errors (secondary outcomes) when compared with conventional preparation methods. Methods The study was a randomized controlled crossover trial with 2 parallel groups comparing PedAMINES with a conventional and internationally used drugs infusion rate table in the preparation of continuous drug infusion. We used a simulation-based pediatric CPR cardiac arrest scenario with a high-fidelity manikin in the shock room of a tertiary care pediatric emergency department. After epinephrine-induced return of spontaneous circulation, pediatric emergency nurses were first asked to prepare a continuous infusion of dopamine, using either PedAMINES (intervention group) or the infusion table (control group), and second, a continuous infusion of norepinephrine by crossing the procedure. The primary outcome was the elapsed time in seconds, in each allocation group, from the oral prescription by the physician to TDD by the nurse. TDD included TDP. The secondary outcome was the medication dosage error rate during the sequence from drug preparation to drug injection. Results A total of 20 nurses were randomized into 2 groups. During the first study period, mean TDP while using PedAMINES and conventional preparation methods was 128.1 s (95% CI 102-154) and 308.1 s (95% CI 216-400), respectively (180 s reduction, P=.002). Mean

  10. A Mobile Device App to Reduce Time to Drug Delivery and Medication Errors During Simulated Pediatric Cardiopulmonary Resuscitation: A Randomized Controlled Trial.

    PubMed

    Siebert, Johan N; Ehrler, Frederic; Combescure, Christophe; Lacroix, Laurence; Haddad, Kevin; Sanchez, Oliver; Gervaix, Alain; Lovis, Christian; Manzano, Sergio

    2017-02-01

    During pediatric cardiopulmonary resuscitation (CPR), vasoactive drug preparation for continuous infusion is both complex and time-consuming, placing children at higher risk than adults for medication errors. Following an evidence-based ergonomic-driven approach, we developed a mobile device app called Pediatric Accurate Medication in Emergency Situations (PedAMINES), intended to guide caregivers step-by-step from preparation to delivery of drugs requiring continuous infusion. The aim of our study was to determine whether the use of PedAMINES reduces drug preparation time (TDP) and time to delivery (TDD; primary outcome), as well as medication errors (secondary outcomes) when compared with conventional preparation methods. The study was a randomized controlled crossover trial with 2 parallel groups comparing PedAMINES with a conventional and internationally used drugs infusion rate table in the preparation of continuous drug infusion. We used a simulation-based pediatric CPR cardiac arrest scenario with a high-fidelity manikin in the shock room of a tertiary care pediatric emergency department. After epinephrine-induced return of spontaneous circulation, pediatric emergency nurses were first asked to prepare a continuous infusion of dopamine, using either PedAMINES (intervention group) or the infusion table (control group), and second, a continuous infusion of norepinephrine by crossing the procedure. The primary outcome was the elapsed time in seconds, in each allocation group, from the oral prescription by the physician to TDD by the nurse. TDD included TDP. The secondary outcome was the medication dosage error rate during the sequence from drug preparation to drug injection. A total of 20 nurses were randomized into 2 groups. During the first study period, mean TDP while using PedAMINES and conventional preparation methods was 128.1 s (95% CI 102-154) and 308.1 s (95% CI 216-400), respectively (180 s reduction, P=.002). Mean TDD was 214 s (95% CI 171-256) and

  11. Drug Delivery Systems for Platinum Drugs

    NASA Astrophysics Data System (ADS)

    Huynh, Vien T.; Scarano, Wei; Stenzel, Martina H.

    2013-09-01

    Since the discovery of cisplatin, drugs based on platinum, have made a significant impact on the treatment of various cancers. The administration of platinum drugs is however accompanied by significant side effects. This chapter discusses the types of drug delivery systems that have been developed in order to enable the targeted delivery while maintaining controlled temporal supply of the drug. The sizes of carriers range from nanometer to micrometer sized particles. The most common types of drug carriers are micelles, liposomes, nanoparticles, and dendrimers, but also a few microspheres have been developed. Most striking aspect of the delivery of platinum drugs is the possibility of physical encapsulation but also the binding of the drug to the polymer carrier coordinate covalent bond. Since platinum drugs have typically two permanent and two leaving ligands, the polymer can be part of either ligand. As the leaving ligand, the platinum drug is released often as cisplatin. If the polymer provides the functionality for the permanent ligand, a new macromolecular drug has been formed. In addition to the attachment of pt(II) drugs, recent offorts are devoted to the conjugation via the Pt((IV) prodrug.

  12. 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

  13. Electroresponsive nanoparticles for drug delivery on demand

    NASA Astrophysics Data System (ADS)

    Samanta, Devleena; Hosseini-Nassab, Niloufar; Zare, Richard N.

    2016-04-01

    The potential of electroresponsive conducting polymer nanoparticles to be used as general drug delivery systems that allow electrically pulsed, linearly scalable, and on demand release of incorporated drugs is demonstrated. As examples, facile release from polypyrrole nanoparticles is shown for fluorescein, a highly water-soluble model compound, piroxicam, a lipophilic small molecule drug, and insulin, a large hydrophilic peptide hormone. The drug loading is about 13 wt% and release is accomplished in a few seconds by applying a weak constant current or voltage. To identify the parameters that should be finely tuned to tailor the carrier system for the release of the therapeutic molecule of interest, a systematic study of the factors that affect drug delivery is performed, using fluorescein as a model compound. The parameters studied include current, time, voltage, pH, temperature, particle concentration, and ionic strength. Results indicate that there are several degrees of freedom that can be optimized for efficient drug delivery. The ability to modulate linearly drug release from conducting polymers with the applied stimulus can be utilized to design programmable and minimally invasive drug delivery devices.

  14. Particle fuel delivery control device

    SciTech Connect

    Eshleman, R. D.

    1985-04-30

    A particle fuel burning furnace has an upper combustion chamber for holding a pile of particle fuel and burning the same from the bottom thereof. The furnace also includes a lower combustion chamber for afterburning combustible gases given off by the burning of solid fuel in the upper chamber and a series of spaced apart verrtically-extending passageways arranged in a row and interconnecting the upper and lower chambers for communicating the combustible gases from the upper to the lower chamber. A first improved feature relates to a particle fuel delivery control device which operates an auger for filling the upper chamber with particle fuel to a particle fuel to a desired level. A beam of light is transmitted and reflected between a photoelectric cell and reflector respectively of the device. When the particle fuel pile has grown in height during filling to the desired level the light beam is interrupted and filling is terminated. A second improved feature relates to a particle fuel diversion structure positioned in space relationship above and overlying the row of passageways. The structure forms a horizontal slot which extends laterally from the passageways which prevents particles of fuel from falling rhoguh the passageways and particles of fuel from falling through the passageways and relocates the flame which burns the particle fuel pile from the bottom to a region away from the passageways.

  15. Local Drug Delivery to Prevent Restenosis

    PubMed Central

    Seedial, Stephen M.; Ghosh, Soumojit; Saunders, R. Scott; Suwanabol, Pasithorn A.; Shi, Xudong; Liu, Bo; Kent, K. Craig

    2013-01-01

    Introduction Despite significant advances in vascular biology, bioengineering and pharmacology, restenosis remains a limitation to the overall efficacy of vascular reconstructions, both percutaneous and open. Although the pathophysiology of intimal hyperplasia is complex, a number of drugs and/or molecular tools have been identified that can prevent restenosis. Moreover, the focal nature of this process lends itself to treatment with local drug administration. In this article we provide a broad overview of current and future techniques for local drug delivery that have been developed to prevent restenosis following vascular intervention. Methods A systematic electronic literature search using PubMed was performed for all accessible published articles through September 2012. In an effort to remain current, additional searches were performed for abstracts presented at relevant societal meetings, filed patents, clinical trials and funded NIH awards. Results The efficacy of local drug delivery has been demonstrated in the coronary circulation with the current clinical use of drug-eluting stents (DES). Until recently, however, DES were not found to be efficacious in the peripheral circulation. Further pursuit of intraluminal devices has led to the development of balloon-based technologies with a recent surge in trials involving drug-eluting balloons. Early data appears encouraging, particularly for treatment of lesions in the superficial femoral artery, with several devices having recently received the CE mark in Europe. Investigators have also explored periadventitial application of biomaterials containing anti-restenotic drugs, an approach that could be particularly useful for surgical bypass or endarterectomy. In the past systemic drug delivery has been unsuccessful, however, there has been recent exploration of intravenous delivery of drugs designed specifically to target injured or reconstructed arteries. Our review revealed a multitude of additional interesting

  16. Mathematical modeling of drug delivery.

    PubMed

    Siepmann, J; Siepmann, F

    2008-12-08

    Due to the significant advances in information technology mathematical modeling of drug delivery is a field of steadily increasing academic and industrial importance with an enormous future potential. The in silico optimization of novel drug delivery systems can be expected to significantly increase in accuracy and easiness of application. Analogous to other scientific disciplines, computer simulations are likely to become an integral part of future research and development in pharmaceutical technology. Mathematical programs can be expected to be routinely used to help optimizing the design of novel dosage forms. Good estimates for the required composition, geometry, dimensions and preparation procedure of various types of delivery systems will be available, taking into account the desired administration route, drug dose and release profile. Thus, the number of required experimental studies during product development can be significantly reduced, saving time and reducing costs. In addition, the quantitative analysis of the physical, chemical and potentially biological phenomena, which are involved in the control of drug release, offers another fundamental advantage: The underlying drug release mechanisms can be elucidated, which is not only of academic interest, but a pre-requisite for an efficient improvement of the safety of the pharmaco-treatments and for effective trouble-shooting during production. This article gives an overview on the current state of the art of mathematical modeling of drug delivery, including empirical/semi-empirical and mechanistic realistic models. Analytical as well as numerical solutions are described and various practical examples are given. One of the major challenges to be addressed in the future is the combination of mechanistic theories describing drug release out of the delivery systems with mathematical models quantifying the subsequent drug transport within the human body in a realistic way. Ideally, the effects of the design

  17. Mucoadhesive drug delivery system: An overview

    PubMed Central

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

    2010-01-01

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

  18. Overview of insulin delivery pen devices.

    PubMed

    Kroon, Lisa

    2009-01-01

    To review currently available insulin delivery pen devices for use in diabetes and to describe their primary benefits and drawbacks in comparison with the traditional vial/syringe method of insulin administration. Not applicable. Insulin delivery pen devices are available for most types of insulin, including all insulin analog preparations and insulin premixes with rapid-acting insulin or regular insulin with neutral protamine Hagedorn insulin. Some devices have a replaceable insulin cartridge (categorized as reusable or durable); other devices are prefilled and are disposed of after the insulin reservoir is emptied. Insulin delivery pens offer several advantages over the vial and syringe method of injection, including greater ease and discretion of use and improved portability, adherence, and dosing accuracy. The tactile and auditory feedback provided by the dosing dial on insulin delivery pen devices may be particularly helpful for patients who have impaired manual dexterity or vision. Studies also show a strong preference among patients in favor of insulin delivery pen devices compared with the vial/syringe method. Finally, despite greater per-unit cost, insulin delivery pen devices have also been associated with reductions in health resource use and associated costs compared with vial/syringe therapy. Insulin delivery pen devices offer another option to patients with diabetes for insulin administration. They are associated with not only improved ease of use but also improved dosing accuracy and adherence to therapy. To develop the most suitable insulin regimens for their patients, health providers should be informed about available insulin delivery pen devices.

  19. Mucoadhesive intestinal devices for oral delivery of salmon calcitonin.

    PubMed

    Gupta, Vivek; Hwang, Byeong Hee; Lee, Joohee; Anselmo, Aaron C; Doshi, Nishit; Mitragotri, Samir

    2013-12-28

    One of the major challenges faced by therapeutic polypeptides remains their invasive route of delivery. Oral administration offers a potential alternative to injections; however, this route cannot be currently used for peptides due to their limited stability in the stomach and poor permeation across the intestine. Here, we report mucoadhesive devices for oral delivery that are inspired by the design of transdermal patches and demonstrate their capabilities in vivo for salmon calcitonin (sCT). The mucoadhesive devices were prepared by compressing a polymeric matrix containing carbopol, pectin and sodium carboxymethylcellulose (1:1:2), and were coated on all sides but one with an impermeable and flexible ethyl cellulose (EC) backing layer. Devices were tested for in vitro dissolution, mucoadhesion to intestinal mucosa, enhancement of drug absorption in vitro (Caco-2 monolayer transport) and in vivo in rats. Devices showed steady drug release with ≈75% cumulative drug released in 5h. Devices also demonstrated strong mucoadhesion to porcine small intestine to withstand forces up to 100 times their own weight. sCT-loaded mucoadhesive devices exhibited delivery of sCT across Caco-2 monolayers and across the intestinal epithelium in vivo in rats. A ≈52-fold (pharmacokinetic) and ≈44-fold (pharmacological) enhancement of oral bioavailability was observed with mucoadhesive devices when compared to direct intestinal injections. Oral delivery of devices in enteric coated capsules resulted in significant bioavailability enhancement.

  20. 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.

  1. Implantable drug-delivery systems.

    PubMed

    Blackshear, P J

    1979-12-01

    Implantable drug-delivery systems are being developed to release drugs to the bloodstream continuously as well as free patients from being hospitalized to receive intravenous infusions or frequent injections. One technique is implantation of a pellet in the subcutaneous tissue so the pellet may be released by erosion. Drugs are also diffused through silicone rubber capsules but only polyacrylamide is able to release large molecules. Contraceptive rings containing progesterone and placed in the uterus or vagina and implanted silicone-rubber capsules use these principles. Disadvantages to the subcutaneous delivery of drugs include: 1) release of the drug in subcutaneous tissue rather than in the bloodstream directly; 2) entry into the circulatory system is controlled by surrounding blood supplies which vary with fat; 3) diffusion may be difficult due to dense layers of fibrous tissue; and 4) drug amounts cannot be readily regulated. The Ommaya reservoir uses a container with a self-sealing membrane implanted in the scalp and connected to a cerebral ventricle to treat forms of leukemia and fungal meningitis. Another development is an implantable disk-shaped infusion pump with 2 compartments, the outer one containing a propellant and the inner chamber containing the drug, holds 45 milliliters and releases about 1 milliliter/day. In the future these systems may release drugs in response to biochemical feedback or deliver a drug to 1 specific area.

  2. 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

  3. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging.

    PubMed

    Parveen, Suphiya; Misra, Ranjita; Sahoo, Sanjeeb K

    2012-02-01

    Drug delivery is an interdisciplinary and independent field of research and is gaining the attention of pharmaceutical researchers, medical doctors and industry. A safe and targeted drug delivery could improve the performance of some classic medicines already on the market, and moreover, will have implications for the development and success of new therapeutic strategies such as anticancer drug delivery, peptide and protein delivery and gene therapy. In the last decade, several drug-delivery technologies have emerged and a fascinating part of this field is the development of nanoscale drug delivery devices. Nanoparticles (NPs) have been developed as an important strategy to deliver conventional drugs, recombinant proteins, vaccines and more recently, nucleotides. NPs and other colloidal drug-delivery systems modify the kinetics, body distribution and drug release of an associated drug. This review article focuses on the potential of nanotechnology in medicine and discusses different nanoparticulate drug-delivery systems including polymeric NPs, ceramic NPs, magnetic NPs, polymeric micelles and dendrimers as well as their applications in therapeutics, diagnostics and imaging. This comprehensive review focuses on different nanoparticulate drug-delivery systems including polymeric NPs, ceramic NPs, magnetic NPs, polymeric micelles and dendrimers as well as their applications in therapeutics, diagnostics and imaging. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. 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.

  5. Drug delivery by lipid cochleates.

    PubMed

    Zarif, Leila

    2005-01-01

    Drug delivery technology has brought additional benefits to pharmaceuticals such as reduction in dosing frequency and side effects, as well as the extension of patient life. To address this need, cochleates, a precipitate obtained as a result of the interaction between phosphatidylserine and calcium, have been developed and proved to have potential in encapsulating and delivering small molecule drugs. This chapter discusses the molecules that can be encapsulated in a cochleate system and describes in detail the methodology that can be used to encapsulate and characterize hydrophobic drugs such as amphotericin B, a potent antifungal agent. Some efficacy data in animal models infected with candidiasis or aspergillosis are described as well.

  6. Mucoadhesive vaginal drug delivery systems.

    PubMed

    Acartürk, Füsun

    2009-11-01

    Vaginal delivery is an important route of drug administration for both local and systemic diseases. The vaginal route has some advantages due to its large surface area, rich blood supply, avoidance of the first-pass effect, relatively high permeability to many drugs and self-insertion. The traditional commercial preparations, such as creams, foams, gels, irrigations and tablets, are known to reside in the vaginal cavity for a relatively short period of time owing to the self-cleaning action of the vaginal tract, and often require multiple daily doses to ensure the desired therapeutic effect. The vaginal route appears to be highly appropriate for bioadhesive drug delivery systems in order to retain drugs for treating largely local conditions, or for use in contraception. In particular, protection against sexually-transmitted diseases is critical. To prolong the residence time in the vaginal cavity, bioadhesive therapeutic systems have been developed in the form of semi-solid and solid dosage forms. The most commonly used mucoadhesive polymers that are capable of forming hydrogels are synthetic polyacrylates, polycarbophil, chitosan, cellulose derivatives (hydroxyethycellulose, hydroxy-propylcellulose and hydroxypropylmethylcellulose), hyaluronic acid derivatives, pectin, tragacanth, carrageenan and sodium alginate. The present article is a comprehensive review of the patents related to mucoadhesive vaginal drug delivery systems.

  7. 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.

  8. 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

  9. Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery.

    PubMed

    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.

  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. Food, physiology and drug delivery.

    PubMed

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

    2013-12-05

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

  12. Considerations in insulin delivery device selection.

    PubMed

    Valentine, Virginia; Kruger, Davida F

    2010-06-01

    Recent guidelines from the American Diabetes Association and the European Association for the Study of Diabetes promote the use of insulin sooner rather than later in patients with type 2 diabetes to achieve goal range glucose control (< 7%) but remain silent on a recommendation for delivery system. Even though there is widespread consensus among experts and payers that people with type 2 diabetes should use insulin earlier to achieve tight control, it still remains an elusive goal. Benefits of pen-type delivery devices include accurate dosing, faster and easier setting of dose and injection times, and increased patient acceptance and adherence. Before healthcare professionals can recommend a delivery device, it is critical they understand not only the medication in the device but also the various features and benefits to the different devices available and how those impact the patient. We will present considerations to assist in making appropriate device selection, to optimize patient success.

  13. Microencapsulation: A promising technique for controlled drug delivery

    PubMed Central

    Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.

    2010-01-01

    Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed. PMID:21589795

  14. Topical Drug Delivery for Chronic Rhinosinusitis

    PubMed Central

    Liang, Jonathan; Lane, Andrew P.

    2013-01-01

    Chronic rhinosinusitis is a multifactorial disorder that may be heterogeneous in presentation and clinical course. While the introduction of endoscopic sinus surgery revolutionized surgical management and has led to significantly improved patient outcomes, medical therapy remains the foundation of long-term care of chronic rhinosinusitis, particularly in surgically recalcitrant cases. A variety of devices and pharmaceutical agents have been developed to apply topical medical therapy to the sinuses, taking advantage of the access provided by endoscopic surgery. The goal of topical therapy is to address the inflammation, infection, and mucociliary dysfunction that underlies the disease. Major factors that impact success include the patient’s sinus anatomy and the dynamics of the delivery device. Despite a growing number of topical treatment options, the evidence-based literature to support their use is limited. In this article, we comprehensively review current delivery methods and the available topical agents. We also discuss biotechnological advances that promise enhanced delivery in the future, and evolving pharmacotherapeutical compounds that may be added to rhinologist’s armamentarium. A complete understand of topical drug delivery is increasingly essential to the management of chronic rhinosinusitis when traditional forms of medical therapy and surgery have failed. PMID:23525506

  15. Advances in image-guided intratumoral drug delivery techniques

    PubMed Central

    Solorio, Luis; Patel, Ravi B; Wu, Hanping; Krupka, Tianyi; Exner, Agata A

    2017-01-01

    Image-guided drug delivery provides a means for treating a variety of diseases with minimal systemic involvement while concurrently monitoring treatment efficacy. These therapies are particularly useful to the field of interventional oncology, where elevation of tumor drug levels, reduction of systemic side effects and post-therapy assessment are essential. This review highlights three such image-guided procedures: transarterial chemoembolization, drug-eluting implants and convection-enhanced delivery. Advancements in medical imaging technology have resulted in a growing number of new applications, including image-guided drug delivery. This minimally invasive approach provides a comprehensive answer to many challenges with local drug delivery. Future evolution of imaging devices, image-acquisition techniques and multifunctional delivery agents will lead to a paradigm shift in patient care. PMID:22816134

  16. Advanced drug delivery approaches against periodontitis.

    PubMed

    Joshi, Deeksha; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Periodontitis is an inflammatory disease of gums involving the degeneration of periodontal ligaments, creation of periodontal pocket and resorption of alveolar bone, resulting in the disruption of the support structure of teeth. According to WHO, 10-15% of the global population suffers from severe periodontitis. The disease results from the growth of a diverse microflora (especially anaerobes) in the pockets and release of toxins, enzymes and stimulation of body's immune response. Various local or systemic approaches were used for an effective treatment of periodontitis. Currently, controlled local drug delivery approach is more favorable as compared to systemic approach because it mainly focuses on improving the therapeutic outcomes by achieving factors like site-specific delivery, low dose requirement, bypass of first-pass metabolism, reduction in gastrointestinal side effects and decrease in dosing frequency. Overall it provides a safe and effective mode of treatment, which enhances patient compliance. Complete eradication of the organisms from the sites was not achieved by using various surgical and mechanical treatments. So a number of polymer-based delivery systems like fibers, films, chips, strips, microparticles, nanoparticles and nanofibers made from a variety of natural and synthetic materials have been successfully tested to deliver a variety of drugs. These systems are biocompatible and biodegradable, completely fill the pockets, and have strong retention on the target site due to excellent mucoadhesion properties. The review summarizes various available and recently developing targeted delivery devices for the treatment of periodontitis.

  17. Trojan Microparticles for Drug Delivery

    PubMed Central

    Anton, Nicolas; Jakhmola, Anshuman; Vandamme, Thierry F.

    2012-01-01

    During the last decade, the US Food and Drug Administration (FDA) have regulated a wide range of products, (foods, cosmetics, drugs, devices, veterinary, and tobacco) which may utilize micro and nanotechnology or contain nanomaterials. Nanotechnology allows scientists to create, explore, and manipulate materials in nano-regime. Such materials have chemical, physical, and biological properties that are quite different from their bulk counterparts. For pharmaceutical applications and in order to improve their administration (oral, pulmonary and dermal), the nanocarriers can be spread into microparticles. These supramolecular associations can also modulate the kinetic releases of drugs entrapped in the nanoparticles. Different strategies to produce these hybrid particles and to optimize the release kinetics of encapsulated drugs are discussed in this review. PMID:24300177

  18. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye.

  19. Recent developments in silicones for topical and transdermal drug delivery.

    PubMed

    Aliyar, Hyder; Schalau, Gerald

    2015-07-01

    Silicones have been used in medicines, cosmetics and medical devices for over 60 years. Polydimethylsiloxanes are polymers that are typically used either as an active in oral drug products or as excipients in topical and transdermal drug products. Inherent characteristics like hydrophobicity, adhesion and aesthetics allow silicones to offer function and performance to drug products. Recent technologies like swollen crosslinked silicone elastomer blend networks, sugar siloxanes, amphiphilic resin linear polymers and silicone hybrid pressure sensitive adhesives promise potential performance advantages and improved drug delivery efficacy. This article presents a review of recent silicone material developments focusing on their function as excipients influencing drug delivery in topical and transdermal systems.

  20. Clinical applications of biomedical microdevices for controlled drug delivery.

    PubMed

    Gurman, Pablo; Miranda, Oscar R; Clayton, Kevin; Rosen, Yitzhak; Elman, Noel M

    2015-01-01

    Miniaturization of devices to micrometer and nanometer scales, combined with the use of biocompatible and functional materials, has created new opportunities for the implementation of drug delivery systems. Advances in biomedical microdevices for controlled drug delivery platforms promise a new generation of capabilities for the treatment of acute conditions and chronic illnesses, which require high adherence to treatment, in which temporal control over the pharmacokinetic profiles is critical. In addition, clinical conditions that require a combination of drugs with specific pharmacodynamic profiles and local delivery will benefit from drug delivery microdevices. This review provides a summary of various clinical applications for state-of-the-art controlled drug delivery microdevices, including cancer, endocrine and ocular disorders, and acute conditions such as hemorrhagic shock. Regulatory considerations for clinical translation of drug delivery microdevices are also discussed. Drug delivery microdevices promise a remarkable gain in clinical outcomes and a substantial social impact. A review of articles covering the field of microdevices for drug delivery was performed between January 1, 1990, and January 1, 2014, using PubMed as a search engine.

  1. Colloidal drug delivery systems in vaccine delivery.

    PubMed

    Beg, Sarwar; Samad, Abdus; Nazish, Iram; Sultana, Ruksar; Rahman, Mahfoozur; Ahmad, Md Zaki; Akbar, Md

    2013-01-01

    Vaccines play a vital role in the field of community medicine to combat against several diseases of human existence. Vaccines primarily trigger the acquired immune system to develop long-lasting immunity against pathogens. Conventional approaches for vaccine delivery lacks potential to target a particular antigen to develop acquired immunity by specific antibodies. Recent advancements in vaccine delivery showed that inclusion of adjuvants in vaccine formulations or delivery of them in a carrier helps in achieving desired targeting ability, reducing the immunogenicity and significant augmentation in the immune response. Colloidal carriers (liposomes, niosomes, microspheres, proteosomes, virosomes and virus like particles (VLPs), antigen cochleates, dendrimers and carbon nanotubes) have been widely explored for vaccine delivery. Further, surface engineering of these carriers with ligands, functional moieties and monoclonal antibodies tend to enhance the immune recognition potential of vaccines by differentiation of antigen specific memory T-cells. The current review, therefore, provides an updated account on the recent advancements in various colloidal delivery systems in vaccine delivery, outlining the mechanism of immune response initiated by them along with potential applications and marketed instances in an explicit manner.

  2. Ungual and transungual drug delivery.

    PubMed

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

    2012-08-01

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

  3. Polymeric conjugates for drug delivery

    PubMed Central

    Larson, Nate; Ghandehari, Hamidreza

    2012-01-01

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

  4. Ligand-Targeted Drug Delivery.

    PubMed

    Srinivasarao, Madduri; Low, Philip S

    2017-09-12

    Safety and efficacy constitute the major criteria governing regulatory approval of any new drug. The best method to maximize safety and efficacy is to deliver a proven therapeutic agent with a targeting ligand that exhibits little affinity for healthy cells but high affinity for pathologic cells. The probability of regulatory approval can conceivably be further enhanced by exploiting the same targeting ligand, conjugated to an imaging agent, to select patients whose diseased tissues display sufficient targeted receptors for therapeutic efficacy. The focus of this Review is to summarize criteria that must be met during design of ligand-targeted drugs (LTDs) to achieve the required therapeutic potency with minimal toxicity. Because most LTDs are composed of a targeting ligand (e.g., organic molecule, aptamer, protein scaffold, or antibody), spacer, cleavable linker, and therapeutic warhead, criteria for successful design of each component will be described. Moreover, because obstacles to successful drug design can differ among human pathologies, limitations to drug delivery imposed by the unique characteristics of different diseases will be considered. With the explosion of genomic and transcriptomic data providing an ever-expanding selection of disease-specific targets, and with tools for high-throughput chemistry offering an escalating diversity of warheads, opportunities for innovating safe and effective LTDs has never been greater.

  5. Planar bioadhesive microdevices: a new technology for oral drug delivery

    PubMed Central

    Fox, Cade B.; Chirra, Hariharasudhan D.; Desai, Tejal A.

    2014-01-01

    The oral route is the most convenient and least expensive route of drug administration. Yet, it is accompanied by many physiological barriers to drug uptake including low stomach pH, intestinal enzymes and transporters, mucosal barriers, and high intestinal fluid shear. While many drug delivery systems have been developed for oral drug administration, the physiological components of the gastro intestinal tract remain formidable barriers to drug uptake. Recently, microfabrication techniques have been applied to create micron-scale devices for oral drug delivery with a high degree of control over microdevice size, shape, chemical composition, drug release profile, and targeting ability. With precise control over device properties, microdevices can be fabricated with characteristics that provide increased adhesion for prolonged drug exposure, unidirectional release which serves to avoid luminal drug loss and enhance drug permeation, and protection of a drug payload from the harsh environment of the intestinal tract. Here we review the recent developments in microdevice technology and discuss the potential of these devices to overcome unsolved challenges in oral drug delivery. PMID:25219863

  6. Planar bioadhesive microdevices: a new technology for oral drug delivery.

    PubMed

    Fox, Cade B; Chirra, Hariharasudhan D; Desai, Tejal A

    2014-01-01

    The oral route is the most convenient and least expensive route of drug administration. Yet, it is accompanied by many physiological barriers to drug uptake including low stomach pH, intestinal enzymes and transporters, mucosal barriers, and high intestinal fluid shear. While many drug delivery systems have been developed for oral drug administration, the physiological components of the gastro intestinal tract remain formidable barriers to drug uptake. Recently, microfabrication techniques have been applied to create micron-scale devices for oral drug delivery with a high degree of control over microdevice size, shape, chemical composition, drug release profile, and targeting ability. With precise control over device properties, microdevices can be fabricated with characteristics that provide increased adhesion for prolonged drug exposure, unidirectional release which serves to avoid luminal drug loss and enhance drug permeation, and protection of a drug payload from the harsh environment of the intestinal tract. Here we review the recent developments in microdevice technology and discuss the potential of these devices to overcome unsolved challenges in oral drug delivery.

  7. Novel Approaches in Formulation and Drug Delivery using Contact Lenses

    PubMed Central

    Singh, Kishan; Nair, Anroop B; Kumar, Ashok; Kumria, Rachna

    2011-01-01

    The success of ocular delivery relies on the potential to enhance the drug bioavailability by controlled and extended release of drug on the eye surface. Several new approaches have been attempted to augment the competence and diminish the intrinsic side effects of existing ocular drug delivery systems. In this contest, progress has been made to develop drug-eluting contact lens using different techniques, which have the potential to control and sustain the delivery of drug. Further, the availability of novel polymers have facilitated and promoted the utility of contact lenses in ocular drug delivery. Several research groups have already explored the feasibility and potential of contact lens using conventional drugs for the treatment of periocular and intraocular diseases. Contact lenses formulated using modern technology exhibits high loading, controlled drug release, apposite thickness, water content, superior mechanical and optical properties as compared to commercial lenses. In general, this review discus various factors and approaches designed and explored for the successful delivery of ophthalmic drugs using contact lenses as drug delivery device PMID:24826007

  8. Controlled release for local delivery of drugs: barriers and models.

    PubMed

    Weiser, Jennifer R; Saltzman, W Mark

    2014-09-28

    Controlled release systems are an effective means for local drug delivery. In local drug delivery, the major goal is to supply therapeutic levels of a drug agent at a physical site in the body for a prolonged period. A second goal is to reduce systemic toxicities, by avoiding the delivery of agents to non-target tissues remote from the site. Understanding the dynamics of drug transport in the vicinity of a local drug delivery device is helpful in achieving both of these goals. Here, we provide an overview of controlled release systems for local delivery and we review mathematical models of drug transport in tissue, which describe the local penetration of drugs into tissue and illustrate the factors - such as diffusion, convection, and elimination - that control drug dispersion and its ultimate fate. This review highlights the important role of controlled release science in development of reliable methods for local delivery, as well as the barriers to accomplishing effective delivery in the brain, blood vessels, mucosal epithelia, and the skin.

  9. Intelligent hydrogels for drug delivery system.

    PubMed

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

    2011-09-01

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

  10. 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.

  11. Drug delivery systems: polymers and drugs monitored by capillary electromigration methods.

    PubMed

    Simó, Carolina; Cifuentes, Alejandro; Gallardo, Alberto

    2003-11-25

    In this paper, different electromigration methods used to monitor drugs and polymers released from drug delivery systems are reviewed. First, an introduction to the most typical arrangements used as drug delivery systems (e.g., polymer-drug covalent conjugates, membrane or matrix-based devices) is presented. Next, the principles of different capillary electromigration procedures are discussed, followed by a revision on the different procedures employed to monitor the release of drugs and the degradation or solubilization of the polymeric matrices from drug delivery systems during both in vitro and in vivo assays. A critical comparison between these capillary electrophoretic methods and the more common chromatographic methods employed to analyze drugs and polymers from drug delivery systems is presented. Finally, future outlooks of these electromigration procedures in the controlled release field are discussed.

  12. Localized Cell and Drug Delivery for Auditory Prostheses

    PubMed Central

    Hendricks, Jeffrey L.; Chikar, Jennifer A.; Crumling, Mark A.; Raphael, Yehoash; Martin, David C.

    2011-01-01

    Localized cell and drug delivery to the cochlea and central auditory pathway can improve the safety and performance of implanted auditory prostheses (APs). While generally successful, these devices have a number of limitations and adverse effects including limited tonal and dynamic ranges, channel interactions, unwanted stimulation of non-auditory nerves, immune rejection, and infections including meningitis. Many of these limitations are associated with the tissue reactions to implanted auditory prosthetic devices and the gradual degeneration of the auditory system following deafness. Strategies to reduce the insertion trauma, degeneration of target neurons, fibrous and bony tissue encapsulation, and immune activation can improve the viability of tissue required for AP function as well as improve the resolution of stimulation for reduced channel interaction and improved place-pitch and level discrimination. Many pharmaceutical compounds have been identified that promote the viability of auditory tissue and prevent inflammation and infection. Cell delivery and gene therapy have provided promising results for treating hearing loss and reversing degeneration. Currently, many clinical and experimental methods can produce extremely localized and sustained drug delivery to address AP limitations. These methods provide better control over drug concentrations while eliminating the adverse effects of systemic delivery. Many of these drug delivery techniques can be integrated into modern auditory prosthetic devices to optimize the tissue response to the implanted device and reduce the risk of infection or rejection. Together, these methods and pharmaceutical agents can be used to optimize the tissue-device interface for improved AP safety and effectiveness. PMID:18573323

  13. Intraperiodontal pocket: An ideal route for local antimicrobial drug delivery

    PubMed Central

    Nair, Sreeja C.; Anoop, K. R.

    2012-01-01

    Periodontal pockets act as a natural reservoir filled with gingival crevicular fluid for the controlled release delivery of antimicrobials directly. This article reflects the present status of nonsurgical controlled local intrapocket delivery of antimicrobials in the treatment of periodontitis. These sites have specialty in terms of anatomy, permeability, and their ability to retain a delivery system for a desired length of time. A number of antimicrobial products and the composition of the delivery systems, its use, clinical results, and their release are summarized. The goal in using an intrapocket device for the delivery of an antimicrobial agent is the achievement and maintenance of therapeutic drug concentration for the desired period of time. Novel controlled drug delivery system are capable of improving patient compliance as well as therapeutic efficacy with precise control of the rate by which a particular drug dosage is released from a delivery system without the need for frequent administration. These are considered superior drug delivery system because of low cost, greater stability, non-toxicity, biocompatibility, non-immunogenicity, and are biodegradable in nature. This review also focus on the importance and ideal features of periodontal pockets as a drug delivery platform for designing a suitable dosage form along with its potential advantage and limitations. The microbes in the periodontal pocket could destroy periodontal tissues, and a complete knowledge of these as well as an ideal treatment strategy could be helpful in treating this disease. PMID:22470888

  14. Intraperiodontal pocket: An ideal route for local antimicrobial drug delivery.

    PubMed

    Nair, Sreeja C; Anoop, K R

    2012-01-01

    Periodontal pockets act as a natural reservoir filled with gingival crevicular fluid for the controlled release delivery of antimicrobials directly. This article reflects the present status of nonsurgical controlled local intrapocket delivery of antimicrobials in the treatment of periodontitis. These sites have specialty in terms of anatomy, permeability, and their ability to retain a delivery system for a desired length of time. A number of antimicrobial products and the composition of the delivery systems, its use, clinical results, and their release are summarized. The goal in using an intrapocket device for the delivery of an antimicrobial agent is the achievement and maintenance of therapeutic drug concentration for the desired period of time. Novel controlled drug delivery system are capable of improving patient compliance as well as therapeutic efficacy with precise control of the rate by which a particular drug dosage is released from a delivery system without the need for frequent administration. These are considered superior drug delivery system because of low cost, greater stability, non-toxicity, biocompatibility, non-immunogenicity, and are biodegradable in nature. This review also focus on the importance and ideal features of periodontal pockets as a drug delivery platform for designing a suitable dosage form along with its potential advantage and limitations. The microbes in the periodontal pocket could destroy periodontal tissues, and a complete knowledge of these as well as an ideal treatment strategy could be helpful in treating this disease.

  15. Magnetic Resonance-Guided Drug Delivery.

    PubMed

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

    2015-11-01

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

  16. In Situ Forming Polymeric Drug Delivery Systems

    PubMed Central

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

    2009-01-01

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

  17. 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

  18. Optimal stent design for drug delivery.

    PubMed

    Rogers, Campbell D K

    2004-01-01

    The efficacy and safety of drug-eluting coronary stents might differ depending on the pharmacologic agents and stent delivery systems used. Recent research has focused on the various constituents of drug-delivery stents, including the stent backbone, materials used as drug-delivery vehicles, and the physicochemical properties of the pharmacotherapeutic agents themselves. Metal stents coated with an outer layer of polymer (bioabsorbable or non-bioabsorbable) can be drug-loaded, thus providing more controlled and sustained drug delivery and allowing more optimal drug-tissue interactions. Among the next generation of drug-eluting stents will be a stent that uses the non-bioabsorbable polymer phosphorylcholine to release the sirolimus analogue ABT-578; another stent will use a highly deliverable cobalt-chromium metal alloy stent platform and, for the first time, a bioabsorbable polymeric coating (thin-film polylactic acid) for drug encapsulation and release.

  19. Refilling drug delivery depots through the blood.

    PubMed

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

    2014-09-02

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

  20. Permeation enhancer strategies in transdermal drug delivery.

    PubMed

    Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

  1. Microsystems Technologies for Drug Delivery to the Inner Ear

    PubMed Central

    Leary Pararas, Erin E.; Borkholder, David A.; Borenstein, Jeffrey T.

    2012-01-01

    The inner ear represents one of the most technologically challenging targets for local drug delivery, but its clinical significance is rapidly increasing. The prevalence of sensorineural hearing loss and other auditory diseases, along with balance disorders and tinnitus, has spurred broad efforts to develop therapeutic compounds and regenerative approaches to treat these conditions, necessitating advances in systems capable of targeted and sustained drug delivery. The delicate nature of hearing structures combined with the relative inaccessibility of the cochlea by means of conventional delivery routes together necessitate significant advancements in both the precision and miniaturization of delivery systems, and the nature of the molecular and cellular targets for these therapies suggests that multiple compounds may need to be delivered in a time-sequenced fashion over an extended duration. Here we address the various approaches being developed for inner ear drug delivery, including micropump-based devices, reciprocating systems, and cochlear prosthesis-mediated delivery, concluding with an analysis of emerging challenges and opportunities for the first generation of technologies suitable for human clinical use. These developments represent exciting advances that have the potential to repair and regenerate hearing structures in millions of patients for whom no currently available medical treatments exist, a situation that requires them to function with electronic hearing augmentation devices or to live with severely impaired auditory function. These advances also have the potential for broader clinical applications that share similar requirements and challenges with the inner ear, such as drug delivery to the central nervous system. PMID:22386561

  2. Prodrug Strategies in Ocular Drug Delivery

    PubMed Central

    Barot, Megha; Bagui, Mahuya; Gokulgandhi, Mitan R.; Mitra, Ashim K.

    2015-01-01

    Poor bioavailability of topically instilled drug is the major concern in the field of ocular drug delivery. Efflux transporters, static and dynamic ocular barriers often possess rate limiting factors for ocular drug therapy. Different formulation strategies like suspension, ointment, gels, nanoparticles, implants, dendrimers and liposomes have been employed in order to improve drug permeation and retention by evading rate limiting factors at the site of absorption. Chemical modification such as prodrug targeting various nutrient transporters (amino acids, peptide and vitamin) has evolved a great deal ofintereSt to improve ocular drug delivery. In this review, we have discussed various prodrug strategies which have been widely applied for enhancing therapeutic efficacy of ophthalmic drugs. The purpose of this review is to provide an update on the utilization of prodrug concept in ocular drug delivery. In addition, this review will highlight ongoing academic and industrial research and development in terms of ocular prodrug design and delivery. PMID:22530907

  3. Delivery of Exenatide and Insulin Using Mucoadhesive Intestinal Devices.

    PubMed

    Gupta, Vivek; Hwang, Byeong-Hee; Doshi, Nishit; Banerjee, Amrita; Anselmo, Aaron C; Mitragotri, Samir

    2016-06-01

    A major disadvantage associated with current diabetes therapy is dependence on injectables for long-term disease management. In addition to insulin, incretin hormone replacement therapies including exenatide have added a new class of drugs for Type-2 diabetes. Although efficacious, patient compliance with current diabetic therapy is poor due to requirement of injections, inability to cross the intestinal epithelium and instability in the gastrointestinal tract. Here, we report the efficacy of a mucoadhesive device in providing therapeutic concentrations of insulin and exenatide via oral administration. Devices were prepared with a blend of FDA-approved polymers, carbopol, pectin and sodium carboxymethylcellulose, and were tested for drug carrying capability, in vitro release, Caco-2 permeability, and in vivo efficacy for insulin and exenatide. Results suggested that mucoadhesive devices successfully provided controlled release of FITC-insulin, released significant amounts of drug, while providing noteworthy enhancement of drug transport across Caco-2 monolayers without compromising monolayer integrity. In-vivo administration of the devices provided significant enhancement of drug absorption with 13- and 80-fold enhancement of relative bioavailability for insulin and exenatide compared to intestinal injections with significant increase in half-lives, thus resulting in prolonged blood glucose reduction. This study validates the efficacy of mucoadhesive devices in promoting oral peptide delivery to improve patient compliance and dose adherence.

  4. Nanoparticles for intracellular-targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Paulo, Cristiana S. O.; Pires das Neves, Ricardo; Ferreira, Lino S.

    2011-12-01

    Nanoparticles (NPs) are very promising for the intracellular delivery of anticancer and immunomodulatory drugs, stem cell differentiation biomolecules and cell activity modulators. Although initial studies in the area of intracellular drug delivery have been performed in the delivery of DNA, there is an increasing interest in the use of other molecules to modulate cell activity. Herein, we review the latest advances in the intracellular-targeted delivery of short interference RNA, proteins and small molecules using NPs. In most cases, the drugs act at different cellular organelles and therefore the drug-containing NPs should be directed to precise locations within the cell. This will lead to the desired magnitude and duration of the drug effects. The spatial control in the intracellular delivery might open new avenues to modulate cell activity while avoiding side-effects.

  5. Microneedles: an emerging transdermal drug delivery system.

    PubMed

    Bariya, Shital H; Gohel, Mukesh C; Mehta, Tejal A; Sharma, Om Prakash

    2012-01-01

    One of the thrust areas in drug delivery research is transdermal drug delivery systems (TDDS) due to their characteristic advantages over oral and parenteral drug delivery systems. Researchers have focused their attention on the use of microneedles to overcome the barrier of the stratum corneum. Microneedles deliver the drug into the epidermis without disruption of nerve endings. Recent advances in the development of microneedles are discussed in this review for the benefit of young scientists and to promote research in the area. Microneedles are fabricated using a microelectromechanical system employing silicon, metals, polymers or polysaccharides. Solid coated microneedles can be used to pierce the superficial skin layer followed by delivery of the drug. Advances in microneedle research led to development of dissolvable/degradable and hollow microneedles to deliver drugs at a higher dose and to engineer drug release. Iontophoresis, sonophoresis and electrophoresis can be used to modify drug delivery when used in concern with hollow microneedles. Microneedles can be used to deliver macromolecules such as insulin, growth hormones, immunobiologicals, proteins and peptides. Microneedles containing 'cosmeceuticals' are currently available to treat acne, pigmentation, scars and wrinkles, as well as for skin tone improvement. Literature survey and patents filled revealed that microneedle-based drug delivery system can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional transdermal techniques. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  6. A review of nebulized drug delivery in COPD

    PubMed Central

    Tashkin, Donald P

    2016-01-01

    Current guidelines recommend inhaled pharmacologic therapy as the preferred route of administration for treating COPD. Bronchodilators (β2-agonists and antimuscarinics) are the mainstay of pharmacologic therapy in patients with COPD, with long-acting agents recommended for patients with moderate to severe symptoms or those who are at a higher risk for COPD exacerbations. Dry powder inhalers and pressurized metered dose inhalers are the most commonly used drug delivery devices, but they may be inadequate in various clinical scenarios (eg, the elderly, the cognitively impaired, and hospitalized patients). As more drugs become available in solution formulations, patients with COPD and their caregivers are becoming increasingly satisfied with nebulized drug delivery, which provides benefits similar to drugs delivered by handheld inhalers in both symptom relief and improved quality of life. This article reviews recent innovations in nebulized drug delivery and the important role of nebulized therapy in the treatment of COPD. PMID:27799757

  7. 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

  8. [Site-specific drug delivery systems. I. Colon targeted delivery].

    PubMed

    Szente, Virág; Zelkó, Romána

    2007-01-01

    Colon specific drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon like Chron's disease, ulcerative colitis, irritable bowel syndrome, cancer or infections, but also for the potential it holds for the systemic delivery of proteins (e.g. insulin) and therapeutic peptides. These systems enable the protection of healthy tissues from the side effects of drugs and the drug intake of targeted cells, as well. The formulation of colon specific drug delivery systems is of great impact in the case of diseases having circadian rhythm (midnight gerd). Such circadian rhythm release drug delivery systems are designed to provide a plasma concentration--time profile, which varies according to physiological need at different times during the dosing period, i.e., mimicking the circadian rhythm and severity/manifestation of gastric acid secretion (and/or midnight gerd). In general four primary approaches have been proposed for colon targeted delivery namely pH-dependent systems, time dependent systems, colonic microflora activated systems and prodrugs.

  9. Polysaccharides in colon-specific drug delivery.

    PubMed

    Sinha, V R; Kumria, R

    2001-08-14

    Natural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon. The rationale for the development of a polysaccharide based delivery system for colon is the presence of large amounts of polysaccharidases in the human colon as the colon is inhabited by a large number and variety of bacteria which secrete many enzymes e.g. beta-D-glucosidase, beta-D-galactosidase, amylase, pectinase, xylanase, beta-D-xylosidase, dextranase, etc. Various major approaches utilizing polysaccharides for colon-specific delivery are fermentable coating of the drug core, embedding of the drug in biodegradable matrix, formulation of drug-saccharide conjugate (prodrugs). A large number of polysaccharides have already been studied for their potential as colon-specific drug carrier systems, such as chitosan, pectin, chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylose and locust bean gum. Recent efforts and approaches exploiting these polysaccharides in colon-specific drug delivery are discussed.

  10. Microneedle arrays for biosensing and drug delivery

    DOEpatents

    Wang, Joseph; Windmiller, Joshua Ray; Narayan, Roger; Miller, Philip

    2017-08-29

    Methods, structures, and systems are disclosed for biosensing and drug delivery techniques. In one aspect, a device for detecting an analyte and/or releasing a biochemical into a biological fluid can include an array of hollowed needles, in which each needle includes a protruded needle structure including an exterior wall forming a hollow interior and an opening at a terminal end of the protruded needle structure that exposes the hollow interior, and a probe inside the exterior wall to interact with one or more chemical or biological substances that come in contact with the probe via the opening to produce a probe sensing signal, and an array of wires that are coupled to probes of the array of hollowed needles, respectively, each wire being electrically conductive to transmit the probe sensing signal produced by a respective probe.

  11. Microneedle arrays for biosensing and drug delivery

    DOEpatents

    Wang, Joseph; Windmiller, Joshua Ray; Narayan, Roger; Miller, Philip; Polsky, Ronen; Edwards, Thayne L.

    2017-08-22

    Methods, structures, and systems are disclosed for biosensing and drug delivery techniques. In one aspect, a^ device for detecting an analyte and/or releasing a biochemical into a biological fluid can include an array of hollowed needles, in which each needle includes a protruded needle structure including an exterior wall forming a hollow interior and an opening at a terminal end of the protruded needle structure that exposes the hollow interior, and a probe inside the exterior wall to interact with one or more chemical or biological substances that come in contact with the probe via the opening to produce a probe sensing signal, and an array of wires that are coupled to probes of the array of hollowed needles, respectively, each wire being electrically conductive to transmit the probe sensing signal produced by a respective probe.

  12. Colloidal microgels in drug delivery applications

    PubMed Central

    Vinogradov, Serguei V.

    2005-01-01

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

  13. Intravenous drug delivery in neonates: lessons learnt.

    PubMed

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

    2014-06-01

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

  14. Nanomedicine and drug delivery: a mini review

    NASA Astrophysics Data System (ADS)

    Mirza, Agha Zeeshan; Siddiqui, Farhan Ahmed

    2014-02-01

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

  15. Magnetic nanoparticles for gene and drug delivery

    PubMed Central

    McBain, Stuart C; Yiu, Humphrey HP; Dobson, Jon

    2008-01-01

    Investigations of magnetic micro- and nanoparticles for targeted drug delivery began over 30 years ago. Since that time, major progress has been made in particle design and synthesis techniques, however, very few clinical trials have taken place. Here we review advances in magnetic nanoparticle design, in vitro and animal experiments with magnetic nanoparticle-based drug and gene delivery, and clinical trials of drug targeting. PMID:18686777

  16. Synthetic Lipoproteins as Carriers for Drug Delivery.

    PubMed

    Huang, Gangliang; Liu, Yang; Huang, Hualiang

    2016-01-01

    Synthetic lipoprotein is an effective carrier of targeted delivery for drugs. It has the very small size, good biocompatibility, suitable half-life, and specific lipoprotein receptorbinding capacity. Compared with the traditional natural lipoprotein, synthetic lipoprotein not only retains the original biological characteristics and functions, but also exhibits the excellent characteristics in drug delivery. Herein, the advantages, development, applications, and prospect of synthetic lipoproteins as drug carriers were summarized.

  17. NanoClusters Enhance Drug Delivery in Mechanical Ventilation

    NASA Astrophysics Data System (ADS)

    Pornputtapitak, Warangkana

    The overall goal of this thesis was to develop a dry powder delivery system for patients on mechanical ventilation. The studies were divided into two parts: the formulation development and the device design. The pulmonary system is an attractive route for drug delivery since the lungs have a large accessible surface area for treatment or drug absorption. For ventilated patients, inhaled drugs have to successfully navigate ventilator tubing and an endotracheal tube. Agglomerates of drug nanoparticles (also known as 'NanoClusters') are fine dry powder aerosols that were hypothesized to enable drug delivery through ventilator circuits. This Thesis systematically investigated formulations of NanoClusters and their aerosol performance in a conventional inhaler and a device designed for use during mechanical ventilation. These engineered powders of budesonide (NC-Bud) were delivered via a MonodoseRTM inhaler or a novel device through commercial endotracheal tubes, and analyzed by cascade impaction. NC-Bud had a higher efficiency of aerosol delivery compared to micronized stock budesonide. The delivery efficiency was independent of ventilator parameters such as inspiration patterns, inspiration volumes, and inspiration flow rates. A novel device designed to fit directly to the ventilator and endotracheal tubing connections and the MonodoseRTM inhaler showed the same efficiency of drug delivery. The new device combined with NanoCluster formulation technology, therefore, allowed convenient and efficient drug delivery through endotracheal tubes. Furthermore, itraconazole (ITZ), a triazole antifungal agent, was formulated as a NanoCluster powder via milling (top-down process) or precipitation (bottom-up process) without using any excipients. ITZ NanoClusters prepared by wet milling showed better aerosol performance compared to micronized stock ITZ and ITZ NanoClusters prepared by precipitation. ITZ NanoClusters prepared by precipitation methods also showed an amorphous state

  18. Marine Origin Polysaccharides in Drug Delivery Systems.

    PubMed

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

    2016-02-05

    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.

  19. 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

  20. Smart Polymers in Nasal Drug Delivery

    PubMed Central

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

    2015-01-01

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

  1. A laser based reusable microjet injector for transdermal drug delivery

    NASA Astrophysics Data System (ADS)

    Han, Tae-hee; Yoh, Jack J.

    2010-05-01

    A laser based needle-free liquid drug injection device has been developed. A laser beam is focused inside the liquid contained in the rubber chamber of microscale. The focused laser beam causes explosive bubble growth, and the sudden volume increase in a sealed chamber drives a microjet of liquid drug through the micronozzle. The exit diameter of a nozzle is 125 μm and the injected microjet reaches an average velocity of 264 m/s. This device adds the time-varying feature of microjet to the current state of liquid injection for drug delivery.

  2. Inorganic Nanomaterials as Carriers for Drug Delivery.

    PubMed

    Chen, Shizhu; Hao, Xiaohong; Liang, Xingjie; Zhang, Qun; Zhang, Cuimiao; Zhou, Guoqiang; Shen, Shigang; Jia, Guang; Zhang, Jinchao

    2016-01-01

    For safe and effective therapy, drugs must be delivered efficiently and with minimal systemic side effects. Nanostructured drug carriers enable the delivery of small-molecule drugs as well as nucleic acids and proteins. Inorganic nanomaterials are ideal for drug delivery platforms due to their unique physicochemical properties, such as facile preparation, good storage stability and biocompatibility. Many inorganic nanostructure-based drug delivery platforms have been prepared. Although there are still many obstacles to overcome, significant advances have been made in recent years. This review focuses on the status and development of inorganic nanostructures, including silica, quantum dots, gold, carbon-based and magnetic iron oxide-based nanostructures, as carriers for chemical and biological drugs. We specifically highlight the extensive use of these inorganic drug carriers for cancer therapy. Finally, we discuss the most important areas in the field that urgently require further study.

  3. Advances in Lymphatic Imaging and Drug Delivery

    SciTech Connect

    Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.; Thallapally, Praveen K.; Laird, Forrest M.

    2011-09-10

    Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastly improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.

  4. Mucosal drug delivery: membranes, methodologies, and applications.

    PubMed

    Song, Yifan; Wang, Yiping; Thakur, Rashmi; Meidan, Victor M; Michniak, Bozena

    2004-01-01

    In recent years, extensive research into novel forms of drug delivery has suggested that mucosal approaches offer a promising therapeutic alternative, especially for systemically acting drugs. Transmucosal drug delivery offers many benefits, including noninvasive administration, convenience, rapid onset, as well as elimination of hepatic first-pass metabolism. The investigated absorptive surfaces consist of the nasal, buccal, ocular, vaginal, and rectal mucosae. Among these, the nasal and buccal routes have proved the most promising to date. The bioavailability achieved mainly depends upon the pathophysiological state of the mucosa and the properties of both the drug and delivery systems. Various agents can increase the efficacy of transmucosal drug delivery. These include cyclodextrins, bile salts, surfactants, fusidic acid derivatives, microspheres, liposomes, and bioadhesive agents. The mechanisms of action, effectiveness, and toxicity profiles of these enhancers have been investigated extensively in both animal and human models.

  5. 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

  6. Radiation sterilization of new drug delivery systems.

    PubMed

    Abuhanoğlu, Gürhan; Ozer, A Yekta

    2014-06-01

    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.

  7. Best practices for intrathecal drug delivery for pain.

    PubMed

    Prager, Joshua; Deer, Timothy; Levy, Robert; Bruel, Brian; Buchser, Eric; Caraway, David; Cousins, Michael; Jacobs, Marilyn; McGlothlen, Gail; Rauck, Richard; Staats, Peter; Stearns, Lisa

    2014-06-01

    The objective of this study was to identify best practices and provide guidance to clinicians to ensure safety and optimize intrathecal drug delivery for chronic intractable pain. Twelve experienced pain medicine practitioners-eight anesthesiologists, one neurosurgeon, one physiatrist, one clinical psychologist, and one advanced practice registered nurse-from the United States, Australia, and Europe gathered to identify and publish consensus on best practices in three areas related to safe intrathecal therapy for pain: safety and monitoring, patient and device management, and patient selection and trialing. Intrathecal drug delivery is a valuable alternative drug delivery system for many patients with severe chronic or end-of-life pain. While device-related complications (mostly with catheters) and surgical-site infections can occur, the main therapy-related safety issues associated with intrathecal drug delivery arise primarily with inadequate patient monitoring (e.g., respiratory depression), inflammatory mass (e.g., high doses and concentrations of opioids), wound healing, dosing errors (e.g., medication concentration and pump programming), pump fills or refills (e.g., pocket fills), and interaction with concomitant systemic medications (e.g., opioids and benzodiazepines). Many of the reported adverse events and complications of intrathecal drug delivery can be prevented by adequate clinician training, implementation of best practices, and experience. In adopting the therapy, patients must be apprised of its risks and benefits. Physicians and patients must partner to achieve both safety and effectiveness. © 2014 International Neuromodulation Society.

  8. Polypeptides and polyaminoacids in drug delivery.

    PubMed

    González-Aramundiz, José Vicente; Lozano, María Victoria; Sousa-Herves, Ana; Fernandez-Megia, Eduardo; Csaba, Noemi

    2012-02-01

    Advances achieved over the last few years in drug delivery have provided novel and versatile possibilities for the treatment of various diseases. Among the biomaterials applied in this field, it is worth highlighting the increasing importance of polyaminoacids and polypeptides. The appealing properties of these polymers are very promising for the design of novel compositions in a variety of drug delivery applications. This review provides an overview on the general characteristics of polyaminoacids and polypeptides and briefly discusses different synthetic pathways for their production. This is followed by a detailed description of different drug delivery applications of these polymers, emphasizing those examples that already reached advanced preclinical development or have entered clinical trials. Polyaminoacids and polypeptides are gaining much attention in drug delivery due to their exceptional properties. Their application as polymers for drug delivery purposes has been sped up by the significant achievements related to their synthesis. Certainly, cancer therapy has benefited the most from these advances, although other fields such as vaccine delivery and alternative administration routes are also being successfully explored. The design of new entities based on polyaminoacids and polypeptides and the improved insight gained in drug delivery guarantee exciting findings in the near future.

  9. Protein-Based Drug-Delivery Materials

    PubMed Central

    Jao, Dave; Xue, Ye; Medina, Jethro; Hu, Xiao

    2017-01-01

    There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function—including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments—are summarized at the end of this review. PMID:28772877

  10. Perspectives on transdermal ultrasound mediated drug delivery

    PubMed Central

    Smith, Nadine Barrie

    2007-01-01

    The use of needles for multiple injection of drugs, such as insulin for diabetes, can be painful. As a result, prescribed drug noncompliance can result in severe medical complications. Several noninvasive methods exist for transdermal drug delivery. These include chemical mediation using liposomes and chemical enhancers or physical mechanisms such as microneedles, iontophoresis, electroporation, and ultrasound. Ultrasound enhanced transdermal drug delivery offers advantages over traditional drug delivery methods which are often invasive and painful. A broad review of the transdermal ultrasound drug delivery literature has shown that this technology offers promising potential for noninvasive drug administration. From a clinical perspective, few drugs, proteins or peptides have been successfully administered transdermally because of the low skin permeability to these relatively large molecules, although much work is underway to resolve this problem. The proposed mechanism of ultrasound has been suggested to be the result of cavitation, which is discussed along with the bioeffects from therapeutic ultrasound. For low frequencies, potential transducers which can be used for drug delivery are discussed, along with cautions regarding ultrasound safety versus efficacy. PMID:18203426

  11. Recent advances in ophthalmic drug delivery

    PubMed Central

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

    2011-01-01

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

  12. Insulin pens: the modern delivery devices.

    PubMed

    Baruah, Manash P

    2011-04-01

    Strict glycemic control helps in reducing complications and mortality in patients with diabetes. Insulin remains the mainstay in treatment of diabetes. One of the most important barriers to insulin therapy is the use of conventional insulin delivery system, which remains time-consuming, cumbersome, inconvenient and painful. Insulin dosing via syringe is associated with a high risk of dosage errors. The modern pen devices have various advantages over the conventional insulin delivery methods. The user-friendliness and comfort of injection makes the initiation of insulin easier. The ease of use of insulin pens and the flexibility of incorporating insulin injections into a busy lifestyle may improve diabetes control with much less effort, while maintaining the quality of life for the diabetic patients. Reusable and prefilled pens are available.

  13. Nanostructured lipid carriers and their current application in targeted drug delivery.

    PubMed

    Jaiswal, Piyush; Gidwani, Bina; Vyas, Amber

    2016-01-01

    In the last few decades, various drug-delivery technologies have emerged and a fascinating part of this has been the development of nanoscale drug delivery devices. Nanoparticles (NPs) and other colloidal drug-delivery systems modify the kinetics, drug distribution in the body and release profile of an associated drug. Nanostructured lipid carriers (NLCs) have been reported to be an alternative system to emulsions, liposomes, microparticles, solid lipid nanoparticles (SLNs) and their polymeric counterparts due to their numerous advantages. This paper basically reviews the types of NLCs, mechanism of skin penetration, stability related issues along with their production techniques, characterisation and applications towards targeted drug delivery.

  14. Inner Ear Drug Delivery for Auditory Applications

    PubMed Central

    Swan, Erin E. Leary; Mescher, Mark J.; Sewell, William F.; Tao, Sarah L.; Borenstein, Jeffrey T.

    2008-01-01

    Many inner ear disorders cannot be adequately treated by systemic drug delivery. A blood-cochlear barrier exists, similar physiologically to the blood-brain barrier, which limits the concentration and size of molecules able to leave the circulation and gain access to the cells of the inner ear. However, research in novel therapeutics and delivery systems has led to significant progress in the development of local methods of drug delivery to the inner ear. Intratympanic approaches, which deliver therapeutics to the middle ear, rely on permeation through tissue for access to the structures of the inner ear, whereas intracochlear methods are able to directly insert drugs into the inner ear. Innovative drug delivery systems to treat various inner ear ailments such as ototoxicity, sudden sensorineural hearing loss, autoimmune inner ear disease, and for preserving neurons and regenerating sensory cells are being explored. PMID:18848590

  15. Carbon Nanotubes Hybrid Hydrogels in Drug Delivery: A Perspective Review

    PubMed Central

    Hampel, Silke; Spizzirri, Umile Gianfranco; Parisi, Ortensia Ilaria; Picci, Nevio; Iemma, Francesca

    2014-01-01

    The use of biologics, polymers, silicon materials, carbon materials, and metals has been proposed for the preparation of innovative drug delivery devices. One of the most promising materials in this field are the carbon-nanotubes composites and hybrid materials coupling the advantages of polymers (biocompatibility and biodegradability) with those of carbon nanotubes (cellular uptake, stability, electromagnatic, and magnetic behavior). The applicability of polymer-carbon nanotubes composites in drug delivery, with particular attention to the controlled release by composites hydrogel, is being extensively investigated in the present review. PMID:24587993

  16. Carbon nanotubes hybrid hydrogels in drug delivery: a perspective review.

    PubMed

    Cirillo, Giuseppe; Hampel, Silke; Spizzirri, Umile Gianfranco; Parisi, Ortensia Ilaria; Picci, Nevio; Iemma, Francesca

    2014-01-01

    The use of biologics, polymers, silicon materials, carbon materials, and metals has been proposed for the preparation of innovative drug delivery devices. One of the most promising materials in this field are the carbon-nanotubes composites and hybrid materials coupling the advantages of polymers (biocompatibility and biodegradability) with those of carbon nanotubes (cellular uptake, stability, electromagnatic, and magnetic behavior). The applicability of polymer-carbon nanotubes composites in drug delivery, with particular attention to the controlled release by composites hydrogel, is being extensively investigated in the present review.

  17. 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

  18. Transpapillary drug delivery to the breast.

    PubMed

    Dave, Kaushalkumar; Averineni, Ranjith; Sahdev, Preety; Perumal, Omathanu

    2014-01-01

    The study was aimed at investigating localized topical drug delivery to the breast via mammary papilla (nipple). 5-fluorouracil (5-FU) and estradiol (EST) were used as model hydrophilic and hydrophobic compounds respectively. Porcine and human nipple were used for in-vitro penetration studies. The removal of keratin plug enhanced the drug transport through the nipple. The drug penetration was significantly higher through the nipple compared to breast skin. The drug's lipophilicity had a significant influence on drug penetration through nipple. The ducts in the nipple served as a major transport pathway to the underlying breast tissue. Results showed that porcine nipple could be a potential model for human nipple. The topical application of 5-FU on the rat nipple resulted in high drug concentration in the breast and minimal drug levels in plasma and other organs. Overall, the findings from this study demonstrate the feasibility of localized drug delivery to the breast through nipple.

  19. Colloidal polymeric nanoparticles and brain drug delivery.

    PubMed

    Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2009-07-01

    The blood brain barrier protects the brain from harmful substances in the blood stream and has stopped the development of many powerful and interesting drugs candidates for central nervous system due to the low poor distribution and by efflux mechanisms. Many different approaches have been developed in order to overcome this barrier and the drug gain access to the brain. The polymeric nanoparticles are efficient colloidal systems that have been investigated to the brain drug delivery. This review will focus on the current strategies for brain drug delivery emphasizing the properties and characteristics of polymeric nanoparticles for this purpose.

  20. Vesicular carriers for dermal drug delivery.

    PubMed

    Sinico, Chiara; Fadda, Anna Maria

    2009-08-01

    The skin can offer several advantages as a route of drug administration although its barrier nature makes it difficult for most drugs to penetrate into and permeate through it. During the past decades there has been a lot of interest in lipid vesicles as a tool to improve drug topical delivery. Vesicular systems such as liposomes, niosomes, ethosomes and elastic, deformable vesicles provide an alternative for improved skin drug delivery. The function of vesicles as topical delivery systems is controversial with variable effects being reported in relation to the type of vesicles and their composition. In fact, vesicles can act as drug carriers controlling active release; they can provide a localized depot in the skin for dermally active compounds and enhance transdermal drug delivery. A wide variety of lipids and surfactants can be used to prepare vesicles, which are commonly composed of phospholipids (liposomes) or non-ionic surfactants (niosomes). Vesicle composition and preparation method influence their physicochemical properties (size, charge, lamellarity, thermodynamic state, deformability) and therefore their efficacy as drug delivery systems. A review of vesicle value in localizing drugs within the skin at the site of action will be provided with emphasis on their potential mechanism of action.

  1. Application of the Refined Integral Method in the mathematical modeling of drug delivery from one-layer torus-shaped devices.

    PubMed

    Helbling, Ignacio M; Ibarra, Juan C D; Luna, Julio A

    2012-02-28

    A mathematical modeling of controlled release of drug from one-layer torus-shaped devices is presented. Analytical solutions based on Refined Integral Method (RIM) are derived. The validity and utility of the model are ascertained by comparison of the simulation results with matrix-type vaginal rings experimental release data reported in the literature. For the comparisons, the pair-wise procedure is used to measure quantitatively the fit of the theoretical predictions to the experimental data. A good agreement between the model prediction and the experimental data is observed. A comparison with a previously reported model is also presented. More accurate results are achieved for small A/C(s) ratios.

  2. Optimal control of objects on the micro- and nano-scale by electrokinetic and electromagnetic manipulation: For bio-sample preparation, quantum information devices and magnetic drug delivery

    NASA Astrophysics Data System (ADS)

    Probst, Roland

    feedback control of magnetic drug delivery to reach deeper tumors in the long term. To this end, I developed and experimentally demonstrated an optimal control algorithm to effectively manipulate a single ferrofluid droplet by magnetic feedback control. This algorithm was explicitly designed to address the nonlinear and cross-coupled nature of dynamic magnetic actuation and to best exploit available electromagnetic forces for the applications of magnetic drug delivery.

  3. Drug delivery and nanodetection in lung cancer.

    PubMed

    Badrzadeh, Fariba; Rahmati-Yamchi, Mohammad; Badrzadeh, Kazem; Valizadeh, Alireza; Zarghami, Nosratollah; Farkhani, Samad Mussa; Akbarzadeh, Abolfazl

    2016-01-01

    Lung carcinoma is the most widespread type of cancer worldwide, and is responsible for more deaths than other types of cancer. Lung cancer remains the chief cause of cancer-related deaths in both men and women worldwide, and is increasingly common in women. Each year, the number of deaths from lung cancer is greater than the number due to breast and colorectal cancer combined. Lung cancer accounted for 13% (1.6 million) of the total cases and 18% (1.4 million) of the deaths in 2008. In Iran, lung cancer is one of the five leading tumors. Among females, it was the fourth most commonly diagnosed cancer, and the second leading cause of cancer death. Nanotechnology can be defined as the science and engineering involved in the design, characterization, and application of materials and devices whose smallest functional organization in at least one dimension is on the nanometer scale, i.e. one billionth of a meter. It is an exciting multidisciplinary field that involves the design and engineering of nano objects or nanotools with diameters less than 500 nanometers (nm), and it is one of the most interesting fields of the 21st century. Nanotechnology also offers the ability to detect diseases, such as tumors, much earlier than ever imaginable. This article presents nano devices for lung cancer detection and drug delivery systems.

  4. Mathematical modeling of drug delivery from one-layer and two-layer torus-shaped devices with external mass transfer resistance.

    PubMed

    Helbling, Ignacio M; Cabrera, María I; Luna, Julio A

    2011-10-09

    A mathematical modeling of controlled release of drug from one-layer and two-layer torus-shaped devices with external mass transfer resistance is presented. Analytical solutions based on the pseudo-steady state approximation are derived. The validity of the equations is established in two stages. In the first stage, the validity of the models derived for more complex systems is determined by comparison with profiles predicted by the simplest model, in asymptotic cases. In the second stage, the reliability and usefulness of the models are ascertained by comparison of the simulation results with vaginal rings experimental release data reported in the literature. In order to measures quantitatively the fit of the theoretical models to the experimental data, the pair-wise procedure is used. A good agreement between the prediction of the models and the experimental data is observed. The models are applicable only to torus-shaped systems in where the initial load of drug is higher than its solubility in the polymer.

  5. Nuclear drug delivery for cancer chemotherapy.

    PubMed

    Sui, Meihua; Liu, Wenwen; Shen, Youqing

    2011-10-30

    Nanosystems with unique physical and biological properties have been extensively explored for cancer targeted intracellular delivery of small-molecular chemotherapeutic drugs to increase their therapeutic efficacies and to minimize their side effects. A large number of anticancer drugs are DNA-toxins that bind nuclear DNA or its associated enzymes to exert their cytotoxicity to cancer cells. After entering tumor cells, they need to be further delivered to the nucleus for actions. Herein, we discuss the biological barriers and summarize recent progress of nuclear drug delivery for cancer chemotherapy, emphasizing strategies that appear useful for design of vehicles capable of delivering drugs to the nucleus, particularly for in vivo applications. The existing obstacles or problems that need to be overcome before successful applications of nuclear drug delivery for cancer chemotherapy are also discussed.

  6. Molecular imprinted polymers as drug delivery vehicles.

    PubMed

    Zaidi, Shabi Abbas

    2016-09-01

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

  7. Electrospun materials for affinity-based engineering and drug delivery

    NASA Astrophysics Data System (ADS)

    Sill, T. J.; von Recum, H. A.

    2015-10-01

    Electrospinning is a process which can quickly and cheaply create materials of high surface to volume and aspect ratios from many materials, however in application toward drug delivery this can be a strong disadvantage as well. Diffusion of drug is proportional to the thickness of that device. In moving from macro to micro to nano-sized electrospun materials drug release rates change to profiles that are too fast to be therapeutically beneficial. In this work we use molecular interactions to further control the rate of release beyond that capable of diffusion alone. To do this we create materials with molecular pockets, which can "hold" therapeutic drugs through a reversible interaction such as a host/guest complexation. Through these complexes we show we are able to impact delivery of drug from electrospun materials, and also apply them in tissue engineering for the reversible presentation of biomolecules on a fiber surface.

  8. Calcium phosphate ceramics in drug delivery

    NASA Astrophysics Data System (ADS)

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

    2011-04-01

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

  9. Designing hydrogels for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Li, Jianyu; Mooney, David J.

    2016-12-01

    Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform on which various physiochemical interactions with the encapsulated drugs occur to control drug release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.

  10. Polymethacrylate microparticles gel for topical drug delivery.

    PubMed

    Labouta, Hagar Ibrahim; El-Khordagui, Labiba K

    2010-10-01

    Evaluating the potentials of particulate delivery systems in topical drug delivery. Polymethacrylate microparticles (MPs) incorporating verapamil hydrochloride (VRP) as a model hydrophilic drug with potential topical clinical uses, using Eudragit RS100 and Eudragit L100 were prepared for the formulation of a composite topical gel. The effect of initial drug loading, polymer composition, particularly the proportion of Eudragit L100 as an interacting polymer component and the HLB of the dispersing agent on MPs characteristics was investigated. A test MPs formulation was incorporated in gel and evaluated for drug release and human skin permeation. MPs showed high % incorporation efficiency and % yield. Composition of the hybrid polymer matrix was a main determinant of MPs characteristics, particularly drug release. Factors known to influence drug release such as MPs size and high drug solubility were outweighed by strong VRP-Eudragit L100 interaction. The developed MPs gel showed controlled VRP release and reduced skin retention compared to a free drug gel. Topical drug delivery and skin retention could be modulated using particulate delivery systems. From a practical standpoint, the VRP gel developed may offer advantage in a range of dermatological conditions, in response to the growing off-label topical use of VRP.

  11. Progress in antiretroviral drug delivery using nanotechnology

    PubMed Central

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-01-01

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

  12. The application of co-melt-extruded poly(ε-caprolactone) as a controlled release drug delivery device when combined with novel bioactive drug candidates: Membrane permeation and Hanson dissolution studies

    PubMed Central

    Gardyne, Stephen J.; Mucalo, Michael R.; Rathbone, Michael J.

    2011-01-01

    Eight bioactive drug compounds (abamectin, amoxicillin, dexamethasone, dexamethasone valerate, ketoprofen, melatonin, oestradiol 17β, and oestradiol benzoate) were combined via melt extrusion and disc pressing processes with a polycaprolactone (PCL) matrix and were then evaluated and compared via membrane diffusion and Hanson dissolution studies. This investigation was to determine the potential of this matrix to act as a controlled release drug delivery vehicle for a number of drugs not previously combined with PCL in a melt extrusion mix. The inclusion of the progesterone/PCL system, for which the drug release behaviour has been well studied before was intended for comparison with the PCL systems incorporating drugs that have received little research attention in the past. Initial studies centred on an evaluation of the permeation ability of the bioactive drugs dissolved in aqueous cyclodextrin solutions through a poly(ε-caprolactone) (PCL) membrane using Valia-Chien side-by-side cells. Permeation rates were mostly low and found to range from 0 to 122 μg h−1 with only ketoprofen, melatonin, and progesterone displaying rates exceeding 20 μg h−1. Hanson dissolution release profiles in aqueous alcohol were subsequently measured for the 9 melt extruded PCL/drug combinations and led to Hanson release rates of 0–556 μg cm−2 h−0.5 with dexamethasone, dexamethasone valerate, ketoprofen, melatonin, and progesterone giving values exceeding 100 μg cm−2 h−0.5. A number of drugs such as the dexamethasones probably performed better than they did in the permeability rate measurements because of the less polar aqueous alcoholic solvent used. In searching for useful correlations between the drug physicochemical properties and release rate, only a moderate correlation (R2=0.5675) between Hanson dissolution release rate and permeation rate was found. This suggests that the release rate and the permeation are both controlled by the rate of drug

  13. Multilayered materials based on biopolymers as drug delivery systems.

    PubMed

    Vilela, Carla; Figueiredo, Ana R P; Silvestre, Armando J D; Freire, Carmen S R

    2017-02-01

    The design of efficient therapeutic delivery devices has become a tremendously active area of research with a strong contribution from the layer-by-layer (LbL) technology. The application of this simple yet firmly established technique for the design of drug reservoirs originates a multitude of multilayered systems of tailored architecture and with a high level of control of drug administration. Areas covered: This review will focus on the most recent and original research on LbL assemblies based on biopolymers including polysaccharides, polypeptides and proteins, with potential use in drug delivery. Herein, drug reservoirs consisting of multilayered planar films and capsules will be examined with emphasis on the ones benefiting from the non-cytotoxic and biocompatible nature of biopolymers, which are suitable to load, protect and release a high payload of toxic and fragile drugs. Expert opinion: The combination of biopolymers with LbL technology has undergone extensive research, still, there is a multitude of R&D opportunities for the design of smart drug delivery systems with distinct multilayered morphologies, low immunological response, non-invasive drug release devices, as well as the design of theranostic systems combining diagnostics and therapeutic features. Further developments in terms of scaling towards mass production in the pharmaceutical industry are expected in the long-term.

  14. Hydrogen peroxide mediated transvaginal drug delivery.

    PubMed

    Fatakdawala, Hussain; Uhland, Scott A

    2011-05-16

    Simple, safe and effective permeability enhancers are crucial for successful non-invasive drug delivery methods. We seek local permeability augmentation mechanisms for integration into passive or active architectures in order to enable novel therapeutic delivery routes of the target drug while minimizing drug formulation challenges. This study explores the efficacy of hydrogen peroxide (HP) as a permeability enhancer for transmucosal delivery of macromolecules. HP at low concentrations (2–8 mM) is an effective permeability enhancer that is locally metabolized and safe. HP improves drug permeation through mucosa by altering tight junctions (TJ) between cells and oxidizing enzymes that function to degrade the foreign species. Results from trans-epithelial electrical resistance measurements and cell viability assay show reversible disassembly of TJ with minimal cell damage demonstrating the feasibility of HP as a safe permeability enhancer for drug delivery. Permeation studies show that HP treatment of cell cultured vaginal mucosa significantly enhances the permeability to insulin by more than an order of magnitude. This work lays foundation for the development of a drug delivery platform that administers drug doses by enhancing the permeability of local epithelial tissue via a separate HP treatment step.

  15. Transpapillary Drug Delivery to the Breast

    PubMed Central

    Dave, Kaushalkumar; Averineni, Ranjith; Sahdev, Preety; Perumal, Omathanu

    2014-01-01

    The study was aimed at investigating localized topical drug delivery to the breast via mammary papilla (nipple). 5-fluorouracil (5-FU) and estradiol (EST) were used as model hydrophilic and hydrophobic compounds respectively. Porcine and human nipple were used for in-vitro penetration studies. The removal of keratin plug enhanced the drug transport through the nipple. The drug penetration was significantly higher through the nipple compared to breast skin. The drug’s lipophilicity had a significant influence on drug penetration through nipple. The ducts in the nipple served as a major transport pathway to the underlying breast tissue. Results showed that porcine nipple could be a potential model for human nipple. The topical application of 5-FU on the rat nipple resulted in high drug concentration in the breast and minimal drug levels in plasma and other organs. Overall, the findings from this study demonstrate the feasibility of localized drug delivery to the breast through nipple. PMID:25545150

  16. Drug delivery implants in the treatment of vitreous inflammation.

    PubMed

    Wang, Jillian; Jiang, Angela; Joshi, Malav; Christoforidis, John

    2013-01-01

    The eye is a model organ for the local delivery of therapeutics. This proves beneficial when treating vitreous inflammation and other ophthalmic pathologies. The chronicity of certain diseases, however, limits the effectiveness of locally administered drugs. To maintain such treatments often requires frequent office visits and can result in increased risk of infection and toxicity to the patient. This paper focuses on the implantable devices and particulate drug delivery systems that are currently being implemented and investigated to overcome these challenges. Implants currently on the market or undergoing clinical trials include those made of nonbiodegradable polymers, containing ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and ranibizumab, and biodegradable polymers, containing dexamethasone, triamcinolone acetonide, and ranibizumab. Investigational intravitreal implants and particulate drug delivery systems, such as nanoparticles, microparticles, and liposomes, are also explored in this review article.

  17. Drug Delivery Implants in the Treatment of Vitreous Inflammation

    PubMed Central

    Wang, Jillian; Jiang, Angela; Joshi, Malav; Christoforidis, John

    2013-01-01

    The eye is a model organ for the local delivery of therapeutics. This proves beneficial when treating vitreous inflammation and other ophthalmic pathologies. The chronicity of certain diseases, however, limits the effectiveness of locally administered drugs. To maintain such treatments often requires frequent office visits and can result in increased risk of infection and toxicity to the patient. This paper focuses on the implantable devices and particulate drug delivery systems that are currently being implemented and investigated to overcome these challenges. Implants currently on the market or undergoing clinical trials include those made of nonbiodegradable polymers, containing ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and ranibizumab, and biodegradable polymers, containing dexamethasone, triamcinolone acetonide, and ranibizumab. Investigational intravitreal implants and particulate drug delivery systems, such as nanoparticles, microparticles, and liposomes, are also explored in this review article. PMID:24191132

  18. Novel biodegradable nanocarriers for enhanced drug delivery.

    PubMed

    Gagliardi, Mariacristina

    2016-12-01

    With the refinement of functional properties, the interest around biodegradable materials, in biorelated applications and, in particular, in their use as controlled drug-delivery systems, increased in the last decades. Biodegradable materials are an ideal platform to obtain nanoparticles for spatiotemporal controlled drug delivery for the in vivo administration, thanks to their biocompatibility, functionalizability, the control exerted on delivery rates and the complete degradation. Their application in systems for cancer treatment, brain and cardiovascular diseases is already a consolidated practice in research, while the bench-to-bedside translation is still late. This review aims at summarizing reported applications of biodegradable materials to obtain drug-delivery nanoparticles in the last few years, giving a complete overview of pros and cons related to degradable nanomedicaments.

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

    PubMed

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

    2013-02-21

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

  20. Novel drug delivery systems for glaucoma

    PubMed Central

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

    2011-01-01

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

  1. Molecular diagnosis using multi drug delivery network and stability.

    PubMed

    Jalil, M A; Innate, K; Suwanpayak, N; Yupapin, P P; Ali, J

    2011-12-01

    By using a pair of tweezers to generate the intense optical vortices within the PANDA ring resonator, the required molecules (drug volumes) can be trapped and moved dynamically within the molecular bus networks, in which the required diagnosis or drug delivery targets can be performed within the network. The advantage of the proposed system is that the proposed diagnostic method can perform within the tiny system (thin film device or circuit), which can be available for a human embedded device for diagnostic use. The channel spacing of the trapped volumes (molecules) within the bus molecular networks can be provided.

  2. Brain Mitochondrial Drug Delivery: Influence of Drug Physicochemical Properties

    PubMed Central

    Durazo, Shelley A.; Kadam, Rajendra S.; Drechsel, Derek; Patel, Manisha

    2017-01-01

    Purpose To determine the influence of drug physicochemical properties on brain mitochondrial delivery of 20 drugs at physiological pH. Methods The delivery of 8 cationic drugs (beta-blockers), 6 neutral drugs (corticosteroids), and 6 anionic drugs (non-steroidal anti-inflammatory drugs, NSAIDs) to isolated rat brain mitochondria was determined with and without membrane depolarization. Multiple linear regression was used to determine whether lipophilicity (Log D), charge, polarizability, polar surface area (PSA), and molecular weight influence mitochondrial delivery. Results The Log D for beta-blockers, corticosteroids, and NSAIDs was in the range of −1.41 to 1.37, 0.72 to 2.97, and −0.98 to 2, respectively. The % mitochondrial uptake increased exponentially with an increase in Log D for each class of drugs, with the uptake at a given lipophilicity obeying the rank order cationic>anionic>neutral. Valinomycin reduced membrane potential and the delivery of positively charged propranolol and betaxolol. The best equation for the combined data set was Log % Uptake=0.333 Log D+ 0.157 Charge – 0.887 Log PSA+2.032 (R2=0.738). Conclusions Drug lipopohilicity, charge, and polar surface area and membrane potential influence mitochondrial drug delivery, with the uptake of positively charged, lipophilic molecules being the most efficient. PMID:21796482

  3. Brain mitochondrial drug delivery: influence of drug physicochemical properties.

    PubMed

    Durazo, Shelley A; Kadam, Rajendra S; Drechsel, Derek; Patel, Manisha; Kompella, Uday B

    2011-11-01

    To determine the influence of drug physicochemical properties on brain mitochondrial delivery of 20 drugs at physiological pH. The delivery of 8 cationic drugs (beta-blockers), 6 neutral drugs (corticosteroids), and 6 anionic drugs (non-steroidal anti-inflammatory drugs, NSAIDs) to isolated rat brain mitochondria was determined with and without membrane depolarization. Multiple linear regression was used to determine whether lipophilicity (Log D), charge, polarizability, polar surface area (PSA), and molecular weight influence mitochondrial delivery. The Log D for beta-blockers, corticosteroids, and NSAIDs was in the range of -1.41 to 1.37, 0.72 to 2.97, and -0.98 to 2, respectively. The % mitochondrial uptake increased exponentially with an increase in Log D for each class of drugs, with the uptake at a given lipophilicity obeying the rank order cationic>anionic>neutral. Valinomycin reduced membrane potential and the delivery of positively charged propranolol and betaxolol. The best equation for the combined data set was Log % Uptake = 0.333 Log D + 0.157 Charge - 0.887 Log PSA + 2.032 (R(2) = 0.738). Drug lipopohilicity, charge, and polar surface area and membrane potential influence mitochondrial drug delivery, with the uptake of positively charged, lipophilic molecules being the most efficient.

  4. Lipid-Based Drug Delivery Systems

    PubMed Central

    Shrestha, Hina; Bala, Rajni; Arora, Sandeep

    2014-01-01

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

  5. Cellulose based polymeric systems in drug delivery

    USDA-ARS?s Scientific Manuscript database

    The pharmaceutical industry requires the development of biodegradable, biocompatible, non toxic, site specific drug delivery polymers, which can be easily coupled with drugs to be delivered orally, topically, locally, or parenterally. The use of the most abundant biopolymer, cellulose along with its...

  6. A Self-Powered Implantable Drug-Delivery System Using Biokinetic Energy.

    PubMed

    Song, Peiyi; Kuang, Shuangyang; Panwar, Nishtha; Yang, Guang; Tng, Danny Jian Hang; Tjin, Swee Chuan; Ng, Wun Jern; Majid, Maszenan Bin Abdul; Zhu, Guang; Yong, Ken-Tye; Wang, Zhong Lin

    2017-03-01

    The first triboelectric-nanogenerator (TENG)-based self-powered implantable drug-delivery system is presented. Pumping flow rates from 5.3 to 40 µL min(-1) under different rotating speeds of the TENG are realized. The implantable drug-delivery system can be powered with a TENG device rotated by human hand motion. Ex vivo trans-sclera drug delivery in porcine eyes is demonstrated by utilizing the biokinetic energies of human hands.

  7. Liposome-like Nanostructures for Drug Delivery

    PubMed Central

    Gao, Weiwei; Hu, Che-Ming J.; Fang, Ronnie H.; Zhang, Liangfang

    2013-01-01

    Liposomes are a class of well-established drug carriers that have found numerous therapeutic applications. The success of liposomes, together with recent advancements in nanotechnology, has motivated the development of various novel liposome-like nanostructures with improved drug delivery performance. These nanostructures can be categorized into five major varieties, namely: (1) polymer-stabilized liposomes, (2) nanoparticle-stabilized liposomes, (3) core-shell lipid-polymer hybrid nanoparticles, (4) natural membrane-derived vesicles, and (5) natural membrane coated nanoparticles. They have received significant attention and have become popular drug delivery platforms. Herein, we discuss the unique strengths of these liposome-like platforms in drug delivery, with a particular emphasis on how liposome-inspired novel designs have led to improved therapeutic efficacy, and review recent progress made by each platform in advancing healthcare. PMID:24392221

  8. 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.

  9. From micro- to nanostructured implantable device for local anesthetic delivery.

    PubMed

    Zorzetto, Laura; Brambilla, Paola; Marcello, Elena; Bloise, Nora; De Gregori, Manuela; Cobianchi, Lorenzo; Peloso, Andrea; Allegri, Massimo; Visai, Livia; Petrini, Paola

    2016-01-01

    Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies

  10. From micro- to nanostructured implantable device for local anesthetic delivery

    PubMed Central

    Zorzetto, Laura; Brambilla, Paola; Marcello, Elena; Bloise, Nora; De Gregori, Manuela; Cobianchi, Lorenzo; Peloso, Andrea; Allegri, Massimo; Visai, Livia; Petrini, Paola

    2016-01-01

    Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies

  11. Drug delivery approaches for breast cancer.

    PubMed

    Singh, Santosh Kumar; Singh, Shriti; Lillard, James W; Singh, Rajesh

    2017-01-01

    Breast cancer is one of the most common cancers affecting women worldwide. The controlled release of drugs to the precise site of the disease using a nanocarrier vehicle increases the therapeutic efficiency of the drugs. Nanotechnology-based approaches used to endorse clinical improvement from a disease also help to understand the interaction of malignant cells with their microenvironment. Receptor-based targeting is another approach for drug delivery which is undergoing clinical trials. Nanoparticles (NPs) delivery has been proven to promise high loading capacity, less toxicity, and stability of the drugs or biomolecules compared to traditional chemotherapeutic drugs. The goal of this review is to present the current problems of breast cancer therapy and discuss the NP-based targeting to overcome the hurdles of conventional drug therapy approach.

  12. Emulsion forming drug delivery system for lipophilic drugs.

    PubMed

    Wadhwa, Jyoti; Nair, Anroop; Kumria, Rachna

    2012-01-01

    In the recent years, there is a growing interest in the lipid-based formulations for delivery of lipophilic drugs. Due to their potential as therapeutic agents, preferably these lipid soluble drugs are incorporated into inert lipid carriers such as oils, surfactant dispersions, emulsions, liposomes etc. Among them, emulsion forming drug delivery systems appear to be a unique and industrially feasible approach to overcome the problem of low oral bioavailability associated with the BCS class II drugs. Self-emulsifying formulations are ideally isotropic mixtures of oils, surfactants and co-solvents that emulsify to form fine oil in water emulsions when introduced in aqueous media. Fine oil droplets would pass rapidly from stomach and promote wide distribution of drug throughout the GI tract, thereby overcome the slow dissolution step typically observed with solid dosage forms. Recent advances in drug carrier technologies have promulgated the development of novel drug carriers such as control release self-emulsifying pellets, microspheres, tablets, capsules etc. that have boosted the use of "self-emulsification" in drug delivery. This article reviews the different types of formulations and excipients used in emulsion forming drug delivery system to enhance the bioavailability of lipophilic drugs.

  13. Drug Delivery Research: The Invention Cycle.

    PubMed

    Park, Kinam

    2016-07-05

    Controlled drug delivery systems have been successful in introducing improved formulations for better use of existing drugs and novel delivery of biologicals. The initial success of producing many oral products and some injectable depot formulations, however, reached a plateau, and the progress over the past three decades has been slow. This is likely due to the difficulties of formulating hydrophilic, high molecular weight drugs, such as proteins and nucleic acids, for targeting specific cells, month-long sustained delivery, and pulsatile release. Since the approaches that have served well for delivery of small molecules are not applicable to large molecules, it is time to develop new methods for biologicals. The process of developing future drug delivery systems, termed as the invention cycle, is proposed, and it starts with clearly defining the problems for developing certain formulations. Once the problems are well-defined, creative imagination examines all potential options and selects the best answer and alternatives. Then, innovation takes over to generate unique solutions for developing new formulations that resolve the previously identified problems. Ultimately, the new delivery systems will have to go through a translational process to produce the final formulations for clinical use. The invention cycle also emphasizes examining the reasons for success of certain formulations, not just the reasons for failure of many systems. Implementation of the new invention cycle requires new mechanisms of funding the younger generation of scientists and a new way of identifying their achievements, thereby releasing them from the burden of short-termism.

  14. Ultrasonic Drug Delivery – A General Review

    PubMed Central

    Pitt, William G.; Husseini, Ghaleb A.; Staples, Bryant J.

    2006-01-01

    Ultrasound (US) has an ever-increasing role in the delivery of therapeutic agents including genetic material, proteins, and chemotherapeutic agents. Cavitating gas bodies such as microbubbles are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilize cell membranes and disrupt the vesicles that carry drugs. Thus the presence of microbubbles enormously enhances delivery of genetic material, proteins and smaller chemical agents. Delivery of genetic material is greatly enhanced by ultrasound in the presence of microbubbles. Attaching the DNA directly to the microbubbles or to gas-containing liposomes enhances gene uptake even further. US-enhanced gene delivery has been studied in various tissues including cardiac, vascular, skeletal muscle, tumor and even fetal tissue. US-enhanced delivery of proteins has found most application in transdermal delivery of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; it also makes the cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has upon cells and drug-carrying vesicles. PMID:16296719

  15. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

    PubMed

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse; Yang, Mingshi; Nielsen, Hanne Mørck; Mu, Huiling

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use of biorelevant media when applicable can increase the knowledge about the quality of DDS for oral protein delivery. Hopefully, the knowledge provided in this review will aid the establishment of improved biorelevant models capable of forecasting the performance of particulate DDS for oral peptide/protein delivery.

  16. Drug delivery systems for brain tumor therapy.

    PubMed

    Rautioa, Jarkko; Chikhale, Prashant J

    2004-01-01

    Brain tumors are one of the most lethal forms of cancer. They are extremely difficult to treat. Although, the rate of brain tumor incidence is relatively low, the field clearly lacks therapeutic strategies capable of overcoming barriers for effective delivery of drugs to brain tumors. Clinical failure of many potentially effective therapeutics for the treatment of brain tumors is usually not due to a lack of drug potency, but rather can be attributed to shortcomings in the methods by which a drug is delivered to the brain and into brain tumors. In response to the lack of efficacy of conventional drug delivery methods, extensive efforts have been made to develop novel strategies to overcome the obstacles for brain tumor drug delivery. The challenge is to design therapeutic strategies that deliver drugs to brain tumors in a safe and effective manner. This review provides some insight into several potential techniques that have been developed to improve drug delivery to brain tumors, and it should be helpful to clinicians and research scientists as well.

  17. Applications of chitosan nanoparticles in drug delivery.

    PubMed

    Tajmir-Riahi, H A; Nafisi, Sh; Sanyakamdhorn, S; Agudelo, D; Chanphai, P

    2014-01-01

    We have reviewed the binding affinities of several antitumor drugs doxorubicin (Dox), N-(trifluoroacetyl) doxorubicin (FDox), tamoxifen (Tam), 4-hydroxytamoxifen (4-Hydroxytam), and endoxifen (Endox) with chitosan nanoparticles of different sizes (chitosan-15, chitosan-100, and chitosan-200 KD) in order to evaluate the efficacy of chitosan nanocarriers in drug delivery systems. Spectroscopic and molecular modeling studies showed the binding sites and the stability of drug-polymer complexes. Drug-chitosan complexation occurred via hydrophobic and hydrophilic contacts as well as H-bonding network. Chitosan-100 KD was the more effective drug carrier than the chitosan-15 and chitosan-200 KD.

  18. Pulmonary drug delivery strategies: A concise, systematic review

    PubMed Central

    Patil, J. S.; Sarasija, S.

    2012-01-01

    Because of limitations associated with the conventional treatment of various chronic diseases a growing attention has been given to the development of targeted drug delivery systems. Pulmonary route of drug delivery gaining much importance in the present day research field as it enables to target the drug delivery directly to lung both for local and systemic treatment. Over the last 2 decades, the systemic absorption of a broad range of therapeutics after pulmonary application has been demonstrated in animals as well as in humans. This review was prepared with an aim to discuss the technical, physiological, and efficacy aspects of the novel pulmonary route of drug targeting. The review also focuses on the mechanisms of pulmonary drug administration along with compatibility of the excipients employed, devices used, and techniques of particulate dosage production. This review was prepared based on the method of extensive literature survey on the topics covering all the aspects discussed in the present subject. Hence, the better understanding of complexes and challenges facing the development of pulmonary drug delivery system offer an opportunity to the pharmaceutical scientist in minimizing the clinical and technical gaps. PMID:22345913

  19. Nanoparticles and microparticles for skin drug delivery.

    PubMed

    Prow, Tarl W; Grice, Jeffrey E; Lin, Lynlee L; Faye, Rokhaya; Butler, Margaret; Becker, Wolfgang; Wurm, Elisabeth M T; Yoong, Corinne; Robertson, Thomas A; Soyer, H Peter; Roberts, Michael S

    2011-05-30

    Skin is a widely used route of delivery for local and systemic drugs and is potentially a route for their delivery as nanoparticles. The skin provides a natural physical barrier against particle penetration, but there are opportunities to deliver therapeutic nanoparticles, especially in diseased skin and to the openings of hair follicles. Whilst nanoparticle drug delivery has been touted as an enabling technology, its potential in treating local skin and systemic diseases has yet to be realised. Most drug delivery particle technologies are based on lipid carriers, i.e. solid lipid nanoparticles and nanoemulsions of around 300 nm in diameter, which are now considered microparticles. Metal nanoparticles are now recognized for seemingly small drug-like characteristics, i.e. antimicrobial activity and skin cancer prevention. We present our unpublished clinical data on nanoparticle penetration and previously published reports that support the hypothesis that nanoparticles >10nm in diameter are unlikely to penetrate through the stratum corneum into viable human skin but will accumulate in the hair follicle openings, especially after massage. However, significant uptake does occur after damage and in certain diseased skin. Current chemistry limits both atom by atom construction of complex particulates and delineating their molecular interactions within biological systems. In this review we discuss the skin as a nanoparticle barrier, recent work in the field of nanoparticle drug delivery to the skin, and future directions currently being explored. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Lung surfactant as a drug delivery system.

    PubMed

    Vermehren, C; Frokjaer, S; Aurstad, T; Hansen, J

    2006-01-03

    Lung surfactant is a complex mixture of mainly phospholipids and proteins. The composition leads to a unique spreading effect of the surfactant as well as spontaneous vesicle formation, which may be favourable characteristics of a drug delivery system for pulmonary delivery. The aim of study was to investigate the potential use of the surfactant extract, HL10 (LeoPharma, DK) as a drug delivery system. Studies involved incorporation of hydrophilic- and amphipathic model drugs (sucrose and acylated peptides) into HL10 and elucidation of the influence of surfactant proteins on the HL10 behaviour. Results showed that HL10 vesicles did not retain sucrose indicating formation of leaky vesicles. Studying the influence of surfactant proteins on release from DPPC-liposomes showed tendencies toward a protein-induced release. Hence, the surfactant proteins may influence the membrane lipid packing and characteristics resulting in leakiness of the membranes. Incorporation of acylated peptides into HL10 depended on the chain length rendering a successful incorporation of the peptide acylated with C14-acyl chains. This study suggests that HL10 may be a promising drug delivery system for the pulmonary delivery of amphipathic drug substances, e.g. therapeutically active acylated peptides (e.g. acylated insulin).

  1. 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'.

  2. A smart multifunctional drug delivery nanoplatform for targeting cancer cells

    NASA Astrophysics Data System (ADS)

    Hoop, M.; Mushtaq, F.; Hurter, C.; Chen, X.-Z.; Nelson, B. J.; Pané, S.

    2016-06-01

    Wirelessly guided magnetic nanomachines are promising vectors for targeted drug delivery, which have the potential to minimize the interaction between anticancer agents and healthy tissues. In this work, we propose a smart multifunctional drug delivery nanomachine for targeted drug delivery that incorporates a stimuli-responsive building block. The nanomachine consists of a magnetic nickel (Ni) nanotube that contains a pH-responsive chitosan hydrogel in its inner cavity. The chitosan inside the nanotube serves as a matrix that can selectively release drugs in acidic environments, such as the extracellular space of most tumors. Approximately a 2.5 times higher drug release from Ni nanotubes at pH = 6 is achieved compared to that at pH = 7.4. The outside of the Ni tube is coated with gold. A fluorescein isothiocyanate (FITC) labeled thiol-ssDNA, a biological marker, was conjugated on its surface by thiol-gold click chemistry, which enables traceability. The Ni nanotube allows the propulsion of the device by means of external magnetic fields. As the proposed nanoarchitecture integrates different functional building blocks, our drug delivery nanoplatform can be employed for carrying molecular drug conjugates and for performing targeted combinatorial therapies, which can provide an alternative and supplementary solution to current drug delivery technologies.Wirelessly guided magnetic nanomachines are promising vectors for targeted drug delivery, which have the potential to minimize the interaction between anticancer agents and healthy tissues. In this work, we propose a smart multifunctional drug delivery nanomachine for targeted drug delivery that incorporates a stimuli-responsive building block. The nanomachine consists of a magnetic nickel (Ni) nanotube that contains a pH-responsive chitosan hydrogel in its inner cavity. The chitosan inside the nanotube serves as a matrix that can selectively release drugs in acidic environments, such as the extracellular space of

  3. Inhalation devices, delivery systems, and patient technique.

    PubMed

    Nelson, Harold S

    2016-12-01

    In real-life clinical settings, physicians often consider the properties of various inhaled corticosteroids (ICSs), but typically little consideration is given to the properties of different inhalers and formulations. To discuss the effects of inhalation devices and user technique on efficacy, safety, and adherence with the aim of improving asthma management. Relevant publications were selected to augment discussion. There are many types of devices available, each with advantages, disadvantages, ease of use, and rate of misuse. Aerosol particle size influences the deposition pattern of a drug in the lungs, and the optimal particle size range is 1 to 5 μm. Retrospective reviews suggest that smaller particles (1-2 μm) could provide improved asthma control, but randomized, prospective studies are needed. Multiple studies have demonstrated high misuse rates in patients for pressurized metered-dose inhalers and dry powder inhalers. Because of this, repeated education should include physical demonstrations of using the device, checking the patient's technique, correcting the technique, and rechecking the technique. This also means that dedicated, trained staff and placebo devices should be available for instructing patients. Furthermore, the device should be selected to be cost effective and to fit the patient's preference and ability to use it correctly to enhance compliance. Asthma management guidelines and algorithms are available to guide the clinician. The choice of inhaler device should depend on cost effectiveness and the patient's preference and ability to use it correctly. Patient inhaler technique should be checked and, if necessary, corrected and rechecked, with retraining if needed, at every opportunity. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Functional Cyclodextrin Polyrotaxanes for Drug Delivery

    NASA Astrophysics Data System (ADS)

    Yui, Nobuhiko; Katoono, Ryo; Yamashita, Atsushi

    The mobility of cyclodextrins (CDs) threaded onto a linear polymeric chain and the dethreading of the CDs from the chain are the most fascinating features seen in polyrotaxanes. These structural characteristics are very promising for their possible applications in drug delivery. Enhanced multivalent interaction between ligand-receptor systems by using ligand-conjugated polyrotaxanes would be just one of the excellent properties related to the CD mobility. Gene delivery using cytocleavable polyrotaxanes is a more practical but highly crucial issue in drug delivery. Complexation of the polyrotaxanes with DNA and its intracellular DNA release ingeniously utilizes both CD mobility and polyrotaxane dissociation to achieve effective gene delivery. Such a supramolecular approach using CD-containing polyrotaxanes is expected to exploit a new paradigm of biomaterials.

  5. Engineered Polymers for Advanced Drug Delivery

    PubMed Central

    Kim, Sungwon; Kim, Jong-Ho; Jeon, Oju; Kwon, Ick Chan; Park, Kinam

    2009-01-01

    Engineered polymers have been utilized for developing advanced drug delivery systems. The development of such polymers has caused advances in polymer chemistry, which, in turn, has resulted in smart polymers that can respond to changes in environmental condition, such as temperature, pH, and biomolecules. The responses vary widely from swelling/deswelling to degradation. Drug-polymer conjugates and drug-containing nano/micro-particles have been used for drug targeting. Engineered polymers and polymeric systems have also been used in new areas, such as molecular imaging as well as in nanotechnology. This review examines the engineered polymers that have been used as traditional drug delivery and as more recent applications in nanotechnology. PMID:18977434

  6. Nanoparticles and nanofibers for topical drug delivery

    PubMed Central

    Goyal, Ritu; Macri, Lauren K.; Kaplan, Hilton M.; Kohn, Joachim

    2016-01-01

    This review provides the first comprehensive overview of the use of both nanoparticles and nanofibers for topical drug delivery. Researchers have explored the use of nanotechnology, specifically nanoparticles and nanofibers, as drug delivery systems for topical and transdermal applications. This approach employs increased drug concentration in the carrier, in order to increase drug flux into and through the skin. Both nanoparticles and nanofibers can be used to deliver hydrophobic and hydrophilic drugs and are capable of controlled release for a prolonged period of time. The examples presented provide significant evidence that this area of research has—and will continue to have — a profound impact on both clinical outcomes and the development of new products. PMID:26518723

  7. Nanofibers: New Insights for Drug Delivery and Tissue Engineering.

    PubMed

    Haidar, Mohammad Karim; Eroglu, Hakan

    2017-01-01

    Nanofibers became one of the major research areas for drug delivery and tissue engineering applications in the last decade. Depending on the simplicity of the preparation method and high drug loading capacity, nanofibers provide many advantages for therapeutic perspectives. In addition, combined systems such as embedding nanoparticles into the nanofiber structures provide a second option for delivery of dual active ingredients in the same formulation. The release rate of the active ingredients can also be modified easily by the formulation parameters depending on the desired release time for treatment. Nanofibers systems are used for the delivery of antibiotics, anticancer drugs, analgesics, hemostatic agents and various proteins for tissue engineering purposes. In addition, various applications such as medical device coating also provide new insights for the clinical use of nanofibers. The most commonly used technique for preparation of nanofibers is the electrospinning, which provides feasibility background for scale up process from laboratory to the industrial applications. The main boundary for nanofibers is the limitations for systemic route. Nanofibers are mainly designed for the delivery of active ingredients for local purposes. Regardless of the therapeutic aim, nanofibers are also perfect 3 dimensional structures that are suitable for tissue regeneration. They provide matrix structure for cell regeneration especially in applications for wound healing. This review is mainly focused on the recent advances on the preparation of nanofibers, applications for drug delivery, tissue engineering and wound healing purposes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Genetically engineered nanocarriers for drug delivery

    PubMed Central

    Shi, Pu; Gustafson, Joshua A; MacKay, J Andrew

    2014-01-01

    Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins. PMID:24741309

  9. Nanoparticles in the ocular drug delivery

    PubMed Central

    Zhou, Hong-Yan; Hao, Ji-Long; Wang, Shuang; Zheng, Yu; Zhang, Wen-Song

    2013-01-01

    Ocular drug transport barriers pose a challenge for drug delivery comprising the ocular surface epithelium, the tear film and internal barriers of the blood-aqueous and blood-retina barriers. Ocular drug delivery efficiency depends on the barriers and the clearance from the choroidal, conjunctival vessels and lymphatic. Traditional drug administration reduces the clinical efficacy especially for poor water soluble molecules and for the posterior segment of the eye. Nanoparticles (NPs) have been designed to overcome the barriers, increase the drug penetration at the target site and prolong the drug levels by few internals of drug administrations in lower doses without any toxicity compared to the conventional eye drops. With the aid of high specificity and multifunctionality, DNA NPs can be resulted in higher transfection efficiency for gene therapy. NPs could target at cornea, retina and choroid by surficial applications and intravitreal injection. This review is concerned with recent findings and applications of NPs drug delivery systems for the treatment of different eye diseases. PMID:23826539

  10. Liposomes as delivery systems for antineoplastic drugs

    NASA Astrophysics Data System (ADS)

    Medina, Luis Alberto

    2014-11-01

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

  11. Barriers to drug delivery in solid tumors

    PubMed Central

    Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

    2014-01-01

    Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic. PMID:25068098

  12. Collagen-coated microparticles in drug delivery.

    PubMed

    Sehgal, Praveen Kumar; Srinivasan, Aishwarya

    2009-07-01

    Advantages of drug-incorporated collagen particles have been described for the controlled delivery system for therapeutic actions. The attractiveness of collagen lies in its low immunogenicity and high biocompatibility. It is also recognized by the body as a natural constituent rather than a foreign body. Our research and development efforts are focused towards addressing some of the limitations of collagen, like the high viscosity of an aqueous phase, nondissolution in neutral pH buffers, thermal instability (denaturation) and biodegradability, to make it an ideal material for drug delivery with particular reference to microparticles. These limitations could be overcome by making collagen conjugates with other biomaterials or chemically modifying collagen monomer without affecting its triple helical conformation and maintaining its native properties. This article highlights collagen microparticles' present status as a carrier in drug delivery.

  13. Ultrasound-mediated gastrointestinal drug delivery.

    PubMed

    Schoellhammer, Carl M; Schroeder, Avi; Maa, Ruby; Lauwers, Gregory Yves; Swiston, Albert; Zervas, Michael; Barman, Ross; DiCiccio, Angela M; Brugge, William R; Anderson, Daniel G; Blankschtein, Daniel; Langer, Robert; Traverso, Giovanni

    2015-10-21

    There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn's and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.

  14. Ultrasound-mediated gastrointestinal drug delivery

    PubMed Central

    Schoellhammer, Carl M.; Schroeder, Avi; Maa, Ruby; Lauwers, Gregory Yves; Swiston, Albert; Zervas, Michael; Barman, Ross; DiCiccio, Angela M.; Brugge, William R.; Anderson, Daniel G.; Blankschtein, Daniel; Langer, Robert; Traverso, Giovanni

    2016-01-01

    There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn’s and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease. PMID:26491078

  15. Ultrasonic drug delivery--a general review.

    PubMed

    Pitt, William G; Husseini, Ghaleb A; Staples, Bryant J

    2004-11-01

    Ultrasound has an ever-increasing role in the delivery of therapeutic agents, including genetic material, protein and chemotherapeutic agents. Cavitating gas bodies, such as microbubbles, are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilise cell membranes and disrupt the vesicles that carry drugs. Thus, the presence of microbubbles enormously enhances ultrasonic delivery of genetic material, proteins and smaller chemical agents. Numerous reports show that the most efficient delivery of genetic material occurs in the presence of cavitating microbubbles. Attaching the DNA directly to the microbubbles, or to gas-containing liposomes, enhances gene uptake even further. Ultrasonic-enhanced gene delivery has been studied in various tissues, including cardiac, vascular, skeletal muscle, tumour and even fetal tissue. Ultrasonic-assisted delivery of proteins has found most application in transdermal transport of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; and makes cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has on cells and drug-carrying vesicles.

  16. Light induced drug delivery into cancer cells.

    PubMed

    Shamay, Yosi; Adar, Lily; Ashkenasy, Gonen; David, Ayelet

    2011-02-01

    Cell-penetrating peptides (CPPs) can be used for intracellular delivery of a broad variety of cargoes, including various nanoparticulate pharmaceutical carriers. However, the cationic nature of all CPP sequences, and thus lack of cell specificity, limits their in vivo use for drug delivery applications. Here, we have devised and tested a strategy for site-specific delivery of dyes and drugs into cancer cells by using polymers bearing a light activated caged CPP (cCPP). The positive charge of Lys residues on the minimum sequence of the CPP penetratin ((52)RRMKWKK(58)) was masked with photo-cleavable groups to minimize non-specific adsorption and cellular uptake. Once illuminated by UV light, these protecting groups were cleaved, the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the polymer-dye or polymer-drug conjugates into cancer cells. We have found that a 10-min light illumination time was sufficient to enhance the penetration of the polymer-CPP conjugates bearing the proapoptotic peptide, (D)(KLAKLAK)(2), into 80% of the target cells, and to promote a 'switch' like cytotoxic activity resulting a shift from 100% to 10% in cell viability after 2 h. This report provides an example for tumor targeting by means of light activation of cell-penetrating peptides for intracellular drug delivery.

  17. Transungual drug delivery: current status.

    PubMed

    Elkeeb, Rania; AliKhan, Ali; Elkeeb, Laila; Hui, Xiaoying; Maibach, Howard I

    2010-01-15

    Topical therapy is highly desirable in treating nail disorders due to its localized effects, which results in minimal adverse systemic events and possibly improved adherence. However, the effectiveness of topical therapies is limited by minimal drug permeability through the nail plate. Current research on nail permeation that focuses on altering the nail plate barrier by means of chemical treatments, penetration enhancers as well as physical and mechanical methods is reviewed. A new method of nail sampling is examined. Finally limitations of current ungual drug permeability studies are briefly discussed.

  18. Applications of polymers in intraocular drug delivery systems

    PubMed Central

    Alhalafi, Ali Mohammed

    2017-01-01

    We are entering a new era of ophthalmic pharmacology where new drugs are rapidly being developed for the treatment of anterior and posterior segment of the eye disease. The pharmacokinetics of drug delivery to the eye remains a very active area of ophthalmic research. Intraocular drug delivery systems allow the release of the drug, bypassing the blood-ocular barrier. The main advantage of these preparations is that they can release the drug over a long time with one single administration. These pharmaceutical systems are of great important in the treatment of the posterior segment diseases, and they can be prepared from biodegradable or nonbiodegradable polymers. Biodegradable polymers have the advantage of disappearing from the site of action after releasing the drug. The majority of intraocular devices are prepared from nonbiodegradable polymers, and they can release controlled amounts of drugs for months. Nonbiodegradable polymers include silicone, polyvinyl alcohol, and ethylene-vinyl acetate. The polymers usually employed to prepare nanoparticles for the topical ophthalmic route are poly (acrylic acid) derivatives (polyalquilcyanocrylates), albumin, poly-ε-caprolactone, and chitosan. Dendrimers are a recent class of polymeric materials with unique nanostructure which has been studied to discover their role in the delivery of therapeutics and imaging agents. Hydrogels are polymers that can swell in aqueous solvent system, and they hold the solvents in a swollen cross-linked gel for delivery. This review exhibits the current literature regarding applications of polymers in ophthalmic drug delivery systems including pharmacokinetics, advantages, disadvantages, and indications aimed to obtain successful eye therapy. Method of Literature Search: A systematic literature review was performed using PubMed databases into two steps. The first step was oriented to classification of intraocular polymers implants focusing on their advantages and disadvantages. The second

  19. Zwitterionic drug nanocarriers: a biomimetic strategy for drug delivery.

    PubMed

    Jin, Qiao; Chen, Yangjun; Wang, Yin; Ji, Jian

    2014-12-01

    Nanomaterials self-assembled from amphiphilic functional copolymers have emerged as safe and efficient nanocarriers for delivery of therapeutics. Surface engineering of the nanocarriers is extremely important for the design of drug delivery systems. Bioinspired zwitterions are considered as novel nonfouling materials to construct biocompatible and bioinert nanocarriers. As an alternative to poly(ethylene glycol) (PEG), zwitterions exhibit some unique properties that PEG do not have. In this review, we highlight recent progress of the design of drug nanocarriers using a zwitterionic strategy. The possible mechanism of stealth properties of zwitterions was proposed. The advantages of zwitterionic drug nanocarriers deriving from phosphorylcholine (PC), carboxybetaine (CB), and sulfobetaine (SB) are also discussed.

  20. 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

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

    PubMed

    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.

  2. Plasmon resonant liposomes for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Knights-Mitchell, Shellie S.; Romanowski, Marek

    2015-03-01

    Nanotechnology use in drug delivery promotes a reduction in systemic toxicity, improved pharmacokinetics, and better drug bioavailability. Liposomes continue to be extensively researched as drug delivery systems (DDS) with formulations such as Doxil® and Ambisome® approved by FDA and successfully marketed in the United States. However, the limited ability to precisely control release of active ingredients from these vesicles continues to challenge the broad implementation of this technology. Moreover, the full potential of the carrier to sequester drugs until it can reach its intended target has yet to be realized. Here, we describe a liposomal DDS that releases therapeutic doses of an anticancer drug in response to external stimulus. Earlier, we introduced degradable plasmon resonant liposomes. These constructs, obtained by reducing gold on the liposome surface, facilitate spatial and temporal release of drugs upon laser light illumination that ultimately induces an increase in temperature. In this work, plasmon resonant liposomes have been developed to stably encapsulate and retain doxorubicin at physiological conditions represented by isotonic saline at 37o C and pH 7.4. Subsequently, they are stimulated to release contents either by a 5o C increase in temperature or by laser illumination (760 nm and 88 mW/cm2 power density). Successful development of degradable plasmon resonant liposomes responsive to near-infrared light or moderate hyperthermia can provide a new delivery method for multiple lipophilic and hydrophilic drugs with pharmacokinetic profiles that limit clinical utility.

  3. 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.

  4. Tuberculosis chemotherapy: current drug delivery approaches

    PubMed Central

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

    2006-01-01

    Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance. PMID:16984627

  5. Advances in Drug Delivery to the Posterior Segment

    PubMed Central

    Pearce, William; Hsu, Jason; Yeh, Steven

    2015-01-01

    Purpose Emerging developments and research for drug delivery to the posterior segment offer a promising future for the treatment of vitreoretinal disease. As new technologies enter the market, clinicians should be aware of new indications and ongoing clinical trials. Recent Findings This review summarizes the advantages and shortcomings of the most commonly used drug delivery methods including vitreous dynamics, physician sustainability and patient preferences. Currently available intravitreal corticosteroid-release devices offer surgical and in-office management of retinal vascular disease and posterior uveitis. The suprachoroidal space offers a new anatomic location for the delivery of lower dose medications directly to the target tissue. Implantable drug reservoirs would potentially allow for less frequent intravitreal injections reducing treatment burdens and associated risks. Newer innovations in encapsulated cell technology offer promising results in early clinical trials. Summary While pars plana intravitreal injection remains the mainstay of therapy for many vitreoretinal diseases, targeted delivery and implantable eluting devices are rapidly demonstrating safety and efficacy. These therapeutic modalities offer promising options for the vitreoretinal therapeutic landscape. PMID:25759965

  6. Advances in drug delivery to the posterior segment.

    PubMed

    Pearce, William; Hsu, Jason; Yeh, Steven

    2015-05-01

    Emerging developments and research for drug delivery to the posterior segment offer a promising future for the treatment of vitreoretinal disease. As new technologies enter the market, clinicians should be aware of new indications and ongoing clinical trials. This review summarizes the advantages and shortcomings of the most commonly used drug delivery methods, including vitreous dynamics, physician sustainability and patient preferences. Currently available, intravitreal, corticosteroid-release devices offer surgical and in-office management of retinal vascular disease and posterior uveitis. The suprachoroidal space offers a new anatomic location for the delivery of lower dose medications directly to the target tissue. Implantable drug reservoirs would potentially allow for less frequent intravitreal injections reducing treatment burdens and associated risks. Newer innovations in encapsulated cell technology offer promising results in early clinical trials. Although pars plana intravitreal injection remains the mainstay of therapy for many vitreoretinal diseases, targeted delivery and implantable eluting devices are rapidly demonstrating safety and efficacy. These therapeutic modalities offer promising options for the vitreoretinal therapeutic landscape.

  7. Ingestion of drugs by "parachuting": a unique drug delivery technique.

    PubMed

    Kenerson, Katherine L; Lear-Kaul, Kelly C

    2012-06-01

    "Parachuting" is a technique of drug delivery where medications or illicit drugs are ingested by wrapping the drug of choice in a covering, which then will dissolve or unravel in the gastrointestinal tract, thereby releasing the drug for absorption. Parachuting of drugs can entail crushing of a pill prior to packaging to theoretically increase the surface area for absorption or may involve the packaging of a higher than usual dose of a drug in attempts to attain a sustained-release effect as the "parachute" dissolves or unravels. A case is presented in which a prescription drug abuser known to parachute his medications dies from obstruction of his airway by the inhaled packet. Risks of parachuting any drug would include overdose and fatal toxic effect from the drug itself and adverse effects from the packaging including bowel obstruction or perforation, or airway obstruction.

  8. Drug delivery applications with ethosomes.

    PubMed

    Ainbinder, D; Paolino, D; Fresta, M; Touitou, E

    2010-10-01

    Ethosomes are specially tailored vesicular carriers able to efficiently deliver various molecules with different physicochemical properties into deep skin layers and across the skin. This paper reviews the unique characteristics of the ethosomal carriers, focusing on work carried out with drug containing ethosomal systems in animal models and in clinical studies. The paper concludes with a discussion on the safety of the ethosomal system applications.

  9. Intracranial drug delivery for subarachnoid hemorrhage.

    PubMed

    Macdonald, Robert Loch; Leung, Ming; Tice, Tom

    2012-01-01

    Tice and colleagues pioneered site-specific, sustained-release drug delivery to the brain almost 30 years ago. Currently there is one drug approved for use in this manner. Clinical trials in subarachnoid hemorrhage have led to approval of nimodipine for oral and intravenous use, but other drugs, such as clazosentan, hydroxymethylglutaryl CoA reductase inhibitors (statins) and magnesium, have not shown consistent clinical efficacy. We propose that intracranial delivery of drugs such as nimodipine, formulated in sustained-release preparations, are good candidates for improving outcome after subarachnoid hemorrhage because they can be administered to patients that are already undergoing surgery and who have a self-limited condition from which full recovery is possible.

  10. Biodegradable Hybrid Stomatocyte Nanomotors for Drug Delivery.

    PubMed

    Tu, Yingfeng; Peng, Fei; André, Alain A M; Men, Yongjun; Srinivas, Mangala; Wilson, Daniela A

    2017-02-28

    We report the self-assembly of a biodegradable platinum nanoparticle-loaded stomatocyte nanomotor containing both PEG-b-PCL and PEG-b-PS as a potential candidate for anticancer drug delivery. Well-defined stomatocyte structures could be formed even after incorporation of 50% PEG-b-PCL polymer. Demixing of the two polymers was expected at high percentage of semicrystalline poly(ε-caprolactone) (PCL), resulting in PCL domain formation onto the membrane due to different properties of two polymers. The biodegradable motor system was further shown to move directionally with speeds up to 39 μm/s by converting chemical fuel, hydrogen peroxide, into mechanical motion as well as rapidly delivering the drug to the targeted cancer cell. Uptake by cancer cells and fast doxorubicin drug release was demonstrated during the degradation of the motor system. Such biodegradable nanomotors provide a convenient and efficient platform for the delivery and controlled release of therapeutic drugs.

  11. Biodegradable Hybrid Stomatocyte Nanomotors for Drug Delivery

    PubMed Central

    2017-01-01

    We report the self-assembly of a biodegradable platinum nanoparticle-loaded stomatocyte nanomotor containing both PEG-b-PCL and PEG-b-PS as a potential candidate for anticancer drug delivery. Well-defined stomatocyte structures could be formed even after incorporation of 50% PEG-b-PCL polymer. Demixing of the two polymers was expected at high percentage of semicrystalline poly(ε-caprolactone) (PCL), resulting in PCL domain formation onto the membrane due to different properties of two polymers. The biodegradable motor system was further shown to move directionally with speeds up to 39 μm/s by converting chemical fuel, hydrogen peroxide, into mechanical motion as well as rapidly delivering the drug to the targeted cancer cell. Uptake by cancer cells and fast doxorubicin drug release was demonstrated during the degradation of the motor system. Such biodegradable nanomotors provide a convenient and efficient platform for the delivery and controlled release of therapeutic drugs. PMID:28187254

  12. Vaginal drug delivery systems for HIV prevention.

    PubMed

    Rohan, Lisa Cencia; Sassi, Alexandra B

    2009-03-01

    Microbicides have become a principal focus for HIV prevention strategies. The successful design of drug delivery systems for vaginal microbicide drug candidates brings with it a multitude of challenges. It is imperative that the chemical and physical characteristics of the drug candidate and its mechanism of action be clearly understood and considered to successfully deliver and target drug candidates efficiently. In addition, an understanding of the dynamic nature of the vaginal environment, the tissue and innate barriers present, as well as patient preferences are critical considerations in the design of effective microbicide products. Although the majority of drug candidates clinically evaluated to date have been delivered using conventional semisolid aqueous-based gel dosage forms, drug delivery system design has recently been extended to include advanced delivery systems such as vaginal rings, quick-dissolve films, and tablets. Ultimately, it may be necessary to develop multiple dosage platforms for a single active agent to provide users with options that can be used within the constraints of their social environment, personal choice, and environmental conditions.

  13. Evaluation of oral medication delivery devices provided by community pharmacies.

    PubMed

    Honey, Brooke L; Condren, Michelle; Phillips, Christina; Votruba, Allyson

    2013-05-01

    Oral liquids remain common medication dosage forms used for patients who have difficulty swallowing. However, liquids require a delivery device and thus have been linked to medication administration errors. This study identified medication delivery devices available at pharmacies. Delivery devices were obtained from area pharmacies and analyzed for units of measurement, abbreviations, and largest/smallest measurable volume. A total of 58 devices were collected from 22 pharmacies. All devices were marked with mL, and 79% were additionally marked in teaspoons. The 5-mL syringe was the only device dispensed at 14% of locations. Other devices included the dosing spoon, dropper, and cup. The largest measurable volume was 30 mL, whereas the smallest was 0.01 mL, with significant variability among devices. A more consistent approach in prescribing units of measurement is needed. Prescribing in milliliters is an optimal choice because of the accessibility of measuring devices containing this measurement.

  14. Multi-access drug delivery network and stability

    PubMed Central

    Mitatha, S; Moongfangklang, N; Jalil, MA; Suwanpayak, N; Ali, J; Yupapin, PP

    2011-01-01

    A novel design of a multi-drug delivery network and diagnosis using a molecular network is proposed. By using a pair of tweezers to generate the intense optical vortices within the PANDA ring resonator, the required molecules (drug volumes) can be trapped and moved dynamically within the molecular bus networks, in which the required drug delivery targets can be achieved within the network. The advantage of the proposed system is that the diagnostic method can be used within a tiny system (thin film device or circuit), which is available as an embedded device for diagnostic use in patients. In practice, the large molecular networks such as ring, star, and bus networks can be integrated to form a large drug delivery system. The channel spacing of the trapped volumes (molecules) within the bus molecular networks can be provided by using the appropriate free spectrum range, which is analyzed and discussed in the terms of crosstalk effects. In this work, crosstalk effects of about 0.1% are noted, which can be neglected and does not affect the network stability. PMID:21980238

  15. Optically generated ultrasound for enhanced drug delivery

    DOEpatents

    Visuri, Steven R.; Campbell, Heather L.; Da Silva, Luiz

    2002-01-01

    High frequency acoustic waves, analogous to ultrasound, can enhance the delivery of therapeutic compounds into cells. The compounds delivered may be chemotherapeutic drugs, antibiotics, photodynamic drugs or gene therapies. The therapeutic compounds are administered systemically, or preferably locally to the targeted site. Local delivery can be accomplished through a needle, cannula, or through a variety of vascular catheters, depending on the location of routes of access. To enhance the systemic or local delivery of the therapeutic compounds, high frequency acoustic waves are generated locally near the target site, and preferably near the site of compound administration. The acoustic waves are produced via laser radiation interaction with an absorbing media and can be produced via thermoelastic expansion, thermodynamic vaporization, material ablation, or plasma formation. Acoustic waves have the effect of temporarily permeabilizing the membranes of local cells, increasing the diffusion of the therapeutic compound into the cells, allowing for decreased total body dosages, decreased side effects, and enabling new therapies.

  16. Recent Perspectives in Ocular Drug Delivery

    PubMed Central

    Gaudana, Ripal; Jwala, J.; Boddu, Sai H. S.; Mitra, Ashim K.

    2015-01-01

    Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders. PMID:18758924

  17. A Two-Layer Mathematical Modelling of Drug Delivery to Biological Tissues

    NASA Astrophysics Data System (ADS)

    Chakravarty, Koyel; Dalal, D. C.

    2016-10-01

    Local drug delivery has received much recognition in recent years, yet it is still unpredictable how drug efficacy depends on physicochemical properties and delivery kinetics. The purpose of the current study is to provide a useful mathematical model for drug release from a drug delivery device and consecutive drug transport in biological tissue, thereby aiding the development of new therapeutic drug by a systemic approach. In order to study the complete process, a two-layer spatio-temporal model depicting drug transport between the coupled media is presented. Drug release is described by considering solubilisation dynamics of drug particle, diffusion of the solubilised drug through porous matrix and also some other processes like reversible dissociation / recrystallization, drug particle-receptor binding and internalization phenomena. The model has led to a system of partial differential equations describing the important properties of drug kinetics. This model contributes towards the perception of the roles played by diffusion, mass-transfer, particle binding and internalization parameters.

  18. Drug delivery strategies for poorly water-soluble drugs.

    PubMed

    Fahr, Alfred; Liu, Xiangli

    2007-07-01

    The drug candidates coming from combinatorial chemistry research and/or the drugs selected from biologically based high-throughput screening are quite often very lipophilic, as these drug candidates exert their pharmacological action at or in biological membranes or membrane-associated proteins. This challenges drug delivery institutions in industry or academia to develop carrier systems for the optimal oral and parenteral administration of these drugs. To mention only a few of the challenges for this class of drugs: their oral bioavailability is poor and highly variable, and carrier development for parenteral administration is faced with problems, including the massive use of surface-active excipients for solubilisation. Formulation specialists are confronted with an even higher level of difficulties when these drugs have to be delivered site specifically. This article addresses the emerging formulation designs for delivering of poorly water-soluble drugs.

  19. Controlled delivery of naltrexone by an intraoral device: in vivo study on human subjects.

    PubMed

    Paderni, Carlo; Campisi, Giuseppina; Schumacher, Axel; Göttsche, Thorsten; Giannola, Libero Italo; De Caro, Viviana; Wolff, Andy

    2013-08-16

    Naltrexone is widely used in the treatment of opiate addiction but its current peroral administration is characterized by low bioavailability with various side effects. The development of a long-acting transbuccal delivery device (IntelliDrug) for NLX may be useful to improve patient compliance and the therapy effectiveness. The aims of the study are (a) to test basic safety and effectiveness of controlled transbuccal drug delivery on human subjects; (b) to compare NLX bioavailability following transbuccal delivery vs per os conventional delivery; and (c) to test the hypothesis that transbuccal delivery is more efficient than the conventional route. In this randomized cross-over pilot study, 12 healthy subjects received in a different order 2 types of NLX administration, per os or transbuccal delivery, based on which group they were randomized to. For per os administration 50mg NLX tablets were used, while for transbuccal administration, a NLX-loaded prototype of the IntelliDrug device was fixed on patients' dental arch. Serial blood samples were drawn and analysed for the NLX concentration. The IntelliDrug prototype functioned properly and it did not exert any adverse side-effect. The transbuccal route resulted in administration efficiency 4-17 times higher than conventional per os route. Transbuccal delivery of NLX appears to be a more efficient drug administration route compared to peroral one. It allows to reach a given therapeutic blood level using a small drug dose. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Applications of ethylene vinyl acetate copolymers (EVA) in drug delivery systems.

    PubMed

    Schneider, Christian; Langer, Robert; Loveday, Donald; Hair, Dirk

    2017-09-28

    The potential for use of polymers in controlled drug delivery systems has been long recognized. Since their appearance in the literature, a wide range of degradable and non-degradable polymers have been demonstrated in drug delivery devices. The significance and features of ethylene-vinyl acetate (EVA) copolymers in initial research and development led to commercial drug delivery systems. This review examines the breadth of EVA use in drug delivery, and will aid the researcher in locating key references and experimental results, as well as understanding the features of EVA as a highly versatile, biocompatible polymer for drug delivery devices. Topics will include. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Annual update: drugs, diagnostics and devices.

    PubMed

    Berardinelli, Candace; Kupecz, Deborah

    2003-03-01

    As NPs continue to play an important role in health care as administers of prescriptions, the value of reviewing the latest Food and Drug Administration (FDA) approvals for new drugs and devices is immeasurable. In 2002, the FDA approved several new drugs and devices, as well as monitored previously approved drugs for adverse reactions and untoward events. This article provides a brief review of relevant primary care topics.

  2. Potential new methods for antiepileptic drug delivery.

    PubMed

    Fisher, Robert S; Ho, Jet

    2002-01-01

    Use of novel drug delivery methods could enhance the efficacy and reduce the toxicity of antiepileptic drugs (AEDs). Slow-release oral forms of medication or depot drugs such as skin patches might improve compliance and therefore seizure control. In emergency situations, administration via rectal, nasal or buccal mucosa can deliver the drug more quickly than can oral administration. Slow-release oral forms and rectal forms of AEDs are already approved for use, nasal and buccal administration is currently off-label and skin patches for AEDs are an attractive but currently hypothetical option. Therapies under development may result in the delivery of AEDs directly to the regions of the brain involved in seizures. Experimental protocols are underway to allow continuous infusion of potent excitatory amino acid antagonists into the CSF. In experiments with animal models of epilepsy, AEDs have been delivered successfully to seizure foci in the brain by programmed infusion pumps, acting in response to computerised EEG seizure detection. Inactive prodrugs can be given systemically and activated at the site of the seizure focus by locally released compounds. One such drug under development is DP-VPA (or DP16), which is cleaved to valproic acid (sodium valproate) by phospholipases at the seizure focus. Liposomes and nanoparticles are engineered micro-reservoirs of a drug, with attached antibodies or receptor-specific binding agents designed to target the particles to a specific region of the body. Liposomes in theory could deliver a high concentration of an AED to a seizure focus. Penetration of the blood-brain barrier can be accomplished by linking large particles to iron transferrin or biological toxins that can cross the barrier. In the near future, it is likely that cell transplants that generate neurotransmitters and neuromodulators will accomplish renewable endogenous drug delivery. However, the survival and viability of transplanted cells have yet to be demonstrated

  3. Advanced materials and nanotechnology for drug delivery.

    PubMed

    Yan, Li; Yang, Yang; Zhang, Wenjun; Chen, Xianfeng

    2014-08-20

    Many biological barriers are of great importance. For example, stratum corneum, the outmost layer of skin, effectively protects people from being invaded by external microorganisms such as bacteria and viruses. Cell membranes help organisms maintain homeostasis by controlling substances to enter and leave cells. However, on the other hand, these biological barriers seriously restrict drug delivery. For instance, stratum corneum has a very dense structure and only allows very small molecules with a molecular weight of below 500 Da to permeate whereas most drug molecules are much larger than that. A wide variety of drugs including genes needs to enter cells for proper functioning but cell membranes are not permeable to them. To overcome these biological barriers, many drug-delivery routes are being actively researched and developed. In this research news, we will focus on two advanced materials and nanotechnology approaches for delivering vaccines through the skin for painless and efficient immunization and transporting drug molecules to cross cell membranes for high-throughput intracellular delivery. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Structural DNA nanotechnology for intelligent drug delivery.

    PubMed

    Chao, Jie; Liu, Huajie; Su, Shao; Wang, Lianhui; Huang, Wei; Fan, Chunhai

    2014-11-01

    Drug delivery carriers have been popularly employed to improve solubility, stability, and efficacy of chemical and biomolecular drugs. Despite the rapid progress in this field, it remains a great challenge to develop an ideal carrier with minimal cytotoxicity, high biocompatibility and intelligence for targeted controlled release. The emergence of DNA nanotechnology offers unprecedented opportunities in this regard. Due to the unparalleled self-recognition properties of DNA molecules, it is possible to create numerous artificial DNA nanostructures with well-defined structures and DNA nanodevices with precisely controlled motions. More importantly, recent studies have proven that DNA nanostructures possess greater permeability to the membrane barrier of cells, which pave the way to developing new drug delivery carriers with nucleic acids, are summarized. In this Concept, recent advances on the design and fabrication of both static and dynamic DNA nanostructures, and the use of these nanostructures for the delivery of various types of drugs, are highlighted. It is also demonstrated that dynamic DNA nanostructures provide the required intelligence to realize logically controlled drug release. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Oral transmucosal drug delivery for pediatric use.

    PubMed

    Lam, Jenny K W; Xu, Yingying; Worsley, Alan; Wong, Ian C K

    2014-06-01

    The formulation of medicines for children remains a challenge. An ideal pediatric formulation must allow accurate dose administration and be in a dosage form that can be handled by the target age group. It is also important to consider the choices and the amount of excipients used in the formulation for this vulnerable age group. Although oral formulations are generally acceptable to most pediatric patients, they are not suitable for drugs with poor oral bioavailability or when a rapid clinical effect is required. In recent years, oral transmucosal delivery has emerged as an attractive route of administration for pediatric patients. With this route of administration, a drug is absorbed through the oral mucosa, therefore bypassing hepatic first pass metabolism and thus avoiding drug degradation or metabolism in the gastrointestinal tract. The high blood flow and relatively high permeability of the oral mucosa allow a quick onset of action to be achieved. It is a simple and non-invasive route of drug administration. However, there are several barriers that need to be overcome in the development of oral transmucosal products. This article aims to provide a comprehensive review of the current development of oral transmucosal delivery specifically for the pediatric population in order to achieve systemic drug delivery. The anatomical and physiological properties of the oral mucosa of infants and young children are carefully examined. The different dosage forms and formulation strategies that are suitable for young patients are discussed.

  6. Chitosan magnetic nanoparticles for drug delivery systems.

    PubMed

    Assa, Farnaz; Jafarizadeh-Malmiri, Hoda; Ajamein, Hossein; Vaghari, Hamideh; Anarjan, Navideh; Ahmadi, Omid; Berenjian, Aydin

    2017-06-01

    The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.

  7. Optimal Control of Objects on the Micro- and Nano-Scale by Electrokinetic and Electromagnetic Manipulation: for Bio-Sample Preparation, Quantum Information Devices and Magnetic Drug Delivery

    DTIC Science & Technology

    2010-01-01

    Tumor Remission in Yoshida Sarcoma -Bearing Rats by Selective Targeting of Magnetic Albumin Microspheres Containing Doxorubicin. PNAS, 1981. 78(1...administered magnetic liposomes in osteosarcoma -bearing hamsters. International Journal of Oncology, 2000. 17(2): p. 309-315. 110. Hirao, K., et al...Targeted gene delivery to human osteosarcoma cells with magnetic cationic liposomes under a magnetic field. International Journal of Oncology, 2003

  8. 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

  9. Mucoadhesive polymeric platforms for controlled drug delivery.

    PubMed

    Andrews, Gavin P; Laverty, Thomas P; Jones, David S

    2009-03-01

    The process of mucoadhesion involving a polymeric drug delivery platform is a complex one that includes wetting, adsorption and interpenetration of polymer chains amongst various other processes. The success and degree of mucoadhesion bonding is influenced by various polymer-based properties such as the degree of cross-linking, chain length and the presence of various functional groupings. The attractiveness of mucosal-targeted controlled drug delivery of active pharmaceutical ingredients (APIs), has led formulation scientists to engineer numerous polymeric systems for such tasks. Formulation scientists have at their disposal a range of in vitro and in vivo mucoadhesion testing setups in order to select candidate adhesive drug delivery platforms. As such, mucoadhesive systems have found wide use throughout many mucosal covered organelles for API delivery for local or systemic effect. Evolution of such mucoadhesive formulations has transgressed from first-generation charged hydrophilic polymer networks to more specific second-generation systems based on lectin, thiol and various other adhesive functional groups.

  10. Drug delivery optimization through Bayesian networks.

    PubMed Central

    Bellazzi, R.

    1992-01-01

    This paper describes how Bayesian Networks can be used in combination with compartmental models to plan Recombinant Human Erythropoietin (r-HuEPO) delivery in the treatment of anemia of chronic uremic patients. Past measurements of hematocrit or hemoglobin concentration in a patient during the therapy can be exploited to adjust the parameters of a compartmental model of the erythropoiesis. This adaptive process allows more accurate patient-specific predictions, and hence a more rational dosage planning. We describe a drug delivery optimization protocol, based on our approach. Some results obtained on real data are presented. PMID:1482938

  11. Mucoadhesive in situ nasal gelling drug delivery systems for modulated drug delivery.

    PubMed

    Singh, Reena M P; Kumar, Anil; Pathak, Kamla

    2013-01-01

    The nasal route is an attractive target for administration of the drug of choice, particularly in overcoming disadvantages such as high first-pass metabolism and drug degradation in the gastrointestinal environment that are associated with the oral and other modes of administration. The major limitation associated is of rapid mucociliary clearance in the nasal delivery that results in low absorption and hence poor bioavailability. In order to overcome this, mucoadhesive in situ nasal gelling drug delivery systems have been explored to develop sustained/controlled delivery via nasal route. The present review critically evaluates the importance of in situ gel for the nasal delivery of drugs, and the polymers used in the formulation of in situ gel along with their mechanism of gelation. It also encompasses the research reports made in this arena of delivery system. The challenges of drug delivery through nose has led to development of in situ nasal gelling systems using a myriad of polymers to deliver the drugs, proteins, amino acids, hormones, vaccines and plasmid DNA for the local, systemic and central nervous system effects. Though a range of preclinical reports are available, clinical intricacies need to be critically worked out.

  12. Multifunctional High Drug Loading Nanocarriers for Cancer Drug Delivery

    NASA Astrophysics Data System (ADS)

    Jin, Erlei

    2011-12-01

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

  13. Enhancing transdermal drug delivery with electroporation.

    PubMed

    Wong, Tak-Wah; Ko, Shu-Fen; Hui, Sek-Wen

    2008-01-01

    The application of electroporation to enhance transdermal delivery has opened up a new possibility to introduce larger molecules such as peptide hormones and vaccines as well as minigenes and RNAi etc. through the transdermal route. Many devices have been developed to deliver the pulse electric field needed to permeate the skin. These devices include both non-puncturing surface electrodes as well as puncturing electrodes of different geometrical arrangements. The latter type uses electroporation only to increase uptake of molecules injected through the puncturing electrode or syringe. Different electroporation protocols have been developed to maximize transport, uptake and minimizing pain. Synergistic effect of chemical enhancers and physical (sonic, vibrational and thermal) treatments are used to enhance the transport. This article reviews the patents pertaining to the instrumentation as well as application protocols of transdermal delivery, uptake enhancement and interstitial fluid sampling by electroporation.

  14. A new brain drug delivery strategy: focused ultrasound-enhanced intranasal drug delivery.

    PubMed

    Chen, Hong; Chen, Cherry C; Acosta, Camilo; Wu, Shih-Ying; Sun, Tao; Konofagou, Elisa E

    2014-01-01

    Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (i.n.) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+i.n.) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After i.n. administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (i.v.) drug injection is employed, FUS was also applied after i.v. injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+i.n. enhanced drug delivery within the targeted region compared with that achieved by i.n. only. Despite the fact that the i.n. route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+i.n. was not significantly different from that of FUS+i.v.. As a new drug delivery platform, the FUS+i.n. technique is potentially useful for treating CNS diseases.

  15. A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery

    PubMed Central

    Chen, Hong; Chen, Cherry C.; Acosta, Camilo; Wu, Shih-Ying; Sun, Tao; Konofagou, Elisa E.

    2014-01-01

    Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (IN) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+IN) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (IV) drug injection is employed, FUS was also applied after IV injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within the targeted region compared with that achieved by IN only. Despite the fact that the IN route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+IN was not significantly different from that of FUS+IV. As a new drug delivery platform, the FUS+IN technique is potentially useful for treating CNS diseases. PMID:25279463

  16. Ultrasound-Mediated Polymeric Micelle Drug Delivery.

    PubMed

    Xia, Hesheng; Zhao, Yue; Tong, Rui

    2016-01-01

    The synthesis of multi-functional nanocarriers and the design of new stimuli-responsive means are equally important for drug delivery. Ultrasound can be used as a remote, non-invasive and controllable trigger for the stimuli-responsive release of nanocarriers. Polymeric micelles are one kind of potential drug nanocarrier. By combining ultrasound and polymeric micelles, a new modality (i.e., ultrasound-mediated polymeric micelle drug delivery) has been developed and has recently received increasing attention. A major challenge remaining in developing ultrasound-responsive polymeric micelles is the improvement of the sensitivity or responsiveness of polymeric micelles to ultrasound. This chapter reviews the recent advance in this field. In order to understand the interaction mechanism between ultrasound stimulus and polymeric micelles, ultrasound effects, such as thermal effect, cavitation effect, ultrasound sonochemistry (including ultrasonic degradation, ultrasound-initiated polymerization, ultrasonic in-situ polymerization and ultrasound site-specific degradation), as well as basic micellar knowledge are introduced. Ultrasound-mediated polymeric micelle drug delivery has been classified into two main streams based on the different interaction mechanism between ultrasound and polymeric micelles; one is based on the ultrasound-induced physical disruption of the micelle and reversible release of payload. The other is based on micellar ultrasound mechanochemical disruption and irreversible release of payload.

  17. Tunable drug delivery using chemoselective functionalization of hydrogels.

    PubMed

    Mauri, Emanuele; Rossi, Filippo; Sacchetti, Alessandro

    2016-04-01

    In the last decades interests on cleavable linkers are growing due to the need to develop controlled drug delivery systems in biochemical and therapeutic applications. The synthesis of hydrogels as devices capable to maintain the drug level within a desired range for a long and sustained period of time is a leading strategy for this aim. However with respect to the good results obtained with antibodies and peptides there are a lot of problems related to the quick and uncontrolled diffusion of small molecules through hydrogel pores. In this work, we propose the functionalization of polyethylene glycol (PEG) chains with two different pH-sensitive linkers, ester and hydrazone, and their application as building blocks of microwave-assisted hydrogels for controlled delivery of small hydrophilic drugs. As drug mimetic we used Rhodamine B, a harmless fluorophore with steric hindrance and reactive groups similar to many small hydrophilic drugs. At physiological and low basic conditions, the cleavability of ester and hydrazone spacer evidenced the possibility to delay the release of drugs from the scaffold compared to hydrogels where drug was entrapped within the network only due to its steric hindrance. The obtained release profiles were compared, underlining the opportunity to tune the release rate using the synthesized hydrogels. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. ATP-triggered anticancer drug delivery

    NASA Astrophysics Data System (ADS)

    Mo, Ran; Jiang, Tianyue; Disanto, Rocco; Tai, Wanyi; Gu, Zhen

    2014-03-01

    Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 μM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.

  19. Drug Delivery Nanoparticles in Skin Cancers

    PubMed Central

    Dianzani, Chiara; Zara, Gian Paolo; Maina, Giovanni; Pettazzoni, Piergiorgio; Pizzimenti, Stefania; Rossi, Federica; Gigliotti, Casimiro Luca; Ciamporcero, Eric Stefano; Daga, Martina; Barrera, Giuseppina

    2014-01-01

    Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported. PMID:25101298

  20. Nanotopographical Cues for Modulating Fibrosis and Drug Delivery

    NASA Astrophysics Data System (ADS)

    Walsh, Laura Aiko Michelle

    Nanotopography in the cellular microenvironment provides biological cues and therefore has potential to be a useful tool for directing cellular behavior. Fibrotic encapsulation of implanted devices and materials can wall off and eventually cause functional failure of the implant. Drug delivery requires penetrating the epithelium, which encapsulates the body and provides a barrier to separate the body from its external environment. Both of these challenges could be elegantly surmounted using nanotopography, which would harness innate cellular responses to topographic cues to elicit desired cellular behavior. To this end, we fabricated high and low aspect ratio nanotopographically patterned thin films. Using scanning electron microscopy, real time polymerase chain reaction, immunofluorescence microscopy, in vitro drug delivery assays, transmission electron microscopy, inhibitor studies, and rabbit and rat in vivo drug delivery studies, we investigated cellular response to our nanotopographic thin films. We determined that high aspect ratio topography altered fibroblast morphology and decreased proliferation, possibly due to decreased protein adsorption. The fibroblasts also down regulated expression of mRNA of key factors associated with fibrosis, such as collagens 1 and 3. Low aspect ratio nanotopography increased drug delivery in vitro across an intestinal epithelial model monolayer by increasing paracellular permeability and remodeling the tight junction. This increase in drug delivery required integrin engagement and MLCK activity, and is consistent with the increased focal adhesion formation. Tight junction remodeling was also observed in a multilayered keratinocyte model, showing this mechanism can be generalized to multiple epithelium types. By facilitating direct contact of nanotopography with the viable epidermis using microneedles to pierce the stratum corneum, we are able to transdermally deliver a 150 kiloDalton, IgG-based therapeutic in vivo..

  1. Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier

    PubMed Central

    Makadia, Hirenkumar K.; Siegel, Steven J.

    2011-01-01

    In past two decades poly lactic-co-glycolic acid (PLGA) has been among the most attractive polymeric candidates used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. In particular, PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. This manuscript describes the various fabrication techniques for these devices and the factors affecting their degradation and drug release. PMID:22577513

  2. Titanium MEMS Technology Development for Drug Delivery and Microfluidic Applications

    NASA Astrophysics Data System (ADS)

    Khandan, Omid

    The use of microelectromechanical systems (MEMS) technology in medical and biological applications has increased dramatically in the past decade due to the potential for enhanced sensitivity, functionality, and performance associated with the miniaturization of devices, as well as the market potential for low-cost, personalized medicine. However, the utility of such devices in clinical medicine is ultimately limited due to factors associated with prevailing micromachined materials such as silicon, as it poses concerns of safety and reliability due to its intrinsically brittle properties, making it prone to catastrophic failure. Recent advances in titanium (Ti) micromachining provides an opportunity to create devices with enhanced safety and performance due to its proven biocompatibility and high fracture toughness, which causes it to fail by means of graceful, plasticity-based deformation. Motivated by this opportunity, we discuss our efforts to advance Ti MEMS technology in two ways: 1) Through the development of titanium-based microneedles (MNs) that seek to provide a safer, simpler, and more efficacious means of ocular drug delivery, and 2) Through the advancement of Ti anodic bonding for future realization of robust microfluidic devices for photocatalysis applications. As for the first of these thrusts, we show that MN devices with in-plane geometry and through-thickness fenestrations that serve as drug reservoirs for passive delivery via diffusive transport from fast-dissolving coatings can be fabricated utilizing Ti deep reactive ion etching (Ti DRIE). Our mechanical testing and finite element analysis (FEA) results suggest that these devices possess sufficient stiffness for reliable corneal insertion. Our MN coating studies show that, relative to solid MNs of identical shank dimension, fenestrated devices can increase drug carrying capacity by 5-fold. Furthermore, we demonstrate that through-etched fenestrations provide a protective cavity for delivering

  3. 75 FR 18219 - Drug and Medical Device Forum on Food and Drug Administration Drug and Device Requirements and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-09

    ... HUMAN SERVICES Food and Drug Administration Drug and Medical Device Forum on Food and Drug Administration Drug and Device Requirements and Supplier Controls; Public Educational Forum AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public educational forum. SUMMARY: The Food and Drug Administration...

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

    PubMed

    Mahnama, Ali; Nourbakhsh, Ahmad; Ghorbaniasl, Ghader

    2014-01-01

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

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

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2016-01-04

    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.

  6. Transdermal drug delivery: from micro to nano

    NASA Astrophysics Data System (ADS)

    Pegoraro, Carla; MacNeil, Sheila; Battaglia, Giuseppe

    2012-03-01

    Delivery across skin offers many advantages compared to oral or intravenous routes of drug administration. Skin however is highly impermeable to most molecules on the basis of size, hydrophilicity, lipophilicity and charge. For this reason it is often necessary to temporarily alter the barrier properties of skin for effective administration. This can be done by applying chemical enhancers, which alter the lipid structure of the top layer of skin (the stratum corneum, SC), by applying external forces such as electric currents and ultrasounds, by bypassing the stratum corneum via minimally invasive microneedles or by using nano-delivery vehicles that can cross and deliver their payload to the deeper layers of skin. Here we present a critical summary of the latest technologies used to increase transdermal delivery.

  7. Porous Hydroxyapatite Bioceramic Scaffolds for Drug Delivery and Bone Regeneration

    NASA Astrophysics Data System (ADS)

    Loca, Dagnija; Locs, Janis; Salma, Kristine; Gulbis, Juris; Salma, Ilze; Berzina-Cimdina, Liga

    2011-10-01

    The conventional methods of supplying a patient with pharmacologic active substances suffer from being very poorly selective, so that damage can occurs to the healthy tissues and organs, different from the intended target. In addition, high drug doses can be required to achieve the desired effect. An alternative approach is based on the use of implantable delivery tools, able to release the active substance in a controlled way. In the current research local drug delivery devices containing 8mg of gentamicin sulphate were prepared using custom developed vacuum impregnation technique. In vitro dissolution tests showed that gentamicin release was sustained for 12h. In order to decrease gentamicin release rate, biopolymer coatings were applied and coating structure investigated. The results showed that gentamicin release can be sustained for more than 70h for poly(epsilon-caprolactone) coated calcium phosphate scaffolds. From poly lactic acid and polyvinyl alcohol coated scaffolds gentamicin was released within 20h and 50h, respectively.

  8. Spermbots: potential impact for drug delivery and assisted reproductive technologies.

    PubMed

    Magdanz, Veronika; Schmidt, Oliver G

    2014-08-01

    Micromotors and nanomotors are an emerging research field that aims at achieving locomotion on the microscale for a variety of applications such as drug delivery, single cell manipulation, microsensors and lab-on-a-chip devices, just to point out a few. The enthusiastic development of hybrid micromotors harnessing biological power sources for physiologically compatible nano/microdevices has recently brought a lot of attention to the international research community that is looking for a solution for the actuation and locomotion on the microscale. This article describes the potential of sperm-driven micro-bio-robots in the biomedical field such as drug delivery or single cell manipulation. Herein, a specific potential of the sperm-driven micro-bio-robot is described that might have impact on the development of assisted reproductive technologies.

  9. Biomimetics in drug delivery systems: A critical review.

    PubMed

    Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

    2017-03-18

    Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems.

  10. Intracarotid Delivery of Drugs: The Potential and the Pitfalls

    PubMed Central

    Joshi, Shailendra; Meyers, Phillip M.; Ornstein, Eugene

    2014-01-01

    The major efforts to selectively deliver drugs to the brain in the last decade have relied on smart molecular techniques to penetrate the blood brain barrier while intraarterial drug delivery has drawn relatively little attention. In the last decade there have been rapid advances in endovascular techniques. Modern endovascular procedures can permit highly targeted drug delivery by intracarotid route. Intracarotid drug delivery can be the primary route of drug delivery or it could be used to facilitate the delivery of smart-neuropharmaceuticals. There have been few attempts to systematically understand the kinetics of intracarotid drugs. Anecdotal data suggests that intracarotid drug delivery is effective in the treatment of cerebral vasospasm, thromboembolic strokes, and neoplasms. Neuroanesthesiologists are frequently involved in the care of such high-risk patients. Therefore, it is necessary to understand the applications of intracarotid drug delivery and the unusual kinetics of intracarotid drugs. PMID:18719453

  11. Viruses as nanomaterials for drug delivery.

    PubMed

    Lockney, Dustin; Franzen, Stefan; Lommel, Steven

    2011-01-01

    Virus delivery vectors are one among the many nanomaterials that are being developed as drug delivery materials. This chapter focuses on methods utilizing plant virus nanoparticles (PVNs) synthesized from the Red clover necrotic mosaic virus (RCNMV). A successful vector must be able to effectively carry and subsequently deliver a drug cargo to a specific target. In the case of the PVNs, we describe two types of ways cargo can be loaded within these structures: encapsidation and infusion. Several targeting approaches have been used for PVNs based on bioconjugate chemistry. Herein, examples of such approaches will be given that have been used for RCNMV as well as for other PVNs in the literature. Further, we describe characterization of PVNs, in vitro cell studies that can be used to test the efficacy of a targeting vector, and potential routes for animal administration.

  12. Nanotechnology Approaches for Ocular Drug Delivery

    PubMed Central

    Xu, Qingguo; Kambhampati, Siva P.; Kannan, Rangaramanujam M.

    2013-01-01

    Blindness is a major health concern worldwide that has a powerful impact on afflicted individuals and their families, and is associated with enormous socio-economical consequences. The Middle East is heavily impacted by blindness, and the problem there is augmented by an increasing incidence of diabetes in the population. An appropriate drug/gene delivery system that can sustain and deliver therapeutics to the target tissues and cells is a key need for ocular therapies. The application of nanotechnology in medicine is undergoing rapid progress, and the recent developments in nanomedicine-based therapeutic approaches may bring significant benefits to address the leading causes of blindness associated with cataract, glaucoma, diabetic retinopathy and retinal degeneration. In this brief review, we highlight some promising nanomedicine-based therapeutic approaches for drug and gene delivery to the anterior and posterior segments. PMID:23580849

  13. Diatomite silica nanoparticles for drug delivery

    NASA Astrophysics Data System (ADS)

    Ruggiero, Immacolata; Terracciano, Monica; Martucci, Nicola M.; De Stefano, Luca; Migliaccio, Nunzia; Tatè, Rosarita; Rendina, Ivo; Arcari, Paolo; Lamberti, Annalisa; Rea, Ilaria

    2014-07-01

    Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery.

  14. Microneedle Coating Techniques for Transdermal Drug Delivery

    PubMed Central

    Haj-Ahmad, Rita; Khan, Hashim; Arshad, Muhammad Sohail; Rasekh, Manoochehr; Hussain, Amjad; Walsh, Susannah; Li, Xiang; Chang, Ming-Wei; Ahmad, Zeeshan

    2015-01-01

    Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates. PMID:26556364

  15. Nanogel Carrier Design for Targeted Drug Delivery

    PubMed Central

    Eckmann, D. M.; Composto, R. J.; Tsourkas, A.; Muzykantov, V. R.

    2014-01-01

    Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions. PMID:25485112

  16. Microneedle Coating Techniques for Transdermal Drug Delivery.

    PubMed

    Haj-Ahmad, Rita; Khan, Hashim; Arshad, Muhammad Sohail; Rasekh, Manoochehr; Hussain, Amjad; Walsh, Susannah; Li, Xiang; Chang, Ming-Wei; Ahmad, Zeeshan

    2015-11-05

    Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates.

  17. Injected nanocrystals for targeted drug delivery

    PubMed Central

    Lu, Yi; Li, Ye; Wu, Wei

    2016-01-01

    Nanocrystals are pure drug crystals with sizes in the nanometer range. Due to the advantages of high drug loading, platform stability, and ease of scaling-up, nanocrystals have been widely used to deliver poorly water-soluble drugs. Nanocrystals in the blood stream can be recognized and sequestered as exogenous materials by mononuclear phagocytic system (MPS) cells, leading to passive accumulation in MPS-rich organs, such as liver, spleen and lung. Particle size, morphology and surface modification affect the biodistribution of nanocrystals. Ligand conjugation and stimuli-responsive polymers can also be used to target nanocrystals to specific pathogenic sites. In this review, the progress on injected nanocrystals for targeted drug delivery is discussed following a brief introduction to nanocrystal preparation methods, i.e., top-down and bottom-up technologies. PMID:27006893

  18. Targeted Delivery of Protein Drugs by Nanocarriers

    PubMed Central

    Solaro, Roberto; Chiellini, Federica; Battisti, Antonella

    2010-01-01

    Recent advances in biotechnology demonstrate that peptides and proteins are the basis of a new generation of drugs. However, the transportation of protein drugs in the body is limited by their high molecular weight, which prevents the crossing of tissue barriers, and by their short lifetime due to immuno response and enzymatic degradation. Moreover, the ability to selectively deliver drugs to target organs, tissues or cells is a major challenge in the treatment of several human diseases, including cancer. Indeed, targeted delivery can be much more efficient than systemic application, while improving bioavailability and limiting undesirable side effects. This review describes how the use of targeted nanocarriers such as nanoparticles and liposomes can improve the pharmacokinetic properties of protein drugs, thus increasing their safety and maximizing the therapeutic effect.

  19. Smart drug delivery injector microsystem based on pyrotechnical actuation

    NASA Astrophysics Data System (ADS)

    Puig-Vidal, Manel; Lopez, Jaime; Miribel, Pere; Samitier-Marti, Josep; Rossi, Carole; Berthold, Axel

    2003-04-01

    A smart drug delivery injector microsystem is presented based on small pyrotechnics to impulse drugs to be injected to a human being. The proposal refers to a feasibility demonstration of the technology for pharmaceutical chips. These chips would be around some cm2 in section and will be able to inject a drug into de subject skin responding to an electrical signal. The product derived from this activity will be useful for astronaut's health, being able to administrate emergency doses of products (for instance cardio-tonic or hypoallegic drugs) enough to survive an emergency situation (as it can be a heart attack during EVA). The system can also be used for easy administration of drugs needed for physiological research. The usefulness of the device in terrestrial applications has no doubt, allowing remote administration of drugs to patients whose biomedical parameters are remotely monitored. The concept proposed here is new in combining the idea of pharmaceutical chip with the ultrasonic droplet technology and the use of pyrotechnics to provide energy to the drug to be injected. The proposed Drug Injector Microsystem is based on 2 main blocks:- Micropyrotechnic system: defines the ignition part based on pyrotechnic.- Microfluidic system: defines the drug injection part. This part is also divided in different critical parts: Expansion chamber, membrane or piston, drug reservoir and a needle. Different sensors are placed on the expansion chamber of microfluidic system and on the micropyrotechnic system. A complete electronic module is implemented with a PC interface to define flexible and user friendly experiences showing the smart drug delivery injector microsystem principle.

  20. Controlled Ocular Drug Delivery with Nanomicelles

    PubMed Central

    Vaishya, Ravi D.; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K.

    2014-01-01

    Many vision threatening ocular diseases such as age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and proliferative vitreoretinopathy may result in blindness. Ocular drug delivery specifically to the intraocular tissues remains a challenging task due to the presence of various physiological barriers. Nonetheless, recent advancements in the field of nanomicelle based novel drug delivery system could fulfil these unmet needs. Nanomicelles consists of amphiphilic molecules that self-assemble in aqueous media to form organized supramolecular structures. Micelles can be prepared in various sizes (10 to 1000nm) and shapes depending on the molecular weights of the core and corona forming blocks. Nanomicelles have been an attractive carriers for their potential to solubilize hydrophobic molecules in aqueous solution. In addition, small size in nanometer range and highly modifiable surface properties have been reported to be advantageous in ocular drug delivery. In the present review various factors influencing rationale design of nanomicelles formulation and disposition are discussed along with case studies. Despite the progress in the field, influence of various properties of nanomicelles such as size, shape, surface charge, rigidity of structure on ocular disposition need to be studied in further details to develop an efficient nanocarrier system. PMID:24888969

  1. Protein and Peptide Drug Delivery: Oral Approaches

    PubMed Central

    Shaji, Jessy; Patole, V.

    2008-01-01

    Till recent, injections remained the most common means for administering therapeutic proteins and peptides because of their poor oral bioavailability. However, oral route would be preferred to any other route because of its high levels of patient acceptance and long term compliance, which increases the therapeutic value of the drug. Designing and formulating a polypeptide drug delivery through the gastro intestinal tract has been a persistent challenge because of their unfavorable physicochemical properties, which includes enzymatic degradation, poor membrane permeability and large molecular size. The main challenge is to improve the oral bioavailability from less than 1% to at least 30-50%. Consequently, efforts have intensified over the past few decades, where every oral dosage form used for the conventional small molecule drugs has been used to explore oral protein and peptide delivery. Various strategies currently under investigation include chemical modification, formulation vehicles and use of enzyme inhibitors, absorption enhancers and mucoadhesive polymers. This review summarizes different pharmaceutical approaches which overcome various physiological barriers that help to improve oral bioavailability that ultimately achieve formulation goals for oral delivery. PMID:20046732

  2. Iontophoretic drug delivery across the nail.

    PubMed

    Delgado-Charro, Maria Begoña

    2012-01-01

    Topical drug delivery to treat nail diseases such as onychomycosis and psoriasis is receiving increasing attention. Topical nail delivery is challenged by the complicated structure of the nail and the low permeability of most drugs across the nail plate. Considerable effort has been directed at developing methods to promote drug permeation across the nail plate. Iontophoresis efficiently enhances molecular transport across the skin and the eye and is now being tested for its potential in ungual delivery. This review covers the basic mechanisms of transport (electro-osmosis and -migration) and their relative contribution to nail iontophoresis as well as the key factors governing nail permselectivity and ionic transport numbers. Methodological issues concerning research in this area are summarized. The data available in vivo on nail iontophoresis of terbinafine specifically are reviewed in separate sections. Our understanding of nail iontophoresis has improved considerably since 2007; most decisively, the feasibility of nail iontophoresis in vivo has been clearly demonstrated. Future work is required to establish the adequate implementation of the technique so that its clinical efficacy to treat onychomycosis and nail psoriasis can be unequivocally determined.

  3. A model of axonal transport drug delivery

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Andrey V.

    2012-04-01

    In this paper a model of targeted drug delivery by means of active (motor-driven) axonal transport is developed. The model is motivated by recent experimental research by Filler et al. (A.G. Filler, G.T. Whiteside, M. Bacon, M. Frederickson, F.A. Howe, M.D. Rabinowitz, A.J. Sokoloff, T.W. Deacon, C. Abell, R. Munglani, J.R. Griffiths, B.A. Bell, A.M.L. Lever, Tri-partite complex for axonal transport drug delivery achieves pharmacological effect, Bmc Neuroscience 11 (2010) 8) that reported synthesis and pharmacological efficiency tests of a tri-partite complex designed for axonal transport drug delivery. The developed model accounts for two populations of pharmaceutical agent complexes (PACs): PACs that are transported retrogradely by dynein motors and PACs that are accumulated in the axon at the Nodes of Ranvier. The transitions between these two populations of PACs are described by first-order reactions. An analytical solution of the coupled system of transient equations describing conservations of these two populations of PACs is obtained by using Laplace transform. Numerical results for various combinations of parameter values are presented and their physical significance is discussed.

  4. Optimization of a polymer composite employing molecular mechanic simulations and artificial neural networks for a novel intravaginal bioadhesive drug delivery device.

    PubMed

    Ndesendo, Valence M K; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Buchmann, Eckhart; Meyer, Leith C R; Khan, Riaz A

    2012-01-01

    This study aimed at elucidating an optimal synergistic polymer composite for achieving a desirable molecular bioadhesivity and Matrix Erosion of a bioactive-loaded Intravaginal Bioadhesive Polymeric Device (IBPD) employing Molecular Mechanic Simulations and Artificial Neural Networks (ANN). Fifteen lead caplet-shaped devices were formulated by direct compression with the model bioactives zidovudine and polystyrene sulfonate. The Matrix Erosion was analyzed in simulated vaginal fluid to assess the critical integrity. Blueprinting the molecular mechanics of bioadhesion between vaginal epithelial glycoprotein (EGP), mucin (MUC) and the IBPD were performed on HyperChem 8.0.8 software (MM+ and AMBER force fields) for the quantification and characterization of correlative molecular interactions during molecular bioadhesion. Results proved that the IBPD bioadhesivity was pivoted on the conformation, orientation, and poly(acrylic acid) (PAA) composition that interacted with EGP and MUC present on the vaginal epithelium due to heterogeneous surface residue distributions (free energy= -46.33 kcalmol(-1)). ANN sensitivity testing as a connectionist model enabled strategic polymer selection for developing an IBPD with an optimally prolonged Matrix Erosion and superior molecular bioadhesivity (ME = 1.21-7.68%; BHN = 2.687-4.981 N/mm(2)). Molecular modeling aptly supported the EGP-MUC-PAA molecular interaction at the vaginal epithelium confirming the role of PAA in bioadhesion of the IBPD once inserted into the posterior fornix of the vagina.

  5. Investigation of Diffusion Characteristics through Microfluidic Channels for Passive Drug Delivery Applications

    PubMed Central

    Ghuman, Alyssa P.; Collins, Stephanie B.; Handa, Hitesh

    2016-01-01

    Microfluidics has many drug delivery applications due to the ability to easily create complex device designs with feature sizes reaching down to the 10s of microns. In this work, three different microchannel designs for an implantable device are investigated for treatment of ocular diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy. Devices were fabricated using polydimethylsiloxane (PDMS) and soft lithography techniques, where surface chemistry of the channels was altered using 2-[methoxy(polyethyleneoxy)propyl]trimethoxysilane (PEG-silane). An estimated delivery rate for a number of common drugs was approximated for each device through the ratio of the diffusion coefficients for the dye and the respective drug. The delivery rate of the model drugs was maintained at a physiological condition and the effects of channel design and surface chemistry on the delivery rate of the model drugs were recorded over a two-week period. Results showed that the surface chemistry of the device had no significant effect on the delivery rate of the model drugs. All designs were successful in delivering a constant daily dose for each model drug. PMID:27313895

  6. Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

    PubMed

    Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

    2016-01-01

    The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

  7. Stretch-Triggered Drug Delivery from Wearable Elastomer Films Containing Therapeutic Depots.

    PubMed

    Di, Jin; Yao, Shanshan; Ye, Yanqi; Cui, Zheng; Yu, Jicheng; Ghosh, Tushar K; Zhu, Yong; Gu, Zhen

    2015-09-22

    Mechanical force-based stimulus provides a simple and easily accessible manner for spatiotemporally controlled drug delivery. Here we describe a wearable, tensile strain-triggered drug delivery device consisting of a stretchable elastomer and microgel depots containing drug loaded nanoparticles. By applying a tensile strain to the elastomer film, the release of drug from the microdepot is promoted due to the enlarged surface area for diffusion and Poisson's ratio-induced compression on the microdepot. Correspondingly, both sustained drug release by daily body motions and pulsatile release by intentional administration can be conveniently achieved. Our work demonstrated that the tensile strain, applied to the stretchable device, facilitated release of therapeutics from microdepots for anticancer and antibacterial treatments. Moreover, polymeric microneedles were further integrated with the stretch-responsive device for transcutaneous delivery of insulin and regulation of blood glucose levels of chemically induced type 1 diabetic mice.

  8. Drug Delivery to the Ischemic Brain

    PubMed Central

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  9. Experimental design for optimizing drug release from silicone elastomer matrix and investigation of transdermal drug delivery.

    PubMed

    Snorradóttir, Bergthóra S; Gudnason, Pálmar I; Thorsteinsson, Freygardur; Másson, Már

    2011-04-18

    Silicone elastomers are commonly used for medical devices and external prosthesis. Recently, there has been growing interest in silicone-based medical devices with enhanced function that release drugs from the elastomer matrix. In the current study, an experimental design approach was used to optimize the release properties of the model drug diclofenac from medical silicone elastomer matrix, including a combination of four permeation enhancers as additives and allowing for constraints in the properties of the material. The D-optimal design included six factors and five responses describing material properties and release of the drug. The first experimental object was screening, to investigate the main and interaction effects, based on 29 experiments. All excipients had a significant effect and were therefore included in the optimization, which also allowed the possible contribution of quadratic terms to the model and was based on 38 experiments. Screening and optimization of release and material properties resulted in the production of two optimized silicone membranes, which were tested for transdermal delivery. The results confirmed the validity of the model for the optimized membranes that were used for further testing for transdermal drug delivery through heat-separated human skin. The optimization resulted in an excipient/drug/silicone composition that resulted in a cured elastomer with good tensile strength and a 4- to 7-fold transdermal delivery increase relative to elastomer that did not contain excipients.

  10. 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.

  11. 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. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. 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.

  13. Radionuclide imaging of liposomal drug delivery.

    PubMed

    van der Geest, Tessa; Laverman, Peter; Metselaar, Josbert M; Storm, Gert; Boerman, Otto C

    2016-09-01

    Ever since their discovery, liposomes have been radiolabeled to monitor their fate in vivo. Despite extensive preclinical studies, only a limited number of radiolabeled liposomal formulations have been examined in patients. Since they can play a crucial role in patient management, it is of importance to enable translation of radiolabeled liposomes into the clinic. Liposomes have demonstrated substantial advantages as drug delivery systems and can be efficiently radiolabeled. Potentially, radiolabeled drug-loaded liposomes form an elegant theranostic system, which can be tracked in vivo using single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. In this review, we discuss important aspects of liposomal research with a focus on the use of radiolabeled liposomes and their potential role in drug delivery and monitoring therapeutic effects. Radiolabeled drug-loaded liposomes have been poorly investigated in patients and no radiolabeled liposomes have been approved for use in clinical practice. Evaluation of the risks, pharmacokinetics, pharmacodynamics and toxicity is necessary to meet pharmaceutical and commercial requirements. It remains to be demonstrated whether the results found in animal studies translate to humans before radiolabeled liposomes can be implemented into clinical practice.

  14. Protein-Based Nanomedicine Platforms for Drug Delivery

    SciTech Connect

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

    2009-08-03

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

  15. Recent development in aerosol devices for pulmonary vaccine delivery.

    PubMed

    Lu, Dong mei

    2012-10-18

    This review will discuss aerosol device technologies available for pulmonary vaccine deliveries. The possibilities of adopting aerosol-generation for the purpose of pulmonary immunization are described. Aerosol-generation systems might offer advantages in respect to vaccine stability and antigenicity. The noninvasive, relatively safe and low-cost net of pulmonary delivery may provide great benefits to the public health vaccination campaign.

  16. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

    NASA Astrophysics Data System (ADS)

    Islam, Nazrul; Ferro, Vito

    2016-07-01

    The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

  17. Multiscale benchmarking of drug delivery vectors.

    PubMed

    Summers, Huw D; Ware, Matthew J; Majithia, Ravish; Meissner, Kenith E; Godin, Biana; Rees, Paul

    2016-10-01

    Cross-system comparisons of drug delivery vectors are essential to ensure optimal design. An in-vitro experimental protocol is presented that separates the role of the delivery vector from that of its cargo in determining the cell response, thus allowing quantitative comparison of different systems. The technique is validated through benchmarking of the dose-response of human fibroblast cells exposed to the cationic molecule, polyethylene imine (PEI); delivered as a free molecule and as a cargo on the surface of CdSe nanoparticles and Silica microparticles. The exposure metrics are converted to a delivered dose with the transport properties of the different scale systems characterized by a delivery time, τ. The benchmarking highlights an agglomeration of the free PEI molecules into micron sized clusters and identifies the metric determining cell death as the total number of PEI molecules presented to cells, determined by the delivery vector dose and the surface density of the cargo. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Design of a multiple drug delivery system directed at periodontitis.

    PubMed

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

    2013-11-01

    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. © 2013 Elsevier Ltd. All rights reserved.

  19. 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

  20. Development of a pH-responsive drug delivery system for enantioselective-controlled delivery of racemic drugs.

    PubMed

    Suedee, Roongnapa; Jantarat, Chutima; Lindner, Wolfgang; Viernstein, Helmut; Songkro, Sarunyoo; Srichana, Teerapol

    2010-02-25

    This study aimed to develop enantioselective-controlled drug delivery systems for selective release of the required (S)-enantiomer in a dose formulation containing a racemic drug in response to pH stimuli. The recognition system was obtained from a nanoparticle-on-microsphere (NOM) molecularly imprinted polymer (MIP) with a multifunctional chiral cinchona anchor synthesised by suspension polymerisation using ethylene glycol dimethacrylate as a cross-linker. (S)-omeprazole was used as an imprinting molecule conferring stereoselectivity upon the polymers. The ability of the prepared recognition polymers to selectively rebind (S)-omeprazole was evident at different pH levels (the highest being at pH 7.4). The partial selective-release phenomenon of the (S)-enantiomer in MIP-containing composite cellulose membranes with increased vehicular racemic omeprazole concentrations was highly pH-dependent. Cinchona-bonded polymers imprinted with (S)-omeprazole could recognise the moldable contact site of (S)-omeprazole independently of its chirality; this is responsible for the delivery of (S)-enantiomer from racemic omeprazole. The controlled-release drug devices were fabricated with synthesised composite latex, and consisted of a pH stimuli-responsive poly(hydroxyethyl methacrylate) (HEMA) and polycaprolactone-triol (PCL-T) blend, and a MIP with preloaded drug, along with pH 7.4 buffer in the device's interior. The results demonstrate that drug delivery systems containing (S)-omeprazole imprinted cinchona-polymer nanoparticle-on-microspheres may maximise efficacy while minimising dose frequency.

  1. Controlling fungal biofilms with functional drug delivery denture biomaterials.

    PubMed

    Wen, Jianchuan; Jiang, Fuguang; Yeh, Chih-Ko; Sun, Yuyu

    2016-04-01

    Candida-associated denture stomatitis (CADS), caused by colonization and biofilm-formation of Candida species on denture surfaces, is a significant clinical concern. We show here that modification of conventional denture materials with functional groups can significantly increase drug binding capacity and control drug release rate of the resulting denture materials for potentially managing CADS. In our approach, poly(methyl methacrylate) (PMMA)-based denture resins were surface grafted with three kinds of polymers, poly(1-vinyl-2-pyrrolidinone) (PNVP), poly(methacrylic acid) (PMAA), and poly(2-hydroxyethyl methacrylate) (PHEMA), through plasma-initiated grafting polymerization. With a grafting yield as low as 2 wt%, the three classes of new functionalized denture materials showed significantly higher drug binding capacities toward miconazole, a widely used antifungal drug, than the original PMMA denture resin control, leading to sustained drug release and potent biofilm-controlling effects against Candida. Among the three classes of functionalized denture materials, PNVP-grafted resin provided the highest miconazole binding capability and the most powerful antifungal and biofilm-controlling activities. Drug binding mechanisms were studied. These results demonstrated the importance of specific interactions between drug molecules and functional groups on biomaterials, shedding lights on future design of CADS-managing denture materials and other related devices for controlled drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Laser Plasma Jet Driven Microparticles for DNA/Drug Delivery

    PubMed Central

    Menezes, Viren; Mathew, Yohan; Takayama, Kazuyoshi; Kanno, Akira; Hosseini, Hamid

    2012-01-01

    This paper describes a microparticle delivery device that generates a plasma jet through laser ablation of a thin metal foil and uses the jet to accomplish particle delivery into soft living targets for transferring biological agents. Pure gold microparticles of 1 µm size were coated with a plasmid DNA, pIG121Hm, and were deposited as a thin layer on one surface of an aluminum foil. The laser (Nd:YAG, 1064 nm wavelength) ablation of the foil generated a plasma jet that carried the DNA coated particles into the living onion cells. The particles could effectively penetrate the target cells and disseminate the DNA, effecting the transfection of the cells. Generation of the plasma jet on laser ablation of the foil and its role as a carrier of microparticles was visualized using a high-speed video camera, Shimadzu HPV-1, at a frame rate of 500 kfps (2 µs interframe interval) in a shadowgraph optical set-up. The particle speed could be measured from the visualized images, which was about 770 m/s initially, increased to a magnitude of 1320 m/s, and after a quasi-steady state over a distance of 10 mm with an average magnitude of 1100 m/s, started declining, which typically is the trend of a high-speed, pulsed, compressible jet. Aluminum launch pad (for the particles) was used in the present study to make the procedure cost-effective, whereas the guided, biocompatible launch pads made of gold, silver or titanium can be used in the device during the actual clinical operations. The particle delivery device has a potential to have a miniature form and can be an effective, hand-held drug/DNA delivery device for biological applications. PMID:23226394

  3. Production of nanoparticle drug delivery systems with microfluidics tools.

    PubMed

    Khan, Ikram Ullah; Serra, Christophe A; Anton, Nicolas; Vandamme, Thierry F

    2015-04-01

    Nowadays the development of composite nano- and microparticles is an extensively studied area of research. This interest is growing because of the potential use of such particles in drug delivery systems. Indeed they can be used in various medical disciplines depending upon their sizes and their size distribution, which determine their final biomedical applications. Amongst the different techniques to produce nanoparticles, microfluidic techniques allow preparing particles having a specific size, a narrow size distribution and high encapsulation efficiency with ease. This review covers the general description of microfluidics, its techniques, advantages and disadvantages with focus on the encapsulation of active principles in polymeric nanoparticles as well as on pure drug nanoparticles. Polymeric nanoparticles constitute the majority of the examples reported; however lipid nanoparticulate systems (DNA, SiRNA nanocarriers) are very comparable and their formulation processes are in most cases exactly similar. Accordingly this review focuses also on active ingredient nanoparticles formulated by nanoprecipitation processes in microfluidic devices in general. It also provides detailed description of the different geometries of most common microfluidic devices and the crucial parameters involved in techniques designed to obtain the desired properties. Although the classical fabrication of nanoparticles drug delivery systems in batch is extremely well-described and developed, their production with microfluidic tools arises today as an emerging field with much more potential. In this review we present and discuss these new possibilities for biomedical applications through the current emerging developments.

  4. 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.

  5. Mechanisms of Drug Diffusion from Polymeric Devices.

    NASA Astrophysics Data System (ADS)

    Sharma, Kuldeepak

    1987-09-01

    A detailed mechanistic study of drug diffusion and the factors which influence drug diffusion through polymeric controlled release systems was undertaken to understand drug diffusion through hydrophilic and hydrophobic polymeric systems. The effect of improved aqueous solubility of the salt form (ionizable form) of selected drugs on diffusion through hydrophilic and hydrophobic polymeric membranes was compared to diffusion of the less soluble (unionizable form) of the drugs. Model drugs chosen for these studies were prednisolone, prednisolone phosphate sodium (prednisolone phosphoric acid disodium salt), pilocarpine, pilocarpine hydrochloride, sulfacetamide and sodium sulfacetamide. The hydrophilic polymers were hydrogels of hydroxyethylmethacrylate (PHEMA) and hydrophobic polymers were copolyether-urethane -urea (Biomer) and polydimethylsiloxane (PDMS). Salt forms of the drugs permeated faster than the free forms through the hydrophilic polymers because of higher aqueous solubility. The free forms of the drugs had higher diffusion rates than the salt forms due to increased solubility in the hydrophobic polymers. Drug solubility in polymers and the water fraction of the polymeric membrane were determined to be the primary factors in diffusion through polymeric membranes. Drug aqueous solubility was of secondary importance. Two controlled release systems were then designed to further study drug release. The Biomer and copolymers of polystyrene and PHEMA were chosen as the polymers for the fabrication of the devices. These copolymers incorporated the favorable attributes of hydrophobic and hydrophilic homopolymers into single polymers. Prednisolone was used as a model drug for these studies. The effects of initial drug load, drug loading solvents and the drug polymer interactions on drug release from the devices were then studied. The drug release from these devices increased as the initial drug load increased. Drug loading solvents had a marked effect on drug

  6. Nasal-to-CNS drug delivery: where are we now and where are we heading? An industrial perspective.

    PubMed

    Landis, Margaret S; Boyden, Tracey; Pegg, Simon

    2012-02-01

    Delivery of drug therapeutics across the blood-brain barrier is a challenging task for pharmaceutical scientists. Nasal-to-CNS drug delivery has shown promising results in preclinical efficacy models and investigatory human clinical trials. The further development of this technology with respect to the establishment of valid, predictable preclinical species models, translatable pharmacokinetic-pharmacodynamic relationships and definition of toxicology impact will help attract additional pharmaceutical investment in this drug-delivery approach. Further discoveries in nasal nanotechnology, targeted delivery devices and diagnostic olfactory imaging will serve to fuel the advancements in this area of drug delivery.

  7. Ultrasound Molecular Imaging and Drug Delivery.

    PubMed

    Caskey, Charles F

    2017-03-02

    Ultrasound is a rapidly advancing field with many emerging diagnostic and therapeutic applications. For diagnostics, new vascular targets are routinely identified and mature technologies are being translated to humans, while other recent innovations may bring about the creation of acoustic reporter genes and micron-scale resolution with ultrasound. As a cancer therapy, ultrasound is being explored as an adjuvant to immune therapies and to deliver acoustically or thermally active drugs to tumor regions. Ultrasound-enhanced delivery across the blood brain barrier (BBB) could potentially be very impactful for brain cancers and neurodegenerative diseases where the BBB often impedes the delivery of therapeutic molecules. In this minireview, we provide an overview of these topics in the field of ultrasound that are especially relevant to the interests of World Molecular Imaging Society.

  8. Drug transport and drug delivery--the Midnight Sun meeting.

    PubMed

    Uchegbu, Ijeoma F

    2004-08-01

    The Midnight Sun Meeting on Drug Transport and Drug Delivery was held on the island of Tromso in northern Norway, where the sun does not set for 2 months during the summer. The meeting was hosted by the University of Tromso's newly established Institute of Pharmacy and the Controlled Release Society (Nordic Chapter). The meeting, attended by approximately 80 delegates from across Europe, showcased recent advances in drug transport through biological barriers, solid-state pharmaceuticals and particulate drug delivery systems. This report will focus on the particulate and solid-state pharmaceuticals sessions, in which lectures were given to demonstrate the benefits in cognitive function associated with omega-3 fish oils, the increase in drug release rates observed on the processing-induced deformation of tablet granules, and the size of polymeric particulates being directly and linearly related to the molecular weight of a polymer. The meeting was held as a single-session event, giving delegates the opportunity to attend all presentations. There was a small poster and exhibitor display, and the meeting attracted sponsorship from a number of companies, namely Polypure AS, Weifa AS, ProBioNeutraceuticals AS, Lipoid GmbH, Clavis Pharma AS and Thermometric AB.

  9. Transdermal patch drug delivery interactions with exercise.

    PubMed

    Lenz, Thomas L; Gillespie, Nicole

    2011-03-01

    Transdermal drug delivery systems, such as the transdermal patch, continue to be a popular and convenient way to administer medications. There are currently several medications that use a transdermal patch drug delivery system. This article describes the potential untoward side effects of increased drug absorption through the use of a transdermal patch in individuals who exercise or participate in sporting events. Four studies have been reported that demonstrate a significant increase in the plasma concentration of nitroglycerin when individuals exercise compared with rest. Likewise, several case reports and two studies have been conducted that demonstrate nicotine toxicity and increased plasma nicotine while wearing a nicotine patch in individuals who exercise or participate in sporting events compared with rest. Healthcare providers, trainers and coaches should be aware of proper transdermal patch use, especially while exercising, in order to provide needed information to their respective patients and athletes to avoid potential untoward side effects. Particular caution should be given to individuals who participate in an extreme sporting event of long duration. Further research that includes more medications is needed in this area.

  10. [Studies on market of drug delivery system product and drug delivery system of compound Chinese medicine].

    PubMed

    Feng, Yi; Xu, De-Sheng; Hong, Yan-Long; Zhang, Ning; Ma, Yue-Ming

    2006-10-01

    Based on the progress in the world market of drug delivery system (DDS) product and the research profile of DDS of compound Chinese Medicine, The article puts forward a new method of studies on DDS of compound Chinese Medicine. It is expected that the theory of compatibility of compound Chinese Medicine can be shown and its role can be exerted to the largest extent with the application of pharmaceutics technology to change the mode of drug delivery of activated components of compound Chinese Medicine.

  11. Recent advances of controlled drug delivery using microfluidic platforms.

    PubMed

    Sanjay, Sharma T; Zhou, Wan; Dou, Maowei; Tavakoli, Hamed; Ma, Lei; Xu, Feng; Li, XiuJun

    2017-09-15

    Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery. Copyright

  12. Drug delivery to the posterior segment of the eye for pharmacologic therapy

    PubMed Central

    Shah, Shalin S; Denham, Lori Vidal; Elison, Jasmine R; Bhattacharjee, Partha S; Clement, Christian; Huq, Tashfin; Hill, James M

    2010-01-01

    Treatment of diseases of the posterior segment of the eye, such as age-related macular degeneration, cytomegalovirus retinitis, diabetic retinopathy, posterior uveitis and retinitis pigmentosa, requires novel drug delivery systems that can overcome the many barriers for efficacious delivery of therapeutic drug concentrations. This challenge has prompted the development of biodegradable and nonbiodegradable sustained-release systems for injection or transplantation into the vitreous as well as drug-loaded nanoparticles, microspheres and liposomes. These drug delivery systems utilize topical, systemic, subconjunctival, intravitreal, transscleral and iontophoretic routes of administration. The focus of research has been the development of methods that will increase the efficacy of spatiotemporal drug application, resulting in more successful therapy for patients with posterior segment diseases. This article summarizes recent advances in the research and development of drug delivery methods of the posterior chamber of the eye, with an emphasis on the use of implantable devices as well as micro- and nanoparticles. PMID:20305803

  13. Drug Delivery to the Inner Ear

    PubMed Central

    Wise, Andrew K; Gillespie, Lisa N

    2012-01-01

    Bionic devices electrically activate neural populations to partially restore lost function. Of fundamental importance is the functional integrity of the targeted neurons. However, in many conditions the ongoing pathology can lead to continued neural degeneration and death that may compromise the effectiveness of the device and limit future strategies to improve performance. The use of drugs that can prevent nerve cell degeneration and promote their regeneration may improve clinical outcomes. In this paper we focus on strategies of delivering neuroprotective drugs to the auditory system in a way that is safe and clinically relevant for use in combination with a cochlear implant. The aim of this approach is to prevent neural degeneration and promote nerve regrowth in order to improve outcomes for cochlear implant recipients using techniques that can be translated to the clinic. PMID:23186937

  14. Drug delivery to the inner ear

    NASA Astrophysics Data System (ADS)

    Wise, Andrew K.; Gillespie, Lisa N.

    2012-12-01

    Bionic devices electrically activate neural populations to partially restore lost function. Of fundamental importance is the functional integrity of the targeted neurons. However, in many conditions the ongoing pathology can lead to continued neural degeneration and death that may compromise the effectiveness of the device and limit future strategies to improve performance. The use of drugs that can prevent nerve cell degeneration and promote their regeneration may improve clinical outcomes. In this paper we focus on strategies of delivering neuroprotective drugs to the auditory system in a way that is safe and clinically relevant for use in combination with a cochlear implant. The aim of this approach is to prevent neural degeneration and promote nerve regrowth in order to improve outcomes for cochlear implant recipients using techniques that can be translated to the clinic.

  15. Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes.

    PubMed

    Zaher, A; Li, S; Wolf, K T; Pirmoradi, F N; Yassine, O; Lin, L; Khashab, N M; Kosel, J

    2015-09-01

    Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5-2 μg/h for higher release rate designs, and 12-40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source.

  16. Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes

    PubMed Central

    Zaher, A.; Li, S.; Wolf, K. T.; Pirmoradi, F. N.; Yassine, O.; Lin, L.; Khashab, N. M.; Kosel, J.

    2015-01-01

    Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5–2 μg/h for higher release rate designs, and 12–40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source. PMID:26487899

  17. Delivery Device and Method for Forming the Same

    NASA Technical Reports Server (NTRS)

    Ma, Peter X. (Inventor); Liu, Xiaohua (Inventor); McCauley, Laurie (Inventor)

    2014-01-01

    A delivery device includes a hollow container, and a plurality of biodegradable and/or erodible polymeric layers established in the container. A layer including a predetermined substance is established between each of the plurality of polymeric layers, whereby degradation of the polymeric layer and release of the predetermined substance occur intermittently. Methods for forming the device are also disclosed herein.

  18. Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma.

    PubMed

    Byrne, James D; Jajja, Mohammad R N; Schorzman, Allison N; Keeler, Amanda W; Luft, J Christopher; Zamboni, William C; DeSimone, Joseph M; Yeh, Jen Jen

    2016-02-23

    Poor delivery and systemic toxicity of many cytotoxic agents, such as the recent promising combination chemotherapy regimen of folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), restrict their full utility in the treatment of pancreatic cancer. Local delivery of chemotherapies has become possible using iontophoretic devices that are implanted directly onto pancreatic tumors. We have fabricated implantable iontophoretic devices and tested the local iontophoretic delivery of FOLFIRINOX for the treatment of pancreatic cancer in an orthotopic patient-derived xenograft model. Iontophoretic delivery of FOLFIRINOX was found to increase tumor exposure by almost an order of magnitude compared with i.v. delivery with substantially lower plasma concentrations. Mice treated for 7 wk with device FOLFIRINOX experienced significantly greater tumor growth inhibition compared with i.v. FOLFIRINOX. A marker of cell proliferation, Ki-67, was stained, showing a significant reduction in tumor cell proliferation. These data capitalize on the unique ability of an implantable iontophoretic device to deliver much higher concentrations of drug to the tumor compared with i.v. delivery. Local iontophoretic delivery of cytotoxic agents should be considered for the treatment of patients with unresectable nonmetastatic disease and for patients with the need for palliation of local symptoms, and may be considered as a neoadjuvant approach to improve resection rates and outcome in patients with localized and locally advanced pancreatic cancer.

  19. Dendrimer based nanotherapeutics for ocular drug delivery

    NASA Astrophysics Data System (ADS)

    Kambhampati, Siva Pramodh

    PAMAM dendrimers are a class of well-defined, hyperbranched polymeric nanocarriers that are being investigated for ocular drug and gene delivery. Their favorable properties such as small size, multivalency and water solubility can provide significant opportunities for many biologically unstable drugs and allows potentially favorable ocular biodistribution. This work exploits hydroxyl terminated dendrimers (G4-OH) as drug/gene delivery vehicles that can target retinal microglia and pigment epithelium via systemic delivery with improved efficacy at much lower concentrations without any side effects. Two different drugs Triamcinolone acetonide (TA) and N-Acetyl Cysteine (NAC) conjugated to G4-OH dendrimers showed tailorable sustained release in physiological relevant solutions and were evaluated in-vitro and in-vivo. Dendrimer-TA conjugates enhanced the solubility of TA and were 100 fold more effective at lower concentrations than free TA in its anti-inflammatory activity in activated microglia and in suppressing VEGF production in hypoxic RPE cells. Dendrimers targeted activated microglia/macrophages and RPE and retained for a period of 21 days in I/R mice model. The relative retention of intravitreal and intravenous dendrimers was comparable, if a 30-fold intravenous dose is used; suggesting intravenous route targeting retinal diseases are possible with dendrimers. D-NAC when injected intravenously attenuated retinal and choroidal inflammation, significantly reduced (˜73%) CNV growth at early stage of AMD in rat model of CNV. A combination therapy of D-NAC + D-TA significantly suppressed microglial activation and promoted CNV regression in late stages of AMD without causing side-effects. G4-OH was modified with linker having minimal amine groups and incorporation of TA as a nuclear localization enhancer resulted in compact gene vectors with favorable safety profile and achieved high levels of transgene expression in hard to transfect human retinal pigment

  20. 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

  1. 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

  2. [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.

  3. Polycaprolactone thin films for retinal tissue engineering and drug delivery

    NASA Astrophysics Data System (ADS)

    Steedman, Mark Rory

    This dissertation focuses on the development of polycaprolactone thin films for retinal tissue engineering and drug delivery. We combined these thin films with techniques such as micro and nanofabrication to develop treatments for age-related macular degeneration (AMD), a disease that leads to the death of rod and cone photoreceptors. Current treatments are only able to slow or limit the progression of the disease, and photoreceptors cannot be regenerated or replaced by the body once lost. The first experiments presented focus on a potential treatment for AMD after photoreceptor death has occurred. We developed a polymer thin film scaffold technology to deliver retinal progenitor cells (RPCs) to the affected area of the eye. Earlier research showed that RPCs destined to become photoreceptors are capable of incorporating into a degenerated retina. In our experiments, we showed that RPC attachment to a micro-welled polycaprolactone (PCL) thin film surface enhanced the differentiation of these cells toward a photoreceptor fate. We then used our PCL thin films to develop a drug delivery device capable of sustained therapeutic release over a multi-month period that would maintain an effective concentration of the drug in the eye and eliminate the need for repeated intraocular injections. We first investigated the biocompatibility of PCL in the rabbit eye. We injected PCL thin films into the anterior chamber or vitreous cavity of rabbit eyes and monitored the animals for up to 6 months. We found that PCL thin films were well tolerated in the rabbit eye, showing no signs of chronic inflammation due to the implant. We then developed a multilayered thin film device containing a microporous membrane. We loaded these devices with lyophilized proteins and quantified drug elution for 10 weeks, finding that both bovine serum albumin and immunoglobulin G elute from these devices with zero order release kinetics. These experiments demonstrate that PCL is an extremely useful

  4. Generation and delivery device for ozone gas

    NASA Technical Reports Server (NTRS)

    Andrews, Craig C. (Inventor); Murphy, Oliver J. (Inventor)

    2002-01-01

    The present invention provides an ozone generation and delivery system that lends itself to small scale applications and requires very low maintenance. The system preferably includes an anode reservoir and a cathode phase separator each having a hydrophobic membrane to allow phase separation of produced gases from water. The hydrogen gas, ozone gas and water containing ozone may be delivered under pressure.

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

    PubMed

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

    2010-01-01

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

  6. Breast Cancer-Targeted Nuclear Drug Delivery Overcoming Drug Resistance for Breast Cancer Chemotherapy

    DTIC Science & Technology

    2013-09-01

    degradable dendrimers and its applications for drug delivery .............................................. 23 3.1 Dendrimer design and synthesis...drug delivery .......................................................... 26 3.3 Dendrimer /lipid nanoassembly as “cluster bomb” for cascade tumor...degradable dendrimers and applied such dendrimers to formulate novel drug delivery systems to improve the limited penetration of anti-cancer drugs within

  7. Light activated liposomes: Functionality and prospects in ocular drug delivery.

    PubMed

    Lajunen, Tatu; Nurmi, Riikka; Kontturi, Leena; Viitala, Lauri; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

    2016-12-28

    Ocular drug delivery, especially to the retina and choroid, is a major challenge in drug development. Liposome technology may be useful in ophthalmology in enabling new routes of delivery, prolongation of drug action and intracellular drug delivery, but drug release from the liposomes should be controlled. For that purpose, light activation may be an approach to release drug at specified time and site in the eye. Technical advances have been made in the field of light activated drug release, particularly indocyanine green loaded liposomes are a promising approach with safe materials and effective light triggered release of small and large molecules. This review discusses the liposomal drug delivery with light activated systems in the context of ophthalmic drug delivery challenges.

  8. [Regulatory authorities expect innovative drug delivery systems (DDS)].

    PubMed

    Mori, Kazuhiko

    2013-01-01

    The Japanese Ministry of Health, Labour and Welfare (MHLW) and the Pharmaceuticals and Medical Devices Agency (PMDA) are responsible for appropriately implementing regulations and providing necessary instructions and advice so that patients have access to safer, more effective drugs. These responsibilities are essential missions of the MHLW/PMDA, although restrictions on drug use or development might be considered to be purely regulatory matters. In the genomic drug discovery era of the 21st century, it is expected that new, innovative drugs will be developed, although the reality can be slightly disturbing. The number of approvals of new molecular entities (NMEs) is only approximately 20 per year both in Japan and the USA and may reach an even lower level. In light of current drug development trends, drug delivery systems (DDS) for targeted therapy or personalized medicines as well as NMEs should be explored more proactively. To promote the development and evaluation of innovative DDS, the MHLW/PMDA considers it important to communicate smoothly among industry-government-academia from the very early stage of development. To promote this, the MHLW/PMDA launched regulatory affairs consultations on R&D strategy for drugs in July 2011. Innovative DDS require not only cutting-edge technology or materials but also extensions of existing pharmaceutical technology. It is most important for innovative DDS to benefit patients in practical clinical settings. The MHLW/PMDA encourages the relevant parties to develop a far-sighted strategy with this goal in mind.

  9. Drug-eluting embolic microspheres for local drug delivery - State of the art.

    PubMed

    Fuchs, Katrin; Duran, Rafael; Denys, Alban; Bize, Pierre E; Borchard, Gerrit; Jordan, Olivier

    2017-09-28

    Embolic microspheres or beads used in transarterial chemoembolization are an established treatment method for hepatocellular carcinoma patients. The occlusion of the tumor-feeding vessels by intra-arterial injection of the beads results in tumor necrosis and shrinkage. In this short review, we describe the utility of using these beads as devices for local drug delivery. We review the latest advances in the development of non-biodegradable and biodegradable drug-eluting beads for transarterial chemoembolization. Their capability to load different drugs, such as chemotherapeutics and anti-angiogenic compounds with different physicochemical properties, like charge and hydrophilicity/hydrophobicity, are discussed. We specifically address controlled and sustained drug release from the microspheres, and the resulting in vivo pharmacokinetics in the plasma vs. drug distribution in the targeted tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. The Research Progress of Targeted Drug Delivery Systems

    NASA Astrophysics Data System (ADS)

    Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

    2017-06-01

    Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

  11. Drug Delivery by Tattooing to Treat Cutaneous Leishmaniasis

    PubMed Central

    Shio, Marina Temi; Paquet, Marilene; Martel, Caroline; Bosschaerts, Tom; Stienstra, Stef; Olivier, Martin; Fortin, Anny

    2014-01-01

    This study establishes a proof-of-concept that a tattoo device can target intra-dermal drug delivery against cutaneous leishmaniasis (CL). The selected drug is oleylphosphocholine (OlPC) formulated as liposomes, particles known to be prone to macrophage ingestion. We first show that treatment of cultured Leishmania-infected macrophages with OlPC-liposomes results in a direct dose-dependent killing of intracellular parasites. Based on this, in vivo efficacy is demonstrated using a 10 day tattooing-mediated treatment in mice infected with L. major and L. mexicana. In both models this regimen results in rapid clinical recovery with complete regression of skin lesions by Day 28. Parasite counts and histopathology examination confirm high treatment efficacy at the parasitic level. Low amount of drug required for tattooing combined with fast clinical recovery may have a positive impact on CL patient management. This first example of tattoo-mediated drug delivery could open to new therapeutic interventions in the treatment of skin diseases. PMID:24561704

  12. Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles

    PubMed Central

    Cai, Shuang; Zhang, Qiuhong; Bagby, Taryn; Forrest, M. Laird

    2011-01-01

    The lymphatic system plays a crucial role in the immune system’s recognition and response to disease, and most solid cancers initially spread from the primary site via the tumor’s surrounding lymphatics before hematological dissemination. Hence, the lymphatic system is an important target for developing new vaccines, cancer treatments, and diagnostic agents. Targeting the lymphatic system by subcutaneous, intestinal, and pulmonary routes has been evaluated and subsequently utilized to improve lymphatic penetration and retention of drug molecules, reduce drug-related systemic toxicities, and enhance bioavailability of poorly soluble and unstable drugs. Lymphatic imaging is an essential tool for the detection and staging of cancer. New nano-based technologies offer improved detection and characterization of the nodal diseases, while new delivery devices can better target and confine treatments to tumors within the nodal space while sparing healthy tissues. This manuscript reviews recent advances in the field of lymphatic drug delivery and imaging and focuses specifically on the development ofliposomes and solid lipid nanoparticles for lymphatic introduction via the subcutaneous, intestinal, and pulmonary routes. PMID:21712055

  13. 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.

  14. Convection-enhanced drug delivery for gliomas

    PubMed Central

    Healy, Andrew T.; Vogelbaum, Michael A.

    2015-01-01

    In spite of aggressive multi-modality treatments, patients diagnosed with anaplastic astrocytoma and glioblastoma continue to display poor median survival. The success of our current conventional and targeted chemotherapies are largely hindered by systemic- and neurotoxicity, as well as poor central nervous system (CNS) penetration. Interstitial drug administration via convection-enhanced delivery (CED) is an alternative that potentially overcomes systemic toxicities and CNS delivery issues by directly bypassing the blood–brain barrier (BBB). This novel approach not only allows for directed administration, but also allows for newer, tumor-selective agents, which would normally be excluded from the CNS due to molecular size alone. To date, randomized trials of CED therapy have yet to definitely show survival advantage as compared with today's standard of care, however, early studies appear to have been limited by “first generation” delivery techniques. Taking into consideration lessons learned from early trials along with decades of research, newer CED technologies and therapeutic agents are emerging, which are reviewed herein. PMID:25722934

  15. Ultrasound-Propelled Nanocups for Drug Delivery

    PubMed Central

    Kwan, James J; Myers, Rachel; Coviello, Christian M; Graham, Susan M; Shah, Apurva R; Stride, Eleanor; Carlisle, Robert C; Coussios, Constantin C

    2015-01-01

    Ultrasound-induced bubble activity (cavitation) has been recently shown to actively transport and improve the distribution of therapeutic agents in tumors. However, existing cavitation-promoting agents are micron-sized and cannot sustain cavitation activity over prolonged time periods because they are rapidly destroyed upon ultrasound exposure. A novel ultrasound-responsive single-cavity polymeric nanoparticle (nanocup) capable of trapping and stabilizing gas against dissolution in the bloodstream is reported. Upon ultrasound exposure at frequencies and intensities achievable with existing diagnostic and therapeutic systems, nanocups initiate and sustain readily detectable cavitation activity for at least four times longer than existing microbubble constructs in an in vivo tumor model. As a proof-of-concept of their ability to enhance the delivery of unmodified therapeutics, intravenously injected nanocups are also found to improve the distribution of a freely circulating IgG mouse antibody when the tumor is exposed to ultrasound. Quantification of the delivery distance and concentration of both the nanocups and coadministered model therapeutic in an in vitro flow phantom shows that the ultrasound-propelled nanocups travel further than the model therapeutic, which is itself delivered to hundreds of microns from the vessel wall. Thus nanocups offer considerable potential for enhanced drug delivery and treatment monitoring in oncological and other biomedical applications. PMID:26296985

  16. Importance of novel drug delivery systems in herbal medicines

    PubMed Central

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

    2010-01-01

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

  17. Importance of novel drug delivery systems in herbal medicines.

    PubMed

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

    2010-01-01

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

  18. Light-sensitive intelligent drug delivery systems.

    PubMed

    Alvarez-Lorenzo, Carmen; Bromberg, Lev; Concheiro, Angel

    2009-01-01

    Drug delivery systems (DDS) capable of releasing an active molecule at the appropriate site and at a rate that adjusts in response to the progression of the disease or to certain functions/biorhythms of the organism are particularly appealing. Biocompatible materials sensitive to certain physiological variables or external physicochemical stimuli (intelligent materials) can be used for achieving this aim. Light-responsiveness is receiving increasing attention owing to the possibility of developing materials sensitive to innocuous electromagnetic radiation (mainly in the UV, visible and near-infrared range), which can be applied on demand at well delimited sites of the body. Some light-responsive DDS are of a single use (i.e. the light triggers an irreversible structural change that provokes the delivery of the entire dose) while others able to undergo reversible structural changes when cycles of light/dark are applied, behave as multi-switchable carriers (releasing the drug in a pulsatile manner). In this review, the mechanisms used to develop polymeric micelles, gels, liposomes and nanocomposites with light-sensitiveness are analyzed. Examples of the capability of some polymeric, lipidic and inorganic structures to regulate the release of small solutes and biomacromolecules are presented and the potential of light-sensitive carriers as functional components of intelligent DDS is discussed.

  19. Challenges in modelling nanoparticles for drug delivery

    NASA Astrophysics Data System (ADS)

    Barnard, Amanda S.

    2016-01-01

    Although there have been significant advances in the fields of theoretical condensed matter and computational physics, when confronted with the complexity and diversity of nanoparticles available in conventional laboratories a number of modeling challenges remain. These challenges are generally shared among application domains, but the impacts of the limitations and approximations we make to overcome them (or circumvent them) can be more significant one area than another. In the case of nanoparticles for drug delivery applications some immediate challenges include the incompatibility of length-scales, our ability to model weak interactions and solvation, the complexity of the thermochemical environment surrounding the nanoparticles, and the role of polydispersivity in determining properties and performance. Some of these challenges can be met with existing technologies, others with emerging technologies including the data-driven sciences; some others require new methods to be developed. In this article we will briefly review some simple methods and techniques that can be applied to these (and other) challenges, and demonstrate some results using nanodiamond-based drug delivery platforms as an exemplar.

  20. A microneedle roller for transdermal drug delivery.

    PubMed

    Park, Jung-Hwan; Choi, Seong-O; Seo, Soonmin; Choy, Young Bin; Prausnitz, Mark R

    2010-10-01

    Microneedle rollers have been used to treat large areas of skin for cosmetic purposes and to increase skin permeability for drug delivery. In this study, we introduce a polymer microneedle roller fabricated by inclined rotational UV lithography, replicated by micromolding hydrophobic polylactic acid and hydrophilic carboxy-methyl-cellulose. These microneedles created micron-scale holes in human and porcine cadaver skin that permitted entry of acetylsalicylic acid, Trypan blue and nanoparticles measuring 50nm and 200nm in diameter. The amount of acetylsalicylic acid delivered increased with the number of holes made in the skin and was 1-2 orders of magnitude greater than in untreated skin. Lateral diffusion in the skin between holes made by microneedles followed expected diffusional kinetics, with effective diffusivity values that were 23-160 times smaller than in water. Compared to inserting microneedles on a flat patch, the sequential insertion of microneedles row by row on a roller required less insertion force in full-thickness porcine skin. Overall, polymer microneedle rollers, prepared from replicated polymer films, offer a simple way to increase skin permeability for drug delivery.

  1. Challenges in modelling nanoparticles for drug delivery.

    PubMed

    Barnard, Amanda S

    2016-01-20

    Although there have been significant advances in the fields of theoretical condensed matter and computational physics, when confronted with the complexity and diversity of nanoparticles available in conventional laboratories a number of modeling challenges remain. These challenges are generally shared among application domains, but the impacts of the limitations and approximations we make to overcome them (or circumvent them) can be more significant one area than another. In the case of nanoparticles for drug delivery applications some immediate challenges include the incompatibility of length-scales, our ability to model weak interactions and solvation, the complexity of the thermochemical environment surrounding the nanoparticles, and the role of polydispersivity in determining properties and performance. Some of these challenges can be met with existing technologies, others with emerging technologies including the data-driven sciences; some others require new methods to be developed. In this article we will briefly review some simple methods and techniques that can be applied to these (and other) challenges, and demonstrate some results using nanodiamond-based drug delivery platforms as an exemplar.

  2. Collagen interactions: Drug design and delivery.

    PubMed

    An, Bo; Lin, Yu-Shan; Brodsky, Barbara

    2016-02-01

    Collagen is a major component in a wide range of drug delivery systems and biomaterial applications. Its basic physical and structural properties, together with its low immunogenicity and natural turnover, are keys to its biocompatibility and effectiveness. In addition to its material properties, the collagen triple-helix interacts with a large number of molecules that trigger biological events. Collagen interactions with cell surface receptors regulate many cellular processes, while interactions with other ECM components are critical for matrix structure and remodeling. Collagen also interacts with enzymes involved in its biosynthesis and degradation, including matrix metalloproteinases. Over the past decade, much information has been gained about the nature and specificity of collagen interactions with its partners. These studies have defined collagen sequences responsible for binding and the high-resolution structures of triple-helical peptides bound to its natural binding partners. Strategies to target collagen interactions are already being developed, including the use of monoclonal antibodies to interfere with collagen fibril formation and the use of triple-helical peptides to direct liposomes to melanoma cells. The molecular information about collagen interactions will further serve as a foundation for computational studies to design small molecules that can interfere with specific interactions or target tumor cells. Intelligent control of collagen biological interactions within a material context will expand the effectiveness of collagen-based drug delivery.

  3. Adapalene microemulsion for transfollicular drug delivery.

    PubMed

    Bhatia, Gaurav; Zhou, Yingcong; Banga, Ajay K

    2013-08-01

    The aim of this study was to develop a microemulsion formulation of adapalene for transfollicular delivery. A pseudoternary phase diagram was developed for microemulsion consisting of oleic acid as oil phase, tween 20 as surfactant, Transcutol® as cosurfactant, and deionized water. Differential tape stripping and confocal laser scanning microscopy were performed to determine the penetration of microemulsion through hair follicles. Transmission electron microscopy, dynamic light scattering, polarizing light microscopy, and differential scanning calorimetry were performed to characterize the microstructures of microemulsion. The pH and viscosity of the microemulsions were also determined. Permeation studies were carried out in vitro on porcine ear skin over a period of 24 h using Franz diffusion cells. The drug penetration in the hair follicles increased from 0.109 ± 0.03 to 0.292 ± 0.094 μg, as the microstructure of microemulsion shifted from oil-in-water to bi-continuous, with increase in water content of microemulsion. Confocal laser scanning microscopy images suggested that hair follicles provided the path for transfollicular permeation of adapalene microemulsion. These results suggest that microemulsion penetrated through hair follicles and are promising for transfollicular drug delivery. Copyright © 2013 Wiley Periodicals, Inc.

  4. Diatomite silica nanoparticles for drug delivery

    PubMed Central

    2014-01-01

    Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery. PACS 87.85.J81.05.Rm; 61.46. + w PMID:25024689

  5. Diatomite silica nanoparticles for drug delivery.

    PubMed

    Ruggiero, Immacolata; Terracciano, Monica; Martucci, Nicola M; De Stefano, Luca; Migliaccio, Nunzia; Tatè, Rosarita; Rendina, Ivo; Arcari, Paolo; Lamberti, Annalisa; Rea, Ilaria

    2014-01-01

    Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery. 87.85.J81.05.Rm; 61.46. + w.

  6. Polymeric micelles for acyclovir drug delivery.

    PubMed

    Sawdon, Alicia J; Peng, Ching-An

    2014-10-01

    Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of ɛ-caprolactone to form ACV-polycaprolactone (ACV-PCL). Through conjugation of hydrophobic ACV-PCL with hydrophilic methoxy poly(ethylene glycol) (MPEG) or chitosan, polymeric micelles for drug delivery were formed. (1)H NMR, FTIR, and gel permeation chromatography were employed to show successful conjugation of MPEG or chitosan to hydrophobic ACV-PCL. Through dynamic light scattering, zeta potential analysis, transmission electron microscopy, and critical micelle concentration (CMC), the synthesized ACV-tagged polymeric micelles were characterized. It was found that the average size of the polymeric micelles was under 200nm and the CMCs of ACV-PCL-MPEG and ACV-PCL-chitosan were 2.0mgL(-1) and 6.6mgL(-1), respectively. The drug release kinetics of ACV was investigated and cytotoxicity assay demonstrates that ACV-tagged polymeric micelles were non-toxic.

  7. Polymeric Micelles for Acyclovir Drug Delivery

    PubMed Central

    Sawdon, Alicia J.; Peng, Ching-An

    2014-01-01

    Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of ε-caprolactone to form ACV-polycaprolactone (ACV-PCL). Through conjugation of hydrophobic ACV-PCL with hydrophilic methoxy poly(ethylene glycol) (MPEG) or chitosan, polymeric micelles for drug delivery were formed. 1H NMR, FTIR, and gel permeation chromatography were employed to show successful conjugation of MPEG or chitosan to hydrophobic ACV-PCL. Through dynamic light scattering, zeta potential analysis, transmission electron microscopy, and critical micelle concentration (CMC), the synthesized ACV-tagged polymeric micelles were characterized. It was found that the average size of the polymeric micelles was under 200 nm and the CMCs of ACV-PCLMPEG and ACV-PCL-chitosan were 2.0 mg L−1 and 6.6 mg L−1, respectively. The drug release kinetics of ACV was investigated and cytotoxicity assay demonstrates that ACV-tagged polymeric micelles were non-toxic. PMID:25193154

  8. Alginate electrodeposition onto three-dimensional porous Co-Ni films as drug delivery platforms.

    PubMed

    García-Torres, J; Gispert, C; Gómez, E; Vallés, E

    2015-01-21

    Three-dimensional porous Co-Ni films/alginate hybrid materials have been successfully prepared by electrodeposition to be used as a steerable magnetic device for drug delivery. Firstly, 3D porous Co-Ni films were prepared as substrates for the subsequent electrodeposition of the alginate biopolymer. Cyclic voltammetry, galvanostatic and potentiostatic studies were performed to establish the best conditions to obtain porous Co-Ni films. The electrochemical experiments were carried out in an electrolyte containing the metal salts and ammonium chloride at low pHs. In a second stage, the electrochemical deposition of alginate as a biocompatible polymer drug delivery carrier was performed. The characteristics of the alginate matrix were investigated in terms of electrochemical properties, morphology and drug release. The hybrid material obtained showed soft-magnetic behavior and drug release indicating its suitability to be used as a steerable magnetic drug delivery device.

  9. Pairwise polymer blends for oral drug delivery.

    PubMed

    Marks, Joyann A; Wegiel, Lindsay A; Taylor, Lynne S; Edgar, Kevin J

    2014-09-01

    Blends of polymers with complementary properties hold promise for addressing the diverse, demanding polymer performance requirements in amorphous solid dispersions (ASDs), but we lack comprehensive property understanding for blends of important ASD polymers. Herein, we prepare pairwise blends of commercially available polymers polyvinylpyrrolidone (PVP), the cationic acrylate copolymer Eudragit 100 (E100), hydroxypropyl methylcellulose acetate succinate (HPMCAS), carboxymethyl cellulose acetate butyrate (CMCAB), hydroxypropyl methylcellulose (HPMC), and the new derivative cellulose acetate adipate propionate (CAAdP). This study identifies miscible binary blends that may find use, for example, in ASDs for solubility and bioavailability enhancement of poorly water-soluble drugs. Differential scanning calorimetry, FTIR spectroscopy, and film clarity were used to determine blend miscibility. Several polymer combinations including HPMCAS/PVP, HPMC/CMCAB, and PVP/HPMC appear to be miscible in all proportions. In contrast, blends of E100/PVP and E100/HPMC showed a miscibility gap. Combinations of water-soluble and hydrophobic polymers like these may permit effective balancing of ASD performance criteria such as release rate and polymer-drug interaction to prevent nucleation and crystal growth of poorly soluble drugs. Miscible polymer combinations described herein will enable further study of their drug delivery capabilities, and provide a potentially valuable set of ASD formulation tools. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Antibody Drug Conjugate Bioinformatics: Drug Delivery through the Letterbox

    PubMed Central

    Vlachakis, Dimitrios

    2013-01-01

    Antibodies appear to be the first line of defence in the adaptive immune response of vertebrates and thereby are involved in a multitude of biochemical mechanisms, such as regulation of infection, autoimmunity, and cancer. It goes without saying that a full understanding of antibody function is required for the development of novel antibody-interacting drugs. These drugs are the Antibody Drug Conjugates (ADCs), which are a new type of targeted therapy, used for example for cancer. They consist of an antibody (or antibody fragment such as a single-chain variable fragment [scFv]) linked to a payload drug (often cytotoxic). Because of the targeting, the side effects should be lower and give a wider therapeutic window. Overall, the underlying principle of ADCs is to discern the delivery of a drug that is cytotoxic to a target that is cancerous, hoping to increase the antitumoural potency of the original drug by reducing adverse effects and side effects, such as toxicity of the cancer target. This is a pioneering field that employs state-of-the-art computational and molecular biology methods in the fight against cancer using ADCs. PMID:23853668

  11. Smart Nanoparticles for Drug Delivery: Boundaries and Opportunities

    PubMed Central

    Lee, Byung Kook; Yun, Yeon Hee; Park, Kinam

    2014-01-01

    Various pharmaceutical particles have been used in developing different drug delivery systems ranging from traditional tablets to state-of-the-art nanoparticle formulations. Nanoparticle formulations are unique in that the small size with huge surface area sometimes provides unique properties that larger particles and bulk materials do not have. Nanoparticle formulations have been used in improving the bioavailability of various drugs, in particular, poorly soluble drugs. Nanoparticle drug delivery systems have found their unique applications in targeted drug delivery to tumors. While nanoparticle formulations have been successful in small animal xenograft models, their translation to clinical applications has been very rare. Developing nanoparticle systems designed for targeted drug delivery, e.g., treating tumors in humans, requires clear understanding of the uniqueness of nanoparticles, as well as limitations and causes of failures in clinical applications. It also requires designing novel smart nanoparticle delivery systems that can increase the drug bioavailability and at the same time reduce the drug's side effects. PMID:25684780

  12. Nanoscale coordination polymers for anticancer drug delivery

    NASA Astrophysics Data System (ADS)

    Phillips, Rachel Huxford

    This dissertation reports the synthesis and characterization of nanoscale coordination polymers (NCPs) for anticancer drug delivery. Nanoparticles have been explored in order to address the limitations of small molecule chemotherapeutics. NCPs have been investigated as drug delivery vehicles as they can exhibit the same beneficial properties as the bulk metal-organic frameworks as well as interesting characteristics that are unique to nanomaterials. Gd-MTX (MTX = methotrexate) NCPs with a MTX loading of 71.6 wt% were synthesized and stabilized by encapsulation within a lipid bilayer containing anisamide (AA), a small molecule that targets sigma receptors which are overexpressed in many cancer tissues. Functionalization with AA allows for targeted delivery and controlled release to cancer cells, as shown by enhanced efficacy against leukemia cells. The NCPs were doped with Ru(bpy)32+ (bpy = 2,2'-bipyridine), and this formulation was utilized as an optical imaging agent by confocal microscopy. NCPs containing the chemotherapeutic pemetrexed (PMX) were synthesized using different binding metals. Zr-based materials could not be stabilized by encapsulation with a lipid bilayer, and Gd-based materials showed that PMX had degraded during synthesis. However, Hf-based NCPs containing 19.7 wt% PMX were stabilized by a lipid coating and showed in vitro efficacy against non-small cell lung cancer (NSCLC) cell lines. Enhanced efficacy was observed for formulations containing AA. Additionally, NCP formulations containing the cisplatin prodrug disuccinatocisplatin were prepared; one of these formulations could be stabilized by encapsulation within a lipid layer. Coating with a lipid layer doped with AA rendered this formulation an active targeting agent. The resulting formulation proved more potent than free cisplatin in NSCLC cell lines. Improved NCP uptake was demonstrated by confocal microscopy and competitive binding assays. Finally, a Pt(IV) oxaliplatin prodrug was

  13. 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. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Drug delivery interfaces in the 21st century: from science fiction ideas to viable technologies.

    PubMed

    Chertok, Beata; Webber, Matthew J; Succi, Marc D; Langer, Robert

    2013-10-07

    Early science fiction envisioned the future of drug delivery as targeted micrometer-scale submarines and "cyborg" body parts. Here we describe the progression of the field toward technologies that are now beginning to capture aspects of this early vision. Specifically, we focus on the two most prominent types of systems in drug delivery: the intravascular micro/nano drug carriers for delivery to the site of pathology and drug-loaded implantable devices that facilitate release with the predefined kinetics or in response to a specific cue. We discuss the unmet clinical needs that inspire these designs, the physiological factors that pose difficult challenges for their realization, and viable technologies that promise robust solutions. We also offer a perspective on where drug delivery may be in the next 50 years based on expected advances in material engineering and in the context of future diagnostics.

  15. Drug Delivery Interfaces in the 21st Century: From Science Fiction Ideas to Viable Technologies

    PubMed Central

    Chertok, Beata; Webber, Matthew J.; Succi, Marc D.; Langer, Robert S.

    2013-01-01

    Early science fiction envisioned the future of drug delivery as targeted micron-scale submarines and ‘Cyborg’ body parts. Here we describe the progression of the field toward technologies that are now beginning to capture aspects of this early vision. Specifically, we focus on the two most prominent types of systems in drug delivery – the intravascular micro/nano drug carriers for delivery to the site of pathology and drug-loaded implantable devices that facilitate release with the pre-defined kinetics or in response to a specific cue. We discuss the unmet clinical needs that inspire these designs, the physiological factors that pose difficult challenges for their realization, and viable technologies that promise robust solutions. We also offer a perspective on where drug delivery may be in the next 50 years based on expected advances in material engineering and in the context of future diagnostics. PMID:23915375

  16. Controlled delivery achieved with bi-layer matrix devices produced by co-injection moulding.

    PubMed

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

    2004-08-09

    The aim of this study was to design new soy protein-based bi-layered co-injection moulded matrix systems aimed to achieve controlled drug delivery. The devices consisted of a drug-free outer layer (skin) and a drug-containing core. The systems overcame the inherent disadvantage of non-linear release associated with diffusion-controlled single-layer matrix devices by providing additional releasing area with time to compensate for the decreasing release rate. As expected, the bi-layer devices presented a significant decrease in drug release rate when compared with a correspondent single layer matrix system. The skin thickness and the degree of crosslinking of the core appeared to be very important tools to tailor the release patterns. Furthermore, due to the amphoteric nature of the soy protein, the developed devices evidenced a pH-dependent behaviour. The mechanisms of drug release were also elucidated at two different pH values: i) pH 5.0, near the isoelectric point of soy (low matrix solubility); and ii) pH 7.4, physiological pH (high matrix solubility). Consequently, changing the release medium from pH 5.0 to pH 7.4 after two hours, led to an abrupt increase in drug release and the devices presented a typical controlled drug delivery profile: slow release/fast release. These evidences may provide for the development of individual systems with different release onsets that in combination may exhibit drug releases at predetermined times in a pre-programmed way. Another possibility is the production of three-layer devices presenting bimodal release profiles (fast release/slow release/fast release) by similar technologies. Scanning electron micrograph of a developed bi-layer device.

  17. Two Photon Polymerization of Microneedles for Transdermal Drug Delivery

    PubMed Central

    Gittard, Shaun D.; Ovsianikov, Aleksandr; Chichkov, Boris N.; Doraiswamy, Anand; Narayan, Roger J.

    2010-01-01

    Importance of the field Microneedles are small-scale devices that are finding use for transdermal delivery of protein-based pharmacologic agents and nucleic acid-based pharmacologic agents; however, microneedles prepared using conventional microelectronics-based technologies have several shortcomings, which have limited translation of these devices into widespread clinical use. Areas covered in this review Two photon polymerization is a laser-based rapid prototyping technique that has been recently used for direct fabrication of hollow microneedles with a wide variety of geometries. In addition, an indirect rapid prototyping method that involves two photon polymerization and polydimethyl siloxane micromolding has been used for fabrication of solid microneedles with exceptional mechanical properties. What the reader will gain In this review, the use of two photon polymerization for fabricating in-plane and out-of-plane hollow microneedle arrays is described. The use of two photon polymerization-micromolding for fabrication of solid microneedles is also reviewed. In addition, fabrication of microneedles with antimicrobial properties is discussed; antimicrobial microneedles may reduce the risk of infection associated with formation of channels through the stratum corneum. Take home message It is anticipated that the use of two photon polymerization as well as two photon polymerization-micromolding for fabrication of microneedles and other microstructured drug delivery devices will increase over the coming years. PMID:20205601

  18. Engineering bioceramic microstructure for customized drug delivery

    NASA Astrophysics Data System (ADS)

    Pacheco Gomez, Hernando Jose

    One of the most efficient approaches to treat cancer and infection is to use biomaterials as a drug delivery system (DDS). The goal is for the material to provide a sustained release of therapeutic drug dose locally to target the ill tissue without affecting other organs. Silica Calcium Phosphate nano composite (SCPC) is a drug delivery platform that successfully demonstrated the ability to bind and release several therapeutics including antibiotics, anticancer drugs, and growth factors. The aim of the present work is to analyze the role of SCPC microstructure on drug binding and release kinetics. The main crystalline phases of SCPC are alpha-cristobalite (SiO2, Cris) and beta-rhenanite (NaCaPO4, Rhe); therefore, these two phases were prepared and characterized separately. Structural and compositional features of Cris, Rhe and SCPC bioceramics demonstrated a significant influence on the loading capacity and release kinetics profile of Vancomycin (Vanc) and Cisplatin (Cis). Fourier Transform Infrared (FTIR) spectroscopy analyses demonstrated that the P-O functional group in Rhe and SCPC has high affinity to the (C=O and N-H) of Vanc and (N-H and O-H) of Cis. By contrast, a weak chemical interaction between the Si-O functional group in Cris and SCPC and the two drugs was observed. Vanc loading per unit surface area increased in the order 8.00 microg Vanc/m2 for Rhe > 4.49 microg Vanc /m2 for SCPC>3.01 microg Vanc /m2 for Cris (p<0.05). Cis loading capacity increased in the order 8.59 microg Vanc /m2 for Cris, 17.8 microg Vanc/m2 for Rhe and 6.03 microg Vanc /m2 for SCPC (p<0.05). Drug release kinetics was dependent on the carrier as well as on the kind of drug. Different burst release and sustained release rates were measured for Vanc and Cis from the same carrier. The percentages of drug amount released from Cris, Rhe and SCPC during the burst stage (the first 2h) were: 50%, 50%, and 46% of Vanc; and 53.4%, 36.6%, and 30.6 % of Cis, respectively. Burst release was

  19. Dendrimeric micelles for controlled drug release and targeted delivery

    PubMed Central

    Ambade, Ashootosh V.; Savariar, Elamprakash N.; Thayumanavan, S.

    2008-01-01

    This review highlights the developments in dendrimer-based micelles for drug delivery. Dendrimers, the perfectly branched monodisperse macromolecules, have certain structural advantages that make them attractive candidates as drug carriers for controlled release or targeted delivery. As polymeric micelle-based approaches precede the work in dendrimers, these are also discussed briefly. The review concludes with a perspective on possible applications of biaryl-based dendrimeric micelles that exhibit environment-dependent conformations, in drug delivery. PMID:16053329

  20. [Research on intelligent controlled drug delivery with polymer].

    PubMed

    Zhang, Zhibin; Tang, Changwei; Chen, Huiqing; Shan, Lianhai; Wan, Changxiu

    2006-02-01

    The intelligent controlled drug delivery systems are a series of the preparations including microcapsules or nanocapsules composed of intelligent polymers and medication. The properties of preparations can change with the external stimuli such as pH value, temperature, chemical substance, light, electricity and magnetism. According to this properties, the drug delivery can be intelligently controlled. This paper has reviewed research on syntheses and applications of intelligent controlled drug delivery systems with polymers.

  1. Silk Fibroin as an Organic Polymer for Controlled Drug Delivery

    SciTech Connect

    Hofmann,S.; Wong Po Foo, C.; Rossetti, F.; Textor, M.; Vunjak-Novakovic, G.; Kaplan, D.; Merkle, H.; Meinel, L.

    2006-01-01

    The pharmaceutical utility of silk fibroin (SF) materials for drug delivery was investigated. SF films were prepared from aqueous solutions of the fibroin protein polymer and crystallinity was induced and controlled by methanol treatment. Dextrans of different molecular weights, as well as proteins, were physically entrapped into the drug delivery device during processing into films. Drug release kinetics were evaluated as a function of dextran molecular weight, and film crystallinity. Treatment with methanol resulted in an increase in {beta}-sheet structure, an increase in crystallinity and an increase in film surface hydrophobicity determined by FTIR, X-ray and contact angle techniques, respectively. The increase in crystallinity resulted in the sustained release of dextrans of molecular weights ranging from 4 to 40 kDa, whereas for less crystalline films sustained release was confined to the 40 kDa dextran. Protein release from the films was studied with horseradish peroxidase (HRP) and lysozyme (Lys) as model compounds. Enzyme release from the less crystalline films resulted in a biphasic release pattern, characterized by an initial release within the first 36 h, followed by a lag phase and continuous release between days 3 and 11. No initial burst was observed for films with higher crystallinity and subsequent release patterns followed linear kinetics for HRP, or no substantial release for Lys. In conclusion, SF is an interesting polymer for drug delivery of polysaccharides and bioactive proteins due to the controllable level of crystallinity and the ability to process the biomaterial in biocompatible fashion under ambient conditions to avoid damage to labile compounds to be delivered.

  2. Albumin nanostructures as advanced drug delivery systems.

    PubMed

    Karimi, Mahdi; Bahrami, Sajad; Ravari, Soodeh Baghaee; Zangabad, Parham Sahandi; Mirshekari, Hamed; Bozorgomid, Mahnaz; Shahreza, Somayeh; Sori, Masume; Hamblin, Michael R

    2016-11-01

    One of the biggest impacts that the nanotechnology has made on medicine and biology, has been in the area of drug delivery systems (DDSs). Many drugs suffer from serious problems concerning insolubility, instability in biological environments, poor uptake into cells and tissues, sub-optimal selectivity for targets and unwanted side effects. Nanocarriers can be designed as DDSs to overcome many of these drawbacks. One of the most versatile building blocks to prepare these nanocarriers is the ubiquitous, readily available and inexpensive protein, serum albumin. Areas covered: This review covers the use of different types of albumin (human, bovine, rat, and chicken egg) to prepare nanoparticle and microparticle-based structures to bind drugs. Various methods have been used to modify the albumin structure. A range of targeting ligands can be attached to the albumin that can be recognized by specific cell receptors that are expressed on target cells or tissues. Expert opinion: The particular advantages of albumin used in DDSs include ready availability, ease of chemical modification, good biocompatibility, and low immunogenicity. The regulatory approvals that have been received for several albumin-based therapeutic agents suggest that this approach will continue to be successfully explored.

  3. Polymeric Microgels as Potential Drug Delivery Vesicles

    NASA Astrophysics Data System (ADS)

    McDonough, Ryan; Streletzky, Kiril; Bayachou, Mekki; Peiris, Pubudu

    2010-03-01

    The temperature dependent volume phase change of cross-linked amphiphilic molecules (microgels) suggests their use as drug delivery vesicles. Drug particles aggregate in the slightly hydrophobic microgel interior. They are stored in equilibrium until the critical temperature (Tv) is reached where the volume phase change limits available space, thus expelling the drugs. This loading property of hydroxypropylcellulose (HPC) microgels was tested using amperometric analytical techniques. Small molecules inside microgels do not approach the electrode surface, which decreases current signal. A room temperature (Troom) flow amperometric measurement comparing microgel/paracetamol solution with control paracetamol samples yielded about 20 percent concentration reduction in the microgel sample. Results from the steady-state electrochemical experiment confirm the 20 percent concentration drop in the microgel sample compared to the control sample at Troom. Using the steady-state experiment with a cyclic temperature ramp from Troom to beyond Tv showed that the paracetamol concentration change between the temperature extremes was greater for the microgels than for the controls. An evolving aspect of the study is the characterization of microgel shrinkage from in situ, temperature controlled liquid AFM images as compared to previously completed DLS characterization of the same microgel sample.

  4. Lipoidal Soft Hybrid Biocarriers of Supramolecular Construction for Drug Delivery

    PubMed Central

    Kumar, Dinesh; Sharma, Deepak; Singh, Gurmeet; Singh, Mankaran; Rathore, Mahendra Singh

    2012-01-01

    Lipid-based innovations have achieved new heights during the last few years as an essential component of drug development. The current challenge of drug delivery is liberation of drug agents at the right time in a safe and reproducible manner to a specific target site. A number of novel drug delivery systems has emerged encompassing various routes of administration, to achieve controlled and targeted drug delivery. Microparticulate lipoidal vesicular system represents a unique technology platform suitable for the oral and systemic administration of a wide variety of molecules with important therapeutic biological activities, including drugs, genes, and vaccine antigens. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. Also, novel lipid carrier-mediated vesicular systems are originated. This paper has focused on the lipid-based supramolecular vesicular carriers that are used in various drug delivery and drug targeting systems. PMID:22888455

  5. Polymeric carriers: role of geometry in drug delivery

    PubMed Central

    Simone, Eric A; Dziubla, Thomas D; Muzykantov, Vladimir R

    2009-01-01

    The unique properties of synthetic nanostructures promise a diverse set of applications as carriers for drug delivery, which are advantageous in terms of biocompatibility, pharmacokinetics, targeting and controlled drug release. Historically, more traditional drug delivery systems have focused on spherical carriers. However, there is a growing interest in pursuing non-spherical carriers, such as elongated or filamentous morphologies, now available due to novel formulation strategies. Unique physiochemical properties of these supramolecular structures offer distinct advantages as drug delivery systems. In particular, results of recent studies in cell cultures and lab animals indicate that rational design of carriers of a given geometry (size and shape) offers an unprecedented control of their longevity in circulation and targeting to selected cellular and subcellular locations. This article reviews drug delivery aspects of non-spherical drug delivery systems, including material selection and formulation, drug loading and release, biocompatibility, circulation behavior, targeting and subcellular addressing. PMID:19040392

  6. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. The Controlled Drug Delivery Systems: Past Forward and Future Back

    PubMed Central

    Park, Kinam

    2014-01-01

    The controlled drug delivery technology has progressed over the last six decades. It began in 1952 with the introduction of the first sustained release formulation. The 1st generation (1950-1980) of drug delivery was focused on developing oral and transdermal sustained release systems and establishing the controlled drug release mechanisms. Attention of the 2nd generation (1980-2010) was dedicated to 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 consumed mostly for studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role during the 2nd generation of drug delivery technologies, and it will continue playing a leading role for the next generation. Taking the right path towards the productive 3rd generation of drug delivery technologies requires honest open dialogues without any preconceived ideas of the past. The drug delivery field needs to take a bold approach of designing the future drug delivery formulations first, based on today’s necessities, and produce necessary innovations. The JCR will provide the forum for sharing the new ideas that will shape the 3rd generation of drug delivery technologies. PMID:24794901

  8. Smart drug delivery through DNA/magnetic nanoparticle gates.

    PubMed

    Ruiz-Hernández, Eduardo; Baeza, Alejandro; Vallet-Regí, María

    2011-02-22

    Mesoporous silica nanoparticles can be modified to perform on-demand stimuli-responsive dosing of therapeutic molecules. The silica network was loaded with iron oxide superparamagnetic nanocrystals, providing the potential to perform targeting and magnetic resonance imaging. Single-stranded DNA was immobilized onto the material surface. The complementary DNA sequence was then attached to magnetic nanoparticles. The present work demonstrates that DNA/magnetic nanoparticle conjugates are able to cap the pores of the magnetic silica particles upon hybridization of both DNA strands. Progressive double-stranded DNA melting as a result of temperature increase gave rise to uncapping and the subsequent release of a mesopore-filled model drug, fluorescein. The reversibility of DNA linkage results in an "on-off" release mechanism. Moreover, the magnetic component of the whole system allows reaching hyperthermic temperatures (42-47 °C) under an alternating magnetic field. This feature leaves open the possibility of a remotely triggered drug delivery. Furthermore, due to its capacity to increase the temperature of the surrounding media, this multifunctional device could play an important role in the development of advanced drug delivery systems for thermochemotherapy against cancer.

  9. Lipid formulation as a drug carrier for drug delivery.

    PubMed

    Tomii, Yoshifumi

    2002-01-01

    In recent years, a Drug Delivery System (DDS), a preparative approach attracts the attention in the development of new drugs. DDS focuses on the regulation of the in vivo dynamics, such as absorption, distribution, metabolism, and elimination, thereby improving the effectiveness and the safety of the drugs by an applicable use of drug preparation technologies. A conventional intravenous dosage form of Amphotericin B (AmB), Fungizone, is the most effective clinically available for treating fungal infections. However, the clinical efficacy of AmB is limited by its adverse effects. Several lipid formulations, such as Liposomal AmB (L-AmB), AmB lipid complex (ABLC), and AmB colloidal dispersion (ABCD), with reduced side effects have been developed. These formulations are reported to have excellent safety and efficacy. However, comparable efficacy can be achieved only when they are administered at high doses than AmB. One of the problems of using these formulations is that they are easily taken up by the reticuloendothelial system (RES). An artificial lipoprotein-like particles, a novel drug carrier Lipid Nano-Sphere (LNS), which is 25 - 50 nm in size and is composed of phospholipids and simple lipid. LNS show a higher plasma concentration of drugs and lower uptake by RES-tissue different forms other lipid base drug carriers. In vitro and in vivo, LNS incorporating AmB, NS-718, shows reduced toxicity, while maintaining activity against fungi. LNS have a unique characteristic as an effective carrier of AmB for treatment of fungal infection.

  10. Herbal Excipients in Novel Drug Delivery Systems

    PubMed Central

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

    2008-01-01

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

  11. Ocular Drug Delivery for Glaucoma Management

    PubMed Central

    Gooch, Nathan; Molokhia, Sarah A.; Condie, Russell; Burr, Randon Michael; Archer, Bonnie; Ambati, Balamurali K.; Wirostko, Barbara

    2012-01-01

    Current glaucoma management modalities are hindered by low patient compliance and adherence. This can be due to highly complex treatment strategies or poor patient understanding. Treatments focus on the management or reduction of intraocular pressure. This is most commonly done through the use of daily topical eye drops. Unfortunately, despite effective therapies, glaucoma continues to progress, possibly due to patients not adhering to their treatments. In order to mitigate these patient compliance issues, many sustained release treatments are being researched and are entering the clinic. Conjunctival, subconjunctival, and intravitreal inserts, punctal plugs, and drug depots are currently in clinical development. Each delivery system has hurdles, yet shows promise and could potentially mitigate the current problems associated with poor patient compliance. PMID:24300188

  12. Drug delivery by organ-specific immunoliposomes

    SciTech Connect

    Maruyama, Kazuo; Mori, Atsuhide; Hunag, Leaf . Dept. of Biochemistry); Kennel, S.J. )

    1990-01-01

    Monoclonal antibodies highly specific to the mouse pulmonary endothelial cells were conjugated to liposomes. The resulting immunoliposomes showed high levels of lung accumulation when injected intravenously into mice. Optimal target binding and retention were achieved if the lipid composition included ganglioside GM{sub 1} to reduce the uptake of immunoliposomes by the reticuloendothelial system. Details of the construction and optimization of these organ-specific immunoliposomes are reviewed. The drug delivery potential of this novel liposome system was demonstrated in an experimental pulmonary metastasis model. Immunoliposomes containing a lipophilic prodrug of deoxyfluorouridine effectively prolonged the survival time of the tumor-bearing mice. This and other therapeutic applications of the immunoliposomes are discussed. 25 refs., 5 figs.

  13. Supramolecular hydrogels as drug delivery systems.

    PubMed

    Saboktakin, Mohammad Reza; Tabatabaei, Roya Mahdavi

    2015-04-01

    Drug delivery from a hydrogel carrier implanted under the kidney capsule is an innovative way to induce kidney tissue regeneration and/or prevent kidney inflammation or fibrosis. We report here on the development of supramolecular hydrogels for this application. Chain-extended hydrogelators containing hydrogen bonding units in the main chain, and bifunctional hydrogelators end-functionalized with hydrogen bonding moieties, were made. The influence of these hydrogels on the renal cortex when implanted under the kidney capsule was studied. The overall tissue response to these hydrogels was found to be mild, and minimal damage to the cortex was observed, using the infiltration of macrophages, formation of myofibroblasts, and the deposition of collagen III as relevant read-out parameters. Differences in tissue response to these hydrogels could be related to the different physico-chemical properties of the three hydrogels.

  14. Biomimetic transport and rational drug delivery.

    PubMed

    Ranney, D F

    2000-01-15

    Medicine and pharmaceutics are encountering critical needs and opportunities for transvascular drug delivery that improves site targeting and tissue permeation by mimicking natural tissue addressing and transport mechanisms. This is driven by the accelerated development of genomic agents requiring targeted controlled release. Although rationally designed for in vitro activity, such agents are not highly effective in vivo, due to opsonization and degradation by plasma constituents, and failure to transport across the local vascular endothelium and tissue matrix. A growing knowledge of the addresses of the body can be applied to engineer "Bio-Logically" staged delivery systems with sequential bioaddressins complementary to the discontinuous compartments encountered--termed discontinuum pharmaceutics. Effective tissue targeting is accomplished by leukocytes, bacteria, and viruses. We are increasingly able to mimic their bioaddressins by genomic means. Approaches described in this commentary include: (a) endothelial-directed adhesion mediated by oligosaccharides and carbohydrates (e.g. dermatan sulfate as a mimic of sulfated CD44) and peptidomimetics interacting with adhesins, selectins, integrins, hyaluronans, and locally induced growth factors (e.g. vascular endothelial growth factor, VEGF) and coagulation factors (e.g. factor VIII antigen); (b) improved tissue permeation conferred by hydrophilically "cloaked" carrier systems; (c) "uncloaking" by matrix dilution or selective triggering near the target cells; and (d) target binding-internalization by terminally exposed hydrophobic moieties, cationic polymers, and receptor-binding lectins, peptides, or carbohydrates. This commentary also describes intermediate technology solutions (e.g. "hybrid drugs"), and highlights the high-resolution, dynamic magnetic resonance imaging and radiopharmaceutical imaging technologies plus the groups and organizations capable of accelerating these important initiatives.

  15. Nanoparticle-based targeted drug delivery

    PubMed Central

    Singh, Rajesh; Lillard, James W.

    2009-01-01

    Nanotechnology could be defined as the technology that has allowed for the control, manipulation, study, and manufacture of structures and devices in the “nanometer” size range. These nano-sized objects, e.g., “nanoparticles”, take on novel properties and functions that differ markedly from those seen from items made of identical materials. The small size, customized surface, improved solubility, and multi-functionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross-disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases such as cancer. This article presents an overview of nanotechnology for the biologist and discusses the attributes of our novel XPclad© nanoparticle formulation that has shown efficacy in treating solid tumors, for single dose vaccination, and oral delivery of therapeutic proteins. PMID:19186176

  16. Application of Fused Deposition Modelling (FDM) Method of 3D Printing in Drug Delivery.

    PubMed

    Long, Jingjunjiao; Gholizadeh, Hamideh; Lu, Jun; Bunt, Craig; Seyfoddin, Ali

    2017-01-01

    Three-dimensional (3D) printing is an emerging manufacturing technology for biomedical and pharmaceutical applications. Fused deposition modelling (FDM) is a low cost extrusion-based 3D printing technique that can deposit materials layer-by-layer to create solid geometries. This review article aims to provide an overview of FDM based 3D printing application in developing new drug delivery systems. The principle methodology, suitable polymers and important parameters in FDM technology and its applications in fabrication of personalised tablets and drug delivery devices are discussed in this review. FDM based 3D printing is a novel and versatile manufacturing technique for creating customised drug delivery devices that contain accurate dose of medicine( s) and provide controlled drug released profiles.

  17. Wireless implantable chip with integrated nitinol-based pump for radio-controlled local drug delivery.

    PubMed

    Fong, Jeffrey; Xiao, Zhiming; Takahata, Kenichi

    2015-02-21

    We demonstrate an active, implantable drug delivery device embedded with a microfluidic pump that is driven by a radio-controlled actuator for temporal drug delivery. The polyimide-packaged 10 × 10 × 2 mm(3) chip contains a micromachined pump chamber and check valves of Parylene C to force the release of the drug from a 76 μL reservoir by wirelessly activating the actuator using external radio-frequency (RF) electromagnetic fields. The rectangular-shaped spiral-coil actuator based on nitinol, a biocompatible shape-memory alloy, is developed to perform cantilever-like actuation for pumping operation. The nitinol-coil actuator itself forms a passive 185 MHz resonant circuit that serves as a self-heat source activated via RF power transfer to enable frequency-selective actuation and pumping. Experimental wireless operation of fabricated prototypes shows successful release of test agents from the devices placed in liquid and excited by radiating tuned RF fields with an output power of 1.1 W. These tests reveal a single release volume of 219 nL, suggesting a device's capacity of ~350 individual ejections of drug from its reservoir. The thermal behavior of the activated device is also reported in detail. This proof-of-concept prototype validates the effectiveness of wireless RF pumping for fully controlled, long-lasting drug delivery, a key step towards enabling patient-tailored, targeted local drug delivery through highly miniaturized implants.

  18. Evolution of Diabetes Insulin Delivery Devices

    PubMed Central

    Selam, Jean-Louis

    2010-01-01

    The first manufactured insulin pump was introduced in the 1970s and the first insulin pens in 1985; since then, many improvements have been made to both devices. The advantages of pens over syringes have been confirmed in numerous studies and include greater accuracy, ease of use, patient satisfaction, quality of life, and adherence. United States claims database analyses indicate that the improved adherence made possible by use of an insulin pen has the potential to reduce diabetes care costs when compared with using a vial and syringe. Features of certain advanced pump models include the ability to connect wirelessly to a blood glucose meter or to a subcutaneous interstitial glucose sensor for semicontinuous glucose-driven insulin rate adjustment. A new trend in the design of insulin pumps is the tubing-free patch pump that adheres directly to the skin. The low rate of insulin pen usage in the United States compared with European countries and the fact that many patients report that they are not offered the option of an insulin pen by their physician suggest that there is a need to increase patient and provider awareness of the currently available devices for insulin administration. PMID:20513314

  19. Light-switchable systems for remotely controlled drug delivery.

    PubMed

    Shim, Gayong; Ko, Seungbeom; Kim, Dongyoon; Le, Quoc-Viet; Park, Gyu Thae; Lee, Jaiwoo; Kwon, Taekhyun; Choi, Han-Gon; Kim, Young Bong; Oh, Yu-Kyoung

    2017-09-06

    Light-switchable systems have recently received attention as a new mode of remotely controlled drug delivery. In the past, a multitude of nanomedicine studies have sought to enhance the specificity of drug delivery to target sites by focusing on receptors overexpressed on malignant cells or environmental features of diseases sites. Despite these immense efforts, however, there are few clinically available nanomedicines. We need a paradigm shift in drug delivery. One strategy that may overcome the limitations of pathophysiology-based drug delivery is the use of remotely controlled delivery technology. Unlike pathophysiology-based active drug targeting strategies, light-switchable systems are not affected by the heterogeneity of cells, tissue types, and/or microenvironments. Instead, they are triggered by remote light (i.e., near-infrared) stimuli, which are absorbed by photoresponsive molecules or three-dimensional nanostructures. The sequential conversion of light to heat or reactive oxygen species can activate drug release and allow it to be spatio-temporally controlled. Light-switchable systems have been used to activate endosomal drug escape, modulate the release of chemical and biological drugs, and alter nanoparticle structures to control the release rates of drugs. This review will address the limitations of pathophysiology-based drug delivery systems, the current status of light-based remote-switch systems, and future directions in the application of light-switchable systems for remotely controlled drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Optimization of Drug Delivery by Drug-Eluting Stents

    PubMed Central

    Bozsak, Franz; Gonzalez-Rodriguez, David; Sternberger, Zachary; Belitz, Paul; Bewley, Thomas; Chomaz, Jean-Marc; Barakat, Abdul I.

    2015-01-01

    Drug-eluting stents (DES), which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours) or very slowly (over periods of several months up to one year) at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices. PMID:26083626

  1. The role of disposable inhalers in pulmonary drug delivery.

    PubMed

    de Boer, Anne H; Hagedoorn, Paul

    2015-01-01

    There is increasing interest in the pulmonary route for both local and systemically acting drugs, vaccines and diagnostics and new applications may require new inhaler technology to obtain the most therapeutically and/or cost-effective administration. Some of these new applications can benefit from the use of disposable inhalers. Current trends in pulmonary drug delivery are presented in this review as well as the possible contribution of disposable inhalers to the improvement of pulmonary administration therein. Arguments in favour of disposable inhalers and the starting points for development of devices and their formulations are discussed. Also, a brief review of the state of the art regarding current disposable inhaler development is given. Prerequisites for the use of disposable inhalers, particularly dry powder inhalers, in applications such as childhood vaccination and for preventing or stopping pandemic outbreaks of highly infectious diseases (like influenza, bird flu, SARS) are that they are simple, cheap and effective. Not only do the devices have to be simple in design, but the drug formulations should also be cheap. This may require a different approach as the formulation may not need to be adapted to improve the inhaler must be designed to enhance formulation dispersion.

  2. [Bench-test evaluation of spacer devices for fluticasone delivery to infants].

    PubMed

    Pourchez, J; Leclerc, L; Sarry, G; Vergnon, J-M; Dubus, J C

    2017-01-01

    Use of a spacer device to optimize the delivery of fluticasone to infants with asthma is an important issue and clinicians require guidance around the choice of device. This in vitro study characterizes the particle size and the fluticasone delivery via 9 spacers. We used an in vitro infant nasal cast with two different inspiratory flow rates (50 and 100mL/s). Fluticasone particle size in the aerosol was evaluated by laser diffractometry and tracheal deposition by spectrophotometric assay. Significant differences in particle size were observed between the 9 spacers (similar D50 but D90 from 5.65±0.65 to 8.80±1.35μm). A 75 % or higher respirable fraction was obtained for only 5 spacers. The 50mL/s flow rate lead to the best drug delivery. At this flow, OptiChamber(®) (62±3 %) and Vortex(®) (91±8.5 %) had a tracheal deposition over 50 % of the initial dose of fluticasone, although the 7 other spacers exhibited a fluticasone deposition less than 25 %. This study shows a wide variation of drug delivery between the 9 spacers studied. We demonstrate that a low inspiratory flow and a spacer showing antistatic properties facilitate drug delivery. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  3. Chronotherapeutic drug delivery systems: an approach to circadian rhythms diseases.

    PubMed

    Sunil, S A; Srikanth, M V; Rao, N Sreenivasa; Uhumwangho, M U; Latha, K; Murthy, K V Ramana

    2011-11-01

    The purpose of writing this review on chronotherapeutic drug delivery systems (ChrDDs) is to review the literatures with special focus on ChrDDs and the various dosage forms, techniques that are used to target the circadian rhythms (CR) of various diseases. Many functions of the human body vary considerably in a day. ChrDDs refers to a treatment method in which in vivo drug availability is timed to match circadian rhythms of disease in order to optimize therapeutic outcomes and minimize side effects. Several techniques have been developed but not many dosage forms for all the diseases are available in the market. ChrDDs are gaining importance in the field of pharmaceutical technology as these systems reduce dosing frequency, toxicity and deliver the drug that matches the CR of that particular disease when the symptoms are maximum to worse. Finally, the ultimate benefit goes to the patient due the compliance and convenience of the dosage form. Some diseases that follow circadian rhythms include cardiovascular diseases, asthma, arthritis, ulcers, diabetes etc. ChrDDs in the market were also discussed and the current technologies used to formulate were also stated. These technologies include Contin® , Chronotopic®, Pulsincaps®, Ceform®, Timerx®, Oros®, Codas®, Diffucaps®, Egalet®, Tablet in capsule device, Core-in-cup tablet technology. A coated drug-core tablet matrix, A bi-layered tablet, Multiparticulate-based chronotherapeutic drug delivery systems, Chronoset and Controlled release microchips.

  4. Multiscale Imaging of Nanoparticle Drug Delivery.

    PubMed

    Dobrucki, Lawrence W; Pan, Dipanjan; Smith, Andrew M

    2015-01-01

    Nanoparticles have recently had a major impact on basic biosciences, the pharmaceutical industry, and preclinical and translational medicine by enabling targeted delivery of therapeutic cargo to cells and tissues. The capacity to specifically tailor the pharmacokinetics, biodistribution, and longterm fate of therapeutic molecules for specific diseases and to avoid off-target side effects is a tremendously promising capability of these materials. However targeting of nanoparticle therapies from systemic circulation is very inefficient, and our understanding of the fundamental processes dictating in vivo fate remains limited, making it challenging to determine how to optimally and rationally design these materials for maximum efficacy. Recently multi-modal, multi-scale imaging technologies have emerged that have helped to improve our insight into these processes. Theranostic imaging agents have provided real-time and quantitative readouts of drug distribution and therapeutic response, multimodal imaging platforms have allowed a multi-scale analysis of distribution from the levels of cells to tissues, and exciting applications in live-animal tissue microscopy have provided key insights at the cellular level. In this review, we describe how multiscale imaging has shaped our ability to optimize nanoparticle drugs and discuss future directions that are expected to further catalyze clinical translation.

  5. Nanostructured porous silicon-mediated drug delivery.

    PubMed

    Martín-Palma, Raúl J; Hernández-Montelongo, Jacobo; Torres-Costa, Vicente; Manso-Silván, Miguel; Muñoz-Noval, Álvaro

    2014-08-01

    The particular properties of nanostructured porous silicon (nanoPS) make it an attractive material for controlled and localized release of therapeutics within the body, aiming at increased efficacy and reduced risks of potential side effects. Since this is a rapidly evolving field as a consequence of the number of research groups involved, a critical review of the state of the art is necessary. In this work, the most promising and successful applications of nanoPS in the field of drug delivery are reviewed and discussed. Two key issues such as drug loading and release are also analyzed in detail. The development of multifunctional (hybrid) systems, aiming at imparting additional functionalities to the nanoPS particles such as luminescence, magnetic response and/or plasmonic effects (allowing simultaneous tracking and guiding), is also examined. Nanostructured materials based on silicon are promising platforms for pharmaceutical applications given their ability to degrade and low toxicity. However, a very limited number of clinical applications have been demonstrated so far.

  6. Detection and drug delivery from superhydrophobic materials

    NASA Astrophysics Data System (ADS)

    Falde, Eric John

    The wetting of a rough material is controlled by surface chemistry and morphology, the liquid phase, solutes, and surfactants that affect the surface tension with the gas phase, and environmental conditions such as temperature and pressure. Materials with high (>150°) apparent contact angles are known as superhydrophobic and are very resistant to wetting. However, in complex biological mixtures eventually protein adsorbs, fouling the surface and facilitating wetting on time scales from seconds to months. The work here uses the partially-wetted (Cassie-Baxter) to fully-wetted (Wenzel) state transition to control drug delivery and to perform surfactant detection via surface tension using hydrophobic and superhydrophobic materials. First there is an overview of the physics of the non-wetting state and the transition to wetting. Then there is a review of how wetting can be controlled by outside stimuli and applications of these materials. Next there is work presented on controlling drug release using superhydrophobic materials with controlled wetting rates, with both in vitro and in vivo results. Then there is work on developing a sensor based on this wetting state transition and its applications toward detecting solute levels in biological fluids for point-of-care diagnosis. Finally, there is work presented on using these sensors for detecting the alcohol content in wine and spirits.

  7. Biodegradable Polymeric Nanoparticles as the Delivery Carrier for Drug.

    PubMed

    Zhao, Kai; Li, Dan; Shi, Ci; Ma, Xueling; Rong, Guangu; Kang, Hong; Wang, Xiaohua; Sun, Bin

    2016-01-01

    Drug research and development has entered into the new epoch of innovation formulation, and the drug delivery system has been in the forefront of pharmaceutical innovation. Nanotechnology is widely used in fiber and textiles, electronics, space, agriculture, forensic science and medical therapeutics. It increasingly plays a significant role in drug delivery system. Compared with traditional delivery system, the nanoparticle drug delivery system has lots of merits, such as the high drug loading ability, the excellent biocompatibility, low toxicity, controlled and targeted drug release. We undertook a structured research of biodegradable polymeric nanoparticles used as delivery carrier for drug using a focused review question and inclusion/exclusion criteria. We have searched the bibliographic databases for peerreviewed research literature. The outstanding characteristics of the screened papers were described respectively, and a systematic content analysis methodology was used to analysis the findings. Seventy-three papers were included in the review, the majority defined leadership and governance approaches that had impacted upon the polymeric nanoparticles as the delivery carrier for drug in therapeutic applications and developments. Seven papers outlined the superiority characteristics of polymeric nanoparticles that applied in the field of vaccine. Forty-seven papers overviewed the application prospects of polymeric nanoparticles used as drug delivery carrier for cancer. These included current advances in research and clinical applications of polymeric nanoparticles. The review identified the drug delivery carrier of biodegradable polymeric nanoparticles, and we described the synthesis methods, applications and challenges of polymeric nanoparticles. The findings of this review identified that the biodegradable polymeric nanoparticles were used as delivery carrier for drug currently. It also indicates that the biodegradable polymeric nanoparticles play an

  8. Drug delivery systems for differential release in combination therapy.

    PubMed

    Zhang, Hongbin; Wang, Guojie; Yang, Huai

    2011-02-01

    Combination therapy with multiple therapeutic agents has wide applicability in medical and surgical treatment, especially in the treatment of cancer. Thus, new drug delivery systems that can differentially release two or more drugs are desired. Utilizing new techniques to engineer the established drug delivery systems and synthesizing new materials and designing carriers with new structures are feasible ways to fabricate proper multi-agent delivery systems, which are critical to meet requirements in the clinic and improve therapeutic efficacy. This paper aims to give an overview about the multi-agent delivery systems developed in the last decade for differential release in combination therapy. Multi-agent delivery systems from nanoscale to bulk scale, such as liposomes, micelles, polymer conjugates, nano/microparticles and hydrogels, developed over the last 10 years, have been collected and summarized. The characteristics of different delivery systems are described and discussed, including the structure of drug carriers, drug-loading techniques, release behaviors and consequent evaluation in biological assays. The chemical structure of drug delivery systems is the key to controlling the release of therapeutic agents in combination therapy, and the differential release of multiple drugs could be realized by the successful design of a proper delivery system. Besides biological evaluation in vitro and in vivo, it is important to speed up practical application of the resulting delivery systems.

  9. Programmable biomaterials for dynamic and responsive drug delivery

    PubMed Central

    Stejskalová, Anna; Kiani, Mehrdad T

    2016-01-01

    Biomaterials are continually being designed that enable new methods for interacting dynamically with cell and tissues, in turn unlocking new capabilities in areas ranging from drug delivery to regenerative medicine. In this review, we explore some of the recent advances being made in regards to programming biomaterials for improved drug delivery, with a focus on cancer and infection. We begin by explaining several of the underlying concepts that are being used to design this new wave of drug delivery vehicles, followed by examining recent materials systems that are able to coordinate the temporal delivery of multiple therapeutics, dynamically respond to changing tissue environments, and reprogram their bioactivity over time. PMID:27190245

  10. Advanced drug delivery and targeting technologies for the ocular diseases

    PubMed Central

    Barar, Jaleh; Aghanejad, Ayuob; Fathi, Marziyeh; Omidi, Yadollah

    2016-01-01

    Introduction: Ocular targeted therapy has enormously been advanced by implementation of new methods of drug delivery and targeting using implantable drug delivery systems (DDSs) or devices (DDDs), stimuli-responsive advanced biomaterials, multimodal nanomedicines, cell therapy modalities and medical bioMEMs. These technologies tackle several ocular diseases such as inflammation-based diseases (e.g., scleritis, keratitis, uveitis, iritis, conjunctivitis, chorioretinitis, choroiditis, retinitis, retinochoroiditis), ocular hypertension and neuropathy, age-related macular degeneration and mucopolysaccharidosis (MPS) due to accumulation of glycosaminoglycans (GAGs). Such therapies appear to provide ultimate treatments, even though much more effective, yet biocompatible, noninvasive therapies are needed to control some disabling ocular diseases/disorders. Methods: In the current study, we have reviewed and discussed recent advancements on ocular targeted therapies. Results: On the ground that the pharmacokinetic and pharmacodynamic analyses of ophthalmic drugs need special techniques, most of ocular DDSs/devices developments have been designed to localized therapy within the eye. Application of advanced DDSs such as Subconjunctival insert/implants (e.g., latanoprost implant, Gamunex-C), episcleral implant (e.g., LX201), cationic emulsions (e.g., Cationorm™, Vekacia™, Cyclokat™), intac/punctal plug DDSs (latanoprost punctal plug delivery system, L-PPDS), and intravitreal implants (I-vitaion™, NT-501, NT- 503, MicroPump, Thethadur, IB-20089 Verisome™, Cortiject, DE-102, Retisert™, Iluvein™ and Ozurdex™) have significantly improved the treatment of ocular diseases. However, most of these DDSs/devices are applied invasively and even need surgical procedures. Of these, use of de novo technologies such as advanced stimuli-responsive nanomaterials, multimodal nanosystems (NSs)/nanoconjugates (NCs), biomacromolecualr scaffolds, and bioengineered cell therapies

  11. Synthetic Tumor Networks for Screening Drug Delivery Systems

    PubMed Central

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

    2015-01-01

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

  12. Clinical Considerations of Focal Drug Delivery In Cancer Treatment.

    PubMed

    Harris, Jamie; Chiu, Bill

    2017-02-24

    According to the US Center for Disease Control, cancer deaths are the second most common cause of mortality in both adults and children. Definitive treatment of solid tumors involves surgical resection with or without systemic chemotherapy and radiation. The advent of local drug delivery presents a unique treatment modality that can offer substantial benefits in cancer management. Local drug delivery offers targeted drug delivery to cancer tissues while minimizing side effects of the medications. Three main phases in solid tumor management exist for the treating physician: initial diagnosis with tissue biopsy, surgical resection with or without chemotherapy, and management of metastatic disease. Image guided studies, using modalities such as MRI, computerized tomography, and ultrasound to sample tumors have been described. The initial diagnosis phase offers a treatment window for local drug delivery with the aid of image guidance. After the diagnosis of malignancy is made, surgical resection can become an important part of tumor management. Currently, FDA approved local drug delivery systems are being used in concert with resection for intracranial glioma. Many other applications of implantation of local drug delivery at the time of surgery in other tumors, including breast and neuroblastoma, are being investigated. Finally, for patients who present with or progress to single sites of metastatic disease, such as brain or liver metastasis, studies have shown potential applications for local drug delivery as well. This review will discuss the current state of local drug delivery in the treatment of solid tumors and possible future directions.

  13. Drug Delivery Approaches for the Treatment of Cervical Cancer

    PubMed Central

    Ordikhani, Farideh; Erdem Arslan, Mustafa; Marcelo, Raymundo; Sahin, Ilyas; Grigsby, Perry; Schwarz, Julie K.; Azab, Abdel Kareem

    2016-01-01

    Cervical cancer is a highly prevalent cancer that affects women around the world. With the availability of new technologies, researchers have increased their efforts to develop new drug delivery systems in cervical cancer chemotherapy. In this review, we summarized some of the recent research in systematic and localized drug delivery systems and compared the advantages and disadvantages of these methods. PMID:27447664

  14. Hydrogels for ocular drug delivery and tissue engineering

    PubMed Central

    Fathi, Marzieh; Barar, Jaleh; Aghanejad, Ayuob; Omidi, Yadollah

    2015-01-01

    Hydrogels, as crosslinked polymeric three dimensional networks, possess unique structure and behavior in response to the internal and/or external stimuli. As a result, they offer great prospective applications in drug delivery, cell therapy and human tissue engineering. Here, we highlight the potential of hydrogels in prolonged intraocular drug delivery and ocular surface therapy using stem cells incorporated hydrogels. PMID:26929918

  15. Nanoparticle-based drug delivery to the vagina: a review

    PubMed Central

    Ensign, Laura M.; Cone, Richard; Hanes, Justin

    2014-01-01

    Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, including sexually transmitted diseases, fungal and bacterial infections, and cancer. However, achieving sustained local drug concentrations in the vagina can be challenging, due to the high permeability of the vaginal epithelium and expulsion of conventional soluble drug dosage forms. Nanoparticle-based drug delivery platforms have received considerable attention for vaginal drug delivery, as nanoparticles can provide sustained release, cellular targeting, and even intrinsic antimicrobial or adjuvant properties that can improve the potency and/or efficacy of prophylactic and therapeutic modalities. Here, we review the use of polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles for vaginal drug delivery. Although most of the work toward nanoparticle-based drug delivery in the vagina has been focused on HIV prevention, strategies for treatment and prevention of other sexually transmitted infections, treatment for reproductive tract cancer, and treatment of fungal and bacterial infections are also highlighted. PMID:24830303

  16. Oral Drug Delivery with Polymeric Nanoparticles: The Gastrointestinal Mucus Barriers

    PubMed Central

    Ensign, Laura M.; Cone, Richard; Hanes, Justin

    2012-01-01

    Oral delivery is the most common method for drug administration. However, poor solubility, stability, and bioavailability of many drugs make achieving therapeutic levels via the gastrointestinal (GI) tract challenging. Drug delivery must overcome numerous hurdles, including the acidic gastric environment and the continuous secretion of mucus that protects the GI tract. Nanoparticle drug carriers that can shield drugs from degradation and deliver them to intended sites within the GI tract may enable more efficient and sustained drug delivery. However, the rapid secretion and shedding of GI tract mucus can significantly limit the effectiveness of nanoparticle drug delivery systems. Many types of nanoparticles are efficiently trapped in and rapidly removed by mucus, making controlled release in the GI tract difficult. This review addresses the protective barrier properties of mucus secretions, how mucus affects the fate of orally administered nanoparticles, and recent developments in nanoparticles engineered to penetrate the mucus barrier. PMID:22212900

  17. Potential of nanoparticulate drug delivery systems by intranasal administration.

    PubMed

    Ali, Javed; Ali, Mushir; Baboota, Sanjula; Sahani, Jasjeet Kaur; Ramassamy, Charles; Dao, Lé; Bhavna

    2010-05-01

    Due to number of problems related with oral, parenteral, rectal and other routes of drug administration, the interest of pharmaceutical scientists has increased towards exploring the possibilities of intranasal delivery of various drugs. Nasal drug delivery system is commonly known for the treatment of local ailments like cold, cough, rhinitis, etc. Efforts have been made to deliver various drugs, especially peptides and proteins, through nasal route for systemic use; utilizing the principles and concepts of various nanoparticulate drug delivery systems using various polymers and absorption promoters. The incorporation of drugs into nanoparticles might be a promising approach, since colloidal formulations have been shown to protect them from the degrading milieu in the nasal cavity and facilitate their transport across the mucosal barriers. The use of nanoparticles for vaccine delivery provides beneficial effect, by achieving good immune responses. This could be due to the fact that small particles can be transported preferentially by the lymphoid tissue of the nasal cavity (NALT). The brain gets benefited through the intranasal delivery as direct olfactory transport bypasses the blood brain barrier and nanoparticles are taken up and conveyed along cell processes of olfactory neurons through the cribriform plate to synaptic junctions with neurons of the olfactory bulb. The intranasal delivery is aimed at optimizing drug bioavailability for systemic drugs, as absorption decreases with increasing molecular weight, and for drugs, which are susceptible to enzymatic degradation such as proteins and polypeptides. This review discusses the potential benefits of using nanoparticles for nasal delivery of drugs and vaccines for brain, systemic and topical delivery. The article aims at giving an insight into nasal cavity, consideration of factors affecting and strategies to improve drug absorption through nasal route, pharmaceutical dosage forms and delivery systems with

  18. Different concepts of drug delivery in disease entities.

    PubMed

    Serafin, A; Stańczak, A

    2009-04-01

    This is a review of classical and novel concepts of drug delivery in particular diseases such as central nervous system disease, ophthalmic disease, cardiovascular disease, cancer and others. Nowadays, scientists are trying to propose efficient and selective drugs for the site of action, with best acceptance of patients, that can be metabolized to non-toxic derivatives. Prodrugs, soft drugs, codrugs are designed to maximize the amount of active drugs that reaches the site of action, through changing the physicochemical, biopharmaceutical or pharmacokinetic properties of the parent drugs. For last years different concepts of drug delivery have been developed to achieve the best patients' tolerance of a drug that has no undesirable properties. It is established that future studies will ameliorate drug properties so as to achieve the best drug delivery system.

  19. The impact of ageing on the barriers to drug delivery.

    PubMed

    Perrie, Yvonne; Badhan, Raj K Singh; Kirby, Daniel J; Lowry, Deborah; Mohammed, Afzal R; Ouyang, Defang

    2012-07-20

    Generally, we like to see ageing as a process that is happening to people older than ourselves. However the process of ageing impacts on a wide range of functions within the human body. Whilst many of the outcomes of ageing can now be delayed or reduced, age-related changes in cellular, molecular and physiological functionality of tissues and organs can also influence how drugs enter, distribute and are eliminated from the body. Therefore, the changing profile of barriers to drug delivery should be considered if we are to develop more age-appropriate medicines. Changes in the drug dissolution and absorption in older patients may require the formulation of oral delivery systems that offer enhanced retention at absorption sites to improve drug delivery. Alternatively, liquid and fast-melt dosage systems may address the need of patients who have difficulties in swallowing medication. Ageing-induced changes in the lung can also result in slower drug absorption, which is further compounded by disease factors, common in an ageing population, that reduce lung capacity. In terms of barriers to drug delivery to the eye, the main consideration is the tear film, which like other barriers to drug delivery, changes with normal ageing and can impact on the bioavailability of drugs delivery using eye drops and suspensions. In contrast, whilst the skin as a barrier changes with age, no significant difference in absorption of drugs from transdermal drug delivery is observed in different age groups. However, due to the age-related pharmacokinetic and pharmacodynamic changes, dose adaptation should still be considered for drug delivery across the skin. Overall it is clear that the increasing age demographic of most populations, presents new (or should that be older) barriers to effective drug delivery.

  20. Nanocrystal for ocular drug delivery: hope or hype.

    PubMed

    Sharma, Om Prakash; Patel, Viral; Mehta, Tejal

    2016-08-01

    The complexity of the structure and nature of the eye emanates a challenge for drug delivery to formulation scientists. Lower bioavailability concern of conventional ocular formulation provokes the interest of researchers in the development of novel drug delivery system. Nanotechnology-based formulations have been extensively investigated and found propitious in improving bioavailability of drugs by overcoming ocular barriers prevailing in the eye. The advent of nanocrystals helped in combating the problem of poorly soluble drugs specifically for oral and parenteral drug delivery and led to development of various marketed products. Nanocrystal-based formulations explored for ocular drug delivery have been found successful in achieving increase in retention time, bioavailability, and permeability of drugs across the corneal and conjunctival epithelium. In this review, we have highlighted the ocular physiology and barriers in drug delivery. A comparative analysis of various nanotechnology-based ocular formulations is done with their pros and cons. Consideration is also given to various methods of preparation of nanocrystals with their patented technology. This article highlights the success achieved in conquering various challenges of ocular delivery by the use of nanocrystals while emphasizing on its advantages and application for ocular formulation. The perspectives of nanocrystals as an emerging flipside to explore the frontiers of ocular drug delivery are discussed.

  1. Permeability control of GPC drug delivery by ion implantation

    SciTech Connect

    Zimmerman, R.L. |; Ila, D.; Poker, D.B.; Withrow, S.P.

    1997-02-01

    MeV Ion beams are used to tailor the drug delivery rate of materials with dual usage of prosthesis devices and drug encapsulation. Available surface porosity and diffusivity can be controlled by the choice of specie, fluence and energy of the bombarding ions. Together with appropriate drug concentration gradients within the capsule, the capsule can be made to deliver an initial dose rate either higher or lower than the steady state value for a predetermined time. The exceptional biocompatibility as well as porosity of glassy polymeric carbon (GPC) make it the favored material for drug encapsulation. A wide range of available porosity in the bulk material can be produced by heat treatment. We demonstrate that lithium diffusivity near the surface of GPC can be increased by carbon, oxygen or silicon ion bombardment and can be decreased by gold ion bombardment. In addition enhanced absorption of lithium in a layer near the end of the range of the implanted ions has been observed. {copyright} {ital 1997 American Institute of Physics.}

  2. SAW atomization application on inhaled pulmonary drug delivery

    NASA Astrophysics Data System (ADS)

    Qi, Aisha; Friend, James; Yeo, Leslie

    2008-12-01

    Pulmonary drug delivery transports the drug formulations directly to the respiratory tract in the form of inhaled particles or droplets. Because of the direct target treatment, it has significant advantages in the treatment of respiratory diseases, for example asthma. However, it is difficult to produce monodispersed particles/droplets in the 1-10 micron range, which is necessary for deposition in the targeted lung area or lower respiratory airways, in a controllable fashion. We demonstrate the use of surface acoustic waves (SAWs) as an efficient method for the generation of monodispersed micron dimension aerosols for the treatment of asthma. SAWs are ten nanometer order amplitude electroacoustic waves generated by applying an oscillating electric field to an interdigital transducer patterned on a piezoelectric substrate. The acoustic energy in the waves induces atomization of the working fluid, which contains a model drug, albuterol. Laser diffraction techniques employed to characterize the aerosols revealed mean diameter of the aerosol was around 3-4 μm. Parallel experiments employing a one-stage (glass) twin impinger as a lung model demonstrated a nearly 80% of atomized drug aerosol was deposited in the lung. The aerosol size distribution is relatively independent of the SAW frequency, which is consistent with our predictive scaling theory which accounts for the dominant balance between viscous and capillary stresses. Moreover, only 1-3 W powers consumption of SAW atomization suggests that the SAW atomizer can be miniaturized into dimensions commensurate with portable consumer devices.

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

    PubMed Central

    2013-01-01

    In the arena of solubility enhancement, several problems are encountered. A novel approach based on lipid drug delivery system has evolved, pharmacosomes. Pharmacosomes are colloidal, nanometric size micelles, vesicles or may be in the form of hexagonal assembly of colloidal drug dispersions attached covalently to the phospholipid. They act as befitting carrier for delivery of drugs quite precisely owing to their unique properties like small size, amphiphilicity, active drug loading, high entrapment efficiency, and stability. They help in controlled release of drug at the site of action as well as in reduction in cos