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Sample records for pharmaceutical drug carriers

  1. Applicability, Commercial Utility and Recent Patents on Starch and Starch Derivative as Pharmaceutical Drug Delivery Carrier.

    PubMed

    Pandey, Shreya; Malviya, Rishabha; Sharma, Pramod K

    2015-01-01

    Natural polymers are widely utilized in pharmaceutical and food industries. Starch, a major carbohydrate is a staple food in human and animal diets which is simply extractable from various sources, like potato, maize, corn, wheat, etc. It is widely used as a raw material in various food and non food industries as well as in paper, textile and other industries. This article summarizes the starch and modification of starch and to produce a novel molecule with various applications in industries including number of advances in pharmaceutical industry. The unique characteristics of starch and their modified form can be successfully used as drug delivery carriers in various pharmaceutical preparations. It is widely used as controlled and sustained release polymer, tablet disintegrant, drug delivery carrier, plasma volume expander and also finds its applicability in bone tissue engineering and in artificial red cells. It also includes the patents related to starch and modified starch based products and their commercial utility. PMID:26205680

  2. Polysaccharide based nanogels in the drug delivery system: Application as the carrier of pharmaceutical agents.

    PubMed

    Debele, Tilahun Ayane; Mekuria, Shewaye Lakew; Tsai, Hsieh-Chih

    2016-11-01

    Polysaccharide-based nanoparticles have fascinated attention as a vesicle of different pharmaceutical agents due to their unique multi-functional groups in addition to their physicochemical properties, including biocompatibility and biodegradability. The existence of multi-functional groups on the polysaccharide backbone permits facile chemical or biochemical modification to synthesize polysaccharide based nanoparticles with miscellaneous structures. Polysaccharide-based nanogels have high water content, large surface area for multivalent bioconjugation, tunable size, and interior network for the incorporation of different pharmaceutical agents. These unique properties offer great potential for the utilization of polysaccharide-based nanogels in the drug delivery systems. Hence, this review describes chemistry of certain common polysaccharides, several methodologies used to synthesize polysaccharide nanoparticles and primarily focused on the polysaccharide (or polysaccharide derivative) based nanogels as the carrier of pharmaceutical agents. PMID:27524098

  3. Lipid-Based Nanoparticles as Pharmaceutical Drug Carriers: From Concepts to Clinic

    PubMed Central

    Puri, Anu; Loomis, Kristin; Smith, Brandon; Lee, Jae-Ho; Yavlovich, Amichai; Heldman, Eli; Blumenthal, Robert

    2010-01-01

    In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nano-emulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We

  4. Lyophilized silica lipid hybrid (SLH) carriers for poorly water-soluble drugs: physicochemical and in vitro pharmaceutical investigations.

    PubMed

    Yasmin, Rokhsana; Tan, Angel; Bremmell, Kristen E; Prestidge, Clive A

    2014-09-01

    Lyophilization was investigated to produce a powdery silica-lipid hybrid (SLH) carrier for oral delivery of poorly water-soluble drugs. The silica to lipid ratio, incorporation of cryoprotectant, and lipid loading level were investigated as performance indicators for lyophilized SLH carriers. Celecoxib, a nonsteroidal anti-inflammatory drug, was used as the model poorly soluble moiety to attain desirable physicochemical and in vitro drug solubilization properties. Scanning electron microscopy and confocal fluorescence imaging verified a nanoporous, homogenous internal matrix structures of the lyophilized SLH particles, prepared from submicron triglyceride emulsions and stabilized by porous silica nanoparticles (Aerosil 380), similar to spray-dried SLH. 20-50 wt % of silica in the formulation have shown to produce nonoily SLH agglomerates with complete lipid encapsulation. The incorporation of a cryoprotectant prevented irreversible aggregation of the silica-stabilized droplets during lyophilization, thereby readily redispersing in water to form micrometre-sized particles (<5 μm). The lyophilized SLH produced approximately 1.5-fold and fivefold increased drug solubilization than the pure drug under nondigesting and digesting conditions, respectively. The feasibility of lyophilization for producing nanostructured SLH formulations with desirable lipid loading and drug solubilization properties for enhanced oral delivery of poorly water-soluble therapeutics is confirmed. PMID:24585389

  5. Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines.

    PubMed

    Aburahma, Mona Hassan

    2016-07-01

    Most of the new drugs, biological therapeutics (proteins/peptides) and vaccines have poor performance after oral administration due to poor solubility or degradation in the gastrointestinal tract (GIT). Though, vesicular carriers exemplified by liposomes or niosomes can protect the entrapped agent to a certain extent from degradation. Nevertheless, the harsh GIT environment exemplified by low pH, presence of bile salts and enzymes limits their capabilities by destabilizing them. In response to that, more resistant bile salts-containing vesicles (BS-vesicles) were developed by inclusion of bile salts into lipid bilayers constructs. The effectiveness of orally administrated BS-vesicles in improving the performance of vesicles has been demonstrated in researches. Yet, these attempts did not gain considerable attention. This is the first review that provides a comprehensive overview of utilizing BS-vesicles as a promising pharmaceutical carrier with a special focus on their successful applications in oral delivery of therapeutic macromolecules and vaccines. Insights on the possible mechanisms by which BS-vesicles improve the oral bioavailability of the encapsulated drug or immunological response of entrapped vaccine are explained. In addition, methods adopted to prepare and characterize BS-vesicles are described. Finally, the gap in the scientific researches tackling BS-vesicles that needs to be addressed is highlighted. PMID:25390191

  6. Nanostructured Lipid Carriers: A potential drug carrier for cancer chemotherapy

    PubMed Central

    2012-01-01

    Nanotechnology having developed exponentially, the aim has been on therapeutic undertaking, particularly for cancerous disease chemotherapy. Nanostructured lipid carriers have attracted expanding scientific and commercial vigilance in the last couple of years as alternate carriers for the pharmaceutical consignment, particularly anticancer pharmaceuticals. Shortcomings often came across with anticancer mixtures, such as poor solubility, normal tissue toxicity, poor specificity and steadiness, as well as the high incidence rate of pharmaceutical resistance and the rapid degradation, need of large-scale output procedures, a fast release of the pharmaceutical from its carrier scheme, steadiness troubles, the residues of the organic solvents utilized in the output method and the toxicity from the polymer with esteem to the carrier scheme are anticipated to be overcome through use of the Nanostructured Lipid Carrier. In this review the benefits, types, drug release modulations, steadiness and output techniques of NLCs are discussed. In supplement, the function of NLC in cancer chemotherapy is presented and hotspots in research are emphasized. It is foreseen that, in the beside future, nanostructured lipid carriers will be further advanced to consign cytotoxic anticancer compounds in a more efficient, exact and protected manner. PMID:23167765

  7. Lipid-based formulations solidified via adsorption onto the mesoporous carrier Neusilin® US2: effect of drug type and formulation composition on in vitro pharmaceutical performance.

    PubMed

    Williams, Hywel D; Van Speybroeck, Michiel; Augustijns, Patrick; Porter, Christopher J H

    2014-06-01

    The current study determined the extent to which the desorption of lipid-based formulations (LBFs) from a mesoporous magnesium aluminometasilicate (Neusilin®-US2) carrier is governed by drug properties, LBF composition, and LBF-to-adsorbent ratio. A secondary objective was to evaluate the impact of testing parameters (medium composition, pH, dilution, and agitation) on in vitro LBF performance. Two self-emulsifying LBFs, with high/low lipid-surfactant ratios were studied in detail using danazol, fenofibrate, cinnarizine, and mefenamic acid as model drugs. A wider range of 38 different danazol-containing LBF were also evaluated, where desorption was evaluated immediately after preparation and after 1 month of storage. The results revealed that incomplete desorption from Neusilin® was a feature of all drugs and LBFs tested. Desorption was insensitive to agitation but increased under conditions where ionizable drugs were charged. In addition, formulations containing a higher proportion (>30%) of hydrophilic surfactant consistently exhibited higher desorption, and were least susceptible to decreased desorption on storage. In summary, although Neusilin® is an effective vehicle for LBF solidification, its use is accompanied by a risk of incomplete desorption of the vehicle from the carrier, irrespective of the drug. Lipid Formulation Classification System (LFCS)Type IIIB LBFs comprising higher quantities of hydrophilic surfactants appear to desorb most from Neusilin®. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. PMID:24740767

  8. Engineering antiphagocytic biomimetic drug carriers

    PubMed Central

    Sawdon, Alicia; Peng, Ching-An

    2014-01-01

    Drug-delivery carriers have the potential to not only treat but also diagnose many diseases; however, they still lack the complexity of natural-particulate systems. Cell-based therapies using tumor-targeting T cells and tumor-homing mesenchymal stem cells have given researchers a means to exploit the characteristics exhibited by innate-biological entities. Similarly, immune evasion by pathogens has inspired the development of natural polymers to cloak drug carriers. The ‘marker-of-self’ CD47 protein, which is found ubiquitously on mammalian cell surfaces, has been used for evading phagocyte clearance of drug carriers. This review will focus on the recent progress of drug carriers co-opting the tricks that cells in nature use to hide safely under the radar of the body’s innate immune system. PMID:23883126

  9. Carrier Deformability in Drug Delivery.

    PubMed

    Morilla, Maria Jose; Romero, Eder Lilia

    2016-01-01

    Deformability is a key property of drug carriers used to increase the mass penetration across the skin without disrupting the lipid barrier. Highly deformable vesicles proved to be more effective than conventional liposomes in delivering drugs into and across the mammalian skin upon topical non occlusive application. In the past five years, highly deformable vesicles have been used for local delivery of drugs on joint diseases, skin cancer, atopic dermatitis, would healing, psoriasis, scar treatment, fungal, bacteria and protozoa infections. Promising topical vaccination strategies rely also in this type of carriers. Here we provide an overview on the main structural and mechanical features of deformable vesicles, to finish with an extensive update on their latest preclinical applications. PMID:26675226

  10. Drug Information Residency Rotation with Pharmaceutical Industry.

    ERIC Educational Resources Information Center

    Cramer, Richard L.

    1986-01-01

    Program objectives of a drug information rotation at the Upjohn Company include improving communication between the pharmaceutical industry and hospital pharmacy/academia, exposing the resident to the challenges the industry encounters, improving proficiency in drug information practice, and providing insight into the working relationships of…

  11. Pharmaceutical policy regarding generic drugs in Belgium.

    PubMed

    Simoens, Steven; De Bruyn, Kristien; Bogaert, Marc; Laekeman, Gert

    2005-01-01

    Pressure to control pharmaceutical expenditure and price competition among pharmaceutical companies are fuelling the development of generic drug markets in EU countries. However, in Belgium, the market for generic drugs is underdeveloped compared with other countries. To promote the use of generic drugs, the government introduced a reference pricing (RP) scheme in 2001. The aim of this paper is to discuss Belgian pharmaceutical policy regarding generic drugs and to analyse how the Belgian drug market has evolved following initiation of the RP scheme. The market share held by generic drugs increased following implementation of the RP scheme. Focusing on volume, average market share (by semester) for generic drugs amounted to 2.05% of the total pharmaceutical market from January 1998 to June 2001, compared with 6.11% from July 2001 to December 2003. As new generic drugs are introduced, their market share tends to increase in the first couple of months, after which it levels off. Faced with increasing generic competition, some manufacturers have launched new variants of their original drug, thereby effectively extending the period of patent protection. Strategies consisting of price reductions in return for the abolition of prescribing conditions and the launch of new dosages or formulations appear to have been successful in maintaining the market share of original drugs. Nevertheless, the introduction of the RP scheme was associated with savings amounting to 1.8% of pharmaceutical expenditure by the third-party payer in 2001 and 2.1% in 2002. The findings of this paper indicate that the RP scheme has stimulated the Belgian generic drug market. However, existing policy has largely failed to take into account the role that physicians and pharmacists can play in stimulating generic drug use. Therefore, further development of the Belgian generic drug market seems to hinge on the creation of appropriate incentives for physicians to prescribe, and for pharmacists to

  12. IVAN: Intelligent Van for the Distribution of Pharmaceutical Drugs

    PubMed Central

    Moreno, Asier; Angulo, Ignacio; Perallos, Asier; Landaluce, Hugo; Zuazola, Ignacio Julio García; Azpilicueta, Leire; Astrain, José Javier; Falcone, Francisco; Villadangos, Jesús

    2012-01-01

    This paper describes a telematic system based on an intelligent van which is capable of tracing pharmaceutical drugs over delivery routes from a warehouse to pharmacies, without altering carriers' daily conventional tasks. The intelligent van understands its environment, taking into account its location, the assets and the predefined delivery route; with the capability of reporting incidences to carriers in case of failure according to the established distribution plan. It is a non-intrusive solution which represents a successful experience of using smart environments and an optimized Radio Frequency Identification (RFID) embedded system in a viable way to resolve a real industrial need in the pharmaceutical industry. The combination of deterministic modeling of the indoor vehicle, the implementation of an ad-hoc radiating element and an agile software platform within an overall system architecture leads to a competitive, flexible and scalable solution. PMID:22778659

  13. Electrosprayed nanoparticles for drug delivery and pharmaceutical applications

    PubMed Central

    Sridhar, Radhakrishnan; Ramakrishna, Seeram

    2013-01-01

    Nanotechnology based Pharma has emerged significantly and has influenced the Pharma industry up to a considerable extent. Nanoparticles technology holds a good share of the nanotech Pharma and is significant in comparison with the other domains. Electrospraying technology answers the potential needs of nanoparticle production such as scalability, reproducibility, effective encapsulation etc. Many drugs have been electrosprayed with and without polymer carriers. Drug release characteristics are improved with the incorporation of biodegradable polymer carriers which sustain the release of encapsulated drug. Electrospraying is acknowledged as an important technique for the preparation of nanoparticles with respect to pharmaceutical applications. Herein we attempted to consolidate the reports pertaining to electrospraying and their corresponding therapeutic application area. PMID:23512013

  14. Controlled Drug Release from Pharmaceutical Nanocarriers

    PubMed Central

    Lee, Jinhyun Hannah; Yeo, Yoon

    2014-01-01

    Nanocarriers providing spatiotemporal control of drug release contribute to reducing toxicity and improving therapeutic efficacy of a drug. On the other hand, nanocarriers face unique challenges in controlling drug release kinetics, due to the large surface area per volume ratio and the short diffusion distance. To develop nanocarriers with desirable release kinetics for target applications, it is important to understand the mechanisms by which a carrier retains and releases a drug, the effects of composition and morphology of the carrier on the drug release kinetics, and current techniques for preparation and modification of nanocarriers. This review provides an overview of drug release mechanisms and various nanocarriers with a specific emphasis on approaches to control the drug release kinetics. PMID:25684779

  15. Pharmaceutical drugs chatter on Online Social Networks.

    PubMed

    Wiley, Matthew T; Jin, Canghong; Hristidis, Vagelis; Esterling, Kevin M

    2014-06-01

    The ubiquity of Online Social Networks (OSNs) is creating new sources for healthcare information, particularly in the context of pharmaceutical drugs. We aimed to examine the impact of a given OSN's characteristics on the content of pharmaceutical drug discussions from that OSN. We compared the effect of four distinguishing characteristics from ten different OSNs on the content of their pharmaceutical drug discussions: (1) General versus Health OSN; (2) OSN moderation; (3) OSN registration requirements; and (4) OSNs with a question and answer format. The effects of these characteristics were measured both quantitatively and qualitatively. Our results show that an OSN's characteristics indeed affect the content of its discussions. Based on their information needs, healthcare providers may use our findings to pick the right OSNs or to advise patients regarding their needs. Our results may also guide the creation of new and more effective domain-specific health OSNs. Further, future researchers of online healthcare content in OSNs may find our results informative while choosing OSNs as data sources. We reported several findings about the impact of OSN characteristics on the content of pharmaceutical drug discussion, and synthesized these findings into actionable items for both healthcare providers and future researchers of healthcare discussions on OSNs. Future research on the impact of OSN characteristics could include user demographics, quality and safety of information, and efficacy of OSN usage. PMID:24637141

  16. Defining Patient Centric Pharmaceutical Drug Product Design.

    PubMed

    Stegemann, Sven; Ternik, Robert L; Onder, Graziano; Khan, Mansoor A; van Riet-Nales, Diana A

    2016-09-01

    The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved. PMID:27317470

  17. 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. PMID:27301169

  18. Essential drugs and registration of pharmaceuticals: the Sri Lankan experience.

    PubMed Central

    Weerasuriya, K.

    1993-01-01

    Many factors influence the regulation of pharmaceuticals in a country. The essential drugs concept, formulated by the World Health Organization to assist developing countries in selecting appropriate drugs, also provides a basis for regulation. Sri Lanka has long regulated pharmaceuticals as part of its health policy. Over 70% of 3436 pharmaceutical product registrations were found to be drugs (or alternatives) named in the country's essential drugs list. This is despite the fact that product registrations are mainly for the private health care sector, and the list is for the state sector. The essential drugs concept therefore appears to have influenced the pharmaceuticals registered in Sri Lanka. PMID:8490987

  19. Synthetic biology for pharmaceutical drug discovery

    PubMed Central

    Trosset, Jean-Yves; Carbonell, Pablo

    2015-01-01

    Synthetic biology (SB) is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell–cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity. PMID:26673570

  20. Pharmaceutical development of microbicide drug products.

    PubMed

    Friend, David R

    2010-12-01

    HIV infection rates in the developing world remain a serious problem. One potential approach to reduce infection rates is to use products known as microbicides, referred to herein as microbicide drug products (MDPs). These are drugs capable of, when administered topically to the vagina (or rectum), interfering with infection by one or more mechanisms. This review article covers the latest pharmaceutical developments in the area of microbicides dosage forms and delivery systems. These products are principally designed for use in the developing world and must therefore address cultural and societal issues generally unknown in the developed world. The first-generation microbicides evaluated clinically were principally polyanions. These drugs, administered intravaginally as gels, were found to be ineffective in preventing transmission of HIV from men to women. Second-generation drugs such as tenofovir, dapivirine, and UC781 are reverse transcriptase inhibitors developed as gels formulations and intravaginal rings (IVRs). Gels are considered coitally-related products while IVRs are coitally-independent systems designed to release the drug over a four-week period or possibly longer (up to 3 or 4 months). Other dosage forms under development include fast dissolving films, tablets/capsules, and possibly vaginal sponges. Dual protection systems are also under development. These systems include formulations capable of preventing HIV infection along with a second drug capable of preventing conception or other viral infections such as HSV. PMID:20017601

  1. Extracellular stability of nanoparticulate drug carriers

    PubMed Central

    Liu, Karen C.; Yeo, Yoon

    2014-01-01

    Nanoparticulate (NP) drug carrier systems are attractive vehicles for selective drug delivery to solid tumors. Ideally, NPs should evade clearance by the reticuloendothelial system while maintaining the ability to interact with tumor cells and facilitate cellular uptake. Great effort has been made to fulfill these design criteria, yielding various types of functionalized NPs. Another important consideration in NP design is the physical and functional stability during circulation, which, if ignored, can significantly undermine the promise of intelligently designed NP drug carriers. This commentary reviews several NP examples with stability issues and their consequences, ending in a discussion of experimental methods for reliable prediction of NP stability. PMID:24214175

  2. 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

  3. Organized polysaccharide fibers as stable drug carriers

    PubMed Central

    Janaswamy, Srinivas; Gill, Kristin L.; Campanella, Osvaldo H.; Pinal, Rodolfo

    2013-01-01

    Many challenges arise during the development of new drug carrier systems, and paramount among them are safety, solubility and controlled release requirements. Although synthetic polymers are effective, the possibility of side effects imposes restrictions on their acceptable use and dose limits. Thus, a new drug carrier system that is safe to handle and free from side effects is very much in need and food grade polysaccharides stand tall as worthy alternatives. Herein, we demonstrate for the first time the feasibility of sodium iota-carrageenan fibers and their distinctive water pockets to embed and release a wide variety of drug molecules. Structural analysis has revealed the existence of crystalline network in the fibers even after encapsulating the drug molecules, and iota-carrageenan maintains its characteristic and reproducible double helical structure suggesting that the composites thus produced are reminiscent of cocrystals. The melting properties of iota-carrageenan:drug complexes are distinctly different from those of either drug or iota-carrageenan fiber. The encapsulated drugs are released in a sustained manner from the fiber matrix. Overall, our research provides an elegant opportunity for developing effective drug carriers with stable network toward enhancing and/or controlling bioavailability and extending shelf-life of drug molecules using GRAS excipients, food polysaccharides, that are inexpensive and non–toxic. PMID:23544530

  4. Hollow mesoporous silica as a high drug loading carrier for regulation insoluble drug release.

    PubMed

    Geng, Hongjian; Zhao, Yating; Liu, Jia; Cui, Yu; Wang, Ying; Zhao, Qinfu; Wang, Siling

    2016-08-20

    The purpose of this study was to develop a high drug loading hollow mesoporous silica nanoparticles (HMS) and apply for regulation insoluble drug release. HMS was synthesized using hard template phenolic resin nanoparticles with the aid of cetyltrimethyl ammonium bromide (CTAB), which was simple and inexpensive. To compare the difference between normal mesoporous silica (NMS) and hollow mesoporous silica in drug loading efficiency, drug release behavior and solid state, NMS was also prepared by soft template method. Transmission electron microscopy (TEM), specific surface area analysis, FT-IR and zeta potential were employed to characterize the morphology structure and physicochemical property of these carriers. The insoluble drugs, carvedilol and fenofibrate(Car and Fen), were chosen as the model drug to be loaded into HMS and NMS. We also chose methylene blue (MB) as a basic dye to estimate the adsorption ability of these carriers from macroscopic and microscopic view, and the drug-loaded carriers were systematically studied by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and UV-vis spectrophotometry. What' more, the in vivo process of HMS was also study by confocal microscopy and in vivo fluorescence imaging. In order to confirm the gastrointestinal safety of HMS, the pathological examination of stomach and intestine also be evaluated. HMS allowed a higher drug loading than NMS and exhibited a relative sustained release curve, while NMS was immediate-release. And the effect of preventing drugs crystallization was weaker than NMS. As for in vivo process, HMS was cleared relatively rapidly from the mouse gastrointestinal and barely uptake by intestinal epithelial cell in this study due to its large particle size. And the damage of HMS to gastrointestinal could be ignored. This study provided a simple method to obtain high drug loading and regulation insoluble drug release, expanded the application of inorganic carriers in drug delivery system

  5. Aptamers as Both Drugs and Drug-Carriers

    PubMed Central

    Ashrafuzzaman, Md.

    2014-01-01

    Aptamers are short nucleic acid oligos. They may serve as both drugs and drug-carriers. Their use as diagnostic tools is also evident. They can be generated using various experimental, theoretical, and computational techniques. The systematic evolution of ligands by exponential enrichment which uses iterative screening of nucleic acid libraries is a popular experimental technique. Theory inspired methodology entropy-based seed-and-grow strategy that designs aptamer templates to bind specifically to targets is another one. Aptamers are predicted to be highly useful in producing general drugs and theranostic drugs occasionally for certain diseases like cancer, Alzheimer's disease, and so on. They bind to various targets like lipids, nucleic acids, proteins, small organic compounds, and even entire organisms. Aptamers may also serve as drug-carriers or nanoparticles helping drugs to get released in specific target regions. Due to better target specific physical binding properties aptamers cause less off-target toxicity effects. Therefore, search for aptamer based drugs, drug-carriers, and even diagnostic tools is expanding fast. The biophysical properties in relation to the target specific binding phenomena of aptamers, energetics behind the aptamer transport of drugs, and the consequent biological implications will be discussed. This review will open up avenues leading to novel drug discovery and drug delivery. PMID:25295268

  6. Intratumoral Drug Delivery with Nanoparticulate Carriers

    PubMed Central

    Holback, Hillary

    2011-01-01

    Stiff extracellular matrix, elevated interstitial fluid pressure, and the affinity for the tumor cells in the peripheral region of a solid tumor mass have long been recognized as significant barriers to diffusion of small-molecular-weight drugs and antibodies. However, their impacts on nanoparticle-based drug delivery have begun to receive due attention only recently. This article reviews biological features of many solid tumors that influence transport of drugs and nanoparticles and properties of nanoparticles relevant to their intratumoral transport, studied in various tumor models. We also discuss several experimental approaches employed to date for enhancement of intratumoral nanoparticle penetration. The impact of nanoparticle distribution on the effectiveness of chemotherapy remains to be investigated and should be considered in the design of new nanoparticulate drug carriers. PMID:21213021

  7. [Drug patents and other ways to protect pharmaceutical research].

    PubMed

    Ohana, Patrick; Tardieu, Sophie; Blin, Olivier; Tassy, Sébastien; Sambuc, Roland

    2004-01-01

    Pharmaceutical research constitutes a significant cost for pharmaceutical companies. Because of the importance of the financial investment in research projects, companies must protect their discoveries. There are multiple ways to do this. First, the legal avenue can be divided into three parts: a pharmaceutical company can protect a new drug by a patent, then an additional patent or a secondary patent; moreover, since 1992 in Europe, the pharmaceutical industry has been able to extend a patent by the "Supplementary Protection Certificate" (le Certificat Complémentaire de Protection [CCP]). The nonjuridical way is to use the chiral "switch", which can extend patents close to expiring, thus enhancing profitability. PMID:15359623

  8. 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. PMID:19569979

  9. Microcap pharmaceutical firms: linking drug pipelines to market value.

    PubMed

    Beach, Robert

    2012-01-01

    This article examines predictors of the future market value of microcap pharmaceutical companies. This is problematic since the large majority of these firms seldom report positive net income. Their value comes from the potential of a liquidity event such as occurs when a key drug is approved by the FDA. The typical scenario is one in which the company is either acquired by a larger pharmaceutical firm or enters into a joint venture with another pharmaceutical firm. Binary logistic regression is used to determine the impact of the firm's drug treatment pipeline and its investment in research and development on the firm's market cap. Using annual financial data from 2007 through 2010, this study finds that the status of the firm's drug treatment pipeline and its research and development expenses are significant predictors of the firm's future stock value relative to other microcap pharmaceutical firms. PMID:23971143

  10. Mucoadhesive Chitosan Derivatives as Novel Drug Carriers.

    PubMed

    Islam, Mohammad Ariful; Park, Tae-Eun; Reesor, Emma; Cherukula, Kondareddy; Hasan, Anwarul; Firdous, Jannatul; Singh, Bijay; Kang, Sang-Kee; Choi, Yun-Jaie; Park, In-Kyu; Cho, Chong-Su

    2015-01-01

    Chitosan on its own is a well-established natural polymer and is widely regarded as a biodegradable, biocompatible and nontoxic material for drug delivery applications. Although unmodified chitosan has some mucoadhesive properties on its own, its bioavailability is limited due to its short retention time in the body. Moreover, the high solubility of chitosan at acidic pH levels limits its use for mucosal drug delivery (especially through the oral route). Chemically-modified mucoadhesive chitosan, especially thiolated chitosan, has arisen as an alternative to create novel mucosal drug delivery systems. The mucoadhesive properties that are conferred to the thiolated chitosan certainly set this novel class of second or third-generation thiomers apart. To understand the significance of mucoadhesive chitosan, we first present the mechanism of mucoadhesion and provide comprehensive coverage of description of a variety of chemical modifications to prepare mucoadhesive thiolated chitosan derivatives. We then present the plethora of applications of these modified chitosan variants in a wide range of drug delivery fields, including the delivery of antigens, proteins and genes through a variety of routes, including oral, nasal, pulmonary, vaginal and others. By presenting the range of applications for mucoadhesive chitosan drug carriers we herein demonstrate that chemically-modified thiolated chitosan is a versatile and effective material for a new class of drug delivery vehicles. PMID:26323422

  11. Uptake Carriers and Oncology Drug Safety

    PubMed Central

    Sprowl, Jason A.

    2014-01-01

    Members of the solute carrier (SLC) family of transporters are responsible for the cellular influx of a broad range of endogenous compounds and xenobiotics in multiple tissues. Many of these transporters are highly expressed in the gastrointestinal tract, liver, and kidney and are considered to be of particular importance in governing drug absorption, elimination, and cellular sensitivity of specific organs to a wide variety of oncology drugs. Although the majority of studies on the interaction of oncology drugs with SLC have been restricted to the use of exploratory in vitro model systems, emerging evidence suggests that several SLCs, including OCT2 and OATP1B1, contribute to clinically important phenotypes associated with those agents. Recent literature has indicated that modulation of SLC activity may result in drug-drug interactions, and genetic polymorphisms in SLC genes have been described that can affect the handling of substrates. Alteration of SLC function by either of these mechanisms has been demonstrated to contribute to interindividual variability in the pharmacokinetics and toxicity associated with several oncology drugs. In this report, we provide an update on this rapidly emerging field. PMID:24378324

  12. Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast

    PubMed Central

    2011-01-01

    Background The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers. Results To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells. Conclusions As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs. PMID:22023736

  13. Dibutyrylchitin nanoparticles as novel drug carrier.

    PubMed

    Jain, Tanvi; Kumar, Sushil; Dutta, P K

    2016-01-01

    Chitin is a ubiquitous renewable biopolymer that is significantly distributed in the natural world. Biopolymeric nanoparticles (Nps) have been developed for various biomedical applications by researchers. Here, chitin derivative, dibutyrylchitin Nps (DBC) was synthesized as a nanocarrier for drug delivery using butyric anhydride and perchloric acid as a catalyst under heterogeneous conditions. The structural characterization was analyzed by FT-IR and FE SEM study showed spherical particles in a size range of 80-90 nm. The physiochemical evaluation involves swelling behavior and in vitro biodegradation studies. The results of in vitro hemolytic assay validate the blood compatibility of the prepared system. Drug release profiles indicate that 5-flourouracil (Fu) loaded dibutyrylchitin Nps (DBC-Fu) gives the enhanced drug release in acidic pH when compared to neutral pH. The encapsulation efficiency of DBC-Fu was found to be 90%. The confocal analysis also confirmed the uptake of both DBC and DBC-Fu Nps by A549 cell lines. Hence, this study shows that the DBC have the potential to be used as a drug carrier and also for other biomedical applications. PMID:26592700

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

    PubMed Central

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

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

  15. Homochiral drugs: a demanding tendency of the pharmaceutical industry.

    PubMed

    Núñez, María C; García-Rubiño, M Eugenia; Conejo-García, Ana; Cruz-López, Olga; Kimatrai, María; Gallo, Miguel A; Espinosa, Antonio; Campos, Joaquín M

    2009-01-01

    The issue of drug chirality is now a major theme in the design and development of new drugs, underpinned by a new understanding of the role of molecular recognition in many pharmacologically relevant events. In general, three methods are utilized for the production of a chiral drug: the chiral pool, separation of racemates, and asymmetric synthesis. Although the use of chiral drugs predates modern medicine, only since the 1980's has there been a significant increase in the development of chiral pharmaceutical drugs. An important commercial reason is that as patents on racemic drugs expire, pharmaceutical companies have the opportunity to extend patent coverage through development of the chiral switch enantiomers with desired bioactivity. Stimulated by the new policy statements issued by the regulatory agencies, the pharmaceutical industry has systematically begun to develop chiral drugs in enantiometrically enriched pure forms. This new trend has caused a tremendous change in the industrial small- and large-scale production to enantiomerically pure drugs, leading to the revisiting and updating of old technologies, and to the development of new methodologies of their large-scale preparation (as the use of stereoselective syntheses and biocatalyzed reactions). The final decision whether a given chiral drug will be marketed in an enantiomerically pure form, or as a racemic mixture of both enantiomers, will be made weighing all the medical, financial and social proficiencies of one or other form. The kinetic, pharmacological and toxicological properties of individual enantiomers need to be characterized, independently of a final decision. PMID:19519381

  16. Amorphization of Molecular Liquids of Pharmaceutical Drugs by Acoustic Levitation

    NASA Astrophysics Data System (ADS)

    Benmore, C. J.; Weber, J. K. R.

    2011-08-01

    It is demonstrated that acoustic levitation is able to produce amorphous forms from a variety of organic molecular compounds with different glass forming abilities. This can lead to enhanced solubility for pharmaceutical applications. High-energy x-ray experiments show that several viscous gels form from saturated pharmaceutical drug solutions after 10-20 min of levitation at room temperature, most of which can be frozen in solid form. Laser heating of ultrasonically levitated drugs can also result in the vitrification of molecular liquids, which is not attainable using conventional amorphization methods.

  17. Drug Design, Development, and Delivery: An Interdisciplinary Course on Pharmaceuticals

    ERIC Educational Resources Information Center

    Prausnitz, Mark R.; Bommarius, Andreas S.

    2011-01-01

    We developed a new interdisciplinary course on pharmaceuticals to address needs of undergraduate and graduate students in chemical engineering and other departments. This course introduces drug design, development, and delivery in an integrated fashion that provides scientific depth in context with broader impacts in business, policy, and ethics.…

  18. [Practice of drug monitoring based on comprehensive pharmaceutical judgment].

    PubMed

    Katayama, Toshiya

    2015-01-01

    With the revisions to the pay for performance of pharmaceutical service of inpatients in April 2012, the ward permanent time of pharmacists grew longer than previously; however, there are as yet few reports on the pharmaceutical outcome of the new medical service. To improve the pharmaceutical service requires that pharmacists collect useful medical information and extract the problems of pharmaceutical care for inpatients. Since many cases of treatment with multidrug regimens are regularly performed, pharmacists cannot contribute to medical treatment only by knowledge of a single disease. Therefore quick and comprehensive judgment of pharmacists is necessary in addition to acquisition of pharmaceutical knowledge. We especially highlight medical emergencies such as severe cases of sepsis and infection to which physicians require rapid judgment. Pharmacists alike require appropriate knowledge of drug administration to avoid medical treatment failure. Moreover, it is necessary for pharmacists to apply advanced drug monitoring in difficult cases. On the other hand, integrated team medical treatment is now advancing, although pharmacists' roles in clinical decision making are increasing, and pharmacists have a greater burden of responsibility than before. PMID:25747207

  19. 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

  20. Core competencies for pharmaceutical physicians and drug development scientists

    PubMed Central

    Silva, Honorio; Stonier, Peter; Buhler, Fritz; Deslypere, Jean-Paul; Criscuolo, Domenico; Nell, Gerfried; Massud, Joao; Geary, Stewart; Schenk, Johanna; Kerpel-Fronius, Sandor; Koski, Greg; Clemens, Norbert; Klingmann, Ingrid; Kesselring, Gustavo; van Olden, Rudolf; Dubois, Dominique

    2013-01-01

    Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine), are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education. The objectives were: to define a set of core competencies for pharmaceutical physicians and drug development scientists, to be summarized in a Statement of Competence and to benchmark and align these identified core competencies with the Learning Outcomes (LO) of the PharmaTrain Base Course. The objectives were successfully achieved. Seven domains and 60 core competencies were identified and aligned accordingly. The effective implementation of training programs using the competencies or the PharmaTrain LO anywhere in the world may transform the drug development process to an efficient and integrated process for better and safer medicines. The PharmaTrain Base Course might provide the cognitive framework to achieve the desired Statement of Competence for Pharmaceutical Physicians and Drug Development Scientists worldwide. PMID:23986704

  1. Cyclodextrin-based nanosponges as drug carriers

    PubMed Central

    Zanetti, Marco; Cavalli, Roberta

    2012-01-01

    Summary Cyclodextrin-based nanosponges, which are proposed as a new nanosized delivery system, are innovative cross-linked cyclodextrin polymers nanostructured within a three-dimensional network. This type of cyclodextrin polymer can form porous insoluble nanoparticles with a crystalline or amorphous structure and spherical shape or swelling properties. The polarity and dimension of the polymer mesh can be easily tuned by varying the type of cross-linker and degree of cross-linking. Nanosponge functionalisation for site-specific targeting can be achieved by conjugating various ligands on their surface. They are a safe and biodegradable material with negligible toxicity on cell cultures and are well-tolerated after injection in mice. Cyclodextrin-based nanosponges can form complexes with different types of lipophilic or hydrophilic molecules. The release of the entrapped molecules can be varied by modifying the structure to achieve prolonged release kinetics or a faster release. The nanosponges could be used to improve the aqueous solubility of poorly water-soluble molecules, protect degradable substances, obtain sustained delivery systems or design innovative drug carriers for nanomedicine. PMID:23243470

  2. [Alcohol, pharmaceuticals, illicit drugs and driving].

    PubMed

    Wennig, Robert; Origer, Alain; Bour, Jean; Pepin, G; Maurer, Hans H; Gillard, Claude; Verstraete, Alain; Maurer, Hans-Jürgen; Willekens, Michel

    2005-01-01

    A great number of clinical, epidemiological, pharmacological and toxicological data on the influence of psychotropics on driving are available. These psychotropics include psycholeptics like ethanol, opioids, psychoanaleptics like cocaine, amphetamines and congeners, psychodysleptics like cannabis, LSD and magic mushrooms. General epidemiology and specific epidemiology for Luxembourg will be outlined. Practical aspects of roadside testing, forensic aspects as well as the place of hair testing in drugs and road safety issues will be discussed. PMID:16042050

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

    PubMed

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

    2015-01-01

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

  4. Augmenting drug-carrier compatibility improves tumour nanotherapy efficacy.

    PubMed

    Zhao, Yiming; Fay, François; Hak, Sjoerd; Manuel Perez-Aguilar, Jose; Sanchez-Gaytan, Brenda L; Goode, Brandon; Duivenvoorden, Raphaël; de Lange Davies, Catharina; Bjørkøy, Astrid; Weinstein, Harel; Fayad, Zahi A; Pérez-Medina, Carlos; Mulder, Willem J M

    2016-01-01

    A major goal of cancer nanotherapy is to use nanoparticles as carriers for targeted delivery of anti-tumour agents. The drug-carrier association after intravenous administration is essential for efficient drug delivery to the tumour. However, a large number of currently available nanocarriers are self-assembled nanoparticles whose drug-loading stability is critically affected by the in vivo environment. Here we used in vivo FRET imaging to systematically investigate how drug-carrier compatibility affects drug release in a tumour mouse model. We found the drug's hydrophobicity and miscibility with the nanoparticles are two independent key parameters that determine its accumulation in the tumour. Next, we applied these findings to improve chemotherapeutic delivery by augmenting the parent drug's compatibility; as a result, we achieved better antitumour efficacy. Our results help elucidate nanomedicines' in vivo fate and provide guidelines for efficient drug delivery. PMID:27071376

  5. Augmenting drug-carrier compatibility improves tumour nanotherapy efficacy

    NASA Astrophysics Data System (ADS)

    Zhao, Yiming; Fay, François; Hak, Sjoerd; Manuel Perez-Aguilar, Jose; Sanchez-Gaytan, Brenda L.; Goode, Brandon; Duivenvoorden, Raphaël; de Lange Davies, Catharina; Bjørkøy, Astrid; Weinstein, Harel; Fayad, Zahi A.; Pérez-Medina, Carlos; Mulder, Willem J. M.

    2016-04-01

    A major goal of cancer nanotherapy is to use nanoparticles as carriers for targeted delivery of anti-tumour agents. The drug-carrier association after intravenous administration is essential for efficient drug delivery to the tumour. However, a large number of currently available nanocarriers are self-assembled nanoparticles whose drug-loading stability is critically affected by the in vivo environment. Here we used in vivo FRET imaging to systematically investigate how drug-carrier compatibility affects drug release in a tumour mouse model. We found the drug's hydrophobicity and miscibility with the nanoparticles are two independent key parameters that determine its accumulation in the tumour. Next, we applied these findings to improve chemotherapeutic delivery by augmenting the parent drug's compatibility; as a result, we achieved better antitumour efficacy. Our results help elucidate nanomedicines' in vivo fate and provide guidelines for efficient drug delivery.

  6. The interaction of encapsulated pharmaceutical drugs with a silica matrix.

    PubMed

    Morais, Everton C; Correa, Gabriel G; Brambilla, Rodrigo; Radtke, Claudio; Baibich, Ione Maluf; dos Santos, João Henrique Z

    2013-03-01

    A series of seven drugs, namely, fluoxetine, gentamicin, lidocaine, morphine, nifedipine, paracetamol and tetracycline, were encapsulated. The encapsulated systems were characterized using a series of complementary techniques: Fourier-transform infrared spectroscopy (FT-IR), diffusive reflectance spectroscopy in the UV-vis region (DRS) and X-ray photoelectron spectroscopy (XPS). According to the DRS spectra, most of the encapsulated systems showed a band shift of the maximum absorption when compared with the corresponding bare pharmaceutical. Additionally, after encapsulation, the drugs exhibited infrared band shifts toward higher wavenumbers, which in turn provided insight into potential sites for interaction with the silica framework. The amine group showed a band shift in the spectra of almost all the drugs (except nifedipine and tetracycline). This finding indicates the possibility of a hydrogen bonding interaction between the drug and the silica via electron donation from the amine group to the silica framework. XPS confirmed this interaction between the pharmaceuticals and the silica through the amine group. A correlation was observed between the textural characteristics of the solids and the spectroscopic data, suggesting that the amine groups from the pharmaceuticals were more perturbed upon encapsulation. PMID:23261562

  7. Linked open drug data for pharmaceutical research and development

    PubMed Central

    2011-01-01

    There is an abundance of information about drugs available on the Web. Data sources range from medicinal chemistry results, over the impact of drugs on gene expression, to the outcomes of drugs in clinical trials. These data are typically not connected together, which reduces the ease with which insights can be gained. Linking Open Drug Data (LODD) is a task force within the World Wide Web Consortium's (W3C) Health Care and Life Sciences Interest Group (HCLS IG). LODD has surveyed publicly available data about drugs, created Linked Data representations of the data sets, and identified interesting scientific and business questions that can be answered once the data sets are connected. The task force provides recommendations for the best practices of exposing data in a Linked Data representation. In this paper, we present past and ongoing work of LODD and discuss the growing importance of Linked Data as a foundation for pharmaceutical R&D data sharing. PMID:21575203

  8. [Essential drugs and pharmaceutical care: reflection on the access to drugs through lawsuits in Brazil].

    PubMed

    Sant'ana, João Maurício Brambati; Pepe, Vera Lúcia Edais; Osorio-de-Castro, Claudia Garcia Serpa; Ventura, Miriam

    2011-02-01

    The guarantee of pharmaceutical care as a legal right established by the Brazilian federal constitution of 1988 led to an increase in lawsuits to put that right into practice. This phenomenon has been dubbed the judicialization of pharmaceutical care. Studies on this topic have revealed, on the one hand, deficiencies in the access of Unified Health Care (SUS) users to drugs included in Ministry of Health pharmaceutical care lists, and, on the other hand, limitations of the legal system to deal with the situation. The present article addresses these issues in the context of the conceptual framework that supports the Brazilian drug policy and pharmaceutical care policy, especially the notions of essential drugs and allocation of scarce resources. PMID:21437372

  9. Recent advances of chitosan nanoparticles as drug carriers

    PubMed Central

    Wang, Jun Jie; Zeng, Zhao Wu; Xiao, Ren Zhong; Xie, Tian; Zhou, Guang Lin; Zhan, Xiao Ri; Wang, Shu Ling

    2011-01-01

    Chitosan nanoparticles are good drug carriers because of their good biocompatibility and biodegradability, and can be readily modified. As a new drug delivery system, they have attracted increasing attention for their wide applications in, for example, loading protein drugs, gene drugs, and anticancer chemical drugs, and via various routes of administration including oral, nasal, intravenous, and ocular. This paper reviews published research on chitosan nanoparticles, including its preparation methods, characteristics, modification, in vivo metabolic processes, and applications. PMID:21589644

  10. Effects of drug-carrier interactions on drug dissolution from binary and ternary matrices

    NASA Astrophysics Data System (ADS)

    Iqbal, Zafar

    For nearly five decades, pharmaceutical researchers have studied solid solutions of drugs in polymers as a potential means to enhance the dissolution of drugs with poor aqueous solubility. This has become of greater importance in recent years because most new potential drug compounds (new chemical entities) exhibit poor water solubility and present great challenges to scientists who must design dosage forms from which the drugs are bioavailable. During the formulation of a solid solution, the drug undergoes physical but not chemical alterations that increase its chemical potential in the formulation relative to that of the pure drug in its stable form. This increased chemical potential is responsible for enhanced dissolution as well as physical instabilities, such as amorphous to crystalline conversions and precipitation within the solid state. The chemical potential is derived from the Gibbs free energy, so it is reasonable to explain the behavior of solid solution systems in terms of thermodynamics. Solid solutions and dispersions have been extensively studied by pharmaceutical scientists, both with regard to manufacturing aspects and the proposal of various models in attempts to explain the physical bases for how these systems work. Recently, Dave and Bellantone proposed a model based on the thermodynamic changes resulting from the formulation of binary solid solutions of a drug in the polymer PVP. Their model introduced a modification of the F-H theory, which was used to quantify the drug-polymer interaction energies and calculate the entropy of mixing of the drug and polymer. In this work, the model of Dave and Bellantone was extended to include three-component systems, consisting of one drug mixed in a carrier matrix consisting of mixture of two polymers or a polymer and a surfactant. For this research, solid solutions were formed using various drug weight fractions in the formulations. The study focused on the following points: (1) Prepare solid solution

  11. Pharmaceutical drug marketing strategies and tactics: a comparative analysis of attitudes held by pharmaceutical representatives and physicians.

    PubMed

    Parker, R Stephen; Pettijohn, Charles E

    2005-01-01

    A variety of promotional strategies have been used to stimulate sales of pharmaceutical drugs. Traditionally, push techniques have been the predominant means used to encourage physicians to prescribe drugs and thus increase sales. Recently, the traditional push strategy has been supplemented by a pull strategy. Direct-to-consumer advertising is increasingly used to encourage consumers to request advertised drugs from their physicians. This research compares the attitudes of two of the most affected participants in the prescriptive sales processes; physicians and pharmaceutical sales representatives. The findings indicate differences between physicians and pharmaceutical sales representatives regarding the efficacy and ethical considerations of various promotional strategies. PMID:16597582

  12. Electrospun fibers as potential carrier systems for enhanced drug release of perphenazine.

    PubMed

    Bruni, Giovanna; Maggi, Lauretta; Tammaro, Loredana; Lorenzo, Rosadele Di; Friuli, Valeria; D'Aniello, Sharon; Maietta, Mariarosa; Berbenni, Vittorio; Milanese, Chiara; Girella, Alessandro; Marini, Amedeo

    2016-09-10

    Solubility represents an important challenge for formulation of drugs, because the therapeutic efficacy of a drug depends on the bioavailability and ultimately on its solubility. Low aqueous solubility is one of the main issues related with formulation design and development of new molecules. Many drug molecules present bioavailability problems due to their poor solubility. For this reason there is a great interest in the development of new carrier systems able to enhance the dissolution of poorly water-soluble drugs. In this work, fibers containing an insoluble model drug and prepared by an electrospinning method, are proposed and evaluated to solve this problem. Two hydrophilic polymers, polyvinylpyrrolidone (Plasdone® K29/32) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) were used to increase the water solubility of perphenazine. The physico-chemical characterization suggests that the drug loaded in the fibers is in the amorphous state. Both polymeric carriers are effective to promote the drug dissolution rate in water, where this active pharmaceutical ingredient is insoluble, due to the fine dispersion of the drug into the polymeric matrices, obtained with this production technique. In fact, the dissolution profiles of the fibers, compared to the simple physical mixture of the two components, and to the reference commercial product Trilafon® 8mg tablets, show that a strong enhancement of the drug dissolution rate can be achieved with the electrospinning technique. PMID:27418562

  13. Polymeric micelles as drug carriers: their lights and shadows.

    PubMed

    Yokoyama, Masayuki

    2014-08-01

    In this review, polymeric micelles as drug-targeting carriers are concisely explained. In the first introduction part, I describe a brief history of polymer micelle's research for drug targeting, and then I explain this review's focus. Since most other review articles concerning polymeric micelle carriers explain only what was achieved in the polymeric micelle's research, I describe this review by focusing on what was not done. In the second part, I take up three characteristics of polymeric micelle carriers by comparing their advantages and disadvantages, what was done and what was not done in the past studies, and what is easily achieved and what is difficult to be achieved with polymeric micelles. In the last part, I discuss three common problems of nano-sized drug carrier systems including polymeric micelles, and then I add a few comments on these problems. PMID:25012065

  14. Recurring Epidemics of Pharmaceutical Drug Abuse in America: Time for an All-Drug Strategy.

    PubMed

    Herzberg, David; Guarino, Honoria; Mateu-Gelabert, Pedro; Bennett, Alex S

    2016-03-01

    Observers describe today's "epidemic" of pharmaceutical drug abuse as a recent phenomenon, but we argue that it is only the most recent of three waves stretching back more than a century. During each wave, policies have followed a similar pattern: voluntary educational campaigns, followed by supply-side policing and--sometimes--public health responses that would today be understood as "harm reduction." These experiences suggest that only broad-based application of all three approaches to users of all drugs (not just pharmaceutical drugs) can produce a reduction in drug-related harm rather than merely shifting it from one type of drug to another. This has rarely happened because policy has been shaped by the racially charged division of drug users into deserving and morally salvageable victims, or fearsome and morally repugnant criminals. PMID:26794163

  15. Intellectual property and pharmaceutical drugs: an ethical analysis.

    PubMed

    De George, Richard T

    2005-10-01

    The pharmaceutical industry has in recent years come under attack from an ethical point of view concerning its patents and the non-accessibility of life-saving drugs for many of the poor in both less developed countries and in the United States. The industry has replied with economic and legal justifications for its actions. The result has been a communication gap between the industry on the one hand and poor nations and American critics on the other. This paper attempts to present and evaluate the arguments on all sides and suggests a possible way out of the current impasse. It attempts to determine the ethical responsibility of the drug industry in making drugs available to the needy, while at the same time developing the parallel responsibilities of individuals, governments, and NGOs. It concludes with the suggestion that the industry develop an international code for its self-regulation. PMID:16358442

  16. SLN for topical application in skin diseases--characterization of drug-carrier and carrier-target interactions.

    PubMed

    Küchler, Sarah; Herrmann, Werner; Panek-Minkin, Grazyna; Blaschke, Tobias; Zoschke, Christian; Kramer, Klaus D; Bittl, Robert; Schäfer-Korting, Monika

    2010-05-10

    The modes of drug-particle interactions considerably influence drug delivery by nanoparticulate carrier systems and drug penetration into the skin. The exact mechanism of the drug loading and its release are still ambiguous. Therefore, the loading process, the interaction of the agent and the lipid matrix of solid lipid nanoparticles (SLNs) as well as the uptake of the loaded agent by skin lipids were analysed by electron spin resonance (ESR) and parelectric spectroscopy (PS) using spin probes (TEMPO, TEMPOL, and CAT-1) as model drugs differing in their lipophilicity. The spin probes were closely attached to the particles lipid surface (TEMPO) or located in the layers of the surfactant (CAT-1), respectively. Furthermore, two distinct sub-compartments on the SLN were found. To simulate the processes at the phase boundary SLN dispersion/skin, skin lipid mixtures were prepared and the transfer process of the spin labels was followed by ESR tomography. Transfer rates were related to the lipophilicity of the spin probe, the lipid mixture and the applied pharmaceutical formulation, SLN dispersion and aqueous solution, respectively. In particular, SLN accelerated in particular the distribution of the lipophilic agents. PMID:20153414

  17. Microfluidics-assisted in vitro drug screening and carrier production

    PubMed Central

    Tsui, Jonathan H.; Lee, Woohyuk; Pun, Suzie H.; Kim, Jungkyu; Kim, Deok-Ho

    2013-01-01

    Microfluidic platforms provide several unique advantages for drug development. In the production of drug carriers, physical properties such as size and shape, and chemical properties such as drug composition and pharmacokinetic parameters, can be modified simply and effectively by tuning the flow rate and geometries. Large numbers of carriers can then be fabricated with minimal effort and with little to no batch-to-batch variation. Additionally, cell or tissue culture models in microfluidic systems can be used as in vitro drug screening tools. Compared to in vivo animal models, microfluidic drug screening platforms allow for high-throughput and reproducible screening at a significantly lower cost, and when combined with current advances in tissue engineering, are also capable of mimicking native tissues. In this review, various microfluidic platforms for drug and gene carrier fabrication are reviewed to provide guidelines for designing appropriate carriers. In vitro microfluidic drug screening platforms designed for high-throughput analysis and replication of in vivo conditions are also reviewed to highlight future directions for drug research and development. PMID:23856409

  18. Diisocyanate mediated polyether modified gelatin drug carrier for controlled release

    PubMed Central

    Vijayakumar, Vediappan; Subramanian, Kaliappagounder

    2013-01-01

    Gelatin is an extensively studied biopolymer hydrogel drug carrier due to its biocompatibility, biodegradability and non-toxicity of its biodegraded products formed in vivo. But with the pristine gelatin it is difficult to achieve a controlled and desirable drug release characteristics due to its structural and thermal lability and high solubility in aqueous biofluids. Hence it is necessary to modify its solubility and structural stability in biofluids to achieve controlled release features with improved drug efficacy and broader carrier applications. In the present explorations an effort is made in this direction by cross linking gelatin to different extents using hitherto not studied isocyanate terminated poly(ether) as a macrocrosslinker prepared from poly(ethylene glycol) and isophorone diisocyanate in dimethyl sulfoxide. The crosslinked samples were analyzed for structure by Fourier transform-infrared spectroscopy, thermal behavior through thermogravimetric analysis and differential scanning calorimetry. The cross linked gelatins were biodegradable, insoluble and swellable in biofluids. They were evaluated as a carrier for in vitro drug delivery taking theophylline as a model drug used in asthma therapy. The crosslinking of gelatin decreased the drug release rate by 10–20% depending upon the extent of crosslinking. The modeled drug release characteristics revealed an anomalous transport mechanism. The release rates for ampicillin sodium, 5-fluorouracil and theophylline drugs in a typical crosslinked gelatin carrier were found to depend on the solubility and hydrophobicity of the drugs, and the pH of the fluid. The observed results indicated that this material can prove its mettle as a viable carrier matrix in drug delivery applications. PMID:24493973

  19. Pharmaceutical aspects of anti-inflammatory TNF-blocking drugs.

    PubMed

    Jinesh, Sandhya

    2015-06-01

    Tumor necrosis factor (TNF) is a key regulator of inflammatory processes in several immune-mediated inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. Inactivating TNF has been found to be a plausible approach in treating these conditions. Two major strategies have been adopted by scientists to inactivate TNF: one is to use monoclonal antibodies (mAbs) that bind to TNF, and the other is to use fusion proteins that bind to TNF, both inactivate TNF and help to prevent TNF-mediated inflammatory processes. Monoclonal antibodies (mAbs) are biological products that selectively bind to specific antigen molecules, and fusion proteins are soluble receptors that bind to TNF. These types of drugs are generally known as biologics and there has been an explosion in the development and testing of biologics since the 1994 US approval and launch of abciximab, a mAb that binds to GPIIb/IIIa on platelets. Anti-TNF drugs that are currently approved by FDA for treating inflammatory conditions include adalimumab, certolizumab pegol, golimumab, infliximab and etanercept. Since these agents are complex protein molecules, the pharmacodynamics and pharmacokinetics of these drugs are different from small-molecule anti-inflammatory agents. This review focuses on the pharmaceutical aspects of these drugs such as mechanism of action, adverse effects, pharmacokinetics and drug interactions. An effort was also taken to compare the pharmacodynamics and pharmacokinetic properties of these drugs, with the available data at this time. PMID:25687751

  20. Role of solid carriers in pharmaceutical performance of solid supersaturable SEDDS of celecoxib.

    PubMed

    Chavan, Rahul B; Modi, Sameer R; Bansal, Arvind K

    2015-11-10

    Self emulsifying drug delivery system (SEDDS) has been increasingly used for improving the oral bioavailability of poorly water soluble drugs. SEDDS can be solidified by adsorbing them on different solid carriers. In the present study, the impact of properties of solid carrier on drug release profile from solid SEDDS was investigated. Celecoxib (CEL) loaded supersaturable SEDDS (S-SEDDS) was prepared and optimized by using optimal response surface design. Optimum composition of S-SEDDS corresponded to 10:45:45% v/v ratio of oil (Capryol 90), surfactant (Tween 20) and cosurfactant (Transcutol HP) with Soluplus (40 mg) as precipitation inhibitor. Different grades of silicon dioxide were selected based on their properties like surface area, porosity and hydrophobicity-hydrophilicity, and used for preparation of solid S-SEDDS (SS-SEDDS) by adsorption method. All SS-SEDDS formulations in release studies, gave droplet size, PDI and zeta potential similar to S-SEDDS. The percent drug release after 120min from CEL powder, S-SEDDS and SS-SEDDS with Sylysia 350 fcp, Aerosil 300 Pharma, Aerosil 200 Pharma and Aerosil R 972 Pharma was found to be 0.58%, 100%, 38.44%, 9.63%, 2.53% and 5.99%, respectively. Drug release profiles were compared by using model independent methods. The differential drug release behavior of SS-SEDDS was attributed to the different physico-chemical properties of solid carriers. SS-SEDDS with Sylysia 350 fcp showed higher drug release and greater dissolution efficiency. Oral bioavailability study also demonstrated 2.34 fold increase in Cmax and 4.82 fold increase in AUC (0-24h) when compared with CEL powder. This study highlights the rational for selection of solid carriers in the formulation development of solid SEDDS. PMID:26364711

  1. Early drug discovery and the rise of pharmaceutical chemistry.

    PubMed

    Jones, Alan Wayne

    2011-06-01

    Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid-nineteenth century nature's pharmaceuticals were all that were available to relieve man's pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative-hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin-offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal-tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p-nitrophenol, both of which were byproducts from coal-tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin®, the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history. PMID:21698778

  2. Recent advancements in the cardiovascular drug carriers.

    PubMed

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

    2016-01-01

    Cardiovascular disease is the disease that affects the cardiovascular system, vascular diseases of the brain and kidney, and peripheral arterial disease. Despite of all advances in pharmacological and clinical treatment, heart failure is a leading cause of morbidness and mortality worldwide. Many new therapeutic advance strategies, including cell transplantation, gene delivery or therapy, and cytokines or other small molecules, have been research to treat heart failure. The main aim of this review article is to focus on nano carriers advancement and addressing the problems associated with old and modern therapeutics such as nonspecific effects and poor stability. PMID:25046615

  3. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery

    PubMed Central

    Ahmed, Tarek A; Aljaeid, Bader M

    2016-01-01

    Naturally occurring polymers, particularly of the polysaccharide type, have been used pharmaceutically for the delivery of a wide variety of therapeutic agents. Chitosan, the second abundant naturally occurring polysaccharide next to cellulose, is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of micro-as well as nanoparticles. The prepared particles have been exploited as a potential carrier for different therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and nonparenteral administration. Therapeutic agent-loaded chitosan micro- or nanoparticles were found to be more stable, permeable, and bioactive. In this review, we are highlighting the different methods of preparation and characterization of chitosan micro- and nanoparticles, while reviewing the pharmaceutical applications of these particles in drug delivery. Moreover, the roles of chitosan derivatives and chitosan metal nanoparticles in drug delivery have been illustrated. PMID:26869768

  4. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery.

    PubMed

    Ahmed, Tarek A; Aljaeid, Bader M

    2016-01-01

    Naturally occurring polymers, particularly of the polysaccharide type, have been used pharmaceutically for the delivery of a wide variety of therapeutic agents. Chitosan, the second abundant naturally occurring polysaccharide next to cellulose, is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of micro-as well as nanoparticles. The prepared particles have been exploited as a potential carrier for different therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and nonparenteral administration. Therapeutic agent-loaded chitosan micro- or nanoparticles were found to be more stable, permeable, and bioactive. In this review, we are highlighting the different methods of preparation and characterization of chitosan micro- and nanoparticles, while reviewing the pharmaceutical applications of these particles in drug delivery. Moreover, the roles of chitosan derivatives and chitosan metal nanoparticles in drug delivery have been illustrated. PMID:26869768

  5. Micellar systems: Novel family for drug carriers

    NASA Astrophysics Data System (ADS)

    Rana, Meenakshi; Chowdhury, Papia

    2016-05-01

    Micellar systems have attracted a great deal of interest, especially in the field of biomedical sciences. The paper deals with the encapsulation behavior of Pyrrole-2-carboxyldehyde (PCL) an anti-cancer drug in different micellar systems. The inculsion capability of PCL is verified experimentally (UV-Vis, Photoluminescence and Raman spectroscopy) in polymer matrix. Two-micellar systems sodium dodecyl sulfate (SDS) and Polysorbate 80 (TWEEN 80) have been studied with a poorly water soluble PCL. The present work provides the effects of biocompatible organic PCL molecule entrap in micellar system in polymer phase due to its vast applicability in drug industry.

  6. The Role of Carrier Geometry in Overcoming Biological Barriers to Drug Delivery.

    PubMed

    Jordan, Carolyn; Shuvaev, Vladimir V; Bailey, Mark; Muzykantov, Vladimir R; Dziubla, Thomas D

    2016-01-01

    For a variety of diseases, effective therapy is severely limited or rendered impossible due to an inability to deliver medications to the intended sites of action. Multiple barriers exist through the body, which have evolved over time to limit the migration of foreign compounds from entering the tissues. Turning toward biology as inspiration, it has been the general goal of drug delivery to create carrier strategies that mimic, in part, features of bacteria/ viruses that allow them overcome these barriers. By packaging drugs into nano and micron scale vehicles, it should be possible to completely change the biodistribution and residence times of pharmaceutically active compounds. Recently, due to advances in formulation technologies, it has become possible to control not just the material selection, surface chemistry, and/or size, but also the overall geometry and plasticity of the drug carriers. These approaches aid in the formulation of nonspherical particles such as, discs, rods, and even unique structures such as cubes and nanodiamonds. The adjustment of size and shape can be used for the aid or prevention in cellular uptake and also to overcome the vascular and mucosal barrier. In this review, we present a summary of some approaches used to control carrier shape and the impact these geometries have upon drug transport across biological barriers. PMID:26675218

  7. Active Targeted Drug Delivery for Microbes Using Nano-Carriers

    PubMed Central

    Lin, Yung-Sheng; Lee, Ming-Yuan; Yang, Chih-Hui; Huang, Keng-Shiang

    2015-01-01

    Although vaccines and antibiotics could kill or inhibit microbes, many infectious diseases remain difficult to treat because of acquired resistance and adverse side effects. Nano-carriers-based technology has made significant progress for a long time and is introducing a new paradigm in drug delivery. However, it still has some challenges like lack of specificity toward targeting the infectious site. Nano-carriers utilized targeting ligands on their surface called ‘active target’ provide the promising way to solve the problems like accelerating drug delivery to infectious areas and preventing toxicity or side-effects. In this mini review, we demonstrate the recent studies using the active targeted strategy to kill or inhibit microbes. The four common nano-carriers (e.g. liposomes, nanoparticles, dendrimers and carbon nanotubes) delivering encapsulated drugs are introduced. PMID:25877093

  8. [Drug carrier nanosystems in malignant pleural mesothelioma].

    PubMed

    Turgut Coşan, Didem; Ak, Güntülü; Dağ, İlknur; Soyocak, Ahu; Dikmen, Gökhan; Dal, Aylin; Güneş, Hasan V; Metintaş, Muzaffer

    2016-03-01

    Malignant pleural mesothelioma (MPM), the incidence increased with each passing day, is an important lethal disease due to the limited survive with available treatment methods and with the lack of a standard treatment. Response and survive rates of cytotoxic agents which is used in MPM treatment are not good enough. Therefore, treatment studies of MPM seem to quite important and urgent. In cancer therapy, convensional chemotherapeutic agent applications, due to the lack of selectivity, lead to systemic toxicity. Besides the limited solubility of the agent used, the distribution between the cells is weak. It is very difficult to the pass through cellular barriers, particularly, drug resistance may develop to the treatment. All of these reasons lead to failure in the treatment process. Because of the fact that cytotoxic drugs either kill the rapidly growing and dividing cells or make them disfunctional by showing toxic effect on them, to avoid the side effects and to make an inherent effect for cytotoxic drug of active ingredient given for treatment on tumor, different studies have been under investigation. At the present time, nanocarriers as one of these solutions seem to have an important place. Nanocarriers are promising for the development of therapeutic effectiveness and safety. It seems that use of the nanocarrier in the treatment of mesothelioma has a potential, as effective alternative a method, with improve of the drug efficacy and reduce of toxicity in normal tissues. PMID:27266287

  9. Sodium montmorillonite/amine-containing drugs complexes: new insights on intercalated drugs arrangement into layered carrier material.

    PubMed

    Bello, Murilo L; Junior, Aridio M; Vieira, Bárbara A; Dias, Luiza R S; de Sousa, Valéria P; Castro, Helena C; Rodrigues, Carlos R; Cabral, Lucio M

    2015-01-01

    Layered drug delivery carriers are current targets of nanotechnology studies since they are able to accommodate pharmacologically active substances and are effective at modulating drug release. Sodium montmorillonite (Na-MMT) is a clay that has suitable properties for developing new pharmaceutical materials due to its high degree of surface area and high capacity for cation exchange. Therefore Na-MMT is a versatile material for the preparation of new drug delivery systems, especially for slow release of protonable drugs. Herein, we describe the intercalation of several amine-containing drugs with Na-MMT so we can derive a better understanding of how these drugs molecules interact with and distribute throughout the Na-MMT interlayer space. Therefore, for this purpose nine sodium montmorillonite/amine-containing drugs complexes (Na-MMT/drug) were prepared and characterized. In addition, the physicochemical properties of the drugs molecules in combination with different experimental conditions were assessed to determine how these factors influenced experimental outcomes (e.g. increase of the interlayer spacing versus drugs arrangement and orientation). We also performed a molecular modeling study of these amine-containing drugs associated with different Na-MMT/drug complex models to analyze the orientation and arrangement of the drugs molecules in the complexes studied. Six amine-containing drugs (rivastigmine, doxazosin, 5-fluorouracil, chlorhexidine, dapsone, nystatin) were found to successfully intercalate Na-MMT. These findings provide important insights on the interlayer aspect of the molecular systems formed and may contribute to produce more efficient drug delivery nanosystems. PMID:25803292

  10. Sodium Montmorillonite/Amine-Containing Drugs Complexes: New Insights on Intercalated Drugs Arrangement into Layered Carrier Material

    PubMed Central

    Vieira, Bárbara A.; Dias, Luiza R. S.; de Sousa, Valéria P.; Castro, Helena C.; Rodrigues, Carlos R.; Cabral, Lucio M.

    2015-01-01

    Layered drug delivery carriers are current targets of nanotechnology studies since they are able to accommodate pharmacologically active substances and are effective at modulating drug release. Sodium montmorillonite (Na-MMT) is a clay that has suitable properties for developing new pharmaceutical materials due to its high degree of surface area and high capacity for cation exchange. Therefore Na-MMT is a versatile material for the preparation of new drug delivery systems, especially for slow release of protonable drugs. Herein, we describe the intercalation of several amine-containing drugs with Na-MMT so we can derive a better understanding of how these drugs molecules interact with and distribute throughout the Na-MMT interlayer space. Therefore, for this purpose nine sodium montmorillonite/amine-containing drugs complexes (Na-MMT/drug) were prepared and characterized. In addition, the physicochemical properties of the drugs molecules in combination with different experimental conditions were assessed to determine how these factors influenced experimental outcomes (e.g. increase of the interlayer spacing versus drugs arrangement and orientation). We also performed a molecular modeling study of these amine-containing drugs associated with different Na-MMT/drug complex models to analyze the orientation and arrangement of the drugs molecules in the complexes studied. Six amine-containing drugs (rivastigmine, doxazosin, 5-fluorouracil, chlorhexidine, dapsone, nystatin) were found to successfully intercalate Na-MMT. These findings provide important insights on the interlayer aspect of the molecular systems formed and may contribute to produce more efficient drug delivery nanosystems. PMID:25803292

  11. Biochemical effects of the pharmaceutical drug paracetamol on Anguilla anguilla.

    PubMed

    Nunes, Bruno; Verde, Maria Francisca; Soares, Amadeu M V M

    2015-08-01

    The ever-increasing presence of pharmaceutical drugs in the environment is a motif of concern, and human-use drugs are of particular importance. This is the case of paracetamol, a widely employed drug in human therapeutics, as analgesic and antipyretic, whose toxicity on aquatic organisms is still not fully characterized. The present study aimed to assess the toxic deleterious effects of paracetamol on European eel, Anguila anguilla, by using a comprehensive battery of antioxidant biomarkers (activities of enzymes such as catalase (CAT) and glutathione S-transferases (GSTs)), and the quantification of oxidative damage (measurement of levels of lipid peroxidation (thiobarbituric acid reactive substances (TBARS) assay)). Other biochemical effects elicited by this substance were also quantified, in terms of anaerobic respiration (activity of lactate dehydrogenase, LDH) and neurotoxicity (acetylcholinesterase, AChE, activity). The obtained results showed the occurrence of an oxidative base response, and paracetamol also seemed to inhibit AChE, showing that this drug can also elicit neurotoxicity. The lack of response by both CAT and LDH show that, despite the occurrence of toxicity, eels have detoxification mechanisms that are effective to cope with paracetamol, preventing additional deleterious alterations, including in the main pathway by which they obtain energy. PMID:25827650

  12. Drug Carrier for Photodynamic Cancer Therapy

    PubMed Central

    Debele, Tilahun Ayane; Peng, Sydney; Tsai, Hsieh-Chih

    2015-01-01

    Photodynamic therapy (PDT) is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS), and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0) to an excited singlet state (S1–Sn), followed by intersystem crossing to an excited triplet state (T1). The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*), which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer. PMID:26389879

  13. Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells

    PubMed Central

    Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar

    2014-01-01

    During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. PMID:24872894

  14. Carbon nanotubes: an emerging drug carrier for targeting cancer cells.

    PubMed

    Rastogi, Vaibhav; Yadav, Pragya; Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar

    2014-01-01

    During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. PMID:24872894

  15. Pharmaceutical drug promotion: how it is being practiced in India?

    PubMed

    Lal, A

    2001-02-01

    The pharmaceutical industries (PI) throughout the World are heavily involved in aggressive drug promotions, with a clear aim to change the prescribing habits of physicians and to encourage the self-medication of patients. Broadly, drug promotion refers to all the informational and persuasive activities of the PI, the effect of which is to induce prescription, supply, purchase, and use of medicinal drugs. It includes the activities of medical representatives, drug advertisements to physicians, provision of gifts and samples, drug package inserts, direct-to-consumer advertisements, periodicals, telemarketing, holding of conferences, symposium and scientific meetings, sponsoring of medical education and conduct of promotional trials. The PI has the right to promote its products, but it should do so in a fair, accurate, and ethical manner. The promotional claims need to be reliable, truthful, informative, balanced, up-to-date, and capable of substantiation in good taste. However, now a days, whilst the promotional methods have become very sophisticated and effective, it was found that while promoting their products, the PI does not adhere to these ethical principles. Hence, in most situations, these lead to irrational use of drugs. This unfortunate situation could be tackled only by the multiple prong strategy involving government, PI, doctors, medical associations and consumers. The government is required to formulate some guidelines in addition to developing their own code. The doctors and consumers are required to be educated on the promotional practices and abuses committed by the PI and different ways to tackle those. Various medical and consumer groups should also intervene to improve the scenario of promotion. PMID:11225144

  16. Novel application of hydrophobin in medical science: a drug carrier for improving serum stability.

    PubMed

    Zhao, Liqiang; Xu, Haijin; Li, Ying; Song, Dongmin; Wang, Xiangxiang; Qiao, Mingqiang; Gong, Min

    2016-01-01

    Multiple physiological properties of glucagon-like peptide-1 (GLP-1) ensure that it is a promising drug candidate for the treatment of type 2 diabetes. However, the in vivo half-life of GLP-1 is short because of rapid degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. The poor serum stability of GLP-1 has significantly limited its clinical utility, although many studies are focused on extending the serum stability of this molecule. Hydrophobin, a self-assembling protein, was first applied as drug carrier to stabilize GLP-1 against protease degradation by forming a cavity. The glucose tolerance test clarified that the complex retained blood glucose clearance activity for 72 hours suggesting that this complex might be utilized as a drug candidate administered every 2-3 days. Additionally, it was found that the mutagenesis of hydrophobin preferred a unique pH condition for self-assembly. These findings suggested that hydrophobin might be a powerful tool as a drug carrier or a pH sensitive drug-release compound. The novel pharmaceutical applications of hydrophobin might result in future widespread interest in hydrophobin. PMID:27212208

  17. Novel application of hydrophobin in medical science: a drug carrier for improving serum stability

    PubMed Central

    Zhao, Liqiang; Xu, Haijin; Li, Ying; Song, Dongmin; Wang, Xiangxiang; Qiao, Mingqiang; Gong, Min

    2016-01-01

    Multiple physiological properties of glucagon-like peptide-1 (GLP-1) ensure that it is a promising drug candidate for the treatment of type 2 diabetes. However, the in vivo half-life of GLP-1 is short because of rapid degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. The poor serum stability of GLP-1 has significantly limited its clinical utility, although many studies are focused on extending the serum stability of this molecule. Hydrophobin, a self-assembling protein, was first applied as drug carrier to stabilize GLP-1 against protease degradation by forming a cavity. The glucose tolerance test clarified that the complex retained blood glucose clearance activity for 72 hours suggesting that this complex might be utilized as a drug candidate administered every 2–3 days. Additionally, it was found that the mutagenesis of hydrophobin preferred a unique pH condition for self-assembly. These findings suggested that hydrophobin might be a powerful tool as a drug carrier or a pH sensitive drug-release compound. The novel pharmaceutical applications of hydrophobin might result in future widespread interest in hydrophobin. PMID:27212208

  18. Pharmaceutical and Toxicological Properties of Engineered Nanomaterials for Drug Delivery

    PubMed Central

    Palombo, Matthew; Deshmukh, Manjeet; Myers, Daniel; Gao, Jieming; Szekely, Zoltan; Sinko, Patrick J.

    2014-01-01

    Novel engineered nanomaterials (ENMs) are being developed to enhance therapy. The physicochemical properties of ENMs can be manipulated to control/direct biodistribution and target delivery, but these alterations also have implications for toxicity. It is well known that size plays a significant role in determining ENM effects since simply nanosizing a safe bulk material can render it toxic. However, charge, shape, rigidity, and surface modifications also have a significant influence on the biodistribution and toxicity of nanoscale drug delivery systems (NDDSs). In this review, NDDSs are considered in terms of platform technologies, materials, and physical properties that impart their pharmaceutical and toxicological effects. Moving forward, the development of safe and effective nanomedicines requires standardized protocols for determining the physical characteristics of ENMs as well as assessing their potential long-term toxicity. When such protocols are established, the remarkable promise of nanomedicine to improve the diagnosis and treatment of human disease can be fulfilled. PMID:24160695

  19. Particles from preformed polymers as carriers for drug delivery

    PubMed Central

    Miladi, K.; Ibraheem, D.; Iqbal, M.; Sfar, S.; Fessi, H.; Elaissari, A.

    2014-01-01

    Biodegradable and biocompatible polymers are widely used for the encapsulation of drug molecules. Various particulate carriers with different sizes and characteristics have been prepared by miscellaneous techniques. In this review, we reported the commonly used preformed polymer based techniques for the preparation of micro and nano-structured materials intended for drug encapsulation. A description of polymer-solvent interaction was provided. The most widely used polymers were reported and described and their related research studies were mentioned. Moreover, principles of each technique and its crucial operating conditions were described and discussed. Recent applications of all the reported techniques in drug delivery were also reviewed. PMID:26417241

  20. Drug carriers for the delivery of therapeutic peptides.

    PubMed

    Du, Alice W; Stenzel, Martina H

    2014-04-14

    Peptides take on an increasingly important role as therapeutics in areas including diabetes, oncology, and metabolic, cardiovascular, and infectious diseases. In addition, many peptides such as insulin have been employed for many years. A challenge in the administration of peptide drugs is their often low hydrolytic stability, as well as other problems that are common to any drug treatment such as systemic distribution. There is a significant attention in the literature of protein drugs and their delivery strategies, but not many overviews are specifically dedicated to peptides. In this review, the different approaches to deliver peptides have been summarized where the focus is only on drug carriers based on organic materials. Initial discussion is on different methods of polymer-peptide conjugation before being followed by physical encapsulation techniques, which is divided into surfactant-based techniques and polymer carriers. Surfactant-based techniques are dominated by liposome, microemulsions and solid-lipid nanoparticles. The field widens further in the polymer field. The delivery of peptides has been enhanced using polymer-decorated liposomes, solid microspheres, polyelectrolyte complex, emulsions, hydrogels, and injectable polymers. The aim of this article is to give the reader an overview over the different types of carriers. PMID:24661025

  1. Nanofibers as novel drug carrier--An overview.

    PubMed

    Morie, Asif; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Presently polymer nanofibers have received much attention due to their unique properties such as large surface area, high porosity, small pore size, superior mechanical properties and ease of addition of surface functionalities compared with any other material. Nanofibers particularly polymeric nanofiber prepared by electrospinning process can be used as carriers for the controlled drug delivery of bioactive molecules such as cytokines, growth factors, anticancer drugs, enzymes and certain vitamins. This article presents an overview of nanofibers, various techniques involved in fabrication of nanofibers, their characterization, parameters affecting electrospinning process and their applications. PMID:25016918

  2. Multifunctional hydroxyapatite nanofibers and microbelts as drug carriers.

    PubMed

    Hou, Zhiyao; Yang, Piaoping; Lian, Hongzhou; Wang, Lili; Zhang, Cuimiao; Li, Chunxia; Chai, Ruitao; Cheng, Ziyong; Lin, Jun

    2009-07-13

    Luminescent, mesoporous, and bioactive europium-doped hydroxyapatite (HAp:Eu(3+)) nanofibers and microbelts have been prepared by a combination of sol-gel and electrospinning processes with a cationic surfactant as template. The obtained multifunctional hydroxyapatite nanofibers and microbelts, which have mesoporous structure and red luminescence, were tested as drug carriers by investigating their drug-storage/release properties with ibuprofen (IBU) as model drug. X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution (HR) TEM, FTIR spectroscopy, N(2) adsorption/desorption, photoluminescence (PL) spectra, and UV/Vis spectroscopy were used to characterize the structural, morphological, textural, and optical properties of the resulting samples. The results reveal that the multifunctional hydroxyapatites exhibit irregular mesostructure, and have fiberlike and beltlike morphologies with sizes of several hundred nanometers in width and several millimeters in length. The IBU-loaded HAp:Eu(3+) system shows red luminescence of Eu(3+) ((5)D(0)-(7)F(0,1,2)) under UV irradiation and controlled release of IBU. In addition, the emission intensity of Eu(3+) in the drug carrier system varies with the released amount of IBU, and thus drug release can be easily tracked and monitored by the change in luminescence intensity. PMID:19496099

  3. Nanoparticles and nanostructured carriers for drug delivery and contrast enhancement

    NASA Astrophysics Data System (ADS)

    Godage, Olga S.; Bucharskaya, Alla B.; Navolokin, Nikita A.; German, Sergey V.; Zuev, Viktor V.; Terentyuk, Georgy S.; Maslyakova, Galina N.; Gorin, Dmitry A.

    2016-04-01

    Currently, nanotechnologies are widely used in science and industry. It is known that the application of drug delivery nanostructured carriers for biomedicine is one of the promising areas of nanotechnology. Nanostructured carriers can be used in the diagnosis process for detecting a neoplastic tumor cells in peripheral blood, for contrast enhancement on magnetic resonance imaging (MRI), as well as for targeted drug delivery to tumor tissues. Agents for the targeted delivery (nanoparticles, liposomes, microcapsules, and etc) can affect the healthy tissues and organs, cause side effects and have a toxic effect. Therefore, it necessary to study the morphological changes that occur not only in the "target", such as a tumor, but also the internal organs, taking place under the influence of both the agents for targeted drug delivery and physical impact induced remote controlled drug release. Thus , the aim of our work is selection of the most promising agents for targeted drug delivery to tumor and contrast agents for in vivo visualization of tumor tissue boundaries , as well as their impact on the organs and tissues as results of nanostructured object biodistribution.

  4. Biocompatibility of Chitosan Carriers with Application in Drug Delivery

    PubMed Central

    Rodrigues, Susana; Dionísio, Marita; Remuñán López, Carmen; Grenha, Ana

    2012-01-01

    Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures. PMID:24955636

  5. Design of Nanoparticle-Based Carriers for Targeted Drug Delivery

    PubMed Central

    Ren, Muqing; Duval, Kayla; Guo, Xing; Chen, Zi

    2016-01-01

    Nanoparticles have shown promise as both drug delivery vehicles and direct antitumor systems, but they must be properly designed in order to maximize efficacy. Computational modeling is often used both to design new nanoparticles and to better understand existing ones. Modeled processes include the release of drugs at the tumor site and the physical interaction between the nanoparticle and cancer cells. In this article, we provide an overview of three different targeted drug delivery methods (passive targeting, active targeting and physical targeting), compare methods of action, advantages, limitations, and the current stage of research. For the most commonly used nanoparticle carriers, fabrication methods are also reviewed. This is followed by a review of computational simulations and models on nanoparticle-based drug delivery. PMID:27398083

  6. Galactosylated fluorescent labeled micelles as a liver targeting drug carrier.

    PubMed

    Wu, De-Qun; Lu, Bo; Chang, Cong; Chen, Chang-Sheng; Wang, Tao; Zhang, Yuan-Yuan; Cheng, Si-Xue; Jiang, Xue-Jun; Zhang, Xian-Zheng; Zhuo, Ren-Xi

    2009-03-01

    Galactosylated and fluorescein isothiocyanate (FITC) labeled polycaprolactone-g-dextran (Gal-PCL-g-Dex-FITC) polymers were synthesized. The grafted polymers can self-assemble into stable micelles in aqueous medium and in serum. Transmission electron microscopy (TEM) images showed that the self-assembled micelles were regularly spherical in shape. Micelle size determined by size analysis was around 120 nm. The anti-inflammation drug prednisone acetate as a model drug was loaded in the polymeric micelles, and the in vitro drug release was investigated. The galactosylated micelles could be selectively recognized by HepG2 cells and subsequently accumulate in HepG2 cells. The in vivo study demonstrated the relative uptake of the micelles by liver is much higher than the other tissues, indicating that the galactosylated micelles have great potential as a liver targeting drug carrier. PMID:19100617

  7. Neuromarketing techniques in pharmaceutical drugs advertising. A discussion and agenda for future research.

    PubMed

    Orzan, G; Zara, I A; Purcarea, V L

    2012-12-15

    Recent years have seen an "explosion" in the abilities of scientists to use neuroscience in new domains. Unfortunately, it is little known and reported on how advertising companies make more effective pharmaceutical drugs commercials. The purpose of this paper is to analyze how neuromarketing techniques may impact the consumer response to pharmaceutical advertising campaigns. The result shows that using neuromarketing methods a pharmaceutical company can better understand the conscious and unconscious consumer's thoughts and tailor specific marketing messages. PMID:23346245

  8. Scanning ion images; analysis of pharmaceutical drugs at organelle levels

    NASA Astrophysics Data System (ADS)

    Larras-Regard, E.; Mony, M.-C.

    1995-05-01

    With the ion analyser IMS 4F used in microprobe mode, it is possible to obtain images of fields of 10 × 10 [mu]m2, corresponding to an effective magnification of 7000 with lateral resolution of 250 nm, technical characteristics that are appropriate for the size of cell organelles. It is possible to characterize organelles by their relative CN-, P- and S- intensities when the tissues are prepared by freeze fixation and freeze substitution. The recognition of organelles enables correlation of the tissue distribution of ebselen, a pharmaceutical drug containing selenium. The various metabolites characterized in plasma, bile and urine during biotransformation of ebselen all contain selenium, so the presence of the drug and its metabolites can be followed by images of Se. We were also able to detect the endogenous content of Se in tissue, due to the increased sensitivity of ion analysis in microprobe mode. Our results show a natural occurrence of Se in the border corresponding to the basal lamina of cells of proximal but not distal tubules of the kidney. After treatment of rats with ebselen, an additional site of Se is found in the lysosomes. We suggest that in addition to direct elimination of ebselen and its metabolites by glomerular filtration and urinary elimination, a second process of elimination may occur: Se compounds reaching the epithelial cells via the basal lamina accumulate in lysosomes prior to excretion into the tubular fluid. The technical developments of using the IMS 4F instrument in the microprobe mode and the improvement in preparation of samples by freeze fixation and substitution further extend the limit of ion analysis in biology. Direct imaging of trace elements and molecules marked with a tracer make it possible to determine their targets by comparison with images of subcellular structures. This is a promising advance in the study of pathways of compounds within tissues, cells and the whole organism.

  9. Assessment of hupu gum for its carrier property in the design and evaluation of solid mixtures of poorly water soluble drug - rofecoxib.

    PubMed

    Vadlamudi, Harini Chowdary; Raju, Y Prasanna; Asuntha, G; Nair, Rahul; Murthy, K V Ramana; Vulava, Jayasri

    2014-01-01

    There are no reports about the pharmaceutical applications of hupu gum (HG). Hence the present study was undertaken to test its suitability in the dissolution enhancement of poorly water soluble drug. Rofecoxib (RFB) was taken as model drug. For comparison solid mixtures were prepared with carriers such as poly vinyl pyrrolidone (PVP), sodium starch glycollate (SSG) and guar gum (GG). Physical mixing (PM), co-grinding (CG), kneading (KT) and solvent evaporation (SE) techniques were used to prepare the solid mixtures, using all the carriers in different carrier and drug ratios. The solid mixtures were characterized by powder X-ray diffraction (XRD) and Fourier-transformed infrared spectroscopy (FTIR). There was a significant improvement in the dissolution rate of solid mixtures of HG, when compared with the solid mixtures of other carriers. There was an increase in dissolution rate with increase in concentration of HG upto 1:1 ratio of carrier and drug. No drug-carrier interaction was found by FTIR studies. XRD studies indicated reduction in crystallinity of the drug with increase in HG concentration. Hence HG could be a useful carrier for the dissolution enhancement of poorly water soluble drugs. PMID:24783235

  10. GELATIN CARRIERS FOR DRUG AND CELL DELIVERY IN TISSUE ENGINEERING

    PubMed Central

    Santoro, Marco; Tatara, Alexander M.; Mikos, Antonios G.

    2014-01-01

    The ability of gelatin to form complexes with different drugs has been investigated for controlled release applications. Gelatin parameters, such as crosslinking density and isoelectric point, have been tuned in order to optimize gelatin degradation and drug delivery kinetics. In recent years, focus has shifted away from the use of gelatin in isolation towards the modification of gelatin with functional groups and the fabrication of material composites with embedded gelatin carriers. In this review, we highlight some of the latest work being performed in these areas and comment on trends in the field. Specifically, we discuss gelatin modifications for immune system evasion, drug stabilization, and targeted delivery, as well as gelatin composite systems based on ceramics, naturally-occurring polymers, and synthetic polymers. PMID:24746627

  11. Synthesis of the KMB-Drug Delivery Carrier

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Xu, Mei; Zhu, Yu-peng; Zhang, Wei-hua; Gong, Yuan-yuan; Li, Dong-sheng

    Purified konjac glucomannan(KGM) was blended with Xanthan gum to prepared gel, which was valued by its viscosity and tenacity. The konjac micro-balls(KMBs) were prepared in drying and wetting method respectively. The diameter of the KMBs was analyzed with laser particle size analyzer. To a carrier of drug deliver, the delivery characteristics of the NMP, which embedded in KMB, was discussed. The results showed that KMB was well dispersed in DMSO, and its diameter was 4.08 μm. In paraffin, KMB was homogeneous disperse with diameter(2.23 μm). In the behavior of drug delivery, the characteristics of drug sustained-release were obvious, and the delivery time was more than 24 h.

  12. Bacterial Magnetosome: A Novel Biogenetic Magnetic Targeted Drug Carrier with Potential Multifunctions

    PubMed Central

    Sun, Jianbo; Li, Ying; Liang, Xing-Jie; Wang, Paul C.

    2012-01-01

    Bacterial magnetosomes (BMs) synthesized by magnetotactic bacteria have recently drawn great interest due to their unique features. BMs are used experimentally as carriers for antibodies, enzymes, ligands, nucleic acids, and chemotherapeutic drugs. In addition to the common attractive properties of magnetic carriers, BMs also show superiority as targeting nanoscale drug carriers, which is hardly matched by artificial magnetic particles. We are presenting the potential applications of BMs as drug carriers by introducing the drug-loading methods and strategies and the recent research progress of BMs which has contributed to the application of BMs as drug carriers. PMID:22448162

  13. [The list of drugs in the Popular Pharmacy Program and the Brazilian National Pharmaceutical Care Policy].

    PubMed

    Yamauti, Sueli Miyuki; Barberato-Filho, Silvio; Lopes, Luciane Cruz

    2015-08-01

    This study aimed to analyze the list of drugs in the Popular Pharmacy Program in Brazil (PFPB) in relation to the country's pharmaceutical care policy. The list of drugs in the PFPB was compared to the Brazilian and international reference lists of essential medicines, the components of pharmaceutical care in Brazilian Unified National Health System (SUS), and drug production by the country's government pharmaceutical laboratories. The PFPB list includes 119 drugs, of which 19.3% and 47.1% were not selected on the Brazilian and international reference lists, respectively; 16.8% are not used in primary care, and 40.3% are not produced by the country's government laboratories. A revision of the PFPB list based on the essential medicines concept (World Health Organization), alignment of pharmaceutical care policies, and production by government laboratories are essential to improve quality of health care, management, training of prescribers, and information for the population. PMID:26375644

  14. Quantitative (13)C Solid-State NMR Spectra by Multiple-Contact Cross-polarization for Drug Delivery: From Active Principles to Excipients and Drug Carriers.

    PubMed

    Saïdi, Fadila; Taulelle, Francis; Martineau, Charlotte

    2016-08-01

    In this contribution, we present an analysis of the main parameters influencing the efficiency of the (1)H → (13)C multiple-contact cross-polarization nuclear magnetic resonance (NMR) experiment in the context of solid pharmaceutical materials. Using the optimum experimental conditions, quantitative (13)C NMR spectra are then obtained for porous metal-organic frameworks (potential drug carriers) and for components present in drug formulations (active principle ingredient and excipients, amorphous or crystalline). Finally, we show that mixtures of components can also be quantified with this method and, hence, that it represents an ideal tool for quantification of pharmaceutical formulations by (13)C cross-polarization under magic-angle spinning NMR in the industry as it is robust and easy to set up, much faster than direct (13)C polarization and is efficient for samples at natural abundance. PMID:27372550

  15. The introduction of new drugs into anaesthetic practice: a perspective in pharmaceutical development and regulation.

    PubMed

    Gilron, I

    1995-06-01

    This article reviews the process by which new drugs are introduced into anaesthetic practice with particular emphasis on pharmaceutical development and government regulation. After a brief overview of the drug development process, new trends in drug development are discussed including implementation of pharmacokinetic, pharmacodynamic and toxicokinetic studies in both preclinical and human phases of drug evaluation. A synopsis of the drug regulatory process is provided and, in particular, the problem of unapproved drug use in anaesthesia is discussed. Ethical issues regarding physician-industry interactions are highlighted by examples of conflict of interest in anaesthesia. The processes of drug development and regulation require much effort and cooperation between clinicians, pharmaceutical manufacturers and government regulators to achieve a common goal; the development and utilization of safe and effective drugs. A fundamental understanding of these processes may further facilitate optimal drug utilization and the active involvement of anaesthetists in the drug development process. PMID:7628033

  16. The validation of analytical methods for drug substances and drug products in UK pharmaceutical laboratories.

    PubMed

    Clarke, G S

    1994-05-01

    Results of a survey on method validation of analytical procedures used in the testing of drug substances and finished products, of most major research based pharmaceutical companies with laboratories in the UK, are presented. The results indicate that although method validation shows an essential similarity in different laboratories (in particular, chromatographic assay methods are validated in a similar manner in most laboratories), there is much diversity in the detailed application of validation parameters. Testing procedures for drug substances are broadly similar to finished products. Many laboratories validate methods at clinical trial stage to the same extent and detail as at the marketing authorization application (MAA)/new drug application (NDA) submission stage, however, only a small minority of laboratories apply the same criteria to methodology at pre-clinical trial stage. Extensive details of method validation parameters are included in the summary tables of this survey, together with details of the median response given for the validation of the most extensively applied methods. These median response details could be useful in suggesting a harmonized approach to method validation as applied by UK pharmaceutical laboratories. These guidelines would extend beyond the recommendations made to date by regulatory authorities and pharmacopoeias in that minimum requirements for each method validation parameter, e.g. number of replicates, range and tolerance, could be harmonized, both between laboratories and also in Product Licence submissions. PMID:7948185

  17. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., a Part D sponsor must require a pharmacy that dispenses a covered Part D drug to inform an enrollee of any differential between the price of that drug and the price of the lowest priced generic version... DRUG BENEFIT Benefits and Beneficiary Protections § 423.132 Public disclosure of pharmaceutical...

  18. [Pharmaceutical drugs containing lactose can as a rule be used by persons with lactose intolerance].

    PubMed

    Vinther, Siri; Rumessen, Jöri Johannes; Christensen, Mikkel

    2015-03-01

    Lactose is often used as an excipient in pharmaceutical drugs. Current evidence indicates that the amount of lactose in most drugs is not sufficient to cause symptoms in persons with lactose intolerance, although interindividual differences in sensitivity probably exist. Patient preferences and/or suboptimal treatment adherence could be reasons for considering lactose-free drug alternatives. PMID:25786702

  19. Does carrier size matter? A fundamental study of drug aerosolisation from carrier based dry powder inhalation systems.

    PubMed

    Ooi, Jesslynn; Traini, Daniela; Hoe, Susan; Wong, William; Young, Paul M

    2011-07-15

    There is plenty of evidence supporting the notion that the size of the carrier influences the aerosolisation performance of drug from a drug-carrier blend. Interestingly, that evidence is contradictory in places and the study of such mechanisms is fraught by the compounding variables associated with comparing crystalline powders (e.g. as size is varied so may the shape, surface chemistry, roughness and the amount of fine excipients). To overcome these limitations, a series of model polystyrene spheres were used to study the influence of size on aerosol performance. Three polystyrene sphere carriers (TS-80, TS-250 and TS-500, describing their approximate diameters) were characterised using laser diffraction, atomic force microscopy, colloid probe microscopy, electron microscopy, true density and dynamic vapour sorption. The model carriers were blended with micronized salbutamol sulphate (67.5:1 ratios) and the aerosolisation performance was tested using a multistage liquid impinger at a range of flow rates (40-100 lmin(-1)). Physico-chemical analysis of the carriers indicated that all carriers were spherical with similar roughness and densities. Furthermore, the adhesion force of drug to the carrier surfaces was independent of carrier size. Significant differences in drug aerosolisation were observed with both flow rate and carrier size. In general, as carrier size was increased, aerosol performance decreased. Furthermore, as flow rate was increased so did performance. Such observations suggest that higher energy processes drive aerosolisation, however this is likely to be due to the number of impaction events (and associated frictional and rotational forces) rather than the actual collision velocity (since the larger carriers had increased momentum and drag forces). This study shows that, in isolation of other variables, as carrier size increases, a concurrent decrease in drug aerosolisation performance is observed. PMID:21501674

  20. Comparison of pharmaceutical nanoformulations for curcumin: Enhancement of aqueous solubility and carrier retention.

    PubMed

    Allijn, Iris E; Schiffelers, Raymond M; Storm, Gert

    2016-06-15

    Curcumin, originally used in traditional medicine and as a spice, is one of the most studied and most popular natural products of the past decade. It has been described to be an effective anti-inflammatory and anti-cancer drug and protects against chronic diseases such as rheumatoid arthritis and atherosclerosis. Despite these promising pharmacological properties, curcumin is also very lipophilic, which makes its formulation challenging. Ideally the nanocarrier should additionally also retain the encapsulated curcumin to provide target tissue accumulation. In this study we aimed to tackle this aqueous solubility and carrier retention challenge of curcumin by encapsulating curcumin in different nanoparticles. We successfully loaded LDL (30nm), polymeric micelles (80nm), liposomes (180nm) and Intralipid (280nm) with curcumin. The relative loading capacity was inversely related to the size of the particle. The stability for all formulations was determined in fetal bovine serum over a course of 24h. Although all curcumin-nanoparticles were stable in buffer solution, all leaked more than 70% of curcumin under physiological conditions. Altogether, tested nanoparticles do solve the aqueous insolubility problem of curcumin, however, because of their leaky nature, the challenge of carrier retention remains. PMID:27139142

  1. Evaluation of mesoporous TCPSi, MCM-41, SBA-15, and TUD-1 materials as API carriers for oral drug delivery.

    PubMed

    Heikkilä, T; Salonen, J; Tuura, J; Kumar, N; Salmi, T; Murzin, D Yu; Hamdy, M S; Mul, G; Laitinen, L; Kaukonen, A M; Hirvonen, J; Lehto, V-P

    2007-08-01

    The feasibility of four mesoporous materials composed of biocompatible Si (TCPSi) or SiO(2) (MCM-41, SBA-15, and TUD-1) were evaluated for oral drug delivery applications. The main focus was to study the effect of the materials different pore systems (unidirectional/2D/3D) and their pore diameters, pore size distributions, pore volumes on the maximal drug load capacity, and release profiles of a loaded active pharmaceutical ingredient. Ibuprofen was used as the model drug. The total pore volume of the mesoporous solid was the main factor limiting the maximum drug load capacity, with SBA-15 reaching a very high drug load of 1:1 in weight due to its high pore volume. Dissolution experiments were performed in HBSS buffers of pH 5.5, 6.8, and 7.4 to mimic the conditions in the small intestine. At pH 5.5 the dissolution rate of ibuprofen released from the mesoporous carriers was significantly faster compared with the standard bulk ibuprofen (86-63% versus 25% released at 45 min), with the fastest release observed from the 3D pore network of TUD-1 carrier. The utilization of mesoporous carriers diminished the pH dependency of ibuprofen dissolution (pK(a) = 4.42), providing an interesting prospect for the formulation of poorly soluble drug compounds. PMID:17701523

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

    PubMed

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

    2013-11-01

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

  3. Australian pharmaceutical policy: price control, equity, and drug innovation in Australia.

    PubMed

    Doran, Evan; Alexander Henry, David

    2008-04-01

    This paper outlines the increasing salience of drug "innovation" in the debate for reform of Australia's pharmaceutical policy, particularly change to Australia's price control mechanisms. The pharmaceutical industry has consistently criticised the central role of price control in Australia's pharmaceutical regulatory regime as an impediment to drug innovation and industry growth. Despite ambivalent or contrary evidence on the impact of price control on drug innovation, this criticism, and the appeals for reform it supports, appear to be increasingly influential in directing pharmaceutical policy. This is particularly evident in the implementation of the Australia/United States Free Trade Agreement, which has led to a weakening of the historical process of evidence-based reference pricing in Australia. Should drug innovation come to dominate Australian pharmaceutical policy, there is the potential to precipitate a devaluing of the current public orientation of regulation and diminish equitable access to affordable pharmaceuticals. The manner in which trade policy has effectively undermined a publicly funded pharmaceutical benefits scheme has clear implications for many countries that maintain such programmes. PMID:18368023

  4. The Effect of Pharmaceutical Patent Term Length on Research and Development and Drug Expenditures in Canada

    PubMed Central

    Grootendorst, Paul; Matteo, Livio Di

    2007-01-01

    While pharmaceutical patent terms have increased in Canada, increases in patented drug spending have been mitigated by price controls and retrenchment of public prescription drug subsidy programs. We estimate the net effects of these offsetting policies on domestic pharmaceutical R&D expenditures and also provide an upper-bound estimate on the effects of these policies on Canadian pharmaceutical spending over the period 1988–2002. We estimate that R&D spending increased by $4.4 billion (1997 dollars). Drug spending increased by $3.9 billion at most and, quite likely, by much less. Cutbacks to public drug subsidies and the introduction of price controls likely mitigated drug spending growth. In cost–benefit terms, we suspect that the patent extension policies have been beneficial to Canada. PMID:19305720

  5. Drug recall: An incubus for pharmaceutical companies and most serious drug recall of history.

    PubMed

    Nagaich, Upendra; Sadhna, Divya

    2015-01-01

    There has been an increasing trend in the number of prescribed and over-the-counter drug recall over the last few years. The recall is usually due to company's discovery, customer's complaint or Food and Drug Administration (FDA) observation. The process of recall involves a planned specific course of action, which addresses the depth of recall, need for public warning, and the extent of effectiveness checks for the recall. The FDA review and/or recommend changes to the firm's recall strategy, as appropriate. The critical recall information list includes the identity of the product; summary of the failure; amount of product produced in the distribution chain and direct account. Product recalls clashes thousands of companies every year affecting: sales, testing customer relationships and disrupting supply chains. Drug recall is incubus for pharmaceutical companies. It effects the reputation of the company. The reason for the recall can be divided into two categories: manufacturing affined and safety/efficacy affined. It is essential to follow all the guidelines related to drug development and manufacturing procedure so as to minimize drug recall. PMID:25599028

  6. Drug recall: An incubus for pharmaceutical companies and most serious drug recall of history

    PubMed Central

    Nagaich, Upendra; Sadhna, Divya

    2015-01-01

    There has been an increasing trend in the number of prescribed and over-the-counter drug recall over the last few years. The recall is usually due to company's discovery, customer's complaint or Food and Drug Administration (FDA) observation. The process of recall involves a planned specific course of action, which addresses the depth of recall, need for public warning, and the extent of effectiveness checks for the recall. The FDA review and/or recommend changes to the firm's recall strategy, as appropriate. The critical recall information list includes the identity of the product; summary of the failure; amount of product produced in the distribution chain and direct account. Product recalls clashes thousands of companies every year affecting: sales, testing customer relationships and disrupting supply chains. Drug recall is incubus for pharmaceutical companies. It effects the reputation of the company. The reason for the recall can be divided into two categories: manufacturing affined and safety/efficacy affined. It is essential to follow all the guidelines related to drug development and manufacturing procedure so as to minimize drug recall. PMID:25599028

  7. Peering into the Pharmaceutical “Pipeline”: Investigational Drugs, Clinical Trials, and Industry Priorities

    PubMed Central

    Cottingham, Marci D.; Kalbaugh, Corey A.

    2014-01-01

    In spite of a growing literature on pharmaceuticalization, little is known about the pharmaceutical industry’s investments in research and development (R&D). Information about the drugs being developed can provide important context for existing case studies detailing the expanding – and often problematic – role of pharmaceuticals in society. To access the pharmaceutical industry’s pipeline, we constructed a database of drugs for which pharmaceutical companies reported initiating clinical trials over a five-year period (July 2006-June 2011), capturing 2,477 different drugs in 4,182 clinical trials. Comparing drugs in the pipeline that target diseases in high-income and low-income countries, we found that the number of drugs for diseases prevalent in high-income countries was 3.46 times higher than drugs for diseases prevalent in low-income countries. We also found that the plurality of drugs in the pipeline were being developed to treat cancers (26.2%). Interpreting our findings through the lens of pharmaceuticalization, we illustrate how investigating the entire drug development pipeline provides important information about patterns of pharmaceuticalization that are invisible when only marketed drugs are considered. PMID:25159693

  8. Feasibility study of pollen-shape drug carriers in dry powder inhalation.

    PubMed

    Hassan, Meer Saiful; Lau, Raymond

    2010-03-01

    The feasibility of using pollen-shape carriers in dry powder inhalation is studied. Pollen-shape hydroxyapatite (HA) particles are synthesized with a geometric diameter range from 21.1 to 48.6 microm and effective density range from 0.21 to 0.41 g/cm(3). The flowability of the particles is characterized by the Carr's compressibility index (CI) and angle of slide (theta). The HA carriers are found to have better flowability than commonly used lactose (LA) carrier with similar size range. The HA carriers are also found to be capable of high drug attachment. The aerosolization and deposition properties of a model drug are compared using HA and LA as carriers. Results indicate that pollen-shape HA carriers have good potential to be used as drug carrier in dry powder inhalation. It can give higher drug emission and respirable fraction than traditional LA carriers. PMID:19862802

  9. UV resonance Raman sensing of pharmaceutical drugs in hollow fibers

    NASA Astrophysics Data System (ADS)

    Yan, D.; Popp, J.; Frosch, T.

    2014-05-01

    We report about the experimental combination of UV resonance Raman sensing (UV-RRS) and fiber enhanced Raman sensing (FERS) on pharmaceuticals. The results show that the chemical sensitivity is highly improved and at the same time the sample volume is reduced compared to conventional measurements. A hundreds-fold improvement of the limit of detection (LOD) has been achieved with the combination of resonance Raman enhancement and fiber enhancement. The enhanced Raman signal has a reliable linear relationship with the concentration of the analyte, and therefore shows great potential for quantitative analysis of pharmaceuticals.

  10. 75 FR 24510 - Drug and Drug-Related Supply Promotion by Pharmaceutical Company Sales Representatives at VA...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... control the promotion of drugs and drug-related supplies at VA facilities and the business relationships... standard of permissible business practice at VA facilities. It would also facilitate mutually beneficial... terms to be inclusive of all items typically promoted by pharmaceutical sales representatives....

  11. When 'drugs' become 'drugs': issues of pharmaceutical abuse in France from the 1960s to the 1990s.

    PubMed

    Marchant, Alexandre

    2014-01-01

    Since the 1970s, media frenzies about drug addiction have focused mainly on illicit drugs taken by rebellious or marginalised addicts, relegating iatrogenic drug abuse, and policies and problems linked to psychotropic pharmaceuticals available by prescription or over-the-counter to the shadows. In this article I go beyond the division between illicit drugs and medicines still configuring both public representations and historiography: using archival materials from the 1960s-1990s in France, I highlight some blind spots in drug history. Firstly I demonstrate the role of pharmaceutical abuse in the career of addicts, and then examine regulation policies, which are the dark side, however complementary, of drug policies and prohibition. Finally, I analyse the role of physicians and pharmacists in this control, and discuss the various professional debates relating to the legal supply of psychoactive drugs. In all these issues, the frame of the Cold War context will also be highlighted. PMID:26054215

  12. Characterisation of biodegradable pectin aerogels and their potential use as drug carriers.

    PubMed

    Veronovski, Anja; Tkalec, Gabrijela; Knez, Željko; Novak, Zoran

    2014-11-26

    The purpose of this work was to prepare stable citrus (CF) and apple (AF) pectin aerogels for potential pharmaceutical applications. Different shapes of low ester pectin aerogels were prepared by two fundamental methods of ionic cross-linking. Pectins' spherical and multi-membrane gels were first formed by the diffusion method using 0.2M CaCl2 solution as an ionic cross-linker. The highest specific surface area (593 m(2)/g) that had so far been reported for pectin aerogels was achieved using this method. Monolithic pectin gels were formed by the internal setting method. Pectin gels were further converted into aerogels by supercritical drying using CO2. As surface area/volume is one of the key parameters in controlling drug release, multi-membrane pectin aerogels were further used as drug delivery carriers. Theophylline and nicotinic acid were used as model drugs for the dissolution study. CF aerogels showed more controlled release behaviour than AF pectin aerogels. Moreover a higher release rate (100%) was observed with CF aerogels. PMID:25256485

  13. Magnetically Stimulated Release of a Model Drug From a Magnetic Drug Carrier

    NASA Astrophysics Data System (ADS)

    Riley, Tom; Evans, Ben

    The use of particles in the micro and nanometer ranges has become increasingly important as therapeutic tools in medicine. In particular, magnetically-active particles may allow for magnetically-controlled release of drugs at targeted locations. The drugs can be delivered directly to cancerous tumors at desired concentrations. While hydrogel-based microspheres have been commonly proposed for such purposes, there is also a need for a lipophilic magnetic microsphere for delivery of poorly-soluble pharmaceuticals. We have created a well-dispersed suspension of iron oxide nanoparticles in a silicone matrix, and have used the material to manufacture microspheres in sizes ranging from 100nm to 50 microns. Our spheres are stable in aqueous suspensions, yet their silicone matrix is uniquely suited for the transport and delivery of hydrophobic pharmaceuticals. A high concentration of magnetic nanoparticles (50% wt.) enables magnetic localization, magnetic heating (hyperthermia), and magnetic stimulation to trigger drug release. Using fluorescein as a model drug, we use UV-visible spectroscopy to show a slow native release rate of the hydrophobic fluorescein from the spheres. We use these measurements to quantify the loading capacity of the microspheres, and we show results of magnetically-stimulated drug release using a DM100 field applicator (nanoScale Biomagnetics).

  14. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Public disclosure of pharmaceutical prices for equivalent drugs. 423.132 Section 423.132 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Benefits and...

  15. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Public disclosure of pharmaceutical prices for equivalent drugs. 423.132 Section 423.132 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Benefits and...

  16. [The effect of amphoteric tensides on the pharmaceutic availability of model drugs according to formulation].

    PubMed

    Bialik, W; Kuferska, E; Jaworski, E

    1992-01-01

    Pharmaceutical availability of chloramphenicol from o/w emulsion ointment and salicylic acid from tablets as influenced by the kind and concentration of amphoteric tenside has been investigated. It has been shown that amphoterics investigated variously influenced drug release, what makes possible to obtain the form of drug showing desired rate of release. PMID:8769076

  17. Pharmaceutical Companies and Their Drugs on Social Media: A Content Analysis of Drug Information on Popular Social Media Sites

    PubMed Central

    2015-01-01

    Background Many concerns have been raised about pharmaceutical companies marketing their drugs directly to consumers on social media. This form of direct-to-consumer advertising (DTCA) can be interactive and, because it is largely unmonitored, the benefits of pharmaceutical treatment could easily be overemphasized compared to the risks. Additionally, nonexpert consumers can share their own drug product testimonials on social media and illegal online pharmacies can market their services on popular social media sites. There is great potential for the public to be exposed to misleading or dangerous information about pharmaceutical drugs on social media. Objective Our central aim was to examine how pharmaceutical companies use social media to interact with the general public and market their drugs. We also sought to analyze the nature of information that appears in search results for widely used pharmaceutical drugs in the United States on Facebook, Twitter, and YouTube with a particular emphasis on the presence of illegal pharmacies. Methods Content analyses were performed on (1) social media content on the Facebook, Twitter, and YouTube accounts of the top 15 pharmaceutical companies in the world and (2) the content that appears when searching on Facebook, Twitter, and YouTube for the top 20 pharmaceutical drugs purchased in the United States. Notably, for the company-specific analysis, we examined the presence of information similar to various forms of DTCA, the audience reach of company postings, and the quantity and quality of company-consumer interaction. For the drug-specific analysis, we documented the presence of illegal pharmacies, personal testimonials, and drug efficacy claims. Results From the company-specific analysis, we found information similar to help-seeking DTCA in 40.7% (301/740) of pharmaceutical companies’ social media posts. Drug product claims were present in only 1.6% (12/740) of posts. Overall, there was a substantial amount of consumers

  18. Neuromarketing techniques in pharmaceutical drugs advertising. A discussion and agenda for future research

    PubMed Central

    Orzan, G; Zara, IA; Purcarea, VL

    2012-01-01

    Recent years have seen an “explosion" in the abilities of scientists to use neuroscience in new domains. Unfortunately, it is little known and reported on how advertising companies make more effective pharmaceutical drugs commercials. The purpose of this paper is to analyze how neuromarketing techniques may impact the consumer response to pharmaceutical advertising campaigns. The result shows that using neuromarketing methods a pharmaceutical company can better understand the conscious and unconscious consumer’s thoughts and tailor specific marketing messages. PMID:23346245

  19. Stability of drug-carrier emulsions containing phosphatidylcholine mixtures.

    PubMed

    Trotta, Michele; Pattarino, Franco; Ignoni, Terenzio

    2002-03-01

    Lipid emulsion particles containing 10% of medium chain triglycerides were prepared using 2% w/w of a mixture 1:1 w/w of purified soya phosphatidylcholine and 2-hexanoyl phosphatidylcholine as emulsifier mixture, for use as drug carriers. The mean droplet sizes of emulsions, prepared using an Ultra Turrax or a high-pressure homogenizer, were about 288 and 158 nm, respectively, compared with 380 and 268 nm for emulsions containing lecithin, or 325 and 240 nm for those containing 6-phosphatidylcholine. The stability of the emulsions, determined by monitoring the decrease of a lipophilic marker at a specified level within the emulsion, and observing coalescence over time, was also greatly increased using the emulsifier mixture. The emulsion stability did not notably change in the presence of a model destabilizing drug, indomethacin. The use of a second hydrophilic surfactant to adjust the packing properties of the lecithin at the oil-water interface provided an increase in the stability of lipid emulsions, and this may be of importance in the formulation of drug delivery systems. PMID:11880004

  20. Fluency of pharmaceutical drug names predicts perceived hazardousness, assumed side effects and willingness to buy.

    PubMed

    Dohle, Simone; Siegrist, Michael

    2014-10-01

    The impact of pharmaceutical drug names on people's evaluations and behavioural intentions is still uncertain. According to the representativeness heuristic, evaluations should be more positive for complex drug names; in contrast, fluency theory suggests that evaluations should be more positive for simple drug names. Results of three experimental studies showed that complex drug names were perceived as more hazardous than simple drug names and negatively influenced willingness to buy. The results are of particular importance given the fact that there is a worldwide trend to make more drugs available for self-medication. PMID:23740259

  1. Lipid-based drug carriers for prodrugs to enhance drug delivery.

    PubMed

    Zaro, Jennica L

    2015-01-01

    The combination of lipid drug delivery systems with prodrugs offers several advantages including improved pharmacokinetics, increased absorption, and facilitated targeting. Lipidization and use of lipid carriers can increase the pharmacological half-life of the drug, thus improving pharmacokinetics and allowing less frequent dosing. Lipids also offer advantages such as increased absorption through the intestines for oral drug absorption and to the CNS for brain delivery. Furthermore, the use of lipid delivery systems can enhance drug targeting. Endogenous proteins bind lipids in the blood and carry them to the liver to enable targeting of this organ. Drugs with significant side effects in the stomach can be specifically delivered to enterocytes by exploiting lipases for prodrug activation. Finally, lipids can be used to target the lymphatic system, thus bypassing the liver and avoiding first-pass metabolism. Lymphatic targeting is also important for antiviral drugs in the protection of B and T lymphocytes. In this review, both lipid-drug conjugates and lipid-based carriers will be discussed. An overview, including the chemistry and assembly of the systems, as well as examples from the clinic and in development, will be provided. PMID:25269430

  2. The interaction of a model active pharmaceutical with cationic surfactant and the subsequent design of drug based ionic liquid surfactants.

    PubMed

    Qamar, Sara; Brown, Paul; Ferguson, Steven; Khan, Rafaqat Ali; Ismail, Bushra; Khan, Abdur Rahman; Sayed, Murtaza; Khan, Asad Muhammad

    2016-11-01

    Interactions of active pharmaceutical ingredients (API) with surfactants remain an important research area due to the need to improve drug delivery systems. In this study, UV-Visible spectrophotometry was used to investigate the interactions between a model low molecular weight hydrophilic drug sodium valproate (SV) and cationic surfactant cetyltrimethylammonium bromide (CTAB). Changes in the spectra of SV were observed in pre- and post-micellar concentrations of CTAB. The binding constant (Kb) values and the number of drug molecules encapsulated per micelle were calculated, which posed the possibility of mixed micelle formation and strong complexation between SV and CTAB. These results were compared to those of a novel room temperature surface active ionic liquid, which was synthesized by the removal of inorganic counterions from a 1:1 mixture of CTAB and SV. In this new compound the drug now constitutes a building block of the carrier and, as such, has considerably different surfactant properties to its building blocks. In addition, enhanced solubility in a range of solvents, including simulated gastric fluid, was observed. The study provides valuable experimental evidence concerning the performance of drug based surfactant ionic liquids and how their chemical manipulation, without altering the architecture of the API, leads to control of surfactant behavior and physicochemical properties. In turn, this should feed through to improved and controlled drug release rates and delivery mechanisms, and the prevention of precipitation or formation of polymorphs typical of crystalline form APIs. PMID:27472069

  3. Towards integrated drug substance and drug product design for an active pharmaceutical ingredient using particle engineering.

    PubMed

    Kougoulos, Eleftherios; Smales, Ian; Verrier, Hugh M

    2011-03-01

    A novel experimental approach describing the integration of drug substance and drug production design using particle engineering techniques such as sonocrystallization, high shear wet milling (HSWM) and dry impact (hammer) milling were used to manufacture samples of an active pharmaceutical ingredient (API) with diverse particle size and size distributions. The API instability was addressed using particle engineering and through judicious selection of excipients to reduce degradation reactions. API produced using a conventional batch cooling crystallization process resulted in content uniformity issues. Hammer milling increased fine particle formation resulting in reduced content uniformity and increased degradation compared to sonocrystallized and HSWM API in the formulation. To ensure at least a 2-year shelf life based on predictions using an Accelerated Stability Assessment Program, this API should have a D [v, 0.1] of 55 μm and a D [v, 0.5] of 140 μm. The particle size of the chief excipient in the drug product formulation needed to be close to that of the API to avoid content uniformity and stability issues but large enough to reduce lactam formation. The novel methodology described here has potential for application to other APIs. PMID:21246419

  4. Swellable Microparticles as Carriers for Sustained Pulmonary Drug Delivery

    PubMed Central

    EL-SHERBINY, IBRAHIM M.; MCGILL, SHAYNA; SMYTH, HUGH D.C.

    2012-01-01

    In this investigation, novel biodegradable physically crosslinked hydrogel micro-particles were developed and evaluated in vitro as potential carriers for sustained pulmonary drug delivery. To facilitate sustained release in the lungs, aerosols must first navigate past efficient aerodynamic filtering to penetrate to the deep lung (requires small particle size) where they must then avoid rapid macrophage clearance (enhanced by large particle size). The strategy suggested in this study to solve this problem is to deliver drug-loaded hydrogel microparticles with aerodynamic characteristics allowing them to be respirable when dry but attain large swollen sizes once deposited on moist lung surfaces to reduce macrophage uptake rates. The microparticles are based on PEG graft copolymerized onto chitosan in combination with Pluronic® F-108 and were prepared via cryomilling. The synthesized polymers used in preparation of the microparticles were characterized using FTIR, EA, 2D-XRD, and differential scanning calorimetry (DSC). The microparticles size, morphology, moisture content, and biodegradation rates were investigated. Swelling studies and in vitro drug release profiles were determined. An aerosolization study was conducted and macrophage uptake rates were evaluated against controls. The microparticles showed a respirable fraction of approximately 15% when prepared as dry powders. Enzymatic degradation of microparticles started within the first hour and about 7–41% weights were remaining after 240 h. Microparticles showed sustained release up to 10 and 20 days in the presence and absence of lysozyme, respectively. Preliminary macrophage interaction studies indicate that the developed hydrogel microparticles significantly delayed phagocytosis and may have the potential for sustained drug delivery to the lung. PMID:19967777

  5. Drug policy in China: pharmaceutical distribution in rural areas.

    PubMed

    Dong, H; Bogg, L; Rehnberg, C; Diwan, V

    1999-03-01

    In 1978, China decided to reform its economy and since then has gradually opened up to the world. The economy has grown rapidly at an average of 9.8% per year from 1978 to 1994. Medical expenditure, especially for drugs, has grown even more rapidly. The increase in medical expenditure can be attributed to changing disease patterns, a higher proportion of older people in the population and fee-for-service incentives for hospitals. Due to the changing economic system and higher cost of health care, the Chinese government has reformed its health care system, including its health and drug policy. The drug policy reform has led to more comprehensive policy elements, including registration, production, distribution, utilization and administration. As a part of drug policy reform, the drug distribution network has also been changed, from a centrally controlled supply system (push system) to a market-oriented demand system (pull system). Hospitals can now purchase drugs directly from drug companies, factories and retailers, leading to increased price competition. Patients have easier access to drugs as more drugs are available on the market. At the same time, this has also entailed negative effects. The old drug administrative system is not suitable for the new drug distribution network. It is easy for people to get drugs on the market and this can lead to overuse and misuse. Marketing factors have influenced drug distribution so strongly that there is a risk of fake or low quality drugs being distributed. The government has taken some measures to fight these negative effects. This paper describes the drug policy reform in China, particularly the distribution of drugs to health care facilities. PMID:10190640

  6. RGD based peptide amphiphiles as drug carriers for cancer targeting

    NASA Astrophysics Data System (ADS)

    Saraf, Poonam S.

    Specific interactions of ligands with receptors is one of the approaches for active targeting of anticancer drugs to cancer cells. Over expression of integrin receptors is a physiological manifestation in several cancers and is associated with cancer progression and metastasis, which makes it an attractive target for cancer chemotherapy. The peptide sequence for this integrin recognition is the Arg-Gly-Asp (RGD). Self-assembly offers a unique way of presenting ligands to target receptors for recognition and binding. This study focuses on development of integrin specific peptide amphiphile self-assemblies as carriers for targeted delivery of paclitaxel to αvbeta 3 integrin overexpressing cancers. Amphiphiles composed of conjugates of different analogs of RGD (linear, cyclic or glycosylated) and aliphatic fatty acid with or without 8-amino-3,6-dioxaoctanoic acid (ADA) as linker were synthesized and characterized. The amphiphiles exhibited Critical Micellar Concentration in the range of 7-30 μM. Transmission electron microscopy images revealed the formation of spherical micelles in the size range of 10-40 nm. Forster Resonance Energy Transfer studies revealed entrapment of hydrophobic dyes within a tight micellar core and provided information regarding the cargo exchange within micelles. The RGD micelles exhibited competitive binding with 55% displacement of a bound fluorescent probe by the cyclic RGD micelles. The internalization of fluorescein isothiocynate (FITC) loaded RGD micelles was significantly higher in A2058 melanoma cells compared to free FITC within 20 minutes of incubation at 37°C. The same micelles showed significantly lower internalization at 4°C and on pretreatment with 0.45M sucrose confirming endocytotic uptake of the RGD micellar carriers. The IC50 of paclitaxel in A2058 melanoma cells was lower when treated within RGD micelles as compared to treatment of free drug. On the other hand, IC50 values increased by 2 to 9 fold for micellar treatment

  7. High-performance thin layer chromatography: A powerful analytical technique in pharmaceutical drug discovery

    PubMed Central

    Attimarad, Mahesh; Ahmed, K. K. Mueen; Aldhubaib, Bandar E.; Harsha, Sree

    2011-01-01

    Analysis of pharmaceutical and natural compounds and newer drugs is commonly used in all the stages of drug discovery and development process. High-performance thin layer chromatography is one of the sophisticated instrumental techniques based on the full capabilities of thin layer chromatography. The advantages of automation, scanning, full optimization, selective detection principle, minimum sample preparation, hyphenation, and so on enable it to be a powerful analytical tool for chromatographic information of complex mixtures of pharmaceuticals, natural products, clinical samples, food stuffs, and so on. PMID:23781433

  8. Integrating research and development: the emergence of rational drug design in the pharmaceutical industry.

    PubMed

    Adam, Matthias

    2005-09-01

    Rational drug design is a method for developing new pharmaceuticals that typically involves the elucidation of fundamental physiological mechanisms. It thus combines the quest for a scientific understanding of natural phenomena with the design of useful technology and hence integrates epistemic and practical aims of research and development. Case studies of the rational design of the cardiovascular drugs propranolol, captopril and losartan provide insights into characteristics and conditions of this integration. Rational drug design became possible in the 1950s when theoretical knowledge of drug-target interaction and experimental drug testing could interlock in cycles of mutual advancement. The integration does not, however, diminish the importance of basic research for pharmaceutical development. Rather, it can be shown that still in the 1990s, linear processes of innovation and the close combination of practical and epistemic work were interdependent. PMID:16137601

  9. Physicians' perceptions and uses of commercial drug information sources: an examination of pharmaceutical marketing to physicians.

    PubMed

    Spiller, L D; Wymer, W W

    2001-01-01

    Data were collected from physicians attending a medical conference. This exploratory study was primarily interested in two areas. First, the investigators were interested in better understanding physicians' responses to different promotional tactics typically used by the pharmaceutical industry. Pharmaceutical representatives were most useful, followed by drug samples and infomercials in medical journals. Direct mail, promotional faxes, and promotional products were used less by physicians. Second, the investigators were interested in learning what information sources influenced physicians' drug choices. Physicians were primarily influenced by their prior experience with a drug, then by drug compendiums, and journal articles. Physicians were also influenced by information provided by the industry and other factors, like the drug's price and their patients' financial situations. Managerial implications for marketing to physicians and ideas for future research are discussed. PMID:11727295

  10. A Collaborative Assessment Among 11 Pharmaceutical Companies of Misinformation in Commonly Used Online Drug Information Compendia

    PubMed Central

    Randhawa, Amarita S.; Babalola, Olakiitan; Henney, Zachary; Miller, Michele; Nelson, Tanya; Oza, Meerat; Patel, Chandni; Randhawa, Anupma S.; Riley, Joyce; Snyder, Scott; So, Sherri

    2016-01-01

    Background: Online drug information compendia (ODIC) are valuable tools that health care professionals (HCPs) and consumers use to educate themselves on pharmaceutical products. Research suggests that these resources, although informative and easily accessible, may contain misinformation, posing risk for product misuse and patient harm. Objective: Evaluate drug summaries within ODIC for accuracy and completeness and identify product-specific misinformation. Methods: Between August 2014 and January 2015, medical information (MI) specialists from 11 pharmaceutical/biotechnology companies systematically evaluated 270 drug summaries within 5 commonly used ODIC for misinformation. Using a standardized approach, errors were identified; classified as inaccurate, incomplete, or omitted; and categorized per sections of the Full Prescribing Information (FPI). On review of each drug summary, content-correction requests were proposed and supported by the respective product’s FPI. Results: Across the 270 drug summaries reviewed within the 5 compendia, the median of the total number of errors identified was 782, with the greatest number of errors occurring in the categories of Dosage and Administration, Patient Education, and Warnings and Precautions. The majority of errors were classified as incomplete, followed by inaccurate and omitted. Conclusion: This analysis demonstrates that ODIC may contain misinformation. HCPs and consumers should be aware of the potential for misinformation and consider more than 1 drug information resource, including the FPI and Medication Guide as well as pharmaceutical/biotechnology companies’ MI departments, to obtain unbiased, accurate, and complete product-specific drug information to help support the safe and effective use of prescription drug products. PMID:26917822

  11. Thermoresponsive hyaluronic acid nanogels as hydrophobic drug carrier to macrophages.

    PubMed

    Fernandes Stefanello, Talitha; Szarpak-Jankowska, Anna; Appaix, Florence; Louage, Benoit; Hamard, Lauriane; De Geest, Bruno G; van der Sanden, Boudewijn; Nakamura, Celso Vataru; Auzély-Velty, Rachel

    2014-11-01

    Delivery systems for macrophages are particularly attractive since these phagocytic cells play a important role in immunological and inflammatory responses, also acting as host cells for microorganisms that are involved in deadly infectious diseases, such as leishmaniasis. Hyaluronic acid (HA) is specifically recognized by macrophages that are known to express HA receptors. Therefore, in this study, we focused on HA-based nanogels as drug carriers for these cells. The drug delivery was validated in an in vivo study on mice using intravital two-photon laser scanning microscopy. HA derivatives were modified with a biocompatible oligo(ethylene glycol)-based thermoresponsive polymer to form nanogels. These HA conjugates were readily prepared by varying the molar mass of initial HA and the degree of substitution via radical-mediated thiol-ene chemistry in aqueous solution. The derivatives were shown to self-assemble into spherical gel particles with diameters ranging from 150 to 214 nm above 37 °C. A poorly water-soluble two-photon dye was successfully loaded into the nanogels during this self-assembly process. In vitro cellular uptake tests using a RAW 264.7 murine macrophage cell line showed successful intracellular delivery of the hydrophobic dye. After intravenous injection in mice, the nanogels circulated freely in the blood but were rapidly phagocytized within 13 min by circulating macrophages and stored in the liver and spleen, as observed by two-photon microscopy. Benefit can be thus expected in using such a delivery system for the liver and spleen macrophage-associated diseases. PMID:25110287

  12. Mechanisms of Drug Toxicity and Relevance to Pharmaceutical Development

    PubMed Central

    Guengerich, F. Peter

    2016-01-01

    Toxicity has been estimated to be responsible for the attrition of ~ 1/3 of drug candidates and is a major contributor to the high cost of drug development, particularly when not recognized until late in the clinical trials or post-marketing. The causes of drug toxicity can be organized in several ways and include mechanism-based (on-target) toxicity, immune hypersensitivity, off-target toxicity, and bioactivation/covalent modification. In addition, idiosyncratic responses are rare but one of the most problematic issues; several hypotheses for these have been advanced. Although covalent binding of drugs to proteins was described almost 40 years ago, the significance to toxicity has been difficult to establish; recent literature in this field is considered. The development of more useful biomarkers and short-term assays for rapid screening of drug toxicity early in the drug discovery/development process is a major goal, and some progress has been made using “omics” approaches. PMID:20978361

  13. Mechanisms of drug toxicity and relevance to pharmaceutical development.

    PubMed

    Guengerich, F Peter

    2011-01-01

    Toxicity has been estimated to be responsible for the attrition of approximately one-third of drug candidates and is a major contributor to the high cost of drug development, particularly when not recognized until late in clinical trials or post-marketing. The causes of drug toxicity can be classified in several ways and include mechanism-based (on-target) toxicity, immune hypersensitivity, off-target toxicity, and bioactivation/covalent modification. In addition, idiosyncratic responses are rare but can be one of the most problematic issues; several hypotheses for these have been advanced. Although covalent binding of drugs to proteins was described almost 40 years ago, the significance to toxicity has been difficult to establish; recent literature in this field is considered. The development of more useful biomarkers and short-term assays for rapid screening of drug toxicity early in the drug discovery/development process is a major goal, and some progress has been made using "omics" approaches. PMID:20978361

  14. The effect of carrier surface treatment on drug particle detachment from crystalline carriers in adhesive mixtures for inhalation.

    PubMed

    Dickhoff, B H J; de Boer, A H; Lambregts, D; Frijlink, H W

    2006-12-11

    In this study, the effect of lactose carrier surface treatment on drug particle detachment during inhalation has been investigated. Crystals of marketed brands of alpha lactose monohydrate brands normally exhibit a certain surface rugosity and contain natural fines and impurities on their surface, which influence the drug-to-carrier interaction in adhesive mixtures for inhalation. Submersion treatment may change these surface characteristics. Two different sieve fractions (63-90 and 250-355microm) were submerged in mixtures of ethanol and water (96 and 80% v/v, respectively). Microscopic observation and laser diffraction analysis revealed that neither the shape nor the size of the carrier particles was changed by the submersion treatment. However, the specific surface area and the amount of impurities appeared to decrease substantially after submersion, and the magnitude of the decrease was different for the different ethanol-water mixtures. The reduction in specific surface area was attributed particularly to the removal of the adhering lactose fines from the carrier surface. Mixtures with budesonide (in a wide range of carrier payloads) were prepared before and after treatment. Drug particle detachment from the various mixtures was studied with a sieve test and with a cascade impactor analysis at 30 and 60l/min. Two different types of inhalers were used, one generating lift- and drag-forces (ISF inhaler) and one generating inertial forces (test inhaler), respectively. The cascade impactor and sieve test experiments showed that an increase in carrier surface smoothness results in a reduced drug particle detachment during inhalation, which was independent of the type of inhaler used. This reduction could be attributed to the removal of the adhering lactose fines which may provide shelter for the drug particles from press-on forces during mixing. PMID:16920287

  15. Drug and drug-related supply promotion by pharmaceutical company representatives at VA facilities. Final rule.

    PubMed

    2012-03-01

    This final rule amends the Department of Veterans Affairs (VA) regulations regarding access to VA facilities by pharmaceutical company representatives. The purposes of the rule are to reduce or eliminate any potential for disruption in the patient care environment, manage activities and promotions at VA facilities, and provide pharmaceutical company representatives with a consistent standard of permissible business practice at VA facilities. The amendments will facilitate mutually beneficial relationships between VA and pharmaceutical company representatives. PMID:22420057

  16. General public knowledge, perceptions and practice towards pharmaceutical drug advertisements in the Western region of KSA.

    PubMed

    Al-Haddad, Mahmoud S; Hamam, Fayez; Al-Shakhshir, Sami M

    2014-04-01

    This study aims to examine general public knowledge and behavior toward pharmaceutical advertisements in the Western part of KSA. A cross sectional convenience sampling technique was used in this study. A total of 1445 valid questionnaires were received and analyzed using SPSS version 16 at alpha value of 0.05. Majority of respondents were aware of different types of drugs to be advertised and drug advertisements should seek approval from the health authorities. Television and Internet showed the highest effect on consumers. Almost half of the participants preferred an advertised drug over non-advertised one. Most of the respondents indicated that the quality of frequently advertised drugs is not better than those prescribed by the doctors. Majority of participants had positive beliefs toward advertised drugs concerning their role in education and spreading of awareness among the public. Pharmaceutical advertisements harm the doctor-patient relationship as evidenced by one-third of the investigated sample. Moreover, majority of the participants mentioned that they would consult another doctor or even change the current doctor if he/she refused to prescribe an advertised medication. Results of this study could be used to develop awareness programs for the general public and try to enforce the regulations and policies to protect the general public and patients from the business oriented pharmaceutical companies and drug suppliers. PMID:24648823

  17. Develop a novel superparamagnetic nano-carrier for drug delivery to brain glioma.

    PubMed

    Zhao, Ming; Li, Anmin; Chang, Jin; Fu, Xiangping; Zhang, Zhiwen; Yan, Runmin; Wang, Hanjie; Liang, Shuli

    2013-01-01

    Magnetic drug carrier has been employed in drug delivery for over 30 years. Modern nanotechnology has improved its efficiency dramatically by decreasing its diameter into nano-scale. It may help chemotherapeutic agents penetrate BBB and raise local drug concentration in brain, which is the ideal model for glioma treatment. In our study, magnetic carrier was fabricated with octadecyl quaternized caroxymethyl chitosan (OQCMC), hydrophobic Fe₃O₄ ferrofluid and cholesterol, which showed a uniform diameter of 20 nm under transmission electronic microscopy and superparamagnetic character in vibration sample magnetical measurement system. To investigate the efficacy of drug delivery, paclitaxel was used as loaded drug and analyzed by the HPLC. Results showed that magnetic carrier released drugs for more than 20 d in vitro and maintain the drug concentration above 0.4 μg/g for 16 h in rat brain after magnetic targeting. Drug concentration increased by 1-3 folds when delivered by carrier without magnetic targeting, and by 3-15 folds after magnetic targeting. Cellular study revealed that the magnetic carrier was clearly localized in the targeted cortex neural cells and U251-MG cell lines. These results showed that this magnetic carrier is capable of maintaining high drug concentration in magnetically targeted area and carrying drugs or genes into cells, which is potentially promising for local chemotherapy to brain tumors. PMID:23701032

  18. Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers.

    PubMed

    Penkina, Anna; Semjonov, Kristian; Hakola, Maija; Vuorinen, Sirpa; Repo, Timo; Yliruusi, Jouko; Aruväli, Jaan; Kogermann, Karin; Veski, Peep; Heinämäki, Jyrki

    2016-03-01

    Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used. PMID:26065533

  19. Collaborative drug therapy management and its application to pharmaceutical compounding.

    PubMed

    Anderson, Derick

    2007-01-01

    Patient care within the US healthcare system is changing constantly, as are the roles of healthcare practitioners, including pharmacists. For over 30 years, pharmacists have promoted the concept of clinical pharmacy, which places pharmacists in a central role in patient medication management. The goal is to allow the pharmacist to become a vital part of treatment planning by individualizing patients' therapeutic regimens. The Collaborative Drug Therapy Management agreement is a step toward that goal. The combination of drug therapy management and compounding pharmacy can be powerful in meeting patients' specific needs. PMID:23974486

  20. Tamoxifen nanostructured lipid carriers: enhanced in vivo antitumor efficacy with reduced adverse drug effects.

    PubMed

    Shete, Harshad K; Selkar, Nilakash; Vanage, Geeta R; Patravale, Vandana B

    2014-07-01

    A novel approach of enhancing the Tamoxifen uptake via Intestinal Lymphatic System is executed by developing long chain lipid and oil based nanostructured lipid carrier system (Tmx-NLC). The aim was to achieve improved systemic bioavailability of Tamoxifen, prevent systemic and hepatotoxicity and enhance antitumor efficacy. Following the proof of concept achieved in cell culture experiments and in vivo pharmacokinetic and biodistribution study, the current work focuses on investigation of antitumor efficacy and treatment associated toxicity in murine mammary tumor mice model. The efficacy study demonstrated greater tumor suppression and 100% survival with 1.5 and 3 mg/kg Tmx-NLC compared to 3 mg/kg Tamoxifen suspension and Mamofen(®) (Khandelwal Pharmaceuticals, Mumbai, India). Tmx-NLC treatment for a month demonstrated improved systemic toxicity profile and no evidences of hepatotoxicity. Thus, developed Tmx-NLC could prove to be a promising delivery strategy to confer superior therapeutic efficacy and ability to address the biopharmaceutical and toxicity associated issues of drug. PMID:24704438

  1. Physicochemical properties of structured phosphatidylcholine in drug carrier lipid emulsions for drug delivery systems.

    PubMed

    Kawaguchi, Emi; Shimokawa, Ken-ichi; Ishii, Fumiyoshi

    2008-03-15

    Drug carrier emulsions were prepared with structured phosphatidylcholine (PC-LM) which has both a long hydrocarbon chain and a medium hydrocarbon chain, and the characteristics of PC-LM as an emulsifier were investigated by measuring the creaming ratio, the surface tension of the emulsion system, and the mean particle size and zeta potential of the oil droplets in emulsions. The emulsion prepared with PC-LM as an emulsifier kept the condition and the ratio of separation was lower than those with purified egg yolk lecithin (PEL). The mean particle size of the emulsion prepared with PC-LM was smaller than that with PEL when using only sonication, approximately 250 nm. When using a high-pressure homogenizer after sonication, the mean emulsion size with PC-LM was also smaller than with PEL, approximately 150 nm. The surface tension of the various emulsions and the zeta potential of the emulsion droplets were measured to investigate the stability of the systems. In emulsions with PC-LM or PEL, the surface tension as an index of stability increased as the pressure of the homogenizer increased. Moreover, the zeta potential of the emulsion droplets prepared with PC-LM also increased with an increase in pressure of the homogenizer. As a result, it was found that the drug carrier emulsion prepared with PC-LM had significant advantages in terms of stability and mean diameter. We considered it could be used for the preparations of nanoparticle dispersion systems in drug delivery systems. PMID:17988839

  2. Muco-inert nanoparticle probes and drug carriers

    NASA Astrophysics Data System (ADS)

    Wang, Ying-Ying

    2011-12-01

    Mucus coats the exposed surfaces of the eyes and respiratory, gastrointestinal (GI) and cervicovaginal (CV) tracts, and protects mucosal tissues against pathogens and other foreign particulates. Most foreign particles are effectively trapped in mucus through steric and adhesive interactions, and are rapidly eliminated by different mucus clearance mechanisms. Nevertheless, mucus also immobilizes conventional drug and gene carriers, thereby precluding sustained and targeted drug delivery to mucosal sites. Synthetic particles engineered with muco-inert surfaces, and some viruses, can readily penetrate mucus gel, and may serve as useful probes to understand the biophysical barrier properties of mucus. Improved understanding of the mucus barrier could provide insights into methods to enhance drug and gene delivery at mucosal surfaces, as well as understanding the occasional failure of mucus to protect against infection or injury. Recently, muco-inert nanoparticles were developed by conjugating a dense layer of low MW polyethylene glycol to particle surfaces. Since they are slowed only by steric obstruction from the mucus mesh, various sized muco-inert nanoparticles can be used to probe the microstructure and microrheology of mucus. I applied this technique to determine whether the mucus barrier may be altered by exogenous factors, including the presence of detergent, pH changes and synthetic nanoparticles. I first studied the microrheology of native human cervicovaginal mucus (CVM), and found that CVM behaves as a viscoelastic solid at length scales ≥ 1 microm (preventing large particles from diffusing through) but as a viscoelastic liquid at length scales up to at least 500 nm (allowing smaller particles to diffuse through low viscosity fluid-filled pores). Treating CVM with a nonionic detergent, N9, shifted the viscoelastic liquid-solid transition point to < 200 nm, suggesting hydrophobic interactions between mucin fibers play an important role in regulating the

  3. [Rapid Delivery of Pharmaceutical Drugs in Home Medical Care].

    PubMed

    Kawamata, Michiko; Hirohara, Masayoshi; Kushida, Kazuki

    2015-12-01

    The population of individuals over age 65 has grown in recent years, leading to a revision of the way medical care is provided, including an increased use of home care services, for example. Medicines are delivered to home care patients in accordance with a specific schedule and based on prescriptions written by home care doctors. Although this system functions perfectly well when the patient's condition is stable, a rapidly worsening condition may lead to changes or additions to the list of prescriptions. Moreover, in addition to specialized check-ups by home care doctors, patients may also visit ophthalmologists, orthopedic specialists, or dermatologists on an outpatient basis. In such cases, the provision of drugs often does not follow a regular schedule and may require special delivery to the patients' homes. These types of alterations to medications often happen suddenly and may require drug delivery outside the pharmacies' normal hours of operation, thus imposing a great burden on them. This report aims to describe the realities faced by pharmacies as they attempt to accommodate these sudden demands for drug delivery. PMID:26809401

  4. Amorphous Silica Based Nanomedicine with Safe Carrier Excretion and Enhanced Drug Efficacy

    NASA Astrophysics Data System (ADS)

    Zhang, Silu

    With recent development of nanoscience and nanotechnology, a great amount of efforts have been devoted to nanomedicine development. Among various nanomaterials, silica nanoparticle (NP) is generally accepted as non-toxic, and can provide a versatile platform for drug loading. In addition, the surface of the silica NP is hydrophilic, being favorable for cellular uptake. Therefore, it is considered as one of the most promising candidates to serve as carriers for drugs. The present thesis mainly focuses on the design of silica based nanocarrier-drug systems, aiming at achieving safe nanocarrier excretion from the biological system and enhanced drug efficacy, which two are considered as most important issues in nanomedicine development. To address the safe carrier excretion issue, we have developed a special type of selfdecomposable SiO2-drug composite NPs. By creating a radial concentration gradient of drug in the NP, the drug release occurred simultaneously with the silica carrier decomposition. Such unique characteristic was different from the conventional dense SiO2-drug NP, in which drug was uniformly distributed and can hardly escape the carrier. We found that the controllable release of the drug was primarily determined by diffusion, which was caused by the radial drug concentration gradient in the NP. Escape of the drug molecules then triggered the silica carrier decomposition, which started from the center of the NP and eventually led to its complete fragmentation. The small size of the final carrier fragments enabled their easy excretion via renal systems. Apart from the feature of safe carrier excretion, we also found the controlled release of drugs contribute significantly to the drug efficacy enhancement. By loading an anticancer drug doxorubicin (Dox) to the decomposable SiO 2-methylene blue (MB) NPs, we achieved a self-decomposable SiO 2(MB)-Dox nanomedicine. The gradual escape of drug molecules from NPs and their enabled cytosolic release by optical

  5. Pharmaceutical properties of freeze-dried formulations of egg albumin, several drugs and olive oil.

    PubMed

    Tsuji, Y; Kakegawa, H; Miyataka, H; Nishiki, M; Matsumoto, H; Satoh, T

    1996-04-01

    The freeze-dried ternary formulations of meclizine (MZ, an anti-motion sickness drug), prednisolone (PRED, an anti-inflammatory drug) and norfloxacin (NFLX, an anti-microbial drug) which are poorly water-soluble and are low bioavailability drugs, were prepared using egg albumin and olive oil. The powder X-ray diffractions, the dissolution rate and the bioavailabilities in vivo of these formulations were studied in comparison with each drug alone. By forming ternary formulations of these drugs, the dissolution rates of the drugs from the formulations were significantly improved compared with each drug alone. The results of their powder X-ray diffraction measurements showed that these drugs in the ternary formulations presented in an amorphous form, indicating increased dissolution rates. On the other hand, the plasma concentrations of these drugs increased significantly after oral administration in formulations to rats, except for the NFLX formulation, and the areas under the concentration-time curves (AUC) of the ternary formulations of MZ, PRED and NFLX were 2.1, 1.6 and 1.3 times those of the drugs alone, respectively. From these results, it was proven that formulations consisting of egg albumin, olive oil and poorly water-soluble drugs were useful preparations for improving the drug's disadvantageous pharmaceutical properties. PMID:9132174

  6. Current drug therapy and pharmaceutical challenges for Chagas disease.

    PubMed

    Bermudez, José; Davies, Carolina; Simonazzi, Analía; Real, Juan Pablo; Palma, Santiago

    2016-04-01

    One of the most significant health problems in the American continent in terms of human health, and socioeconomic impact is Chagas disease, caused by the protozoan parasite Trypanosoma cruzi. Infection was originally transmitted by reduviid insects, congenitally from mother to fetus, and by oral ingestion in sylvatic/rural environments, but blood transfusions, organ transplants, laboratory accidents, and sharing of contaminated syringes also contribute to modern day transmission. Likewise, Chagas disease used to be endemic from Northern Mexico to Argentina, but migrations have earned it global. The parasite has a complex life cycle, infecting different species, and invading a variety of cells - including muscle and nerve cells of the heart and gastrointestinal tract - in the mammalian host. Human infection outcome is a potentially fatal cardiomyopathy, and gastrointestinal tract lesions. In absence of a vaccine, vector control and treatment of patients are the only tools to control the disease. Unfortunately, the only drugs now available for Chagas' disease, Nifurtimox and Benznidazole, are relatively toxic for adult patients, and require prolonged administration. Benznidazole is the first choice for Chagas disease treatment due to its lower side effects than Nifurtimox. However, different strategies are being sought to overcome Benznidazole's toxicity including shorter or intermittent administration schedules-either alone or in combination with other drugs. In addition, a long list of compounds has shown trypanocidal activity, ranging from natural products to specially designed molecules, re-purposing drugs commercialized to treat other maladies, and homeopathy. In the present review, we will briefly summarize the upturns of current treatment of Chagas disease, discuss the increment on research and scientific publications about this topic, and give an overview of the state-of-the-art research aiming to produce an alternative medication to treat T. cruzi infection

  7. [Application of personal drug (P-drug) seminar to clinical pharmacy education in the graduate school of pharmaceutical sciences].

    PubMed

    Kawakami, Junichi; Mimura, Yasuhiko; Adachi, Isao; Takeguchi, Noriaki

    2002-10-01

    The P-drug seminar, a novel method of teaching the process of rational pharmacotherapy, was introduced in 2000 into the practice program of the clinical pharmacy course in the Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University (TMPU). The P-drug concept is evidence-based drug selection according to criteria (i.e., efficacy, safety, suitability and cost) deter mined in advance and rational prescribing by each physician. The P-drug seminar originated from educational courses for medical students at the University of Groningen and has been propagated by the WHO Action Programme on Essential Drugs world wide. In the TMPU, the seminar consists of 5 half-days before the start of bedside teaching during clinical pharmacy practice. Each term, 8 graduate students licensed as pharmacists form one seminar group, and 32 students have completed it successfully in the past 2 years. Problem-based learning and self-awareness methods are applied through discussion among students. The same teaching materials as those used in the WHO P-drug workshop and the English textbook Guide to Good Prescribing were adopted. A short lecture on the pharmacist's role in the rational use of drugs was added to modify the original P-drug workshop for medical students since this was considered suitable for graduate students in clinical pharmacy. Our graduate students were able to learn the process of pharmacotherapy by following the steps of P-drug selection and rational treatment under the P-drug concept and also understand the viewpoint of prescribers and pharmacists' roles as medical staff. In conclusion, this is the first report on application of the P-drug method to clinical pharmacy education. PMID:12400163

  8. Integration of active pharmaceutical ingredient solid form selection and particle engineering into drug product design.

    PubMed

    Ticehurst, Martyn David; Marziano, Ivan

    2015-06-01

    This review seeks to offer a broad perspective that encompasses an understanding of the drug product attributes affected by active pharmaceutical ingredient (API) physical properties, their link to solid form selection and the role of particle engineering. While the crucial role of active pharmaceutical ingredient (API) solid form selection is universally acknowledged in the pharmaceutical industry, the value of increasing effort to understanding the link between solid form, API physical properties and drug product formulation and manufacture is now also being recognised. A truly holistic strategy for drug product development should focus on connecting solid form selection, particle engineering and formulation design to both exploit opportunities to access simpler manufacturing operations and prevent failures. Modelling and predictive tools that assist in establishing these links early in product development are discussed. In addition, the potential for differences between the ingoing API physical properties and those in the final product caused by drug product processing is considered. The focus of this review is on oral solid dosage forms and dry powder inhaler products for lung delivery. PMID:25677227

  9. The pharmaceutical economics of child psychiatric drug treatment.

    PubMed

    Schlander, Michael

    2010-01-01

    The last decade, the number of health economic evaluations has increased substantially in the field of child psychiatry. The objective of the present paper is to offer an overview of economic evaluations of child psychiatric drug treatment. Major electronic databases, as well as abstract booklets from international clinical and health economics conferences with an external peer review process, were examined to search for comparative economic evaluations of child and adolescent psychiatric drug treatment. Most studies of pharmacotreatment were cost effectiveness analyses (CEAs) concerned with attention-deficit/hyperactivity disorder (ADHD). Three evaluations were done by or on behalf of agencies as part of ADHD-related health technology assessments. A number of economic studies used patient-level data from specific randomized clinical trials, especially the NIMH-initiated MTA (in childhood ADHD) and TADS (in adolescent major depression) studies. Almost all studies relied on narrow scale symptom scales to assess effects of treatment, even when quality-adjusted life years (QALYs) were reported. In many cases, effectiveness data came from short-term studies, and extrapolation to a one-year time horizon was usually based on assumptions. Even those evaluations attempting to address longer time horizons by way of modeling did not include the impact of treatment on long-term sequelae of the conditions studied, mainly due to a paucity of robust clinical data. Nevertheless, currently available health economic evaluations broadly suggest an acceptable to attractive cost effectiveness of medication management of ADHD, whereas there is no such evidence for child psychiatric disorders other than ADHD. PMID:20513230

  10. Nanoscale covalent organic frameworks as smart carriers for drug delivery.

    PubMed

    Bai, Linyi; Phua, Soo Zeng Fiona; Lim, Wei Qi; Jana, Avijit; Luo, Zhong; Tham, Huijun Phoebe; Zhao, Lingzhi; Gao, Qiang; Zhao, Yanli

    2016-03-18

    Two porous covalent organic frameworks (COFs) with good biocompatibility were employed as drug nanocarriers, where three different drugs were loaded for subsequent drug release in vitro. The present work demonstrates that COFs are applicable in drug delivery for therapeutic applications. PMID:26877025

  11. Investigation of pharmaceutical drugs and caffeine-containing foods using Fourier and terahertz time-domain spectroscopy

    NASA Astrophysics Data System (ADS)

    KaraliÅ«nas, Mindaugas; Venckevičius, Rimvydas; Kašalynas, Irmantas; Puc, Uroš; Abina, Andreja; Jeglič, Anton; Zidanšek, Aleksander; Valušis, Gintaras

    2015-08-01

    Several pharmaceutical drugs, such as alprazolam, ibuprofen, acetaminophen, activated carbon and others, and caffeine-containing foods were tested using terahertz (THz) time domain spectroscopy in the range from 0.3 to 2 THz. The dry powder of pharmaceutical drugs was mixed with HDPE and pressed into the pellets using hydraulic press. The coffee grounds were also pressed into the pellets after ball-milling and mixing with HDPE. The caffeine containing liquid foods were dried out on the paper strips of various stacking. Experiments allow one to determine characteristic spectral signatures of the investigated substances within THz range caused by active pharmaceutical ingredients, like in the case of caffeine, as well as supporting pharmaceutical ingredients. Spectroscopic THz imaging approach is considered as a possible option to identify packaged pharmaceutical drugs. The caffeine spectral features in the tested caffeine containing foods are difficult to observed due to the low caffeine concentration and complex caffeine chemical surrounding.

  12. Recent Techniques and Patents on Solid Lipid Nanoparticles as Novel Carrier for Drug Delivery.

    PubMed

    Khatak, Sunil; Dureja, Harish

    2015-01-01

    The various approaches have been utilized in the treatment of a variety of diseases by applying drug delivery system such as polymeric nanoparticles, self-emulsifying delivery systems, liposomes, microemulsions and micellar solutions. Recently, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and lipid-drug conjugates (LDCs) have been exploited as a carrier of lipophilic and hydrophilic/amphiphilic substances for invasive and non-invasive routes of delivery. SLNs are colloidal drug carrier system and are like nanoemulsion, however, the lipid content in SLNs is solid in nature. These novel type of lipid nanoparticles with solid matrix offers to develop new prototype therapeutics in drug delivery, which could be used for controlled release, drug targeting, gene therapy, physical and chemical stability and site-specific drug delivery and thereby attracted the research groups worldwide. This manuscript overviews the recent patents, advantages, formulation techniques, stability aspects and applications of SLNs. PMID:27009132

  13. Contribution of Tumoral and Host Solute Carriers to Clinical Drug Response

    PubMed Central

    Sprowl, Jason A; Mikkelsen, Torben S; Giovinazzo, Hugh; Sparreboom, Alex

    2012-01-01

    Members of the solute carrier family of transporters are responsible for the cellular uptake of a broad range of endogenous compounds and xenobiotics in multiple tissues. Several of these solute carriers are known to be expressed in cancer cells or cancer cell lines, and decreased cellular uptake of drugs potentially contributes to the development of resistance. As result, the expression levels of these proteins in humans have important consequences for an individual’s susceptibility to certain drug-induced side effects, interactions, and treatment efficacy. In this review article, we provide an update of this rapidly emerging field, with specific emphasis on the direct contribution of solute carriers to anticancer drug uptake in tumors, the role of these carriers in regulation of anticancer drug disposition, and recent advances in attempts to evaluate these proteins as therapeutic targets. PMID:22459901

  14. The efficient use of pharmaceuticals: does Europe have any lessons for a Medicare drug benefit?

    PubMed

    Towse, Adrian

    2003-01-01

    Managing drug use in a way that maximizes the value obtained from total health care spending faces obstacles; hence, payers and policymakers tend to look at pharmaceutical expenditures in isolation from the rest of health care spending. Currently there are both regulatory and putative market-based approaches to containing pharmaceutical spending worldwide. But evidence suggests that regulatory efforts in Europe and elsewhere have not proved effective in containing costs or improving efficiency or access, and supposedly market-based solutions now in vogue, such as reference pricing, pose their own set of challenges and may in practice violate market principles. In the end, silo-based budgeting is short-sighted; the emphasis in Europe and in the United States should be on measures that achieve efficient health care rather than the containment of drug spending. PMID:12757270

  15. Vesicles: a recently developed novel carrier for enhanced topical drug delivery.

    PubMed

    Akhtar, Nida

    2014-01-01

    As skin is one of the crucial and important organs of the human body, delivering the drug across it requires an effective development in the field of research. Topical drug delivery system is specifically designed with the objective to accomplish the delivery of therapeutically active drugs across the skin. Though skin is considered to be a multifunctional organ of a human body, it has the limitation of lesser permeability across the stratum corneum. As this layer constitutes an effective barrier for the drugs, various carrier systems have been developed to overcome this barrier. Vesicular carriers are one of the recently invented carriers. Liposomes, niosomes, transferosomes and ethosomes constitute the major part of these vesicles that have been sufficiently employed for the treatment of variety of topical skin diseases. In the past few years various research reports on the development of topical carrier systems showed that these carriers have emerged as a novel vesicular carrier. These are considered to be effective enough for the enhanced and safe delivery of both hydrophilic and lipophilic drugs. The present review focuses on the topical delivery via these vesicles, emphasizing on various aspects of all these carriers. PMID:24533724

  16. 77 FR 24723 - AstraZeneca Pharmaceuticals LP; Withdrawal of Approval of a New Drug Application for IRESSA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration AstraZeneca Pharmaceuticals LP; Withdrawal of Approval of a... IRESSA (gefitinib) Tablets held by AstraZeneca Pharmaceuticals LP (AstraZeneca), 1800 Concord Pike,...

  17. The role of degradant profiling in active pharmaceutical ingredients and drug products.

    PubMed

    Alsante, Karen M; Ando, Akemi; Brown, Roland; Ensing, Janice; Hatajik, Todd D; Kong, Wei; Tsuda, Yoshiko

    2007-01-10

    Forced degradation studies are used to facilitate the development of analytical methodology, to gain a better understanding of active pharmaceutical ingredient (API) and drug product (DP) stability, and to provide information about degradation pathways and degradation products. In order to fulfill development and regulatory needs, this publication provides a roadmap for when and how to perform studies, helpful tools in designing rugged scientific studies, and guidance on how to record and communicate results. PMID:17187892

  18. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges.

    PubMed

    Ha, Dinh; Yang, Ningning; Nadithe, Venkatareddy

    2016-07-01

    Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body׳s own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed. PMID:27471669

  19. Muco-inert nanoparticle probes and drug carriers

    NASA Astrophysics Data System (ADS)

    Wang, Ying-Ying

    2011-12-01

    Mucus coats the exposed surfaces of the eyes and respiratory, gastrointestinal (GI) and cervicovaginal (CV) tracts, and protects mucosal tissues against pathogens and other foreign particulates. Most foreign particles are effectively trapped in mucus through steric and adhesive interactions, and are rapidly eliminated by different mucus clearance mechanisms. Nevertheless, mucus also immobilizes conventional drug and gene carriers, thereby precluding sustained and targeted drug delivery to mucosal sites. Synthetic particles engineered with muco-inert surfaces, and some viruses, can readily penetrate mucus gel, and may serve as useful probes to understand the biophysical barrier properties of mucus. Improved understanding of the mucus barrier could provide insights into methods to enhance drug and gene delivery at mucosal surfaces, as well as understanding the occasional failure of mucus to protect against infection or injury. Recently, muco-inert nanoparticles were developed by conjugating a dense layer of low MW polyethylene glycol to particle surfaces. Since they are slowed only by steric obstruction from the mucus mesh, various sized muco-inert nanoparticles can be used to probe the microstructure and microrheology of mucus. I applied this technique to determine whether the mucus barrier may be altered by exogenous factors, including the presence of detergent, pH changes and synthetic nanoparticles. I first studied the microrheology of native human cervicovaginal mucus (CVM), and found that CVM behaves as a viscoelastic solid at length scales ≥ 1 microm (preventing large particles from diffusing through) but as a viscoelastic liquid at length scales up to at least 500 nm (allowing smaller particles to diffuse through low viscosity fluid-filled pores). Treating CVM with a nonionic detergent, N9, shifted the viscoelastic liquid-solid transition point to < 200 nm, suggesting hydrophobic interactions between mucin fibers play an important role in regulating the

  20. A versatile, quantitative analytical method for pharmaceutical relevant lipids in drug delivery systems.

    PubMed

    Jeschek, Dominik; Lhota, Gabriele; Wallner, Jakob; Vorauer-Uhl, Karola

    2016-02-01

    Over the past few years, liposomal formulations as drug carrier systems have markedly advanced in pharmaceutical research and development. Therefore, analytical methods to characterize liposome-based formulations are required. One particular issue in liposome analysis is the imbalance of lipid ratios within the vesicle formulations and the detectability of degradation products such as lysophospholipids and fatty acids caused by hydrolysis, especially in low molar ranges. Here, a highly sensitive and selective reversed-phase high-performance liquid chromatography (rp-HPLC) method is described by the combination of an organic solvent/trifluoroacetic acid (TFA) triggered gradient and the application of an evaporative light scattering detector (ELSD). Gain setting adjustments of the ELSD were applied to obtain an optimal detection profile of the analyzed substances. This optimization provides simultaneous separation and quantification of 16 components, including different phosphatidylcholines, phosphatidylglycerols and their degradation products, as well as cholesterol. Parameters such as limit of detection (LOD) and limit of quantification (LOQ) were determined for each of the components and had ranges from 0.25-1.00mg/mL (LOD) and 0.50-2.50μg/mL (LOQ), respectively. The intra-day precision for all analytes is less than 3% (RSD) and inter-day precision is about 8%. The applicability of the method was verified by analyzing two different liposome formulations consisting of DSPC:DPPC:DSPG:Chol (35:35:20:10) and DSPC:DPPC:DSPG (38:38:24). For degradation studies, both formulations were stored at 4°C and at ambient temperature. Additionally, forced degradation experiments were performed to determine hydrolysis mass balances. A total recovery of 96-102% for phospholipid compounds was found. Analytical data revealed that the sensitivity, selectivity, accuracy, and resolution are appropriate for the detection and quantification of phospholipids and their hydrolysis products

  1. Ionic liquid-in-oil microemulsion as a potential carrier of sparingly soluble drug: characterization and cytotoxicity evaluation.

    PubMed

    Moniruzzaman, Muhammad; Tamura, Miki; Tahara, Yoshiro; Kamiya, Noriho; Goto, Masahiro

    2010-11-15

    Pharmaceutical industries have posed challenges in the topical and transdermal administration of drugs which are poorly soluble or insoluble in water and most of organic solvents. In an approach to overcome this limitation, ionic liquid-in-oil (IL/o) microemulsions (MEs) were employed to increase the solubility of a sparingly soluble drug to enhance its topical and transdermal delivery. The formulation of MEs was composed of a blend of nonionic surfactants, polyoxyethylene sorbitan monooleate (Tween-80) and sorbitan laurate (Span-20), isopropyl myristate (IPM) as an oil phase, and IL [C(1)mim] [(CH(3)O)(2)PO(2)] (dimethylimidazolium dimethylphosphate) as a pseudophase. Among various weight ratios of Tween-80 to Span-20 investigated in the ME systems, the ratio 3:2 showed excellent solubility and skin permeation enhancing effect for acyclovir (ACV) used as a model sparingly soluble drug. The size and size distribution of the ME droplets with and without drug were determined by dynamic light scattering. The permeability study of ACV incorporated in IL droplets as well as other formulations was performed into and across the Yucatan micropig (YMP) porcine skin, and the use of IL/o MEs has been shown to dramatically increase ACV administration. Finally, the cytotoxicity of the new carrier was evaluated in vitro using the reconstructed human epidermal model LabCyte™ EPI-MODEL12. It was found that the cell viability of IL/o MEs containing 4wt% IL was over 80% compared to Dulbecco's Phosphate-Buffered Salines, indicating low cytotoxicity of the carrier. Taken together these results, it can be assumed that IL-assisted nonaqueous ME could serve as a versatile and efficient nanodelivery system for insoluble or sparingly soluble drug molecules that require solubilizing agents for delivery. PMID:20813174

  2. [Rheologic properties of some pharmaceutical excipients in drug forms and cosmetic preparation technology].

    PubMed

    Tsagareishvili, G V; Bashura, A A; Alekseeva, M A; Bashura, G S

    2012-06-01

    The establishment of mechanisms and principles of the formation of deformation (fracture) of spatial structure of bentonite solutions and various solutions and disperse systems is one or the most important problems of modern pharmaceutical technology. The article presents the results of a long-term research of influence of high-molecular compounds and surfactants on the properties of designed dosage drug forms and cosmetic preparation. Research data, as the basis for drug combinations "gel" with dekamitoksin, extract Aesculus hippocastanum L and probiotics. PMID:22859452

  3. Cardiovascular Drug Discovery: A Perspective from a Research-Based Pharmaceutical Company

    PubMed Central

    Gromo, G.; Mann, J.; Fitzgerald, J.D.

    2014-01-01

    The theme of this review is to summarize the evolving processes in cardiovascular drug discovery and development within a large pharmaceutical company. Emphasis is placed on the contrast between the academic and industrial research operating environments, which can influence the effectiveness of research collaboration between the two constituencies, but which plays such an important role in drug innovation. The strategic challenges that research directors face are also emphasized. The need for improved therapy in many cardiovascular indications remains high, but the feasibility in making progress, despite the advances in molecular biology and genomics, is also assessed. PMID:24890831

  4. Adequacy of pharmacological information provided in pharmaceutical drug advertisements in African medical journals

    PubMed Central

    Oshikoya, Kazeem A.; Senbanjo, Idowu O.; Soipe, Ayo

    2008-01-01

    Pharmaceutical advertisement of drugs is a means of advocating drug use and their selling but not a substitute for drug formulary to guide physicians in safe prescribing. Objectives: To evaluate drug advertisements in Nigerian and other African medical journals for their adequacy of pharmacological information. Methods: Twenty four issues from each of West African Journal of Medicine (WAJM), East African Medical Journal (EAMJ), South African Medical Journal (SAMJ), Nigerian Medical Practitioner (NMP), Nigerian Quarterly Journal of Hospital Medicine (NQJHM) and Nigerian Postgraduate Medical Journal (NPMJ) were reviewed. While EAMJ, SAMJ and NMP are published monthly, the WAJM, NQJHM and NPMJ are published quarterly. The monthly journals were reviewed between January 2005 and December 2006, and the quarterly journals between January 2001 and December 2006. The drug information with regards to brand/non-proprietary name, pharmacological data, clinical information, pharmaceutical information and legal aspects was evaluated as per World Health Organisation (WHO) criteria. Counts in all categories were collated for each advertiser. Results: Forty one pharmaceutical companies made 192 advertisements. 112 (58.3%) of these advertisements were made in the African medical journals. Pfizer (20.3%) and Swipha (12.5%) topped the list of the advertising companies. Four (2.1%) adverts mentioned generic names only, 157 (81.8%) mentioned clinical indications. Adults and children dosage (39.6%), use in special situations such as pregnancy and renal or liver problems (36.5%), adverse effects (30.2%), average duration of treatment (26.0%), and potential for interaction with other drugs (18.7%) were less discussed. Pharmaceutical information such as available dosage forms and product and package information {summary of the generic and proprietary names, the formulation strength, active ingredient, route of administration, batch number, manufactured and expiry dates, and the manufacturer

  5. [Access to drugs and the situation of the pharmaceutical market in Ecuador].

    PubMed

    Ortiz-Prado, Esteban; Galarza, Claudio; León, Fernando Cornejo; Ponce, Jorge

    2014-07-01

    In the area of public health, it is fundamental to understand the structure and dynamics of the Ecuadorian pharmaceutical market, its segmentation between the public and private sectors, and its relationship with supply and demand, both for generic and brand-name drugs. To achieve this, an observational descriptive study was conducted with information obtained from the available scientific, institutional, technical-administrative, and economic databases. Furthermore, the scientific information concerning the Ecuadorian and regional pharmaceutical market was reviewed through the PubMed and Ovid search engines. In Ecuador, 69.6% of dispensed drugs are brand-name and 30.4% are generics. Of all registered drugs in the country, 1,829 (13.6%) are considered over-the-counter and 11,622 (86.4%) are for sale under medical prescription. In terms of sales, 93.15% correspond to brand-name drugs and only 6.85% to generics. Ninety percent of the pharmacies are located in urban areas and only 10% in rural areas. In the last five years, prices have increased by 12.5% for brand-name drugs and 0.86% for generics. Brand-name drugs are dispensed and consumed 2.3 times more than generics. The majority of pharmacies are located in urban areas, showing that there is a relationship between purchasing power and access to drugs. Although the regulatory authority stipulates that 13% of drugs should be over-the-counter, approximately 60% of the population acquires drugs without a medical prescription. PMID:25211679

  6. Polymeric micelles and nanoemulsions as drug carriers: Therapeutic efficacy, toxicity, and drug resistance.

    PubMed

    Gupta, Roohi; Shea, Jill; Scafe, Courtney; Shurlygina, Anna; Rapoport, Natalya

    2015-08-28

    is in contrast to the treatment with PEG-PLLA micelles or nanoemulsions where all resolved tumors quickly recurred after the completion of treatment and proved resistant to the repeated treatment. The prevention of drug resistance in tumors treated with PEG-PDLA stabilized formulations was attributed to the presence and preventive effect of copolymer unimers that were in equilibrium with PEG-PDLA micelles. PEG-PDLA stabilized nanoemulsions manifested lower hematological toxicity than corresponding micelles suggesting higher drug retention in circulation. Summarizing, micelles with elastic cores appear preferable to those with solid cores as drug carriers. Micelles with elastic cores and corresponding nanoemulsions both manifest high therapeutic efficacy, with nanoemulsions exerting lower systemic toxicity than micelles. The presence of a small fraction of micelles with elastic cores in nanoemulsion formulations is desirable for prevention of the development of drug resistance. PMID:26091919

  7. Desperately seeking cancer drugs: explaining the emergence and outcomes of accelerated pharmaceutical regulation.

    PubMed

    Davis, Courtney; Abraham, John

    2011-07-01

    Government regulators have increasingly accelerated new cancer drugs on to the market by granting them approval based on less clinical data supporting drug efficacy than permitted under standard regulations. With more lenient regulatory standards, pharmaceutical companies have keenly sought to develop cancer drugs. Focusing on the US, this article examines how the emergence and implementation of such accelerated approvals should be understood, particularly in relation to corporate bias and disease-politics theories. Drawing on longitudinal and case study data analysis, it is argued that the emergence of accelerated approval regulations for cancer drugs should be regarded primarily as part of a deregulatory regime driven by the interests of the pharmaceutical industry in partnership with all major aspects of the state, rather than as a response to patient activism in the aftermath of AIDS. Furthermore, even in cases when some patients successfully demand accelerated marketing approval of cancer drugs, such approval by regulators, while in manufacturers' interests, may not be in the interests of patients' health because the political culture of the regulatory agency is reluctant to uphold its own techno-regulatory standards of public-health protection when that would challenge the agenda-setting influence of manufacturers, including industry collaborations with patients and the medical profession. PMID:21314687

  8. Magnetic Nanoparticle Drug Carriers and their Study by Quadrupole Magnetic Field-Flow Fractionation

    PubMed Central

    Williams, P. Stephen; Carpino, Francesca; Zborowski, Maciej

    2009-01-01

    Magnetic nanoparticle drug carriers continue to attract considerable interest for drug targeting in the treatment of cancers and other pathological conditions. The efficient delivery of therapeutic levels of drug to a target site while limiting nonspecific, systemic toxicity requires optimization of the drug delivery materials, the applied magnetic field, and the treatment protocol. The history and current state of magnetic drug targeting is reviewed. While initial studies involved micron-sized and larger carriers, and work with these microcarriers continues, it is the sub-micron carriers or nanocarriers that are of increasing interest. An aspect of magnetic drug targeting using nanoparticle carriers that has not been considered is then addressed. This aspect involves the variation in the magnetic properties of the nanocarriers. Quadrupole magnetic field-flow fractionation (QMgFFF) is a relatively new technique for characterizing magnetic nanoparticles. It is unique in its capability of determining the distribution in magnetic properties of a nanoparticle sample in suspension. The development and current state of this technique is also reviewed. Magnetic nanoparticle drug carriers have been found by QMgFFF analysis to be highly polydisperse in their magnetic properties, and the strength of response of the particles to magnetic field gradients is predicted to vary by orders of magnitude. It is expected that the least magnetic fraction of a formulation will contribute the most to systemic toxicity, and the depletion of this fraction will result in a more effective drug carrying material. A material that has a reduced systemic toxicity will allow higher doses of cytotoxic drugs to be delivered to the tumor with reduced side effects. Preliminary experiments involving a novel method of refining a magnetic nanoparticle drug carrier to achieve this result are described. QMgFFF is used to characterize the refined and unrefined material. PMID:19591456

  9. Particle Shape: A New Design Parameter for Micro- and Nanoscale Drug Delivery Carriers

    PubMed Central

    Champion, Julie A.; Katare, Yogesh K.; Mitragotri, Samir

    2014-01-01

    Encapsulation of therapeutic agents in polymer particles has been successfully used in the development of new drug carriers. A number of design parameters that govern the functional behavior of carriers, including the choice of polymer, particle size and surface chemistry, have been tuned to optimize their performance in vivo. However, particle shape, which may also have a strong impact on carrier performance, has not been investigated. This is perhaps due to the limited availability of techniques to produce non-spherical polymer particles. In recent years, a number of reports have emerged to directly address this bottleneck and initial studies have indeed confirmed that particle shape can significantly impact the performance of polymer drug carriers. This article provides a review of this field with respect to methods of particle preparation and the role of particle shape in drug delivery. PMID:17544538

  10. 78 FR 3900 - Generic Drug User Fee-Active Pharmaceutical Ingredient and Finished Dosage Form Facility Fee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-17

    ...The Food and Drug Administration (FDA) is announcing the rate for the generic drug active pharmaceutical ingredient (API) and finished dosage form (FDF) facilities user fees for fiscal year (FY) 2013. The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Generic Drug User Fee Amendments of 2012 (GDUFA), enacted the Food and Drug Administration Safety and Innovation Act, as......

  11. Bolaamphiphiles: A Pharmaceutical Review

    PubMed Central

    Fariya, Mayur; Jain, Ankitkumar; Dhawan, Vivek; Shah, Sanket; Nagarsenker, Mangal S.

    2014-01-01

    The field of drug discovery is ever growing and excipients play a major role in it. A novel class of amphiphiles has been discussed in the review. The review focuses on natural as well as synthetic bolaamphiphiles, their chemical structures and importantly, their ability to self assemble rendering them of great use to pharmaceutical industry. Recent reports on their ability to be used in fabrication of suitable nanosized carriers for drug as well as genes to target site, has been discussed substantially to understand the potential of bolaamphiphiles in field of drug delivery. PMID:25671179

  12. Luminescent, mesoporous, and bioactive europium-doped calcium silicate (MCS: Eu3+) as a drug carrier.

    PubMed

    Fan, Yong; Huang, Shanshan; Jiang, Jinhua; Li, Guogang; Yang, Piaoping; Lian, Hongzhou; Cheng, Ziyong; Lin, Jun

    2011-05-15

    Luminescent, mesoporous, and bioactive europium-doped calcium silicate (MCS: Eu) was successfully synthesized. The obtained MCS: Eu(3+) was performed as a drug delivery carrier to investigate the drug storage/release properties using ibuprofen (IBU) as the model drug. The structural, morphological, textural, and optical properties were well characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), N(2) adsorption/desorption, and photoluminescence (PL) spectra, respectively. The results reveal that the MCS: Eu exhibits the typical ordered characteristics of the mesostructure. This composite shows a sustained release profile with IBU as the model drug. The IBU-loaded samples still present red luminescence of Eu(3+) ((5)D(0)-(7)F(1,2)) under UV irradiation. The emission intensities of Eu(3+) in the drug carrier system vary with the amount of released IBU, making the drug release easily tracked and monitored. The system demonstrates a great potential for drug delivery and disease therapy. PMID:21376337

  13. The Research and Applications of Quantum Dots as Nano-Carriers for Targeted Drug Delivery and Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Zhao, Mei-Xia; Zhu, Bing-Jie

    2016-04-01

    Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields.

  14. The Research and Applications of Quantum Dots as Nano-Carriers for Targeted Drug Delivery and Cancer Therapy.

    PubMed

    Zhao, Mei-Xia; Zhu, Bing-Jie

    2016-12-01

    Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields. PMID:27090658

  15. Illicit and pharmaceutical drug consumption estimated via wastewater analysis. Part A: chemical analysis and drug use estimates.

    PubMed

    Baker, David R; Barron, Leon; Kasprzyk-Hordern, Barbara

    2014-07-15

    This paper presents, for the first time, community-wide estimation of drug and pharmaceuticals consumption in England using wastewater analysis and a large number of compounds. Among groups of compounds studied were: stimulants, hallucinogens and their metabolites, opioids, morphine derivatives, benzodiazepines, antidepressants and others. Obtained results showed the usefulness of wastewater analysis in order to provide estimates of local community drug consumption. It is noticeable that where target compounds could be compared to NHS prescription statistics, good comparisons were apparent between the two sets of data. These compounds include oxycodone, dihydrocodeine, methadone, tramadol, temazepam and diazepam. Whereas, discrepancies were observed for propoxyphene, codeine, dosulepin and venlafaxine (over-estimations in each case except codeine). Potential reasons for discrepancies include: sales of drugs sold without prescription and not included within NHS data, abuse of a drug with the compound trafficked through illegal sources, different consumption patterns in different areas, direct disposal leading to over estimations when using parent compound as the drug target residue and excretion factors not being representative of the local community. It is noticeable that using a metabolite (and not a parent drug) as a biomarker leads to higher certainty of obtained estimates. With regard to illicit drugs, consistent and logical results were reported. Monitoring of these compounds over a one week period highlighted the expected recreational use of many of these drugs (e.g. cocaine and MDMA) and the more consistent use of others (e.g. methadone). PMID:24377678

  16. Chondroitin sulfate functionalized mesostructured silica nanoparticles as biocompatible carriers for drug delivery

    PubMed Central

    Xi, Juqun; Qin, Jin; Fan, Lei

    2012-01-01

    Mesoporous silica nanoparticles (MSNs) have garnered a great deal of attention as potential carriers for therapeutic payloads. Here, we report a pH-responsive drug-carrier based on chondroitin sulfate functionalized mesostructured silica nanoparticles (NMChS-MSNs) ie, the amidation between NMChS macromer and amino group functionalized MSNs. The prepared nanoparticles were characterized using dynamic light scattering, fourier transform infrared spectroscopy and transmission electron microscopy. The resultant NMChS-MSNs were uniform spherical nanoparticles with a mean diameter of approximately 74 nm. Due to the covalent graft of hydrophilic and pH responsive NMChS, the NMChS-MSNs could be well dispersed in aqueous solution, which is favorable to being utilized as drug carriers to construct a pH-responsive controlled drug delivery system. Doxorubicin hydrochloride (DOX), a well-known anticancer drug, could be effectively loaded into the channels of NMChS-MSNs through electrostatic interactions between drug and matrix. The drug release rate of DOX@NMChS-MSNs was pH dependent and increased with the decrease of pH. The in vitro cytotoxicity test indicated that NMChS-MSNs were highly biocompatible and suitable to use as drug carriers. Our results imply that chondroitin sulfate functionalized nanoparticles are promising platforms to construct the pH-responsive controlled drug delivery systems for cancer therapy. PMID:23091377

  17. The synthesis and application of heparin-based smart drug carrier.

    PubMed

    Li, Qingxuan; Gan, Lu; Tao, Hong; Wang, Qian; Ye, Lin; Zhang, Aiying; Feng, Zengguo

    2016-04-20

    Heparin based polymer drug which could self-assemble into sphere micelle in water was firstly prepared by grafting paclitaxel (PTX) into the hydroxyl of heparin via aconitic bond as pH sensitive spacer. Positive charged drug DOX·HCl and cationic folic acid (CFA) can be further loaded into the polymer drug via electrostatic interaction in aqueous solution so as to prepare smart drug carrier. The drug carrier was able to release more PTX and DOX at pH 4.8 than that at pH 7.4, exhibiting pH sensitivity for two drugs. Furthermore, tumor cell cytotoxicity test proved it possessed significant cytotoxicity against tumor cells MDA-MB-231 as well as its active tumor targeting ability resulting from the loading of CFA. Cellular uptake and intracellular distribution were further revealed by confocal laser scanning microscopy (CLSM). In conclusion, this paper not only provided a simple strategy but also indicated heparin is a versatile platform for the design of smart drug carrier. The as-prepared drug carrier also showed promising potential in chemotherapy. PMID:26876853

  18. Canadian policy makers' views on pharmaceutical reimbursement contracts involving confidential discounts from drug manufacturers.

    PubMed

    Morgan, Steven G; Thomson, Paige A; Daw, Jamie R; Friesen, Melissa K

    2013-10-01

    Pharmaceutical policy makers are increasingly negotiating reimbursement contracts that include confidential price terms that may be affected by drug utilization volumes, patterns, or outcomes. Though such contracts may offer a variety of benefits, including the ability to tie payment to the actual performance of a product, they may also create potential policy challenges. Through telephone interviews about this type of contract, we studied the views of officials in nine of ten Canadian provinces. Use of reimbursement contracts involving confidential discounts is new in Canada and ideas about power and equity emerged as cross-cutting themes in our interviews. Though confidential rebates can lower prices and thereby increase coverage of new medicines, several policy makers felt they had little power in the decision to negotiate rebates. Study participants explained that the recent rise in the use of rebates had been driven by manufacturers' pricing tactics and precedent set by other jurisdictions. Several policy makers expressed concerns that confidential rebates could result in inter-jurisdictional inequities in drug pricing and coverage. Policy makers also noted un-insured and under-insured patients must pay inflated "list prices" even if rebates are negotiated by drug plans. The establishment of policies for disciplined negotiations, inter-jurisdictional cooperation, and provision of drug coverage for all citizens are potential solutions to the challenges created by this new pharmaceutical pricing paradigm. PMID:23809914

  19. Improving pharmaceutical innovation by building a more comprehensive database on drug development and use.

    PubMed

    Daniel, Gregory W; Cazé, Alexis; Romine, Morgan H; Audibert, Céline; Leff, Jonathan S; McClellan, Mark B

    2015-02-01

    New drugs and biologics have had a tremendous impact on the treatment of many diseases. However, available measures suggest that pharmaceutical innovation has remained relatively flat, despite substantial growth in research and development spending. We review recent literature on pharmaceutical innovation to identify limitations in measuring and assessing innovation, and we describe the framework and collaborative approach we are using to develop more comprehensive, publicly available metrics for innovation. Our research teams at the Brookings Institution and Deerfield Institute are collaborating with experts from multiple areas of drug development and regulatory review to identify and collect comprehensive data elements related to key development and regulatory characteristics for each new molecular entity approved over the past several decades in the United States and the European Union. Subsequent phases of our effort will add data on downstream product use and patient outcomes and will also include drugs that have failed or been abandoned in development. Such a database will enable researchers to better analyze the drivers of drug innovation, trends in the output of new medicines, and the effect of policy efforts designed to improve innovation. PMID:25646113

  20. Application of DPD in the design of polymeric nano-micelles as drug carriers.

    PubMed

    Ramezani, Mohammad; Shamsara, Jamal

    2016-05-01

    Developing new drug carrier systems are of a great importance in the treatment approach for a wide range of diseases. The simulation techniques can be valuable for decreasing the time and cost of developing novel drug carriers. Among the simulation methods there are a vast number of studies using dissipative particle dynamics (DPD) method for the prediction of different aspects of polymeric nano-micelles for encapsulating drugs. Here, we reviewed the results of the studies employing DPD for the simulation of drug loading and release in different polymeric micelles carriers. In some cases the simulation results were compared with the experimental results by the authors that were demonstrated the reliability of the DPD predictions. PMID:26990730

  1. Carriers

    MedlinePlus

    ... for those known to be at risk for genetic diseases. Reproductive Choices For couples who are carriers, reproductive decisions can be sensitive. A number of options are available, such as adoption, prenatal testing, and pre-implantation genetic diagnosis (PGD). PGD screens ...

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

    PubMed

    Lakkakula, Jaya Raju; Maçedo Krause, Rui Werner

    2014-05-01

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

  3. The politics of access to expensive drugs: INESSS and the innovative pharmaceutical industry.

    PubMed

    Hughes, David

    2012-05-01

    The innovative pharmaceutical industry employs thousands of people in Quebec and so has the ability to exert strong political pressure; the public statements of Sanofi-Aventis concerning the provincial reimbursement of certain expensive drugs are an example. "Maintaining a dynamic biopharmaceutical industry" is one of four main axes of the drug policy of Quebec's ministry of health. However, this role of government should not take precedence over the efficient and equitable management of health resources. We defend the legitimate and responsible choice of the Institut national d'excellence en santé et en services sociaux du Québec (INESSS) to require an acceptable cost-effectiveness ratio from expensive new drugs. PMID:23634161

  4. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    PubMed Central

    Lohcharoenkal, Warangkana; Wang, Liying; Chen, Yi Charlie

    2014-01-01

    Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy. PMID:24772414

  5. Institutional corruption of pharmaceuticals and the myth of safe and effective drugs.

    PubMed

    Light, Donald W; Lexchin, Joel; Darrow, Jonathan J

    2013-01-01

    Over the past 35 years, patients have suffered from a largely hidden epidemic of side effects from drugs that usually have few offsetting benefits. The pharmaceutical industry has corrupted the practice of medicine through its influence over what drugs are developed, how they are tested, and how medical knowledge is created. Since 1906, heavy commercial influence has compromised congressional legislation to protect the public from unsafe drugs. The authorization of user fees in 1992 has turned drug companies into the FDA's prime clients, deepening the regulatory and cultural capture of the agency. Industry has demanded shorter average review times and, with less time to thoroughly review evidence, increased hospitalizations and deaths have resulted. Meeting the needs of the drug companies has taken priority over meeting the needs of patients. Unless this corruption of regulatory intent is reversed, the situation will continue to deteriorate. We offer practical suggestions including: separating the funding of clinical trials from their conduct, analysis, and publication; independent FDA leadership; full public funding for all FDA activities; measures to discourage R&D on drugs with few, if any, new clinical benefits; and the creation of a National Drug Safety Board. PMID:24088149

  6. [Generic drugs: we must cut pharmaceutical spending but undertaking drug quality].

    PubMed

    Carrillo Norte, Juan Antonio; Postigo Mota, Salvador

    2012-02-01

    The World Health Organization and all drug regulatory agencies (DRA) support the commercialization of generic medicines because they control costs and are irreplaceable therapeutic options in countries lacking the innovator product. Generic drugs are widely considered to be cost-efficient substitutes for brand-name medications. They make up about 20% of the total number of prescriptions in Spain, a figure that is still far from the use of generic drugs in USA and other European countries. Despite economical interest in this issue, in this article we review the interest of generic drugs from a pharmacological and clinical perspective that must undertake drug quality to ensure drug efficacy and safety of the patients. A generic drug (generic drugs, short: generics) is defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use". Both the reference drug and the generic drug have to demonstrate previously they are therapeutically equivalent. With the exception of parenteral drugs, two products have demonstrated to be therapeutically equivalent if after administration in the same molar dose, their effects with respect to both efficacy and safety are essentially the same, as determined from bioequivalence studies in terms of comparison of appropriate pharmacokinetic parameters and bioavailability. Parenteral formulations, however, are not required to demonstrate therapeutic equivalence because it may be considered self-evident. Such assumptions have never been challenged, but there are reasons to do so for parenteral antimicrobials. It is interesting to highlight that although brand-name drugs and generic drugs are both approved by DRA and may be interchangeable with respect to their clinical effects, they can differ substantially in their appearance. Consumers of brand-name medications receive identical-appearing batches of pills with

  7. Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

    PubMed

    Tan, Angel; Rao, Shasha; Prestidge, Clive A

    2013-12-01

    The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications. PMID:23775443

  8. A porphyrin-based metal-organic framework as a pH-responsive drug carrier

    NASA Astrophysics Data System (ADS)

    Lin, Wenxin; Hu, Quan; Jiang, Ke; Yang, Yanyu; Yang, Yu; Cui, Yuanjing; Qian, Guodong

    2016-05-01

    A low cytotoxic porphyrin-based metal-organic framework (MOF) PCN-221, which exhibited high PC12 cell viability via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay, was selected as an oral drug carrier. Methotrexate (MTX) was chosen as the model drug molecule which was absorbed into inner pores and channels of MOFs by diffusion. PCN-221 showed high drug loading and sustained release behavior under physiological environment without "burst effect". The controlled pH-responsive release of drugs by PCN-221 revealed its promising application in oral drug delivery.

  9. Determination of 76 pharmaceutical drugs by liquid chromatography-tandem mass spectrometry in slaughterhouse wastewater.

    PubMed

    Shao, Bing; Chen, Dong; Zhang, Jing; Wu, Yongning; Sun, Chengjun

    2009-11-20

    A multi-residue method for the analysis of 76 pharmaceutical agents of nine classes of drugs (tetracyclines, macrolides, fluoroquinolones, beta-agonists, beta-blockers, diuretics, sedatives, sulfonamides and chloramphenicol) in slaughterhouse wastewater and a receiving river is presented. After simultaneous extraction with an Oasis HLB solid-phase extraction (SPE) cartridge and further purification using an amino SPE cartridge, analytes were detected by liquid chromatography-electrospray ionization-tandem mass spectrometry in positive or negative ion mode. Standard addition was used for quantification to overcome unavoidable matrix effects during ESI-MS analysis. Recoveries for most analytes based on matrix-matched calibration in different test matrices were >60%. The method quantification limits of 76 pharmaceuticals were in the range 0.2-30 ng/L. Nineteen compounds of 76 drugs were found in raw and treated slaughterhouse wastewater from four main slaughterhouses in Beijing. Sulfanamides (sulfanilamide, sulfameter), fluoroquenones (ofloxacin, pefloxacin, norfloxacin, ciprofloxacin, enrofloxacin), tetracyclines (tetracycline, oxytetracycline) and macrolides (kitasamycin, tylosin, erythromycin) were most frequently detected, with the highest levels up to approximately 3 microg/L in slaughterhouse wastewater and approximately 1 microg/L in treated wastewater. Illicit drugs for animal feeding such as clenbuterol and diazepam were commonly detected in slaughterhouse wastewater. These analytes were also observed in a river receiving slaughterhouse wastewater, with a highest level of up to 0.2 microg/L. PMID:19825501

  10. Can open-source drug R&D repower pharmaceutical innovation?

    PubMed

    Munos, B

    2010-05-01

    Open-source R&D initiatives are multiplying across biomedical research. Some of them-such as public-private partnerships-have achieved notable success in bringing new drugs to market economically, whereas others reflect the pharmaceutical industry's efforts to retool its R&D model. Is open innovation the answer to the innovation crisis? This Commentary argues that although it may likely be part of the solution, significant cultural, scientific, and regulatory barriers can prevent it from delivering on its promise. PMID:20407458

  11. Apomaghemite as a doxorubicin carrier for anticancer drug delivery.

    PubMed

    Jurado, Rocío; Frączek, Paulina; Droetto, Mélissa; Sánchez, Purificación; Valero, Elsa; Domínguez-Vera, José M; Gálvez, Natividad

    2016-04-01

    Protein cages have well-defined structures and can be chemically and biologically engineered in many ways, making them useful platforms for drug delivery applications. Taking advantage of the unique structure feature of apoferritin, a new theranostic nanocarrier is proposed herein. The apoferritin protein is effective for the encapsulation of maghemite nanoparticles and for loading a significant dose of doxorubicin (DOX) drug. This simultaneous loading of maghemite nanoparticles and DOX has been achieved using either co-encapsulation or surface-binding approaches. Maghemite nanoparticles coated with the protein apoferritin are an effective long-term MRI liver contrast agent and we report here that additionally they can serve as an anticancer drug-delivery system. In particular we show that maghemite-containing apoferritin can sustain the DOX delivery under period of 10 to 25 days depending on the environmental conditions. PMID:26826473

  12. Charge-reversal nanoparticles: novel targeted drug delivery carriers.

    PubMed

    Chen, Xinli; Liu, Lisha; Jiang, Chen

    2016-07-01

    Spurred by significant progress in materials chemistry and drug delivery, charge-reversal nanocarriers are being developed to deliver anticancer formulations in spatial-, temporal- and dosage-controlled approaches. Charge-reversal nanoparticles can release their drug payload in response to specific stimuli that alter the charge on their surface. They can elude clearance from the circulation and be activated by protonation, enzymatic cleavage, or a molecular conformational change. In this review, we discuss the physiological basis for, and recent advances in the design of charge-reversal nanoparticles that are able to control drug biodistribution in response to specific stimuli, endogenous factors (changes in pH, redox gradients, or enzyme concentration) or exogenous factors (light or thermos-stimulation). PMID:27471667

  13. The journey of a drug-carrier in the body: an anatomo-physiological perspective.

    PubMed

    Bertrand, Nicolas; Leroux, Jean-Christophe

    2012-07-20

    Recent advances in chemistry and material sciences have witnessed the emergence of an increasing number of novel and complex nanosized carriers for the delivery of drugs and imaging agents. Nevertheless, this raise in complexity does not necessarily offer more efficient systems. The lack of performance experienced by several colloidal drug carriers during the preclinical and clinical development processes can be explained by inadequate pharmacokinetic/biodistribution profiles and/or unacceptable toxicities. A comprehensive understanding of the body characteristics is necessary to predict and prevent these problems from the early stages of nanomaterial conception. In this manuscript, we review and discuss the anatomical and physiological elements which must be taken into account when designing new carriers for delivery or imaging purposes. This article gives a general overview of the main organs involved in the elimination of nanosized materials and briefly summarizes the knowledge acquired over more than 30 years of research and development in the field of drug targeting. PMID:22001607

  14. Role of transport proteins in drug discovery and development: a pharmaceutical perspective.

    PubMed

    Ayrton, A; Morgan, P

    2008-07-01

    1. This review will explore, from a pharmaceutical industry perspective, the evidence and consequences of transport protein involvement in pharmacokinetic variability and safety of drugs in humans. With the preclinical and clinical evidence available, the transport proteins that are considered to be the most important in respect of pharmacokinetic variability and safety in humans will be highlighted. 2. A large number of transport proteins have been identified, at both the genetic and the cellular level, which have been suggested to play some role in the absorption, distribution or elimination of endogenous, xenobiotic or drug substrates. 3. The weight of evidence suggests that only a small number of transport proteins need to be routinely considered in the drug-discovery setting driven by the magnitude of their impact on tissue distribution, pharmacokinetic variability and drug-drug interactions. 4. For the majority of candidate drugs, an assessment of the role of transporter proteins in their disposition and safety need only be assessed if in vivo properties suggest that active transport is likely to be a significant factor, if transport proteins are implicated in a particular therapeutic target area or if the disposition and safety of a likely co-medication are known to be significantly modulated by transport proteins. PMID:18668427

  15. Preliminary thermoluminescence investigation of commercial pharmaceutical glass containers towards the sterilization dosimetry of liquid drugs.

    PubMed

    Kazakis, Nikolaos A; Tsirliganis, Nestor C; Kitis, George

    2015-11-01

    Drug sterilization with ionizing radiation is a well-established technology, which is constantly extending to several products due to its numerous advantages, since it allows the heat-free sterilization of heat-sensitive pharmaceutical preparations. In a previous study, the possibility to identify irradiated solid-state drugs by means of OSL and TL was examined with very promising findings. In the same respect, the present work aims, for the first time to the authors' best knowledge, to explore whether TL can be employed as a method for post-sterilization dosimetry on commercial liquid-state drugs, by studying the properties of their glass containers. Two different types of glass containers (bottle and ampoule) of two widely used liquid drugs, i.e., Hexalen® and Voltaren®, are used for this purpose. Both glass containers exhibit a linear TL dose response for doses up to 6kGy with a stable behavior through time, while no significant sensitization of the main peaks is observed. Thus, preliminary findings are very promising towards the post-sterilization dosimetry of liquid drugs and the use of the containers of commercial liquid drugs for normal and/or accidental dosimetry. PMID:26296060

  16. Structure and dynamics of drug-carrier systems as studied by parelectric spectroscopy.

    PubMed

    Blaschke, T; Kankate, L; Kramer, K D

    2007-07-10

    In the field of topical application without or with little systemic side-effects to reach anti-inflammatory or anti-androgeneous effects, nanoparticles as carriers for drugs as beta-methason-17-valerate, prednicarbate, prednisolone, RU 58841-myristate or cyproterone acetate have proven to enhance the transdermal delivery. This enhancement is closely connected to the interaction of the drug molecules with the lipid carrier systems, i.e. incorporation into the carriers or attachment to their surfaces. Whereas the techniques to measure the penetration profiles in the cutaneous region of the skin are well established in the case of fluorescence microscopy applied to thin slices of epidermis or being established in the case of multiphoton microscopy to monitor this fluorescence, the methods for the investigation of the type of interaction between drugs and carrier systems are relatively new: in the case of electron spin resonance the sample volumes have to be restricted to capillary sizes to avoid parelectric losses in the microwave cavities, in the case of the novel method of parelectric spectroscopy we are free from such restrictions. The application of the latter method will be presented here in detail concerning the underlying theory, the experimental aspects as well as the algorithms to extract the parameters of interest from the measured samples. As samples we restrict ourselves to solid lipid nanoparticles coated with different surfactants as carriers for drug-, dye- or spin label molecules. PMID:17573146

  17. Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers

    PubMed Central

    Wahajuddin; Arora, Sumit

    2012-01-01

    A targeted drug delivery system is the need of the hour. Guiding magnetic iron oxide nanoparticles with the help of an external magnetic field to its target is the principle behind the development of superparamagnetic iron oxide nanoparticles (SPIONs) as novel drug delivery vehicles. SPIONs are small synthetic γ-Fe2O3 (maghemite) or Fe3O4 (magnetite) particles with a core ranging between 10 nm and 100 nm in diameter. These magnetic particles are coated with certain biocompatible polymers, such as dextran or polyethylene glycol, which provide chemical handles for the conjugation of therapeutic agents and also improve their blood distribution profile. The current research on SPIONs is opening up wide horizons for their use as diagnostic agents in magnetic resonance imaging as well as for drug delivery vehicles. Delivery of anticancer drugs by coupling with functionalized SPIONs to their targeted site is one of the most pursued areas of research in the development of cancer treatment strategies. SPIONs have also demonstrated their efficiency as nonviral gene vectors that facilitate the introduction of plasmids into the nucleus at rates multifold those of routinely available standard technologies. SPION-induced hyperthermia has also been utilized for localized killing of cancerous cells. Despite their potential biomedical application, alteration in gene expression profiles, disturbance in iron homeostasis, oxidative stress, and altered cellular responses are some SPION-related toxicological aspects which require due consideration. This review provides a comprehensive understanding of SPIONs with regard to their method of preparation, their utility as drug delivery vehicles, and some concerns which need to be resolved before they can be moved from bench top to bedside. PMID:22848170

  18. Promote potential applications of nanoparticles as respiratory drug carrier: insights from molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Lin, Xubo; Bai, Tingting; Zuo, Yi Y.; Gu, Ning

    2014-02-01

    Nanoparticles (NPs) show great promises in biomedical applications as the respiratory drug carrier system. Once reaching the alveolar region, NPs first interact with the pulmonary surfactant (PS) film, which serves as the first biological barrier and plays an important role in maintaining the normal respiratory mechanics. Therefore, understanding the interactions between NPs and PS can help promote the NP-based respiratory drug carrier systems. Using coarse-grained molecular dynamics simulations, we studied the effect of rigid spherical NPs with different hydrophobicity and sizes on a dipalmitoylphosphatidylcholine (DPPC) monolayer at the air-water interface. Four different NPs were considered, including hydrophilic and hydrophobic NPs, each with two diameters of 3 nm and 5 nm (the sizes are comparable to that of generation 3 and 5 PAMAM dendrimers, which have been widely used for nanoscale drug carrier systems). Our simulations showed that hydrophilic NPs can readily penetrate into the aqueous phase with little or no disturbance on the DPPC monolayer. However, hydrophobic NPs tend to induce large structural disruptions, thus inhibiting the normal phase transition of the DPPC monolayer upon film compression. Our simulations also showed that this inhibitory effect of hydrophobic NPs can be mitigated through PEGylation. Our results provide useful guidelines for molecular design of NPs as carrier systems for pulmonary drug delivery.Nanoparticles (NPs) show great promises in biomedical applications as the respiratory drug carrier system. Once reaching the alveolar region, NPs first interact with the pulmonary surfactant (PS) film, which serves as the first biological barrier and plays an important role in maintaining the normal respiratory mechanics. Therefore, understanding the interactions between NPs and PS can help promote the NP-based respiratory drug carrier systems. Using coarse-grained molecular dynamics simulations, we studied the effect of rigid spherical NPs

  19. Thiolated graphene oxide as promising mucoadhesive carrier for hydrophobic drugs.

    PubMed

    Pereira de Sousa, Irene; Buttenhauser, Katrin; Suchaoin, Wongsakorn; Partenhauser, Alexandra; Perrone, Mara; Matuszczak, Barbara; Bernkop-Schnürch, Andreas

    2016-07-25

    The aim of this study was to improve the mucoadhesive properties of graphene by conjugating thiol ligands, in order to formulate an oral delivery system for hydrophobic drugs showing long mucus residence time. Graphene oxide was obtained by oxidation of graphite and then was thiolated following two synthetic paths. On the one hand, the hydroxyl groups were conjugated with thiourea passing through the formation of a brominated intermediate. On the other hand, the carboxylic acid groups were conjugated with cysteamine via carbodiimide chemistry. The mucoadhesive properties of thiolated graphene were evaluated by rheological measurements and by residence time assay. Then, valsartan was loaded on thiolated graphene and the release profile was evaluated in simulated intestinal fluid. Following both synthetic paths it was possible to obtain thiolated graphene bearing 215-302μmol SH/g product. Both products induced after 1h incubation an increase of mucus viscosity of about 22-33-fold compared to unmodified graphite. The residence time assay confirmed that 60% of thiolated graphene could be retained on intestinal mucosa after 4h incubation, whereas just 20% of unmodified graphite could be retained. Valsartan could be loaded with a drug loading of about 31±0.3% and a sustained release profile was observed for both formulations. According to the presented data, the thiolation of graphene could improve its mucoadhesive properties. Therefore, thiolated graphene represents a promising platform for oral delivery of hydrophobic drugs, possessing a long residence time on intestinal mucosa which allows the release of the loaded drug close to the adsorptive epithelium. PMID:27246816

  20. The influence of drug loading on formulation structure and aerosol performance in carrier based dry powder inhalers.

    PubMed

    Young, Paul M; Wood, Owen; Ooi, Jesslynn; Traini, Daniela

    2011-09-15

    Previous studies have reported that carrier:drug ratio and carrier size influence the aerosol performance of dry powder inhalation systems. These previous studies were complicated by the heterogeneous nature of the carriers used, making it difficult to define an explicit relationship between parameters and performance. Here, the authors studied the influence of drug loading and carrier size on drug aerosol performance using homogeneous spherical model carriers. Different formulations containing drug (salbutamol sulphate) and carriers (polystyrene beads with median diameters of 82.8μm, 277.5μm and 582.9μm, respectively) were prepared by varying the ratio of carrier to drug (from ∼5:1 to ∼85:1). The surface morphology of the carrier particles and force of adhesion were investigated using atomic force microscopy, while the aerosol performance was evaluated using a multi-stage liquid impinger. The carrier surface morphology for all carrier sizes was homogenous with root-mean square roughness values ≤112nm. No significant difference in the force of adhesion between salbutamol sulphate and the three carrier sizes was observed. Significant differences in aerosol performance of salbutamol sulphate (measured as fine particle dose (FPD) and fraction (FPF)≤5μm) from the carriers were observed. Specifically, as carrier size increased FPF decreased. In comparison, as drug loading increased there was no change in FPF until a critical threshold was exceeded. Such observations suggest that: (A) aerosolisation performance is governed by carrier collisions and (B) when homogeneous carriers are used, the aerosol performance remains constant with respect to drug concentration, until the formulation transitions from an ordered mix to an agglomerated and/or segregated powder bed. PMID:21708238

  1. Rapid screening of pharmaceutical drugs using thermal desorption - SALDI mass spectrometry

    NASA Astrophysics Data System (ADS)

    Grechnikov, A. A.; Kubasov, A. E.; Georgieva, V. B.; Borodkov, A. S.; Nikiforov, S. M.; Simanovsky, Ya O.; Alimpiev, S. S.

    2012-12-01

    A novel approach to the rapid screening of pharmaceutical drugs by surface assisted laser desorption-ionization (SALDI) mass spectrometry with the rotating ball interface coupled with temperature programmed thermal desorption has been developed. Analytes were thermally desorbed and deposited onto the surface of amorphous silicon substrate attached to the rotating ball. The ball was rotated and the deposited analytes were analyzed using SALDI. The effectiveness of coupling SALDI mass spectrometry with thermal desorption was evaluated by the direct and rapid analysis of tablets containing lidocaine, diphenhydramine and propranolol without any sample pretreatment. The overall duration of the screening procedure was 30÷40 sec. Real urine samples were studied for drug analysis. It is shown that with simple preparation steps, urine samples can be quantitatively analyzed using the proposed technique with the detection limits in the range of 0.2÷0.5 ng/ml.

  2. Rapid delivery of drug carriers propelled and navigated by catalytic nanoshuttles.

    PubMed

    Kagan, Daniel; Laocharoensuk, Rawiwan; Zimmerman, Maria; Clawson, Corbin; Balasubramanian, Shankar; Kang, Dae; Bishop, Daniel; Sattayasamitsathit, Sirilak; Zhang, Liangfang; Wang, Joseph

    2010-12-01

    This paper reports the first proof-of-concept of using catalytic nanoshuttles to pick up, transport, and release common drug carriers including biocompatible and biodegradable polymeric particles and liposomes. The rapid transport of a wide size range of drug-loaded particles (100 nm-3.0 μm) with a speed approximately three orders of magnitude faster than that of the particles transported by Brownian motion demonstrates the high propulsion power of the nanoshuttles. The nanoshuttles' navigation ability is illustrated by the transport of the drug carriers through a microchannel from the pick-up to the release microwell. Such ability of nanomotors to rapidly deliver drug-loaded polymeric particles and liposomes to their target destination represents a novel approach towards transporting drug carriers in a target-specific manner. This also potentially addresses the obstacles of current nanoparticle drug delivery, such as off-targeting of particles. While an initial concept of actively transporting therapeutic particles is demonstrated in vitro in this paper, future efforts will focus on practical in vivo motor-based targeted drug delivery in connection to fuel-free nanovehicles. PMID:20979242

  3. New chimeric advanced Drug Delivery nano Systems (chi-aDDnSs) as doxorubicin carriers.

    PubMed

    Gardikis, Konstantinos; Tsimplouli, Chrisiida; Dimas, Konstantinos; Micha-Screttas, Maria; Demetzos, Costas

    2010-12-15

    Since the late 1960s, the field of drug delivery has focused on the creation of new formulations with improved properties, taking much attention to drug release from the carrier. Liposomes and dendrimers represent two of the most studied drug carriers. A Modulatory Liposomal Controlled Release System (MLCRS) combining liposomal and dendrimeric technology has been recently published as well as Liposomal locked-in Dendrimers (LLDs) technology which was considered to be a class of MLCRSs. Chimeric advanced Drug Delivery nano Systems (chi-aDDnSs) can be defined as mixed nanosystems due to the combination of the bionanomaterials used and can offer advantages as drug carriers. This work deals with the production of two new chi-aDDnSs incorporating the newly synthesized dendrimer PG1. One of the two formulations bears the exact lipidic composition as the commercial liposomal drug "Myocet". Doxorubicin (Dox) was incorporated into conventional (free of dendrimer) liposomal formulations and into the corresponding chi-aDDnSs, and the physicochemical characteristics, the in vitro drug release and the in vitro cytotoxicity against human cancer cell lines were assessed. The results revealed a different modulation release effect of doxorubicin from the chi-aDDnS, compared to the Myocet replica. Pharmacological cytotoxicity concerning all the chi-aDDnSs was very close to that of the conventional liposomal systems. PMID:20934501

  4. Spectrophotometric determination of some histamine H1-antagonists drugs in their pharmaceutical preparations

    NASA Astrophysics Data System (ADS)

    Hassan, Wafaa S.; El-Henawee, Magda M.; Gouda, Ayman A.

    2008-01-01

    Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of three histamine H1-antagonists drugs, e.g., chlorphenoxamine hydrochloride (CPX), diphenhydramine hydrochloride (DPH) and clemastine (CMT) in bulk and in their pharmaceutical formulations. The first method depend upon the reaction of molybdenum(V) thiocyanate ions (Method A) with the cited drugs to form stable ion-pair complexes which extractable with methylene chloride, the orange red color complex was determined colorimetrically at λmax 470 nm. The second method is based on the formation of an ion-association complex with alizarin red S as chromogenic reagents in acidic medium (Method B), which is extracted into chloroform. The complexes have a maximum absorbance at 425 and 426 nm for (DPH or CMT) and CPX, respectively. Regression analysis of Beer-Lambert plots showed a good correlation in the concentration ranges of 5.0-40 and 5-70 μg mL -1 for molybdenum(V) thiocyanate (Method A) and alizarin red S (Method B), respectively. For more accurate analysis, Ringbom optimum concentration ranges were calculated. The molar absorptivity, Sandell sensitivity, detection and quantification limits were calculated. Applications of the procedure to the analysis of various pharmaceutical preparations gave reproducible and accurate results. Further, the validity of the procedure was confirmed by applying the standard addition technique and the results obtained in good agreement well with those obtained by the official method.

  5. Short-term effects of neuroactive pharmaceutical drugs on a fish species: biochemical and behavioural effects.

    PubMed

    Brandão, F P; Rodrigues, S; Castro, B B; Gonçalves, F; Antunes, S C; Nunes, B

    2013-11-15

    The presence of pharmaceutical residues in the aquatic environment is receiving great attention since significant levels of contamination have been found, not only in sewage treatment plant effluents, but also in open waters. In our study, the toxicity of three anticonvulsant drugs commonly found in the environment (diazepam, carbamazepine, and phenytoin) was evaluated in Lepomis gibbosus (pumpkinseed sunfish). This study focused on oxidative stress parameters, namely: glutathione reductase (GRed), glutathione S-transferases (GSTs), catalase (CAT), and lipid peroxidation (thiobarbituric acid reactive substances, TBARS) in the hepatic, digestive, and gill tissues of exposed animals. Simultaneously, we assessed the effects of these drugs in terms of behavioural parameters, such as scototaxis and activity. Exposure to diazepam caused an increase in GST activities in the gills and an inhibition of GRed in the digestive tract, relative to control, suggesting an antioxidant response. It also caused fish to spend more time swimming and less time in a refuge area (black compartment of an aquarium). Exposure to carbamazepine caused an increase in GSTs and GRed activity in the digestive tract, which is not always consistent with the literature. A significant positive correlation was found between carbamazepine concentration and time spent in motion and a negative correlation with time spent in black compartment. Exposure to phenytoin was responsible for adaptive responses in the activities of CAT and GSTs (in the liver), but it did not elicit any behavioural alterations. Although all three drugs seemed to induce oxidative stress in some organs, peroxidative damage (measured as TBARS concentrations) was not found at the selected range of concentrations. Our results enlighten the need for more research on the ecological consequences of pharmaceuticals in the aquatic environment, especially drugs that interfere with the CNS and behaviour, because the net outcome of these

  6. Measurement of drug diffusivities in pharmaceutical solvents using Taylor dispersion analysis.

    PubMed

    Ye, Fengbin; Jensen, Henrik; Larsen, Susan W; Yaghmur, Anan; Larsen, Claus; Østergaard, Jesper

    2012-03-01

    Knowledge of drug diffusivity is of key importance in the understanding of a number of pharmaceutical and biological processes. However, experimentally determined diffusion coefficients and hydrodynamic radii are only reported for a limited number of drug substances. In this work, Taylor dispersion analysis conducted using capillary electrophoresis instrumentation coupled with a UV imaging detector, with two detection windows along the capillary, is introduced as a powerful method for the determination of drug diffusivities in nanoliter samples. Several potential advantages associated with applying two detection windows instead of one window as done in most previous studies were identified. Overall diffusion coefficient measurements performed using two detection windows are more robust and correction for changes in flow rate and sample volume is not required. The experimental conditions applied were suboptimal for performing single detection window measurements due to the relatively large sample volumes and may be optimized to alleviate the need for tedious correction procedures for this setup. The diffusivities of eleven aromatic compounds in water at 25 °C were determined, and showed a good agreement with the literature values. Furthermore, the diffusivities and hydrodynamic radii of four selected drug substances were determined in acetonitrile, methanol, isopropyl myristate, medium chain triglyceride, and propylene glycol in addition to water. The solvent viscosity was determined simultaneously along with the measurement of analyte diffusivity. Drug diffusivities decreased with increasing solvent viscosity. Taylor dispersion analysis is a robust, simple and automated method of quantification of diffusion coefficients even in media with a relatively higher viscosity than water. PMID:22197153

  7. Stability-indicating HPTLC determination of ambroxol hydrochloride in bulk drug and pharmaceutical dosage form.

    PubMed

    Jain, P S

    2010-01-01

    A simple, selective, precise, and stability-indicating high-performance thin-layer chromatographic (HPTLC) method for the analysis of ambroxol hydrochloride both as a bulk drug and in formulations was developed and validated. The method employed HPTLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of methanol-triethylamine (4:6 v/v). The system was found to give a compact spot for ambroxol hydrochloride (R(f) value of 0.53 +/- 0.02). Densitometric analysis of ambroxol hydrochloride was carried out in the absorbance mode at 254 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r(2) = 0.9966 +/- 0.0013 with respect to peak area in the concentration range 100-1000 ng/spot. The mean value +/- standard deviation of slope and intercept were 164.85 +/- 0.72 and 1168.3 +/- 8.26 with respect to peak area. The method was validated for precision, recovery, and robustness. The limits of detection and quantitation were 10 and 30 ng/spot, respectively. Ambroxol hydrochloride was subjected to oxidation and thermal degradation. The drug undergoes degradation under oxidation and heat conditions. This indicates that the drug is susceptible to oxidation and heat. Statistical analysis proves that the method is repeatable, selective, and accurate for the estimation of said drug. Stability indicating of new chemical entities is an important part for the drug development of ambroxol hydrochloride and for its estimation in plasma and other biological fluids; the novel Statistical analysis proves that the method is repeatable and selective for the analysis of ambroxol hydrochloride as bulk drug and in pharmaceutical formulations. The proposed developed HPTLC method can be applied for identification and quantitative determination of ambroxol hydrochloride in bulk drug and dosage forms. This work is to determine the purity of the drug available from the various sources by detecting

  8. Tobacco Mosaic Virus-Based 1D Nanorod-Drug Carrier via the Integrin-Mediated Endocytosis Pathway.

    PubMed

    Tian, Ye; Gao, Sijia; Wu, Man; Liu, Xiangxiang; Qiao, Jing; Zhou, Quan; Jiang, Shidong; Niu, Zhongwei

    2016-05-01

    For cancer therapy, viruses have been utilized as excellent delivery vehicles because of their facile transfection efficiency in their host cells. However, their inherent immunogenicity has become the major obstacle for their translation into approved pharmaceuticals. Herein, we utilized rodlike plant virus, tobacco mosaic virus (TMV), which is nontoxic to mammals and mainly infects tobacco species, as anticancer nanorod-drug vector for cancer therapy study. Doxorubicin (DOX) was installed in the inner cavity of TMV by hydrazone bond, which enabled the pH-sensitive drug release property. Conjugation of cyclic Arg-Gly-Asp (cRGD) on the surface of TMV can enhance HeLa cell uptake of the carrier via the integrin-mediated endocytosis pathway. Comparing with free DOX, the cRGD-TMV-hydra-DOX vector had similar cell growth inhibition and much higher apoptosis efficiency on HeLa cells. Moreover, the in vivo assay assumed that cRGD-TMV-hydra-DOX behaved similar antitumor efficiency but much lower side effect on HeLa bearing Balb/c-nu mice. Our work provides novel insights into potentially cancer therapy based on rodlike plant viral nanocarriers. PMID:27062971

  9. Drug loading and release on tumor cells using silk fibroin-albumin nanoparticles as carriers

    NASA Astrophysics Data System (ADS)

    Subia, B.; Kundu, S. C.

    2013-01-01

    Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin-albumin blended nanoparticles were prepared using the desolvation method without any surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin-albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules.

  10. Dual Functionalized Bacteriophage Qβ as a Photocaged Drug Carrier.

    PubMed

    Chen, Zhuo; Li, Na; Chen, Luxi; Lee, Jiyong; Gassensmith, Jeremiah J

    2016-09-01

    Proteinatious nanoparticles are emerging as promising materials in biomedical research owing to their many unique properties and our interest focuses on integrating environmental responsivity into these systems. In this work, the use of a virus-like particle (VLP) derived from bacteriophage Qβ as a photocaged drug delivery system is investigated. Ideally, a photocaged nanoparticle platform should be harmless and inert without activation by light yet, upon photoirradiation, should cause cell death. Approximately 530 photocleavable doxorubicin complexes are installed initially onto the surface of Qβ by CuAAC reaction for photocaging therapy; however, aggregation and precipitation are found to cause cell death at higher concentrations. In order to improve solution stability, thiol-dibromomaleimide chemistry has been developed to orthogonally modify the VLP. This chemistry provides a robust method of incorporating additional functionality at the disulfides on Qβ, which was used to increase the stability and solubility of the drug-loaded VLPs. As a result, the dual functionalied VLPs with polyethylene glycol and photocaged doxorubicin show not only negligible cytotoxicity before photoactivation but also highly controllable photorelease and cell killing power. PMID:27351167

  11. Theoretical analysis of a transdermal ferromagnetic implant for retention of magnetic drug carrier particles

    NASA Astrophysics Data System (ADS)

    Avilés, Misael O.; Ebner, Armin D.; Chen, Haitao; Rosengart, Axel J.; Kaminski, Michael D.; Ritter, James A.

    2005-05-01

    The use of a ferromagnetic wire implant placed near an artery to assist the collection of magnetic drug carrier particles (MDCPs) using an external magnet is theoretically studied. Three magnetic drug targeting (MDT) systems are evaluated in terms of their MDCP collection efficiency (CE): a permanent magnet and wire is better than a permanent magnet alone, which is better than a homogeneous magnetic field and wire.

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

    SciTech Connect

    Xie, Y.; Kaminski, M. D.; Mertz, C. J.; Finck, M. R.; Guy, S. G.; Chen, H.; Rosengart, A. J.; Chemical Engineering; Univ. of Chicago, Pritzker School of Medicine

    2005-01-01

    Novel methods for drug delivery may be based on nanotechnology using non-invasive magnetic guidance of drug loaded magnetic carriers to the targeted site and thereafter released by external ultrasound energy. The key building block of this system is to successfully synthesize biodegradable, magnetic drug carriers. Magnetic carriers using poly(D,L-lactide-co-glycolide) (PLGA) or poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) as matrix materials were loaded with bovine serum albumin (BSA) by a double-emulsion technique. BSA-loaded magnetic microspheres were characterized for size, morphology, surface charge, and magnetization. The BSA encapsulation efficiency was determined by recovering albumin from the microspheres using dimethyl sulfoxide and 0.05N NaOH/0.5% SDS then quantifying with the Micro-BCA protein assay. BSA release profiles were also determined by the Micro-BCA protein assay. The microspheres had drug encapsulation efficiencies up to 90% depending on synthesis parameters. Particles were spherical with a smooth or porous surface having a size range less than 5 {mu}m. The surface charge (expressed as zeta potential) was near neutral, optimal for prolonged intravascular survival. The magnetization of these BSA loaded magnetic carriers was 2 to 6 emu/g, depending on the specific magnetic materials used during synthesis.

  13. In silico modelling of drug-polymer interactions for pharmaceutical formulations.

    PubMed

    Ahmad, Samina; Johnston, Blair F; Mackay, Simon P; Schatzlein, Andreas G; Gellert, Paul; Sengupta, Durba; Uchegbu, Ijeoma F

    2010-08-01

    Selecting polymers for drug encapsulation in pharmaceutical formulations is usually made after extensive trial and error experiments. To speed up excipient choice procedures, we have explored coarse-grained computer simulations (dissipative particle dynamics (DPD) and coarse-grained molecular dynamics using the MARTINI force field) of polymer-drug interactions to study the encapsulation of prednisolone (log p = 1.6), paracetamol (log p = 0.3) and isoniazid (log p = -1.1) in poly(L-lactic acid) (PLA) controlled release microspheres, as well as the encapsulation of propofol (log p = 4.1) in bioavailability enhancing quaternary ammonium palmitoyl glycol chitosan (GCPQ) micelles. Simulations have been compared with experimental data. DPD simulations, in good correlation with experimental data, correctly revealed that hydrophobic drugs (prednisolone and paracetamol) could be encapsulated within PLA microspheres and predicted the experimentally observed paracetamol encapsulation levels (5-8% of the initial drug level) in 50 mg ml(-1) PLA microspheres, but only when initial paracetamol levels exceeded 5 mg ml(-1). However, the mesoscale technique was unable to model the hydrophilic drug (isoniazid) encapsulation (4-9% of the initial drug level) which was observed in experiments. Molecular dynamics simulations using the MARTINI force field indicated that the self-assembly of GCPQ is rapid, with propofol residing at the interface between micellar hydrophobic and hydrophilic groups, and that there is a heterogeneous distribution of propofol within the GCPQ micelle population. GCPQ-propofol experiments also revealed a population of relatively empty and drug-filled GCPQ particles. PMID:20519214

  14. Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers.

    PubMed

    Sosnik, Alejandro; Seremeta, Katia P

    2015-09-01

    Spray-drying is a rapid, continuous, cost-effective, reproducible and scalable process for the production of dry powders from a fluid material by atomization through an atomizer into a hot drying gas medium, usually air. Often spray-drying is considered only a dehydration process, though it also can be used for the encapsulation of hydrophilic and hydrophobic active compounds within different carriers without substantial thermal degradation, even of heat-sensitive substances due to fast drying (seconds or milliseconds) and relatively short exposure time to heat. The solid particles obtained present relatively narrow size distribution at the submicron-to-micron scale. Generally, the yield% of spray-drying at laboratory scale with conventional spray-dryers is not optimal (20-70%) due to the loss of product in the walls of the drying chamber and the low capacity of the cyclone to separate fine particles (<2 μm). Aiming to overcome this crucial drawback in early development stages, new devices that enable the production of submicron particles with high yield, even for small sample amounts, have been introduced into the market. This review describes the most outstanding advantages and challenges of the spray-drying method for the production of pure drug particles and drug-loaded polymeric particles and discusses the potential of this technique and the more advanced equipment to pave the way toward reproducible and scalable processes that are critical to the bench-to-bedside translation of innovative pharmaceutical products. PMID:26043877

  15. Physicians' decision process for drug prescription and the impact of pharmaceutical marketing mix instruments.

    PubMed

    Campo, Katia; De Staebel, Odette; Gijsbrechts, Els; van Waterschoot, Walter

    2005-01-01

    This paper provides an in-depth, qualitative analysis of the physicians' decision process for drug prescription. Drugs in the considered therapeutic classes are mainly prescribed by specialists, treating patients with obligatory medical insurance, for a prolonged period of time. The research approach is specifically designed to capture the full complexity and sensitive nature of the physician's choice behavior, which appears to be more hybrid and less rational in nature than is often assumed in quantitative, model-based analyses of prescription behavior. Several interesting findings emerge from the analysis: (i) non-compensatory decision rules seem to dominate the decision process, (ii) consideration sets are typically small and change-resistant, (iii) drug cost is not a major issue for most physicians, (iv) detailing remains one of the most powerful pharmaceutical marketing instruments and is highly appreciated as a valuable and quick source of information, and (v) certain types of non-medical marketing incentives (such as free conference participation) may in some situations also influence drug choices. PMID:16597584

  16. Where do pharmaceuticals on the market originate? An analysis of the informal drug supply in Cotonou, Benin.

    PubMed

    Baxerres, Carine; Le Hesran, Jean-Yves

    2011-10-01

    This anthropological study, conducted in Cotonou, Benin between 2005 and 2007, investigates the informal pharmaceuticals market. It was carried out through a long-term participant observation of informal vendors and semi-directive and unstructured interviews. A classification of products sold in the informal market was developed. The fact that a high percentage of them come from Anglophone countries near Benin (Nigeria and Ghana) led to a comparison of the sources of pharmaceutical supply in these three countries as well as their current legislation regarding pharmaceutical distribution. Our study results highlight a new understanding of the phenomenon of the informal market. Nigeria and Ghana rely on a liberal pharmaceutical distribution system with little intervention from public authorities. Conversely, the government maintains considerable influence over pharmaceutical distribution in Benin. Hence, the differences between these three countries in terms of variety of supply sources and flexibility of access to drugs are understood through an investigation of Benin's informal market. Therefore, it appears that beyond issues concerning the quality of the pharmaceuticals, this phenomenon illustrates a kind of liberalization of pharmaceutical distribution and the ensuing public health issues. PMID:21962151

  17. Acute toxicities of pharmaceuticals toward green algae. mode of action, biopharmaceutical drug disposition classification system and quantile regression models.

    PubMed

    Villain, Jonathan; Minguez, Laetitia; Halm-Lemeille, Marie-Pierre; Durrieu, Gilles; Bureau, Ronan

    2016-02-01

    The acute toxicities of 36 pharmaceuticals towards green algae were estimated from a set of quantile regression models representing the first global quantitative structure-activity relationships. The selection of these pharmaceuticals was based on their predicted environmental concentrations. An agreement between the estimated values and the observed acute toxicity values was found for several families of pharmaceuticals, in particular, for antidepressants. A recent classification (BDDCS) of drugs based on ADME properties (Absorption, Distribution, Metabolism and Excretion) was clearly correlated with the acute ecotoxicities towards algae. Over-estimation of toxicity from our QSAR models was observed for classes 2, 3 and 4 whereas our model results were in agreement for the class 1 pharmaceuticals. Clarithromycin, a class 3 antibiotic characterized by weak metabolism and high solubility, was the most toxic to algae (molecular stability and presence in surface water). PMID:26590695

  18. The changing world of oncology drug development-A global pharmaceutical company's perspective.

    PubMed

    Galbraith, Susan

    2014-06-01

    Recent approvals for oncology drugs have seen an increasing proportion directed to specific genetic targets identified with an associated companion diagnostic test. In addition, there is a wave of drugs directed against immune 'checkpoints' which promise to transform the way cancer is treated in the next decade. We can increase the probability of success in drug development based on a thorough mechanistic understanding of how a target drug affects cancer biology and the specific biological and genotypic context in which it operates. This article compares and contrasts the discovery and development of gefitinib-the first EGFR tyrosine kinase inhibitor and AZD9291, an irreversible inhibitor of both sensitizing and resistant mutated EGFR. This demonstrates how the better understanding we now have of the genetic changes driving the cancer growth and the biochemical structure and function of the mutated proteins, has led to a much faster developmental path with higher likelihood of success in pivotal trials. An emerging trend in response to the challenge of the increasing segmentation of cancers based on their genetic makeup is the development of 'basket' studies which include one or more screening tests for multiple genetic aberrations and the direction of patients to one of several arms of a clinical trial based on the specific aberration in their tumor. In the face of both the wealth of genetic information about cancer and the challenges of drug development, collaboration across academia and industry is vital. There is great potential to benefit from more 'open innovation' to address some of these challenges and opportunities. Far from there being a decline in innovation in pharmaceutical development, I see that we are in one of the most exciting times in cancer drug development with innovation in every aspect of how we discover and develop new therapies. PMID:25841416

  19. Polymer coating of carrier excipients modify aerosol performance of adhered drugs used in dry powder inhalation therapy.

    PubMed

    Traini, Daniela; Scalia, Santo; Adi, Handoko; Marangoni, Elisabetta; Young, Paul M

    2012-11-15

    The potential of excipient coating to enhance aerosol performance of micronized drugs in carrier excipient-drug blends, used in dry powder inhalers, was investigated. Both EC (ethyl cellulose) and PVP (polyvinylpyrrolidone) were used as coating agents. Carriers were prepared via sieve fractioning followed by spray drying, with and without polymer additive. Each uncoated and coated carrier salbutamol sulphate (SS) blended systems were evaluated for particle size, morphology, drug carrier adhesion and aerosolisation performance, after blending and storage for 24h. All carrier-based systems prepared had similar particle sizes and morphologies. The surface chemistries of the carriers were significantly different, as was drug-carrier adhesion and aerosolisation performance. Particle adhesion between SS and aerosol performance (fine particle fraction; FPF) followed the rank: PVP coated>un-coated>EC coated lactose. This rank order could be attributed to the surface energy measured by contact goniometry and related to the chemistry of lactose and each polymer. Storage did not significantly affect aerosol performance, however a rank increase in mean FPF value was observed for uncoated and EC coated lactose. Finally, the net electrostatic charge across the aerosol cloud indicated that the EC coated lactose transferred less charge to SS particles. The performance of each carrier system could be attributed to the carrier surface chemistry and, in general, by careful selection of the coating polymer, drug-carrier adhesion, electrostatic charge and aerosol performance could be controlled. PMID:22964399

  20. [Development and Distribution of Drugs for NTDs: Efforts of One Pharmaceutical Company].

    PubMed

    Asada, Makoto

    2016-01-01

    The Pharmaceutical Industry is expected to play a proactive global role in combatting neglected tropical diseases (NTDs) and other tropical diseases affecting low-income countries. Such a role would include novel medicine R&D, manufacturing and distribution. In order to succeed in this role, several challenges need to be overcome: a) the economic challenge or cost benefit balance for the development of these medicines, and b) sparse in-house experience with these diseases within the Industry. During the last decade, the Product Development Partnership (PDP) model has become an effective strategy to address such challenges. Organizations such as the Medicines for Malaria Venture (MMV), Drugs for Neglected Diseases initiative (DNDi), TB alliance, PATH (formerly the Program for Appropriate Technology in Health), and others have linked pharmaceutical companies, funding organizations, academic researchers and others, and have thus been able to successfully populate treatment pipelines directed at NTDs, Malaria, tuberculosis (TB), and human immunodeficiency virus (HIV)/AIDS. In this paper, our experience working with one of these organizations, DNDi, is described. We have been collaborating with DNDi in evaluating the actions of Eisai's antifungal compound, E1224, in a clinical study for treating Chagas Disease. In addition, other Eisai initiatives directed at NTDs and improving patients' access to medicines are introduced. PMID:26831797

  1. Design of Chitosan and Its Water Soluble Derivatives-Based Drug Carriers with Polyelectrolyte Complexes

    PubMed Central

    Wu, Qing-Xi; Lin, Dong-Qiang; Yao, Shan-Jing

    2014-01-01

    Chitosan, the cationic polysaccharide derived from the natural polysaccharide chitin, has been studied as a biomaterial for more than two decades. As a polycationic polymer with favorable properties, it has been widely used to form polyelectrolyte complexes with polyanions for various applications in drug delivery fields. In recent years, a growing number of studies have been focused on the preparation of polyelectrolyte complexes based on chitosan and its water soluble derivatives. They have been considered well-suited as biomaterials for a number of vital drug carriers with targeted/controlled release profiles, e.g., films, capsules, microcapsules. In this work, an overview highlights not only the favorable properties of chitosan and its water soluble derivatives but also the good performance of the polyelectrolyte complexes produced based on chitosan. Their various types of applications as drug carriers are reviewed in detail. PMID:25532565

  2. Biodistribution of doxorubicin and nanostructured ferrocarbon carrier particles in organism during magnetically controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Anatoly A.; Filippov, Victor I.; Nikolskaya, Tatiana A.; Budko, Andrei P.; Kovarskii, Alexander L.; Zontov, Sergei V.; Kogan, Boris Ya.; Kuznetsov, Oleg A.

    2009-05-01

    Biodistribution of doxorubicin and ferrocarbon carrier particles in organism during and after magnetically controlled anti-tumor drug delivery and deposition was studied. Animal tests show high concentration of the cytostatic drug in the target zone, while its concentration is three orders of magnitude lower in bloodstream and other organs. A significant depot of the drug remains on the deposited particles days after the procedure. Macrophages actively phagocytose the ferrocarbon (FeC) particles and remain viable long enough to carry them to the lymph nodes.

  3. Application of silicified microcrystalline cellulose (Prosolv) as a polymer carrier of Epilobium parviflorum Schreb. extract in oral solid drug form.

    PubMed

    Marczyński, Zbigniew; Zgoda, Marian Mikołaj; Jambor, Jerzy

    2007-01-01

    Direct tableting is simpler and more cost-effective from the point of view of good manufacturing practice (GMP) than wet granulation or dry compacting. Thus, pharmaceutical industry more and more frequently uses this particular process. Only few therapeutic substances form under compression tablets meeting current requirements. Very often additional adjuvants must be used. These substances have the ability of increasing plastic deformation and tablet mass liquidity. Microcrystalline cellulose belongs to the best adjuvant substances of the type. It has binding, disintegrating and improving liquidity properties. This study aims at investigating the usefulness of selected high-molecular substances with particular consideration of silici-fled microcrystalline cellulose (Prosolv) and croscarmellose sodium (Vivasol) as a carrier of E. parviflorum Schreb. extract in oral solid drug form in the process of direct tab-leting. The manufactured tablets were subjected to morphological tests and pharmaceutical availability tests of biologically active substances from a tablet to the acceptor fluid. The investigations were based on general and detailed principles of Polish Pharmacopoeia VI. The obtained results allow to state that the applied high-molecular adjuvant substances proved to be useful in adequate proportions in the production of tablets from dry extract from Epilobium parviflo-rum Schreb. Generally, a significant shortening of the tablets disintegration time was obtained as compared to earlier produced tablets with the method of initial granulation. The tablets formed from E. parviflorum Schreb. extract with silicified microcrystalline cellulose (Prosolv SMCC 50) and croscarmellose sodium can be included into preparations of short dissolution time of the therapeutic substance. PMID:17957946

  4. Fenton-like reaction: a possible way to efficiently remove illicit drugs and pharmaceuticals from wastewater.

    PubMed

    Mackuľak, Tomáš; Mosný, Michal; Grabic, Roman; Golovko, Oksana; Koba, Olga; Birošová, Lucia

    2015-03-01

    We analyzed 13 psychoactive pharmaceuticals, illicit drugs and their metabolites in wastewater treatment plant influent and effluent and the possibility of their degradation by biological and chemical processes. Tramadol (413-853 ng/L) and methamphetamine (460-682 ng/L) were the most concentrated compounds in the wastewater in winter and summer, respectively. A significant decrease in the concentration of tramadol in wastewater was measured during the summer. The lowest efficiency was observed for tramadol, venlafaxine, citalopram and oxazepam (∼ 10%) and the highest efficiency was observed for amphetamine and THC-COOH (∼ 80%). The efficiency of compound degradation via the Fenton reaction, a modified Fenton reaction and different degradation (by algae, wood-rotting fungi and enzymes at influent versus effluent) was determined. The Fenton reaction and its modification were efficient at eliminating these substances in comparison with the tested biological processes. PMID:25680092

  5. 3D printing in pharmaceutics: A new tool for designing customized drug delivery systems.

    PubMed

    Jonathan, Goole; Karim, Amighi

    2016-02-29

    Three-dimensional printing includes a wide variety of manufacturing techniques, which are all based on digitally-controlled depositing of materials (layer-by-layer) to create freeform geometries. Therefore, three-dimensional printing processes are commonly associated with freeform fabrication techniques. For years, these methods were extensively used in the field of biomanufacturing (especially for bone and tissue engineering) to produce sophisticated and tailor-made scaffolds from patient scans. This paper aims to review the processes that can be used in pharmaceutics, including the parameters to be controlled. In practice, it not straightforward for a formulator to be aware of the various technical advances made in this field, which is gaining more and more interest. Thus, a particular aim of this review is to give an overview on the pragmatic tools, which can be used for designing customized drug delivery systems using 3D printing. PMID:26757150

  6. Assessment of MEKC suitability for residue drug monitoring on pharmaceutical manufacturing equipment.

    PubMed

    Boca, Madalina Brindusa; Pretorius, Etheresia; Kgaje, Christopher; Apostolides, Zeno

    2008-03-13

    The suitability of micellar electrokinetic chromatography for the simultaneous trace determination of several compounds (sulfamethoxazole, trimethoprim, sulfanilic acid, sulfanilamide, 3,4,5-trimethoxybenzoic acid and nonoxynol-9) was assessed. The mixture was separated within 14min at an applied voltage of 22kV by using 30mM phosphate electrolyte, containing 10mM SDS, adjusted to pH 7.8. Under optimized separation conditions acceptable levels of linearity, precision and accuracy were obtained for all compounds. The method could be used as part of a cleaning validation study when assaying trace levels of co-trimoxazole drug, some of its decomposition products and detergent in the swab samples collected from pharmaceutical manufacturing equipment, after cleaning. PMID:18178359

  7. Bioactive, luminescent and mesoporous europium-doped hydroxyapatite as a drug carrier.

    PubMed

    Yang, Piaoping; Quan, Zewei; Li, Chunxia; Kang, Xiaojiao; Lian, Hongzhou; Lin, Jun

    2008-11-01

    Bioactive, luminescent and mesoporous europium-doped hydroxyapatite (Eu:HAp) was successfully prepared through a simple one-step route using cationic surfactant as template. The obtained multifunctional hydroxyapatite was performed as a drug delivery carrier to investigate the drug storage/release properties using ibuprofen (IBU) as a model drug. The structural, morphological, textural and optical properties were well characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectra (XPS), Fourier transform infrared spectroscopy (FT-IR), N(2) adsorption/desorption, and photoluminescence (PL) spectra, respectively. The results reveal that the multifunctional hydroxyapatites exhibit the typical ordered characteristics of the hexagonal mesostructure, and have rod-like morphology with the particle size of 20-40 nm in width and 100-200 nm in length. The drug storage/release test indicates that the luminescent HAp shows much similar drug loading amount and cumulative release rate to those of pure HAp. Interestingly, the IBU-loaded samples still show red luminescence of Eu(3+) ((5)D(0)-(7)F(1),(2)) under UV irradiation, and the emission intensities of Eu(3+) in the drug carrier system vary with the released amount of IBU, thus making the drug release be easily tracked and monitored by the change of the luminescence intensity. PMID:18715638

  8. DNA Polyplexes as Combinatory Drug Carriers of Doxorubicin and Cisplatin: An In Vitro Study

    PubMed Central

    Kang, Han Chang; Cho, Hana; Bae, You Han

    2015-01-01

    Double helix nucleic acids were used as a combination drug carrier for doxorubicin (DOX), which physically intercalates with DNA double helices, and cisplatin (CDDP), which binds to DNA without an alkylation reaction. DNA interacting with DOX, CDDP, or both was complexed with positively charged, endosomolytic polymers. Compared with the free drug, the polyplexes (100 ~ 170 nm in size) delivered more drug into the cytosol and the nucleus and demonstrated similar or superior (up to a 7-fold increase) in vitro cell-killing activity. Additionally, the gene expression activities of most of the chemical drug-loaded plasmid DNA (pDNA) polyplexes were not impaired by the physical interactions between the nucleic acid and DOX/CDDP. When a model reporter pDNA (luciferase) was employed, it expressed luciferase protein at 0.7- ~ 1.4-fold the amount expressed by the polyplex with no bound drugs (a control), which indicated the fast translocation of the intercalated or bound drugs from the “carrier DNA” to the “nuclear DNA” of target cells. The proposed concept may offer the possibility of versatile combination therapies of genetic materials and small molecule drugs that bind to nucleic acids to treat various diseases. PMID:26132975

  9. Topiramate: A Review of Analytical Approaches for the Drug Substance, Its Impurities and Pharmaceutical Formulations.

    PubMed

    Pinto, Eduardo Costa; Dolzan, Maressa Danielli; Cabral, Lucio Mendes; Armstrong, Daniel W; de Sousa, Valéria Pereira

    2016-02-01

    An important step during the development of high-performance liquid chromatography (HPLC) methods for quantitative analysis of drugs is choosing the appropriate detector. High sensitivity, reproducibility, stability, wide linear range, compatibility with gradient elution, non-destructive detection of the analyte and response unaffected by changes in the temperature/flow are some of the ideal characteristics of a universal HPLC detector. Topiramate is an anticonvulsant drug mainly used for the treatment of different types of seizures and prophylactic treatment of migraine. Different analytical approaches to quantify topiramate by HPLC have been described because of the lack of chromophoric moieties on its structure, such as derivatization with fluorescent moieties and UV-absorbing moieties, conductivity detection, evaporative light scattering detection, refractive index detection, chemiluminescent nitrogen detection and MS detection. Some methods for the determination of topiramate by capillary electrophoresis and gas chromatography have also been published. This systematic review provides a description of the main analytical methods presented in the literature to analyze topiramate in the drug substance and in pharmaceutical formulations. Each of these methods is briefly discussed, especially considering the detector used with HPLC. In addition, this article presents a review of the data available regarding topiramate stability, degradation products and impurities. PMID:26276847

  10. Gradient HPLC-DAD determination of two pharmaceutical mixtures containing the antihistaminic drug ebastine.

    PubMed

    Haggag, Rim S; Belal, Tarek S

    2012-01-01

    This work describes the development, validation and application of a simple and reliable high-performance liquid chromatography-diode array detection (HPLC-DAD) procedure for the analysis of two pharmaceutical mixtures. The first mixture contains the antihistaminic drug ebastine (EBS) and the famous sympathomimetic drug pseudoephedrine hydrochloride (PSD), and the second mixture is composed of EBS and another sympathomimetic agent, phenylephrine hydrochloride (PHR). Effective chromatographic separation of EBS, PSD and PHR was achieved using a Zorbax SB-C8 (4.6 × 250 mm, 5 μm) column with gradient elution of the mobile phase composed of 0.05M phosphoric acid and acetonitrile. The gradient elution started with 20% (by volume) acetonitrile, ramped up linearly to 90% in 5 min, then kept constant until the end of the run. The mobile phase was pumped at a flow rate of 1 mL/min. The multiple wavelength detector was set at 254 (for EBS and PSD) and 274 nm (for PHR) and quantification of the analytes was based on measuring their peak areas. The retention times for PHR, PSD and EBS were approximately 2.5, 2.9 and 7.1 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness and detection and quantification limits. Calibration curves were linear in the ranges 5-100, 100-1,000 and 10-200 µg/mL for EBS, PSD and PHR, respectively, with correlation coefficients > 0.9996. The validated HPLC method was applied to the analysis of the two pharmaceutical mixtures in laboratory-made tablets in which the analytes were successfully quantified with good recovery values and no interfering peaks were encountered from the inactive ingredients. Finally, the proposed method made use of DAD as a tool for peak identity and purity confirmation. PMID:22677488

  11. Caveat medicus: consequences of federal investigations of marketing activities of pharmaceutical suppliers of prostate cancer drugs.

    PubMed

    McKoy, June M; Lyons, E Allison; Obadina, Eniola; Carson, Kenneth; Pickard, A Simon; Schellhammer, Paul; McLeod, David; Boyd, Cynthia E; McWilliams, Norene; Sartor, Oliver; Schumock, Glen T; McCaffery, Kathryn; Bennett, Charles L

    2005-12-01

    In the course of recent health care fraud investigations against TAP Pharmaceuticals (Lake Forest, IL) and AstraZeneca International (London, United Kingdom), each pled guilty to one violation of the Prescription Drug Marketing Act, settled claims related to alleged violations of the False Claims Act without admitting guilt, and paid fines, settlements for liabilities, and reimbursements of dollar 850 million and dollar 355 million, respectively. In a unique aspect of these cases, federal investigators brought criminal charges against 14 TAP employees and investigated the billing practices of several urologists. These investigations resulted in guilty pleas from both urologists and industry employees relative to the Prescription Drug Marketing Act or the False Claims Act and probationary sentences with payments of fines and restitution to the government for urologists who cooperated with federal investigations. One uncooperative urologist was found guilty of violating the Federal False Claims Act and sentenced to 6 months of home arrest, excluded from Medicare for 5 years, required to provide 600 hours of free medical care to indigent patients and patients covered by Medicare or Medicaid, and paid fines and restitution to the government. The cases against TAP and AstraZeneca have been followed by federal and state investigations of allegedly illegal marketing practices of other pharmaceutical firms and have resulted in negotiated settlements of dollar 3.8 billion and dollar 71.5 million, respectively. Believing that an Average Wholesale Price-based reimbursement system was an important driving factor for these marketing activities, Medicare has shifted to an Average Sales Price-based reimbursement system. This is expected to greatly impact the practice of outpatient oncology nationwide. PMID:16314650

  12. Design and evaluation of a PEGylated lipopeptide equipped with drug-interactive motifs as an improved drug carrier.

    PubMed

    Zhang, Peng; Lu, Jianqin; Huang, Yixian; Zhao, Wenchen; Zhang, Yifei; Zhang, Xiaolan; Li, Jiang; Venkataramanan, Raman; Gao, Xiang; Li, Song

    2014-01-01

    Micelles are attractive delivery systems for hydrophobic drugs due to their small size and the ease of application. However, the limited drug loading capacity and the intrinsic poor stability of drug-loaded formulations represent two major issues for some micellar systems. In this study, we designed and synthesized a micelle-forming PEG-lipopeptide conjugate with two Fmoc groups located at the interfacial region, and two oleoyl chains as the hydrophobic core. The significance of Fmoc groups as a broadly applicable drug-interactive motif that enhances the carrier-drug interaction was examined using eight model drugs of diverse structures. Compared with an analogue without carrying a Fmoc motif, PEG5000-(Fmoc-OA)₂ demonstrated a lower value of critical micelle concentration and three-fold increases of loading capacity for paclitaxel (PTX). These micelles showed tubular structures and small particle sizes (∼70 nm), which can be lyophilized and readily reconstituted with water without significant changes in particle sizes. Fluorescence quenching study illustrated the Fmoc/PTX π-π stacking contributes to the carrier/PTX interaction, and drug-release study demonstrated a much slower kinetics than Taxol, a clinically used PTX formulation. PTX/PEG5000-(Fmoc-OA)₂ mixed micelles exhibited higher levels of cytotoxicity than Taxol in several cancer cell lines and more potent inhibitory effects on tumor growth than Taxol in a syngeneic murine breast cancer model (4T1.2). We have further shown that seven other drugs can be effectively formulated in PEG5000-(Fmoc-OA)₂ micelles. Our study suggests that micelle-forming PEG-lipopeptide surfactants with interfacial Fmoc motifs may represent a promising formulation platform for a broad range of drugs with diverse structures. PMID:24281690

  13. [Do pharmaceutical waste and drug residue pose a risk to public health?].

    PubMed

    Haguenoer, Jean-Marie

    2010-01-01

    Recently, awareness has developed of the environmental consequences of drug waste and disposal. These residues are identified as coming from either diffuse sources, the most significant of which is via the discharge of these residues in urine and feces, and thus the sewage system and water contains these drug remnants and their metabolites, or from point sources, sometimes with very high levels of concentration in waste from chemical and pharmaceutical industries, health care settings, but also from intensive livestock farming and aquaculture. Depending on their physical chemistry properties, these substances are more or less naturally biodegradable and easily treated in sewage purification plants. The effectiveness of these treatment processes is highly random and unpredictable, but is overall around 60%, nevertheless with variations of 2-99% according to the molecules. The silt from these treatment plants, sometimes very rich in lipophilic substances is on occasion reused for agricultural application as fertilizer, paving the way for a possible contamination of crops. Furthermore, the use of veterinary drugs in animals can lead to soil contamination either directly or through manure and slurry. The contamination can equally reach and affect surface water, groundwater and sometimes the water intended for human consumption. The National academy of Pharmacy has established some general recommendations on the proper use of drugs, environmental monitoring and surveillance, risk assessment for humans and the environment, prevention and the need for prevention. Several categories of drugs are more worrying: cancer treatments, antibiotics as well as transfers of anti-bio-resistance, and hormonal derivatives which has been previously demonstrated to contribute, along with other molecules, to detrimental effects on endocrines. PMID:20858332

  14. Natural mucoadhesive microspheres of Abelmoschus esculentus polysaccharide as a new carrier for nasal drug delivery.

    PubMed

    Sharma, Nitin; Kulkarni, Giriraj T; Sharma, Anjana; Bhatnagar, Aseem; Kumar, Neeraj

    2013-01-01

    This work describes the preparation and evaluation of mucoadhesive microspheres, using Abelmoschus esculentus polysaccharide as a novel carrier for safe and effective delivery of rizatriptan benzoate into nasal cavity. The polysaccharide was extracted from the fruit of A. esculentus and mucoadhesive microspheres were prepared by emulsification, followed by crosslinking using epichlorohydrin. Prepared microspheres were evaluated for size, morphology, swelling properties, mucoadhesive strength, encapsulation efficiency and drug release. Microspheres were found to release 50% of drug within 15 min and rest of the drug was released within 60 min. The drug release was found to decrease with increasing concentration of polysaccharide. To determine the retention time of the microspheres in the nasal cavity of rabbits, the microspheres were radiolabelled with (99m)Tc and subjected to gamma scintigraphy. The results showed a significant improvement in the nasal retention of the microspheres as compared to the aqueous solution of radiolabelled free-drug. PMID:23379506

  15. Safety monitoring of drugs granted exclusivity under the Best Pharmaceuticals for Children Act: what the FDA has learned.

    PubMed

    Mathis, L L; Iyasu, S

    2007-08-01

    The Best Pharmaceuticals for Children Act (BPCA) was signed into law on 4 January 2002, shortly after the pediatric exclusivity provision of the Food and Drug Administration (FDA) Modernization Act expired on 1 January 2002. This Act provides six months of marketing exclusivity for a drug when a pharmaceutical company studies that drug for use in the pediatric population as requested by the FDA. Section 17 of the BPCA specifically requires that the FDA review all adverse events reported for drugs that receive pediatric exclusivity. In most of the cases, no unexpected adverse events were reported in the pediatric population; however, in some cases, this focused safety review provided information important to the safety of medication use in children. PMID:17632537

  16. Flavonoid-based pH-responsive hydrogels as carrier of unstable drugs in oxidative conditions.

    PubMed

    Spizzirri, Umile Gianfranco; Cirillo, Giuseppe; Curcio, Manuela; Picci, Nevio; Iemma, Francesca

    2015-05-01

    In this study, pH-responsive hydrogels, synthesized by the coupling reaction of polyacrylic acid and catechin, are proposed as carriers of oxidable drugs toward the GI tract. The presence of polyphenolic moieties in the network gives the polymers properties suitable for the release of unstable drugs in oxidative conditions. The characterization of the hydrogels is obtained by means of morphological and physico-chemical analyses, antioxidant assays and evaluation of the swelling behavior in media simulating the gastric (pH 1.0) and the intestinal (pH 7.4) tracts. The hydrogels are tested as pH-responsive carriers in in vitro release studies of folic acid and thiamine, two model drugs easily degraded by oxidative conditions simulated by UV irradiation and t-butyl hydroperoxide treatment, respectively. Results show that catechin-based carriers are able to control the release of drugs at different pH values, giving a remarkable improvement in the stability of the therapeutics. PMID:24289106

  17. Drug carriers based on highly protein-resistant materials for prolonged in vivo circulation time

    PubMed Central

    Liu, Ruiyuan; Li, Yan; Zhang, Zhenzhong; Zhang, Xin

    2015-01-01

    Long-circulating drug carriers are highly desirable in drug delivery system. However, nonspecific protein adsorption leaves a great challenge in drug delivery of intravenous administration and significantly affects both the pharmacokinetic profiles of the carrier and drugs, resulting in negatively affect of therapeutic efficiency. Therefore, it is important to make surface modification of drug carriers by protein-resistant materials to prolong the blood circulation time and increase the targeted accumulation of therapeutic agents. In this review, we highlight the possible mechanism of protein resistance and recent progress of the alternative protein-resistant materials and their drug carriers, such as poly(ethylene glycol), oligo(ethylene glycol), zwitterionic materials, and red blood cells adhesion. PMID:26813147

  18. A Laboratory Experiment in Pharmaceutical Analysis: Determination of Drugs of Abuse in Human Urine by Thin-Layer Chromatography.

    ERIC Educational Resources Information Center

    Bailey, Leonard C.

    1979-01-01

    An experiment is described that was developed for a course in Inorganic and Analytical Pharmaceutical Chemistry at Rutgers University to provide pharmacy students with practical experience in the thin-layer chromatography used for the analysis of urine to monitor patient compliance with drug abuse treatment programs. (JMD)

  19. 77 FR 40367 - Wyeth Pharmaceuticals, Inc.; Withdrawal of Approval of a New Drug Application for DURACT Capsules

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-09

    ... DURACT (bromfenac sodium) Capsules, held by Wyeth Pharmaceuticals, Inc. (Wyeth), P.O. Box 8299.... SUPPLEMENTARY INFORMATION: In June 1998, Wyeth voluntarily withdrew DURACT (bromfenac sodium) Capsules from the market. DURACT (bromfenac sodium) Capsules, a nonsteroidal anti-inflammatory drug indicated for the...

  20. Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging.

    PubMed

    Horcajada, Patricia; Chalati, Tamim; Serre, Christian; Gillet, Brigitte; Sebrie, Catherine; Baati, Tarek; Eubank, Jarrod F; Heurtaux, Daniela; Clayette, Pascal; Kreuz, Christine; Chang, Jong-San; Hwang, Young Kyu; Marsaud, Veronique; Bories, Phuong-Nhi; Cynober, Luc; Gil, Sophie; Férey, Gérard; Couvreur, Patrick; Gref, Ruxandra

    2010-02-01

    In the domain of health, one important challenge is the efficient delivery of drugs in the body using non-toxic nanocarriers. Most of the existing carrier materials show poor drug loading (usually less than 5 wt% of the transported drug versus the carrier material) and/or rapid release of the proportion of the drug that is simply adsorbed (or anchored) at the external surface of the nanocarrier. In this context, porous hybrid solids, with the ability to tune their structures and porosities for better drug interactions and high loadings, are well suited to serve as nanocarriers for delivery and imaging applications. Here we show that specific non-toxic porous iron(III)-based metal-organic frameworks with engineered cores and surfaces, as well as imaging properties, function as superior nanocarriers for efficient controlled delivery of challenging antitumoural and retroviral drugs (that is, busulfan, azidothymidine triphosphate, doxorubicin or cidofovir) against cancer and AIDS. In addition to their high loadings, they also potentially associate therapeutics and diagnostics, thus opening the way for theranostics, or personalized patient treatments. PMID:20010827

  1. Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging

    NASA Astrophysics Data System (ADS)

    Horcajada, Patricia; Chalati, Tamim; Serre, Christian; Gillet, Brigitte; Sebrie, Catherine; Baati, Tarek; Eubank, Jarrod F.; Heurtaux, Daniela; Clayette, Pascal; Kreuz, Christine; Chang, Jong-San; Hwang, Young Kyu; Marsaud, Veronique; Bories, Phuong-Nhi; Cynober, Luc; Gil, Sophie; Férey, Gérard; Couvreur, Patrick; Gref, Ruxandra

    2010-02-01

    In the domain of health, one important challenge is the efficient delivery of drugs in the body using non-toxic nanocarriers. Most of the existing carrier materials show poor drug loading (usually less than 5wt% of the transported drug versus the carrier material) and/or rapid release of the proportion of the drug that is simply adsorbed (or anchored) at the external surface of the nanocarrier. In this context, porous hybrid solids, with the ability to tune their structures and porosities for better drug interactions and high loadings, are well suited to serve as nanocarriers for delivery and imaging applications. Here we show that specific non-toxic porous iron(III)-based metal-organic frameworks with engineered cores and surfaces, as well as imaging properties, function as superior nanocarriers for efficient controlled delivery of challenging antitumoural and retroviral drugs (that is, busulfan, azidothymidine triphosphate, doxorubicin or cidofovir) against cancer and AIDS. In addition to their high loadings, they also potentially associate therapeutics and diagnostics, thus opening the way for theranostics, or personalized patient treatments.

  2. An Enzyme-Responsive Nanogel Carrier Based on PAMAM Dendrimers for Drug Delivery.

    PubMed

    Wang, Yao; Luo, Yiyang; Zhao, Qiang; Wang, Zhijian; Xu, Zejun; Jia, Xinru

    2016-08-10

    G4 PAMAM dendrimer molecules were modified via covalently conjugating RGDC, RAADyC, and PEG chains on the periphery (Mac-1), by which a nanogel drug carrier with enzyme-sensitivity (NG-1) was constructed through an oxidation reaction by using NaIO4 to initiate the chemical cross-link of the functional groups on the periphery of dendrimers. Mac-1 and NG-1 both had a spherelike shape with a relatively uniform size of 20 nm for Mac-1 and 50 nm for NG-1 as evidenced by TEM, SEM, and DLS measurements. NG-1 showed much higher drug loading capacity as compared with that of Mac-1 although the cavities in the dendritic structure were used to encapsulate drug molecules as reported in many literatures. In addition, the size of NG-1 with embedded doxorubicin hydrochloride (DOX) decreased significantly to 15 nm in the presence of elastase, which indicated the decomposition of the nanogel triggered by enzyme, leading to drug release in a sustained manner in vitro. The NG-1 carrier was noncytotoxic and biocompatible, and it achieved the same cytotoxicity as free DOX when the drug molecules were loaded inside. From confocal images, the penetrative process of DOX from nanogel could be clearly observed in 8 h. Such a dendrimer-based nanogel may be a potential nanocarrier for drug delivery in cancer therapy. PMID:27420576

  3. Biosafe Nanoscale Pharmaceutical Adjuvant Materials

    PubMed Central

    Jin, Shubin; Li, Shengliang; Wang, Chongxi; Liu, Juan; Yang, Xiaolong; Wang, Paul C.; Zhang, Xin; Liang, Xing-Jie

    2014-01-01

    Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique properties which could be employed to develop drug carriers with longer circulation time, higher loading capacity, better stability in physiological conditions, controlled drug release, and targeted drug delivery. In this review article, we will review recent progress in the application of representative organic, inorganic and hybrid biosafe nanoscale materials in pharmaceutical research, especially focusing on nanomaterial-based novel drug delivery systems. In addition, we briefly discuss the advantages and notable functions that make these nanomaterials suitable for the design of new medicines; the biosafety of each material discussed in this article is also highlighted to provide a comprehensive understanding of their adjuvant attributes. PMID:25429253

  4. An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei

    PubMed Central

    de Macêdo, Juan P.; Schumann Burkard, Gabriela; Niemann, Moritz; Barrett, Michael P.; Vial, Henri; Mäser, Pascal; Roditi, Isabel; Schneider, André; Bütikofer, Peter

    2015-01-01

    Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug action or targeting. PMID

  5. An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.

    PubMed

    de Macêdo, Juan P; Schumann Burkard, Gabriela; Niemann, Moritz; Barrett, Michael P; Vial, Henri; Mäser, Pascal; Roditi, Isabel; Schneider, André; Bütikofer, Peter

    2015-05-01

    Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug action or targeting. PMID

  6. Pharmaceutical drugs supporting regeneration of small-intestinal mucosa severely damaged by ionizing radiation in mice

    PubMed Central

    Ishihara, Hiroshi; Tanaka, Izumi; Yakumaru, Haruko; Tanaka, Mika; Yokochi, Kazuko; Akashi, Makoto

    2013-01-01

    Accidental exposure of the abdomen to high-dose radiation leads to severe consequences initiated by disruption of the mucosa in the small intestine. Therapeutic options are limited, even though various treatments have been investigated, particularly in the field of regenerative therapy. In order to identify readily available treatment methods, we included several current pharmaceutical drugs, for which the clinical trials have already been completed, in tests on mice that had undergone severe mucosal damage by radiation. The drugs were injected into mice 24 h after exposure to 15.7 Gy X-rays. The effects of the drugs on the damaged mucosa of the small intestine were evaluated using early regeneration indices [the expression of c-myb mRNA, and proliferation of epithelial cells in the form of microcolonies (MCs) by Days 4 and 5 post-irradiation] and the survival rate of the mice. Enhancement of mucosal regeneration at Day 4 (c-myb: P < 0.01, MC: P < 0.05) and improvement of the survival rate (P < 0.05) were observed when a clinical dose of gonadotropin, a stimulator of androgen, was injected. Similarly, a clinical dose of thiamazole (which prevents secretion of thyroid hormone) stimulated mucosal growth by Day 5 (c-myb: P < 0.01, MC: P < 0.05) and also improved the survival rate (P < 0.05). The nonclinical drugs histamine and high-dose octreotide (a growth hormone antagonist) also gave significant survival-enhancing benefits (P < 0.01 and P < 0.05, respectively). These results can be used to construct therapeutic programs and applied in various experimental studies to control the regeneration of damaged mucosa. PMID:23728323

  7. Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals

    PubMed Central

    Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

    2015-01-01

    Introduction Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Objectives Trends in FDA approved FDC in the period 1980–2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. Materials and Methods New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. Results During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. Conclusion FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination. PMID:26469277

  8. Nanohybrid structure analysis and biomolecule release behavior of polysaccharide-CDHA drug carriers

    NASA Astrophysics Data System (ADS)

    Huang, Li-Ying; Liu, Ting-Yu; Liu, Tse-Ying; Mevold, Andreas; Hardiansyah, Andri; Liao, Hung-Chou; Lin, Chin-Ching; Yang, Ming-Chien

    2013-10-01

    Nanoscaled polymer composites were prepared from polysaccharide chitosan (CS) and Ca-deficient hydroxyapatite (CDHA). CS-CDHA nanocomposites were synthesized by in situ precipitation at pH 9, and the CS-CDHA carriers were then fabricated by ionic cross-linking methods using tripolyphosphate and chemical cross-linking methods by glutaraldehyde and genipin. Certain biomolecules such as vitamin B12, cytochrome c, and bovine serum albumin were loaded into the CS-CDHA carriers, and their release behaviors were investigated. Furthermore, these CS-CDHA carriers were examined by transmission electron microscopy, electron spectroscopy for chemical analysis, and X-ray diffraction. The release behavior of the biomolecules was controlled by the CS/CDHA ratios and cross-linked agents. By increasing the concentration of CS and the concentration of the cross-linking agents, cross-linking within carriers increases, and the release rate of the biomolecules is decreased. Moreover, the release rate of the biomolecules from the CS-CDHA carriers at pH 4 was higher than that at pH 10, displaying a pH-sensitive behavior. Therefore, these CS-CDHA hydrogel beads may be useful for intelligent drug release and accelerate bone reconstruction.

  9. A simple and sensitive spectrofluorimetric method for analysis of some nitrofuran drugs in pharmaceutical preparations.

    PubMed

    Belal, Tarek Saied

    2008-09-01

    A simple, rapid, selective and sensitive spectrofluorimetric method was described for the analysis of three nitrofuran drugs, namely, nifuroxazide (NX), nitrofurantoin (NT) and nitrofurazone (NZ). The method involved the alkaline hydrolysis of the studied drugs by warming with 0.1 M sodium hydroxide solution then dilution with distilled water for NX or 2-propanol for NT and NZ. The formed fluorophores were measured at 465 nm (lambda (Ex) 265 nm), 458 nm (lambda (Ex) 245 nm) and 445 nm (lambda (Ex) 245 nm) for NX, NT and NZ, respectively. The reaction pathway was discussed and the structures of the fluorescent products were proposed. The different experimental parameters were studied and optimized. Regression analysis showed good correlation between fluorescence intensity and concentration over the ranges 0.08-1.00, 0.02-0.24 and 0.004-0.050 microg ml(-1) for NX, NT and NZ, respectively. The limits of detection of the method were 8.0, 1.9 and 0.3 ng ml(-1) for NX, NT and NZ, respectively. The proposed method was validated in terms of accuracy, precision and specificity, and it was successfully applied for the assay of the three nitrofurans in their different dosage forms. No interference was observed from common pharmaceutical adjuvants. The results were favorably compared with those obtained by reference spectrophotometric methods. PMID:18246413

  10. Stereoisomeric profiling of drugs of abuse and pharmaceuticals in wastewaters of Valencia (Spain).

    PubMed

    Vazquez-Roig, Pablo; Kasprzyk-Hordern, Barbara; Blasco, Cristina; Picó, Yolanda

    2014-10-01

    The enantiomeric and diastereomeric profiling of chiral pharmaceuticals (ephedrine, norephedrine, atenolol and venlafaxine) and illicit drugs (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)) was undertaken over a period of fourteen consecutive days in three wastewater treatment plants (WWTPs) in the city of Valencia, Spain. Degradation efficiency of WWTPs was found to be compound and enantiomer dependent. Selective enantiomer enrichment was observed for several target analytes. Amphetamine and MDMA were enriched with R(-)-enantiomers. 1S,2S(+)-pseudoephedrine was found to be more readily degradable during activated sludge treatment than its diastereomer 1R,2S(-)-ephedrine. Atenolol underwent enrichment with either S(-)- or R(+)-enantiomer in different WWTPs. This unexpected enantiomeric variation in the stereoselective degradation of atenolol could be attributed to different processes utilized during activated sludge treatment. The application of (enantiomeric) profiling of wastewater revealed usage patterns of chiral drugs in the Valencia region. PMID:25029504

  11. Apoferritin Modified Magnetic Particles as Doxorubicin Carriers for Anticancer Drug Delivery

    PubMed Central

    Blazkova, Iva; Nguyen, Hoai Viet; Dostalova, Simona; Kopel, Pavel; Stanisavljevic, Maja; Vaculovicova, Marketa; Stiborova, Marie; Eckschlager, Tomas; Kizek, Rene; Adam, Vojtech

    2013-01-01

    Magnetic particle mediated transport in combination with nanomaterial based drug carrier has a great potential for targeted cancer therapy. In this study, doxorubicin encapsulation into the apoferritin and its conjugation with magnetic particles was investigated by capillary electrophoresis with laser-induced fluorescence detection (CE-LIF). The quantification of encapsulated doxorubicin was performed by fluorescence spectroscopy and compared to CE-LIF. Moreover, the significant enhancement of the doxorubicin signal was observed by addition of methanol into the sample solution. PMID:23807501

  12. Peptides in Cancer Nanomedicine: Drug Carriers, Targeting Ligands and Protease Substrates

    PubMed Central

    Zhang, Xiao-Xiang; Eden, Henry S.; Chen, Xiaoyuan

    2011-01-01

    Peptides are attracting increasing attention as therapeutic agents, as the technologies for peptide development and manufacture continue to mature. Concurrently, with booming researches in nanotechnology for biomedical applications, peptides have been studied as an important class of components in nanomedicine, and they have been used either alone or in combination with nanomaterials of every reported composition. Peptides possess many advantages, such as smallness, ease of synthesis and modification, and good biocompatibility. Their functions in cancer nanomedicine, discussed in this review, include serving as drug carriers; as targeting ligands; and as protease-responsive substrates for drug delivery. PMID:22056916

  13. Occurrence and spatial distribution of 158 pharmaceuticals, drugs of abuse and related metabolites in offshore seawater.

    PubMed

    Alygizakis, Nikiforos A; Gago-Ferrero, Pablo; Borova, Viola L; Pavlidou, Alexandra; Hatzianestis, Ioannis; Thomaidis, Nikolaos S

    2016-01-15

    The occurrence and spatial distribution of 158 pharmaceuticals and drugs of abuse were studied in seawater of the Eastern Mediterranean Sea (Saronikos Gulf and Elefsis Bay in central Aegean Sea). This area is affected by various anthropogenic pressures as it receives the treated wastewater of the greatest Athens area and off-shore input fluxes. This study constitutes the largest one in terms of number of analytes in this environmental compartment. It provides the first evidence on the occurrence of several pharmaceuticals in marine environment including amoxicillin, lidocaine, citalopram or tramadol, among others. 22 samples were collected at three different depths in 9 sampling stations in order to assess the presence and the spatial distribution of the target compounds. A multi-residue method based on solid phase extraction and liquid chromatography coupled to tandem mass spectrometry was developed for the determination of the 158 target substances and validated for seawater sample analysis. 38 out of the 158 target compounds were detected, 15 of them with frequencies of detection equal to or higher than 50%. The highest detected values corresponded to amoxicillin, caffeine and salicylic acid, with concentrations in the range of < 5.0-127.8 ng L(-1); 5.2-78.2 ng L(-1) and < 0.4-53.3 ng L(-1), respectively. Inputs from the wastewater treatment plant (WWTP) of Athens revealed to be the main source of pollution in the Inner Saronikos Gulf, whereas, other anthropogenic pressures such as contamination from shipping activity, industrial effluents, dredging and/or inputs from land proved to be also relevant. Τhe concentrations of some compounds varied significantly with depth suggesting that currents play an important role in the dilution of the target compounds. PMID:26473711

  14. A Comprehensive Review on Cyclodextrin-Based Carriers for Delivery of Chemotherapeutic Cytotoxic Anticancer Drugs

    PubMed Central

    Gidwani, Bina; Vyas, Amber

    2015-01-01

    Most of the cytotoxic chemotherapeutic agents have poor aqueous solubility. These molecules are associated with poor physicochemical and biopharmaceutical properties, which makes the formulation difficult. An important approach in this regard is the use of combination of cyclodextrin and nanotechnology in delivery system. This paper provides an overview of limitations associated with anticancer drugs, their complexation with cyclodextrins, loading/encapsulating the complexed drugs into carriers, and various approaches used for the delivery. The present review article aims to assess the utility of cyclodextrin-based carriers like liposomes, niosomes, nanoparticles, micelles, millirods, and siRNA for delivery of antineoplastic agents. These systems based on cyclodextrin complexation and nanotechnology will camouflage the undesirable properties of drug and lead to synergistic or additive effect. Cyclodextrin-based nanotechnology seems to provide better therapeutic effect and sustain long life of healthy and recovered cells. Still, considerable study on delivery system and administration routes of cyclodextrin-based carriers is necessary with respect to their pharmacokinetics and toxicology to substantiate their safety and efficiency. In future, it would be possible to resolve the conventional and current issues associated with the development and commercialization of antineoplastic agents. PMID:26582104

  15. Modified local diatomite as potential functional drug carrier--A model study for diclofenac sodium.

    PubMed

    Janićijević, Jelena; Krajišnik, Danina; Čalija, Bojan; Vasiljević, Bojana Nedić; Dobričić, Vladimir; Daković, Aleksandra; Antonijević, Milan D; Milić, Jela

    2015-12-30

    Diatomite makes a promising candidate for a drug carrier because of its high porosity, large surface area, modifiable surface chemistry and biocompatibility. Herein, refined diatomite from Kolubara coal basin, which complied with the pharmacopoeial requirements for heavy metals content and microbiological quality, was used as a starting material. Inorganic modification of the starting material was performed through a simple, one-step procedure. Significant increase in adsorbent loading with diclofenac sodium (DS) was achieved after the modification process (∼373mg/g) which enabled the preparation of comprimates containing therapeutic dose of the adsorbed drug. Adsorption of DS onto modified diatomite resulted in the alteration of the drug's XRD pattern and FTIR spectrum. In vitro drug release studies in phosphate buffer pH 7.5 demonstrated prolonged DS release over 8h from comprimates containing DS adsorbed on modified diatomite (up to 37% after 8h) and those containing physical mixture of the same composition (up to 45% after 8h). The results of in vivo toxicity testing on mice pointed on potential safety of both unmodified (starting) and modified diatomite. All these findings favor the application of diatomite as a potential functional drug carrier. PMID:26498370

  16. Non-polymeric nano-carriers in HIV/AIDS drug delivery and targeting.

    PubMed

    Gupta, Umesh; Jain, Narendra K

    2010-03-18

    Development of an effective drug delivery approach for the treatment of HIV/AIDS is a global challenge. The conventional drug delivery approaches including Highly Active Anti Retroviral Therapy (HAART) have increased the life span of the HIV/AIDS patient. However, the eradication of HIV is still not possible with these approaches due to some limitations. Emergence of polymeric and non-polymeric nanotechnological approaches can be opportunistic in this direction. Polymeric carriers like, dendrimers and nanoparticles have been reported for the targeting of anti HIV drugs. The synthetic pathways as well polymeric framework create some hurdles in their successful formulation development as well as in the possible drug delivery approaches. In the present article, we have discussed the general physiological aspects of the infection along with the relevance of non-polymeric nanocarriers like liposomes, solid lipid nanoparticles (SLN), ethosomes, etc. in the treatment of this disastrous disease. PMID:19913579

  17. Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear

    PubMed Central

    2014-01-01

    Nanoparticles have attracted increasing attention for local drug delivery to the inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method followed by glutaraldehyde fixation or heat denaturation. The nanoparticles were spherical in shape with an average diameter of 492 nm. The heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could adhere on and penetrate through the round window membrane of guinea pigs. The nanoparticles were analyzed as drug carriers to investigate the loading capacity and release behaviors. Rhodamine B was used as a model drug in this paper. Rhodamine B-loaded nanoparticles showed a controlled release profile and could be deposited on the osseous spiral lamina. We considered that the bovine serum albumin nanoparticles may have potential applications in the field of local drug delivery in the treatment of inner ear disorders. PMID:25114637

  18. Mesoporous Silica Nanoparticles as Controlled Release Drug Delivery and Gene Transfection Carriers

    SciTech Connect

    Igor I. Slowing; Juan L. Viveo-Escoto; Chia-Wen Wu; Victor S. Y. Lin

    2008-04-10

    In this review, we highlight the recent research developments of a series of surface-functionalized mesoporous silica nanoparticle (MSN) materials as efficient drug delivery carriers. The synthesis of this type of MSN materials is described along with the current methods for controlling the structural properties and chemical functionalization for biotechnological and biomedical applications. We summarized the advantages of using MSN for several drug delivery applications. The recent investigations of the biocompatibility of MSN in vitro are discussed. We also describe the exciting progress on using MSN to penetrate various cell membranes in animal and plant cells. The novel concept of gatekeeping is introduced and applied to the design of a variety of stimuli-responsive nanodevices. We envision that these MSN-based systems have a great potential for a variety of drug delivery applications, such as the site-specific delivery and intracellular controlled release of drugs, genes, and other therapeutic agents.

  19. Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear

    NASA Astrophysics Data System (ADS)

    Yu, Zhan; Yu, Min; Zhang, Zhibao; Hong, Ge; Xiong, Qingqing

    2014-07-01

    Nanoparticles have attracted increasing attention for local drug delivery to the inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method followed by glutaraldehyde fixation or heat denaturation. The nanoparticles were spherical in shape with an average diameter of 492 nm. The heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could adhere on and penetrate through the round window membrane of guinea pigs. The nanoparticles were analyzed as drug carriers to investigate the loading capacity and release behaviors. Rhodamine B was used as a model drug in this paper. Rhodamine B-loaded nanoparticles showed a controlled release profile and could be deposited on the osseous spiral lamina. We considered that the bovine serum albumin nanoparticles may have potential applications in the field of local drug delivery in the treatment of inner ear disorders.

  20. A drug carrier targeting murine uPAR for photodynamic therapy and tumor imaging.

    PubMed

    Zhou, Xiaolei; Zheng, Ke; Li, Rui; Chen, Zhuo; Yuan, Cai; Hu, Ping; Chen, Jincan; Xue, Jinping; Huang, Mingdong

    2015-09-01

    Photodynamic therapy (PDT) has been used as an effective therapeutical modality for tumors. In PDT, a photosensitizer was used to capture the light of specific wavelength, leading to the generation of reactive oxygen species and cytotoxicity surrounding the photosensitizer. Modifications of photosensitizers to enhance tumor specificity are common approaches to increase the efficacy and reduce the side effects of PDT. Previously, we developed a human serum albumin (HSA)-based drug carrier fused with the human amino-terminal fragment (hATF), which binds to a tumor surface marker (urokinase receptor, uPAR). However, hATF-HSA binds to murine uPAR much weaker (79-fold) than to human uPAR, and is not optimal for applications on murine tumor models. In this study, we developed a murine version of the drug carrier (mATF-HSA). A photosensitizer (mono-substituted β-carboxy phthalocyanine zinc, CPZ) was loaded into this carrier, giving a rather stable macromolecule (mATF-HSA:CPZ) that was shown to bind to murine uPAR in vitro. In addition, we evaluated both the photodynamic therapy efficacy and tumor retention capability of the macromolecule (at a dose of 0.05mg CPZ/kg mouse body weight) on murine hepatoma-22 (H22) tumor bearing mouse model. mATF-HSA:CPZ showed more accumulation in tumors compared to its human counterpart (hATF-HSA:CPZ) measured by quantitative fluorescence molecular tomography (FMT). Besides, mATF-HSA:CPZ exhibited a higher tumor killing efficacy than hATF-HSA:CPZ. Together, the macromolecule mATF-HSA is a promising tumor-specific drug carrier on murine tumor models and is an useful tool to study tumor biology on murine tumor models. PMID:26004218

  1. Chitosan-graft-β-cyclodextrin nanoparticles as a carrier for controlled drug release.

    PubMed

    Yuan, Zeting; Ye, Yajing; Gao, Feng; Yuan, Huihui; Lan, Minbo; Lou, Kaiyan; Wang, Wei

    2013-03-25

    Chitosan (CS) grafted with β-cyclodextrin (CD-g-CS) nanoparticles as a new carrier for poorly water-soluble drugs has been developed. The CD-g-CS polymer is readily synthesized from chitosan and mono-6-deoxy-6-(p-toluenesulfonyl)-β-cyclodextrin. Three different degrees of substitution (DS) of β-cyclodextrin (β-CD) on CD-g-CS (9.6, 14.0 and 20.0%) are designed and evaluated by controlling the mole ratio of β-CD to chitosan. Then CD-g-CS nanoparticles are prepared by an ionic gelation method, with the controlled size of 202.0-589.0 nm. Stable colloidal dispersion of the nanoparticles has been formed with the zeta potential of +23.0 to +43.0 mV. In vitro stability test indicates that CD-g-CS nanoparticles are more stable in phosphate-buffered saline compared with CS nanoparticles. Finally, the poorly water-soluble drug, ketoprofen (KTP), is used as a model drug to evaluate the efficiency of the new drug delivery carrier. It is found that the encapsulation efficiency of KTP in the nanoparticles with 20% DS of CD is as high as 1.36-fold than that of CS nanoparticles. Moreover, notably KTP is released from the nanoparticles in a controlled-release manner and is pH-responsive on DS of CD. In summary, these results suggest that the CD-g-CS nanoparticles, as a general promising drug delivery system, can be used as a potential biodegradable nano-drug delivery system for controlled release of poorly water-soluble drugs with pH-responsive capability. PMID:23422276

  2. Graphene oxide used as a carrier for adriamycin can reverse drug resistance in breast cancer cells

    NASA Astrophysics Data System (ADS)

    Wu, Jing; Wang, Yin-song; Yang, Xiao-ying; Liu, Yuan-yuan; Yang, Jin-rong; Yang, Rui; Zhang, Ning

    2012-09-01

    This study evaluates the reversal effects of graphene oxide (GO) used as a carrier for adriamycin (ADR) in cancer drug resistance, and provides a preliminary investigation into the reversal mechanism. ADR was loaded onto the GO surface (ADR-GO) by physical mixing and drug loading content was found to be high, up to 93.6%. In vitro releases of ADR from ADR-GO were studied using a dialysis method, and they exhibited a significant pH-sensitive property. Cell experiments showed that GO significantly enhanced the accumulation of ADR in MCF-7/ADR cells (an ADR resistant breast cancer cell line) and exhibited much higher cytotoxicity than free ADR, suggesting that ADR-GO could effectively reverse ADR resistance of MCF-7/ADR, with the reversal index reaching 8.35. Microscopy studies found that GO could effectively carry drug molecules into cells in both endocytosis-dependent and independent manners. In conclusion, use of GO as a carrier for chemotherapeutic agents is favorable for the treatment of drug resistant cancers.

  3. Polydopamine-coated liposomes as pH-sensitive anticancer drug carriers.

    PubMed

    Zong, Wei; Hu, Ying; Su, Yingchun; Luo, Nan; Zhang, Xunan; Li, Qingchuan; Han, Xiaojun

    2016-05-01

    Stimuli-responsive drug carriers are considered to play important roles in chemotherapy. We fabricated pH-sensitive polydopamine-protected liposomes (liposome@PDA) drug delivery systems, which were characterised with microscope, scanning electron microscope (SEM), UV-vis spectrometer and Fourier transform infrared (FTIR) technieques. The typical chemotherapeutic agent, 5-fluorouracil (5-FU), was loaded into liposome@PDA capsules. The maximum release percentages of 5-FU are 3.2%, 29.5%, 52.7%, 76.7% in the solution with pH 7.42, 6.87, 4.11 and 3.16, respectively. The in vitro cell cytotoxity experiments were carried out using 5-FU-loaded capsules at pH 6.87 solution, which simulate the true pH around cancerous cells. At 1.5 μM concentration, the free 5-FU, 5-FU-loaded liposome capsules and 5-FU-loaded capsules showed the cell viability of 50.56%, 22.66% and 21.63%, respectively. It confirms that drug-loaded capsules performed better than free drug. The results demonstrate the great potential of liposome@PDA capsules as carriers in biomedical applications. PMID:27174396

  4. A novel drug carrier based on functional modified nanofiber cellulose and the control release behavior

    NASA Astrophysics Data System (ADS)

    Shi, Xiangning; Zheng, Yudong; Zhang, Wei; Zhang, Zeyu; Peng, Yunling

    2013-08-01

    This study developed a novel drug carrier based on functional modified bacterial cellulose(BC) which was conjugated with Ibuprofen(IBU) by esterification. BC-Ibuprofen as the macro- molecular prodrugs and drug carrier used to improve the short half-life of the drug, and was able to control release through the hydrolysis of ester bond between the hydroxyl groups of BC with Ibuprofen under different condition. Fourier transform infrared analysis revealed that Ibuprofen had been successfully grafted onto the bacterial cellulose (BC). Thermal and morphological characterization indicated the formation of the BC-Ibuprofen system incompletely reacted maintained the bulk structure of the pristine material such as crystallinity, 3-dimentional network and so on. The drug release behaviours were affected by the ester bond hydrolysis as well as the microstructure characteristics of the modified nanofiber. The release of BC-IBU showed an apparent pH-dependent, fast in alkaline and acid solution but slow relatively in neutral. Such pH-responsiveness, in addition to its morphological characteristics, in this paper suggested a great potential of BC-IBU as a more effective, safe, and stable prodrug candidate.

  5. [Drug utilization and pharmaceutical cost-containment in germany-perspectives 1 year after enactment of the GMG].

    PubMed

    Schlander, Michael

    2005-06-15

    After 3 decades of health care cost containment in Germany, enactment of the most recent reform (Health Insurance Modernization Act, GMG) marks a watershed insofar as, apparently, the potential has been largely exhausted for further savings in pharmaceutical spending. Yet the new drugs segment maintains its role as a growth driver, owing to the continuing shift from older to new, and frequently more expensive, products. This observation holds true even after introducing phase 2 reference pricing, covering so-called me too products. Health economic analyses would be required to better differentiate pharmaceutical products based on their incremental cost-effectiveness ratio. However, the opportunity was missed with the GMG to introduce formal health-economic evaluations and thus overcome the counterproductive silo mentality associated with traditional German component management. International experience from Australia, Canada, and the United Kingdom suggests that economic evaluations, while informing rational reimbursement decisions, may in fact contribute to increasing pharmaceutical expenditures. Further tightening of pharmaceutical component management in Germany may result in increasing inefficiencies due to underuse of effective products; furthermore, it appears conceivable that ("second order") dynamic inefficiencies and, hence, social costs might be the consequence of reduced pharmaceutical research and development expenditures. PMID:15968483

  6. All-trans retinoic acid-loaded lipid nanoparticles as a transdermal drug delivery carrier.

    PubMed

    Charoenputtakhun, Ponwanit; Opanasopit, Praneet; Rojanarata, Theerasak; Ngawhirunpat, Tanasait

    2014-03-01

    The objective of this study was to investigate the effects of drug amounts (0.1%, 0.2% and 0.3% w/w), amounts of the oil (10%, 15% and 20% w/w of lipid matrix) and types of the oil (soybean oil (S), medium chain triglycerides (M), oleic acids (O) and linoleic acids (L)) in lipid matrix of all-trans retinoic acid (ATRA)-loaded nanostructured lipid carriers (NLCs) for transdermal drug delivery. The ATRA-loaded solid lipid nanoparticles (SLNs) were formulated with 30% w/w cetyl palmitate. All lipid nanoparticles had average sizes between 130 and 241 nm and had negative zeta potentials. The drug loading of all formulations was higher than 95%. The release of drug from all lipid nanoparticles followed zero-order kinetics. The amount of drug released from all the NLCs and SLNs was significantly greater than the drug released from the ATRA suspension. The ATRA flux of the SLNs was higher than the NLCs. The flux of the NLCs containing oleic acid was significantly higher than the other types of oils. The chemical stability at 4 °C, the percentage of ATRA remaining in all the lipid nanoparticles tested was higher than 80%. It can be concluded that both the SLNs and NLCs are promising dermal drug delivery systems for ATRA. PMID:23356887

  7. Nanostructured lipid carriers: An emerging platform for improving oral bioavailability of lipophilic drugs

    PubMed Central

    Khan, Saba; Baboota, Sanjula; Ali, Javed; Khan, Sana; Narang, Ramandeep Singh; Narang, Jasjeet Kaur

    2015-01-01

    Nowadays exploration of novel lipid-based formulations is akin to a magnet for researchers worldwide for improving the in vivo performance of highly lipophilic drugs. Over the last few years, new compositions of lipids have been developed, and the probable bioavailability enhancement has been investigated. We reviewed the most recent data dealing with backlogs of conventional lipid-based formulations such as physical instability, limited drug loading capacities, drug expulsion during storage along with all the possible hindrances resulting in poor absorption of highly lipophilic drugs such as P-glycoprotein efflux, extensive metabolism by cytochrome P450 etc. In tandem with these aspects, an exclusive formulation approach has been discussed in detail in this paper. Therefore, this review focuses on resolving the concerned ambiguity with successful oral administration of highly lipophilic drugs through designing novel lipidic formulations (nanostructured lipid carriers [NLC]) that constitute a blend of solid and liquid lipids. The article highlights the potential role of such formulation in normalizing the in vivo fate of poorly soluble drugs. Finally, the present manuscript discusses the dominance of NLC over other lipid-based formulations and provides a perspective of how they defeat and overcome the barriers that lead to the poor bioavailability of hydrophobic drugs. PMID:26682188

  8. Nanostructured lipid carriers: An emerging platform for improving oral bioavailability of lipophilic drugs.

    PubMed

    Khan, Saba; Baboota, Sanjula; Ali, Javed; Khan, Sana; Narang, Ramandeep Singh; Narang, Jasjeet Kaur

    2015-01-01

    Nowadays exploration of novel lipid-based formulations is akin to a magnet for researchers worldwide for improving the in vivo performance of highly lipophilic drugs. Over the last few years, new compositions of lipids have been developed, and the probable bioavailability enhancement has been investigated. We reviewed the most recent data dealing with backlogs of conventional lipid-based formulations such as physical instability, limited drug loading capacities, drug expulsion during storage along with all the possible hindrances resulting in poor absorption of highly lipophilic drugs such as P-glycoprotein efflux, extensive metabolism by cytochrome P450 etc. In tandem with these aspects, an exclusive formulation approach has been discussed in detail in this paper. Therefore, this review focuses on resolving the concerned ambiguity with successful oral administration of highly lipophilic drugs through designing novel lipidic formulations (nanostructured lipid carriers [NLC]) that constitute a blend of solid and liquid lipids. The article highlights the potential role of such formulation in normalizing the in vivo fate of poorly soluble drugs. Finally, the present manuscript discusses the dominance of NLC over other lipid-based formulations and provides a perspective of how they defeat and overcome the barriers that lead to the poor bioavailability of hydrophobic drugs. PMID:26682188

  9. Exploiting the Tumor Phenotype Using Biodegradable Submicron Carriers of Chemotherapeutic Drugs

    PubMed Central

    Geary, Sean M.; Salem, Aliasger K.

    2014-01-01

    Tumor tissues possess characteristics that distinguish them from healthy tissues and make them attractive targets for submicron carriers of chemotherapeutic drugs (CTX). CTX are generally administered systemically in free form to cancer patients resulting in unwanted cytotoxic effects and placing limitations on the deliverable CTX dose. In an effort to raise the therapeutic index of CTX there are now liposome-based CTX formulations in clinical use that are more tumor specific than the free form of CTX. However, progression to liposome-based chemotherapy in the clinic has been slow and there have been no approved formulations introduced in the last decade. Alternative carrier systems such as those made from the biodegradable polymer poly(lactic-co-glycolic) acid (PLGA) have been investigated in preclinical settings with promising outcomes. Here we review the principle behind biodegradable submicron carriers as CTX delivery vehicles for solid tumors with a specific focUS on liposomes and PLGA-based carriers, highlighting the strengths and weaknesses of each system. PMID:25271435

  10. Co-suppression of vitamin C composite nano-drug carrier and its drug delivery to nidus in tumor cells.

    PubMed

    Liu, H Z; Liu, X M; Liu, X C; Zhang, C Z; Liu, H Q

    2016-01-01

    This study aimed to discuss the co-suppression of vitamin C-contained composite nano-drug carrier and its drug delivery to nidus in tumor cells. Amphiphilic polymers PLA-block-PAAA and block polymer PLA-PEG4000-Maleimide, PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelles were prepared, and, PLA-block-PAAA polymer-coated Nile red nano-micelle, PLA-block-PAA and PLA-PEG4000-Maleimide composite nano-micelles as well as paclitaxel-carrying composite nano-micelle in different molar ratios were given stability tests. Lastly, PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelle cancer cells and paclitaxel-carrying composite nano-micelle cancer cells were given toxicity tests. Stability tests showed that self stability of PLA-block-PAAA (63/8) nano-micelle was not sufficient; the stability was good when the molar ratio of PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelle was 3:1; paclitaxel-carrying composite nano-micelle had good stability within 48 hours; PAAA segment had an inhibiting effect on C6 cancer cells and paclitaxel-carrying composite nano-micelle had a strong inhibiting effect also on tumors. After 24 hours, with the continuous release of paclitaxel, the tumor inhibiting effect of paclitaxel-carrying composite nano-micelle enhanced gradually, and the controlled-release of drugs had continuous inhibiting effect on tumor cells. Therefore, PAAA segment and paclitaxel had time-postponed synergistic effect. In conclusion, vitamin C-contained composite nanometer drug carrier materials can deliver anti-cancer drugs to nidus and thus inhibit tumor cells. PMID:27358123

  11. Sub-100 nm gold nanoparticle vesicles as a drug delivery carrier enabling rapid drug release upon light irradiation.

    PubMed

    Niikura, Kenichi; Iyo, Naoki; Matsuo, Yasutaka; Mitomo, Hideyuki; Ijiro, Kuniharu

    2013-05-01

    Previously, we reported gold nanoparticles coated with semifluorinated ligands self-assembled into gold nanoparticle vesicles (AuNVs) with a sub-100 nm diameter in tetrahydrofuran (THF). (1) Although this size is potentially useful for in vivo use, the biomedical applications of AuNVs were limited, as the vesicular structure collapsed in water. In this paper, we demonstrate that the AuNVs can be dispersed in water by cross-linking each gold nanoparticle with thiol-terminated PEG so that the cross-linked vesicles can work as a drug delivery carrier enabling light-triggered release. Rhodamine dyes or anticancer drugs were encapsulated within the cross-linked vesicles by heating to 62.5 °C. At this temperature, the gaps between nanoparticles open, as confirmed by a blue shift in the plasmon peak and the more efficient encapsulation than that observed at room temperature. The cross-linked AuNVs released encapsulated drugs upon short-term laser irradiation (5 min, 532 nm) by again opening the nanogaps between each nanoparticle in the vesicle. On the contrary, when heating the solution to 70 °C, the release speed of encapsulated dyes was much lower (more than 2 h) than that triggered by laser irradiation, indicating that cross-linked AuNVs are highly responsive to light. The vesicles were efficiently internalized into cells compared to discrete gold nanoparticles and released anticancer drugs upon laser irradiation in cells. These results indicate that cross-linked AuNVs, sub-100 nm in size, could be a new type of light-responsive drug delivery carrier applicable to the biomedical field. PMID:23566248

  12. 78 FR 26375 - Food and Drug Administration/International Society for Pharmaceutical Engineering Co-Sponsorship...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-06

    ... Pharmaceutical Engineering Co-Sponsorship Educational Workshop: Redefining the `C' in CGMP (Current Good Manufacturing Practices): Creating, Implementing, and Sustaining a Culture of Quality AGENCY: Food and...

  13. β-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

    NASA Astrophysics Data System (ADS)

    Baradari, Hiba; Damia, Chantal; Dutreih-Colas, Maggy; Champion, Eric; Chulia, Dominique; Viana, Marylène

    2011-10-01

    Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous β-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous β-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and β-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on β-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.

  14. Design and Application of Rolling Circle Amplification for a Tumor-Specific Drug Carrier.

    PubMed

    Kim, Jong Hwan; Jang, Mihue; Kim, Young-Je; Ahn, Hyung Jun

    2015-10-01

    It is challenging to design rolling circle amplification (RCA) for tumor-selective delivery of drugs. Here, we devise a doxorubicin nanocarrier composed of RCA products, cholesterol-DNA, and folate-DNA conjugates. RCA products, designed to contain tandem repeats of short hairpin DNA, employ the repeated sequences complementary to both DNA conjugates, and thus RCA products/cholesterol-DNA/folate-DNA complexes, generated via sequential base pairing processes, acquire the amphiphilic properties that facilitate self-assembly into the highly condensed nanoparticles (RCA nanoparticles). Doxorubicin-loaded RCA nanoparticles, especially with high cargo capacity, release drugs to the environment with the aid of acidity and show selective cytotoxicity to cancer cells. Particularly, the condensed structures enable RCA nanoparticles to be resistant to nucleases in the blood. These results show that RCA nanoparticles have great potential as a doxorubicin carrier for targeted cancer therapy, and furthermore, our strategy provides an alternative tool to exploit RCA techniques on drug delivery systems. PMID:26361253

  15. Nanoassembly of surfactants with interfacial drug-interactive motifs as tailor-designed drug carriers.

    PubMed

    Gao, Xiang; Huang, Yixian; Makhov, Alexander M; Epperly, Michael; Lu, Jianqin; Grab, Sheila; Zhang, Peijun; Rohan, Lisa; Xie, Xiang-Qun; Wipf, Peter; Greenberger, Joel; Li, Song

    2013-01-01

    PEGylated lipopeptide surfactants carrying drug-interactive motifs specific for a peptide-nitroxide antioxidant, JP4-039, were designed and constructed to facilitate the solubilization of this drug candidate as micelles and emulsion nanoparticles. A simple screening process based on the ability that prevents the formation of crystals of JP4-039 in aqueous solution was used to identify agents that have potential drug-interactive activities. Several protected lysine derivatives possessing this activity were identified, of which α-Fmoc-ε-t-Boc lysine is the most potent, followed by α-Cbz- and α-iso-butyloxycarbonyl-ε-t-Boc-lysine. Using a polymer-supported liquid-phase synthesis approach, a series of synthetic lipopeptide surfactants with PEG headgroup, varied numbers and geometries of α-Fmoc or α-Cbz-lysyl groups located at interfacial region as the drug-interactive domains, and oleoyl chains as the hydrophobic tails were synthesized. All α-Fmoc-lysyl-containing lipopeptide surfactants were able to solubilize JP4-039 as micelles, with enhanced solubilizing activity for surfactants with increased numbers of α-Fmoc groups. The PEGylated lipopeptide surfactants with α-Fmoc-lysyl groups alone tend to form filamentous or wormlike micelles. The presence of JP4-039 transformed α-Fmoc-containing filamentous micelles into dots and barlike mixed micelles with substantially reduced sizes. Fluorescence quenching and NMR studies revealed that the drug and surfactant molecules were in close proximity in the complex. JP4-039-loaded emulsion carrying α-Cbz-containing surfactants demonstrated enhanced stability over drug-loaded emulsion without lipopeptide surfactants. JP4-039 emulsion showed a significant mitigation effect on mice exposed to a lethal dose of radiation. PEGylated lipopeptides with an interfacially located drug-interactive domain are therefore tailor-designed formulation materials potentially useful for drug development. PMID:23244299

  16. Inductively coupled plasma mass spectrometry in the analysis of biological samples and pharmaceutical drugs

    NASA Astrophysics Data System (ADS)

    Ossipov, K.; Seregina, I. F.; Bolshov, M. A.

    2016-04-01

    Inductively coupled plasma mass spectrometry (ICP-MS) is widely used in the analysis of biological samples (whole blood, serum, blood plasma, urine, tissues, etc.) and pharmaceutical drugs. The shortcomings of this method related to spectral and non-spectral interferences are manifested in full measure in determination of the target analytes in these complex samples strongly differing in composition. The spectral interferences are caused by similarity of masses of the target component and sample matrix components. Non-spectral interferences are related to the influence of sample matrix components on the physicochemical processes taking place during formation and transportation of liquid sample aerosols into the plasma, on the value and spatial distribution of plasma temperature and on the transmission of the ion beam from the interface to mass spectrometer detector. The review is devoted to analysis of different mechanisms of appearance of non-spectral interferences and to ways for their minimization or elimination. Special attention is paid to the techniques of biological sample preparation, which largely determine the mechanisms of the influence of sample composition on the results of element determination. The ways of lowering non-spectral interferences by instrumental parameter tuning and application of internal standards are considered. The bibliography includes 189 references.

  17. Animals on drugs: understanding the role of pharmaceutical companies in the animal-industrial complex.

    PubMed

    Twine, Richard

    2013-12-01

    In this paper I revisit previous critiques that I have made of much, though by no means all, bioethical discourse. These pertain to faithfulness to dualistic ontology, a taken-for-granted normative anthropocentrism, and the exclusion of a consideration of how political economy shapes the conditions for bioethical discourse (Twine Medicine, Health Care and Philosophy 8(3):285-295, 2005; International Journal of Sociology of Agriculture and Food 16(3):1-18, 2007, 2010). Part of my argument around bioethical dualist ontology is to critique the assumption of a division between the "medical" (human) and "agricultural" (nonhuman) and to show various ways in which they are interrelated. I deepen this analysis with a focus on transnational pharmaceutical companies, with specific attention to their role in enhancing agricultural production through animal drug administration. I employ the topical case of antibiotics in order to speak to current debates in not only the interdisciplinary field of bioethics but also that of animal studies. More generally, the animal-industrial complex (Twine Journal for Critical Animal Studies 10(1):12-39, 2012) is underlined as a highly relevant bioethical object that deserves more conceptual and empirical attention. PMID:24092398

  18. Pharmaceutical Evaluation of Cefuroxime Axetil Tablets Available in Drug Market of Pakistan

    PubMed Central

    Israr, F.; Mahmood, Z. A.; Hassan, F.; Hasan, S. M. F.

    2016-01-01

    Cefuroxime is a second generation cephalosporin antibiotic with a broad spectrum activity against Gram positive and Gram negative bacteria. The purpose of this research work was to evaluate the pharmaceutical quality standards of four different brands of cefuroxime axetil 125 mg tablets with different price ranges purchased from retail pharmacies of Pakistan. The brands were tested for physicochemical evaluation and in vitro dissolution studies in different medium like 0.07N HCl, distilled water, 0.1N HCl of pH 1.2 and phosphate buffers of pH 4.5 and pH 6.8. Statistical analysis, model dependent (zero order, first order, Korsmeyer-Peppas, Hixson-Crowell, Weibull) and model independent (Difference f1, similarity f2) approaches were applied to multiple dissolution profile of all brands. All brands were found to be similar with reference and meeting the compendial quality standard. Inter brand variation was observed in disintegration time and assay which was resulted in significant differences (P<0.05) in drug release data and Weibull was observed as best fill model. PMID:27168677

  19. Pharmaceutical Evaluation of Cefuroxime Axetil Tablets Available in Drug Market of Pakistan.

    PubMed

    Israr, F; Mahmood, Z A; Hassan, F; Hasan, S M F

    2016-01-01

    Cefuroxime is a second generation cephalosporin antibiotic with a broad spectrum activity against Gram positive and Gram negative bacteria. The purpose of this research work was to evaluate the pharmaceutical quality standards of four different brands of cefuroxime axetil 125 mg tablets with different price ranges purchased from retail pharmacies of Pakistan. The brands were tested for physicochemical evaluation and in vitro dissolution studies in different medium like 0.07N HCl, distilled water, 0.1N HCl of pH 1.2 and phosphate buffers of pH 4.5 and pH 6.8. Statistical analysis, model dependent (zero order, first order, Korsmeyer-Peppas, Hixson-Crowell, Weibull) and model independent (Difference f1, similarity f2) approaches were applied to multiple dissolution profile of all brands. All brands were found to be similar with reference and meeting the compendial quality standard. Inter brand variation was observed in disintegration time and assay which was resulted in significant differences (P<0.05) in drug release data and Weibull was observed as best fill model. PMID:27168677

  20. [Drug advertising as communication between the pharmaceutical industry and the physician: advertisements for psychotropic drugs in the Dutch medical journal, Nederlands Tijdschrift voor Geneeskunde, 1900-1940].

    PubMed

    van der Hoogte, Arjo Roersch; Pieters, Toine

    2010-01-01

    In this article we explore the historical development of drug advertisements for psychotropic drugs in the leading Dutch medical journal from 1900 to 1940. The advertisements for hypnotics and sedatives, in The Nederlands Tijdschrift voor Geneeskunde (Dutch medical journal) reflected the changes in the vocabulary and image promoted by the pharmaceutical companies. In the first two decades, the advertisements were sober and to the point, and included the trademark, company name, molecular formula and therapeutic properties of the medication. The emphasis was on creating a scientific image of reliable symptom control for the therapeutic drug. In doing so, the ethical drug companies tried (successfully) to distinguish themselves from the producers of patent medicines. Once scientific credibility was established, the form and content of the advertisements changed significantly. In the late 1920s and 1930s drug companies embraced modern advertising techniques, developing a figurative language to address the changing beliefs and practices of Dutch physicians. Instead of promoting therapeutic drugs as safe and scientific, the emphasis was on their effectiveness in comparison to similar drugs. In the process, scientific information was reduced to an indispensable standardized minimum, whereby therapeutic drugs were advertised according to the latest pharmacological taxonomy rather than molecular formulas. The image-making of 'ethical marketing' began during the interwar years when marketers applied modern advertising techniques and infotainment strategies. The scanty black and white informational bulletins transitioned into colourful advertisements. The pharmaceutical companies employed the same medical language as used by physicians, so that one word or image in an advertisement would suffice for the physician to recognize a drug and its therapeutic properties. These developments show the changing relationship between the modern ethical pharmaceutical industry and Dutch

  1. Milk derived colloid as a novel drug delivery carrier for breast cancer

    PubMed Central

    Hayashi, Masamichi; Silanikove, Nissim; Chang, Xiaofei; Ravi, Rajani; Pham, Vui; Baia, Gilson; Paz, Keren; Brait, Mariana; Sidransky, David; Koch, Wayne M

    2015-01-01

    Triple negative breast cancer has an extremely poor prognosis when chemotherapy is no longer effective. To overcome drug resistance, novel drug delivery systems based on nanoparticles have had remarkable success. We produced a novel nanoparticle component ‘MDC’ from milk-derived colloid. In order to evaluate the anti-cancer effect of MDC, we conducted in vitro and in vivo experiments on cancer cell lines and a primary tumor derived breast xenograft. Doxorubicin (Dox) conjugated to MDC (MDC-Dox) showed higher cancer cell growth inhibition than MDC alone especially in cell lines with high EGFR expression. In a mouse melanoma model, MDC-Dox significantly suppressed tumor growth when compared with free Dox. Moreover, in a primary tumor derived breast xenograft, one of the mice treated with MDC-Dox showed partial regression, while mice treated with free Dox failed to show any suppression of tumor growth. We have shown that a novel nanoparticle compound made of simple milk-derived colloid has the capability for drug conjugation, and serves as a tumor-specific carrier of anti-cancer drugs. Further research on its safety and ability to carry various anti-cancer drugs into multiple drug-resistant primary breast models is warranted. PMID:26046946

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

    PubMed

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

    2016-03-01

    Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Current treatment options are limited and require repeated administrations which led to the development of new therapeutics to satisfy the unmet clinical needs. Many potent wound healing agents were discovered but most of them are fragile and/or sensitive to in vivo conditions. Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer approved by food and drug administration and European medicines agency as an excipient for parenteral administrations. It is a well-established drug delivery system in various medical applications. The aim of the current review is to elaborate the applications of PLGA based drug delivery systems carrying different wound healing agents and also present PLGA itself as a wound healing promoter. PLGA carriers encapsulating drugs such as antibiotics, anti-inflammatory drugs, proteins/peptides, and nucleic acids targeting various phases/signaling cycles of wound healing, are discussed with examples. The combined therapeutic effects of PLGA and a loaded drug on wound healing are also mentioned. PMID:26749322

  3. Drug carrier interaction with blood: a critical aspect for high-efficient vascular-targeted drug delivery systems

    PubMed Central

    Sobczynski, Daniel J; Fish, Margaret B; Fromen, Catherine A; Carasco-Teja, Mariana; Coleman, Rhima M; Eniola-Adefeso, Omolola

    2015-01-01

    Vascular wall endothelial cells control several physiological processes and are implicated in many diseases, making them an attractive candidate for drug targeting. Vascular-targeted drug carriers (VTCs) offer potential for reduced side effects and improved therapeutic efficacy, however, only limited therapeutic success has been achieved to date. This is perhaps due to complex interactions of VTCs with blood components, which dictate VTC transport and adhesion to endothelial cells. This review focuses on VTC interaction with blood as well as novel ‘bio-inspired’ designs to mimic and exploit features of blood in VTC development. Advanced approaches for enhancing VTCs are discussed along with applications in regenerative medicine, an area of massive potential growth and expansion of VTC utility in the near future. PMID:26272334

  4. Drug delivery by red blood cells: vascular carriers designed by Mother Nature

    PubMed Central

    Muzykantov, Vladimir R.

    2010-01-01

    Importance of the field Vascular delivery of several classes of therapeutic agents may benefit from carriage by red blood cells (RBC), for example, drugs that require delivery into phagocytic cells and those that must act within the vascular lumen. The fact that several protocols of infusion of RBC-encapsulated drugs are been currently explored in patients illustrates a high biomedical importance for the field. Areas covered by this review Two strategies for RBC drug delivery are discussed: encapsulation into isolated RBC ex vivo followed by infusion in compatible recipients and coupling therapeutics to surface of RBC. Studies of pharmacokinetics and effects in animal models and in human studies of diverse therapeutic enzymes, antibiotics and other drugs encapsulated in RBC are described and critically analyzed. Coupling to RBC surface of compounds regulating immune response and complement, affinity ligands, polyethylene glycol alleviating immune response to donor RBC and fibrinolytic plasminogen activators is d escribed. Also described is a novel, translation-prone approach for RBC drug delivery by injecting of therapeutics conjugated with fragments of antibodies providing safe anchoring of cargoes to circulating RBC, without need for ex vivo modification and infusion of RBC. What the reader will gain The readers will gain historical perspective, current status, challenges and perspectives of medical applications of RBC for drug delivery. Take home message RBC represent naturally designed carriers for intravascular drug delivery, characterized by unique longevity in the bloodstream, biocompatibility and safe physiological mechanisms for metabolism. Novel approaches for encapsulating drugs into RBC and coupling to RBC surface provide promising avenues for safe and widely useful improvement of drug delivery in the vascular system. PMID:20192900

  5. An overview on the delivery of antitumor drug doxorubicin by carrier proteins.

    PubMed

    Agudelo, D; Bérubé, G; Tajmir-Riahi, H A

    2016-07-01

    Serum proteins play an increasing role as drug carriers in the clinical settings. In this review, we have compared the binding modalities of anticancer drug doxorubicin (DOX) to three model carrier proteins, human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (β-LG) in order to determine the potential application of these model proteins in DOX delivery. Molecular modeling studies showed stronger binding of DOX with HSA than BSA and β-LG with the free binding energies of -10.75 (DOX-HSA), -9.31 (DOX-BSA) and -8.12kcal/mol (DOX-β-LG). Extensive H-boding network stabilizes DOX-protein conjugation and played a major role in drug-protein complex formation. DOX complexation induced major alterations of HSA and BSA conformations, while did not alter β-LG secondary structure. The literature review shows that these proteins can potentially be used for delivery of DOX in vitro and in vivo. PMID:27037051

  6. Triblock polymeric micelles as carriers for anti-inflammatory drug delivery.

    PubMed

    Yoncheva, Krassimira; Petrov, Petar; Pencheva, Ivanka; Konstantinov, Spiro

    2015-01-01

    This study evaluated the properties of poly(ethylene oxide)-b-poly(n-butyl acrylate)-b-poly(acrylic acid) (PEO-PnBA-PAA) polymeric micelles as carriers for anti-inflammatory drugs (prednisolone and budesonide). The micelles comprising a hydrophobic PnBA core and a PEO/PAA corona showed average diameter less than 40 nm. The size of the drug-loaded micelles did not change during eight hours into media that mimic physiological fluids indicating high colloidal stability. The calculation of Flory-Huggins parameter showed greater compatibility between budesonide and micellar core suggesting its location in the micellar core, whereas prednisolone was located also into the interface layer. This observation correlated further with slower release of budesonide, especially in acid medium (pH = 1.2). The inclusion of budesonide into micelles showed significant protective effect against the cytotoxic damage induced by the co-cultivation of differentiated human EOL-1 and HT-29 cells. This study revealed the capacity of PEO-PnBA-PAA terpolymer as carrier of nanosized micelles suitable for oral delivery of anti-inflammatory drugs. PMID:25539075

  7. Guar gum succinate as a carrier for colon-specific drug delivery.

    PubMed

    Seeli, D Sathya; Prabaharan, M

    2016-03-01

    A novel type of pH-sensitive colon-specific controlled drug delivery carrier based on guar gum succinate (GGS) was prepared by reacting guar gum (GG) with succinic anhydride (SA) in the presence of 4-dimethylaminopyridine (DMAP). The formation of GGS was confirmed by FT-IR and (1)H NMR and characterized using XRD techniques. GGS microparticles with 460-740 μm in size were prepared using sodium trimetaphosphate (STMP) as a cross-linking agent. The size and morphologies of GGS microparticles were assessed by scanning electron microscopy (SEM). The swelling degree of the GGS microparticles was found to be higher in pH 7.4 than in pH 1.2. In addition, GGS microparticles showed a pH dependent drug release profile when compared to the GG microparticles. The MTT assay revealed that there is no apparent cytotoxicity of GGS against a mouse mesenchymal stem cell line at a concentration range of 0-200 μg/ml. These results confirm that GGS could be used as a carrier for colon-specific drug delivery. PMID:26675135

  8. Mind the gap: a survey of how cancer drug carriers are susceptible to the gap between research and practice

    PubMed Central

    Stirland, Darren Lars; Nichols, Joseph W.; Miura, Seiji; Bae, You Han

    2013-01-01

    With countless research papers using preclinical models and showing the superiority of nanoparticle design over current drug therapies used to treat cancers, it is surprising how deficient the translation of these nano-sized drug carriers into the clinical setting is. This review article seeks to compare the preclinical and clinical results for Doxil®, PK1, Abraxane®, Genexol-PM®, Xyotax™, NC-6004, Mylotarg®, PK2, and CALAA-01. While not comprehensive, it covers nano-sized drug carriers designed to improve the efficacy of common drugs used in chemotherapy. While not always available or comparable, effort was made to compare the pharmacokinetics, toxicity, and efficacy between the animal and human studies. Discussion is provided to suggest what might be causing the gap. Finally, suggestions and encouragement are dispensed for the potential that nano-sized drug carriers hold. PMID:24096014

  9. Tracking Drug Loading Capacities of Calcium Silicate Hydrate Carrier: A Comparative X-ray Absorption Near Edge Structures Study.

    PubMed

    Guo, Xiaoxuan; Wang, Zhiqiang; Wu, Jin; Yiu, Yun-Mui; Hu, Yongfeng; Zhu, Ying-Jie; Sham, Tsun-Kong

    2015-08-01

    Mesoporous spheres of calcium silicate hydrate (MS-CSH) have been prepared by an ultrasonic method. Following an earlier work in which we have revealed the interactions between ibuprofen (IBU) and CSH carriers with different morphologies by X-ray absorption near edge structures (XANES) analysis. In the present investigation, two new drug molecules, alendronate sodium (ALN) and gentamicin sulfate (GS), were incorporated into MS-CSH, and their drug loading capacities (DLCs) were measured using thermogravimetric analysis to establish the relationship between drug-carrier interactions and DLCs. The XANES spectra clearly indicate that acidic functional groups of the drug molecules linked to the active sites (Ca-OH and Si-OH groups) of MS-CSH on the surface by electrostatic interactions. In addition, it is found that the stoichiometric ratio of Ca(2+) ions of CSH carriers and the functional groups of drug molecules may significantly influence the DLCs. PMID:26162602

  10. Responsive theranostic systems: integration of diagnostic imaging agents and responsive controlled release drug delivery carriers.

    PubMed

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

    2011-10-18

    For decades, researchers and medical professionals have aspired to develop mechanisms for noninvasive treatment and monitoring of pathological conditions within the human body. The emergence of nanotechnology has spawned new opportunities for novel drug delivery vehicles capable of concomitant detection, monitoring, and localized treatment of specific disease sites. In turn, researchers have endeavored to develop an imaging moiety that could be functionalized to seek out specific diseased conditions and could be monitored with conventional clinical imaging modalities. Such nanoscale detection systems have the potential to increase early detection of pathophysiological conditions because they can detect abnormal cells before they even develop into diseased tissue or tumors. Ideally, once the diseased cells are detected, clinicians would like to treat those cells simultaneously. This idea led to the concept of multifunctional carriers that could target, detect, and treat diseased cells. The term "theranostics" has been created to describe this promising area of research that focuses on the combination of diagnostic detection agents with therapeutic drug delivery carriers. Targeted theranostic nanocarriers offer an attractive improvement to disease treatment because of their ability to execute simultaneous functions at targeted diseased sites. Research efforts in the field of theranostics encompass a broad variety of drug delivery vehicles, imaging contrast agents, and targeting modalities for the development of an all-in-one, localized detection and treatment system. Nanotheranostic systems that utilize metallic or magnetic imaging nanoparticles can also be used as thermal therapeutic systems. This Account explores recent advances in the field of nanotheranostics and the various fundamental components of an effective theranostic carrier. PMID:21932809

  11. Drug reformulations and repositioning in pharmaceutical industry and its impact on market access: reassessment of nomenclature

    PubMed Central

    Murteira, Susana; Ghezaiel, Zied; Karray, Slim; Lamure, Michel

    2013-01-01

    Background Medicinal products that have been developed and approved for one disease may be the object of additional clinical development in other disease areas or of additional pharmaceutical development for new and different formulations. The newly developed products can be named as repositioned or reformulated products, respectively. Market access of repositioned or reformulated products in Europe and the United States is an interesting object of study as it may provide clarity about which parameters are assessed and considered to bring added value, other than the molecule itself. As such, we aim to evaluate if the added value of repositioned or reformulated medicinal products can be systematically described, quantified, and predicted. As a first step toward investigating the impact of market access on drug research and development trends for repositioned and reformulated products, it is necessary to have consistency in the designations for the case studies evaluated in this project. In an attempt to achieve that consistency, the current study aims to propose harmonized definitions for the repositioning and reformulation strategies and to propose a taxonomy for the medicinal products derived thereof. Methods A systematic literature review was conducted to collect information on existing cases of repositioning or reformulation. A search strategy was developed by defining the search objectives, targeted data sources, search keywords, and inclusion/exclusion criteria for the retrieved documents. Results A total of 505 publications were retrieved through a search of the main data sources. The screenings and the ad hoc search led to a total of 56 publications to be used for the case study data extraction. In total, 87 repositioning and/or reformulation cases were found described in the literature, 23 of which presented different definitions and/or classifications by different authors. Conclusion Given the disparity and inconsistency of terminologies and

  12. Antitumor and Antimetastasis Activities of Heparin-based Micelle Served As Both Carrier and Drug.

    PubMed

    Mei, Ling; Liu, Yayuan; Zhang, HuaJin; Zhang, Zhirong; Gao, Huile; He, Qin

    2016-04-20

    Effective treatments for tumors are not easy to achieve due to the existence of metastases, which are responsible for most tumor death. Hence, a new drug delivery system is a pressing need, which should be biocompatible, stimuli-responsive, and multifunctional, including antitumor, antimetastasis, and antiangiogenesis effects. However, it is challenging to achieve all of these properties in one drug delivery system. Here, we developed a system of drug DOX and heparin into one self-assemble nanoparticle via pH-sensitive hydrazone bond and hydrophobic groups, deoxycholate. In the process, heparin itself was not only as the hydrophilic segments of the carrier, but also processed multiple biological functions such as antiangiogenesis and antimetastasis effect. The micelle nanoparticle HD-DOX processed good stability and acidic pH-triggered drug release property. After systemic administration, heparin-based micelle nanoparticle showed longer half-time and enhanced accumulation of DOX in tumors through the enhanced permeability and retention effect, leading to more efficient antitumor effects. In addition, heparin could hinder platelet-induced tumor cells epithelial-mesenchymal transition (EMT) and partially affect cell actin cytoskeletal arrangement, resulting in the disorganization of the actin cytoskeleton. Therefore, HD-DOX exhibited significant inhibitory effect on the metastasis in melanoma animal model in C57BL/6 mouse. Meanwhile, benefited from the antiangiogenesis effect of heparin, tube formations in endothelial cells were effectively inhibited and tumor vascular density was decreased by HD-DOX. Taken together, our study developed a self-assembly nanoplatform that both the drug and carrier had therapeutic effects with ideal antitumor efficacy. PMID:27058058

  13. Nano carriers that enable co-delivery of chemotherapy and RNAi agents for treatment of drug-resistant cancers.

    PubMed

    Tsouris, Vasilios; Joo, Min Kyung; Kim, Sun Hwa; Kwon, Ick Chan; Won, You-Yeon

    2014-01-01

    Tumor cells exhibit drug resistant phenotypes that decrease the efficacy of chemotherapeutic treatments. The drug resistance has a genetic basis that is caused by an abnormal gene expression. There are several types of drug resistance: efflux pumps reducing the cellular concentration of the drug, alterations in membrane lipids that reduce cellular uptake, increased or altered drug targets, metabolic alteration of the drug, inhibition of apoptosis, repair of the damaged DNA, and alteration of the cell cycle checkpoints (Gottesman et al., 2002; Holohan et al., 2013). siRNA is used to silence the drug resistant phenotype and prevent this drug resistance response. Of the listed types of drug resistance, pump-type resistance (e.g., high expression of ATP-binding cassette transporter proteins such as P-glycoproteins (Pgp; also known as multi-drug resistance protein 1 or MDR1, encoded by the ATP-Binding Cassette Sub-Family B Member 1 (ABCB1) gene)) and apoptosis inhibition (e.g., expression of anti-apoptotic proteins such as Bcl-2) are the most frequently targeted for gene silencing. The co-delivery of siRNA and chemotherapeutic drugs has a synergistic effect, but many of the current projects do not control the drug release from the nanocarrier. This means that the drug payload is released before the drug resistance proteins have degraded and the drug resistance phenotype has been silenced. Current research focuses on cross-linking the carrier's polymers to prevent premature drug release, but these carriers still rely on environmental cues to release the drug payload, and the drug may be released too early. In this review, we studied the release kinetics of siRNA and chemotherapeutic drugs from a broad range of carriers. We also give examples of carriers used to co-deliver siRNA and drugs to drug-resistant tumor cells, and we examine how modifications to the carrier affect the delivery. Lastly, we give our recommendations for the future directions of the co-delivery of si

  14. A new Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) to evaluate pulmonary drug absorption for metered dose dry powder formulations.

    PubMed

    Hein, Stephanie; Bur, Michael; Schaefer, Ulrich F; Lehr, Claus-Michael

    2011-01-01

    Absorption studies with aerosol formulation delivered by metered dose inhalers across cell- and tissue-based in vitro models of the pulmonary epithelia are not trivial due to the complexity of the processes involved: (i) aerosol generation and deposition, (ii) drug release from the carrier, and (iii) absorption across the epithelial air-blood barrier. In contrast to the intestinal mucosa, pulmonary epithelia are only covered by a thin film of lining fluid. Submersed cell culture systems would not allow to studying the deposition of aerosol particles and their effects on this delicate epithelial tissue. We developed a new Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) to mimic the inhalation of a single metered aerosol dose and its subsequent deposition on filter-grown pulmonary epithelial cell monolayers exposed to an air-liquid interface. The reproducibility of deposition of these dry powder aerosols and subsequent drug transport across Calu-3 monolayers with commercially available dry powder inhalers containing salbutamol sulphate or budesonide could be demonstrated. In the context of developing new dry powder aerosol formulations, PADDOCC appears as a useful tool, allowing reducing animal testing and faster translation into clinical trials. PMID:20951200

  15. Functionalized graphene oxide as a drug carrier for loading pirfenidone in treatment of subarachnoid hemorrhage.

    PubMed

    Yang, Lijun; Wang, Feng; Han, Haie; Yang, Liang; Zhang, Gengshen; Fan, Zhenzeng

    2015-05-01

    Subarachnoid hemorrhage (SAH) is a life-threatening disease that causes high morbidity and mortality. Pirfenidone is a SAH drug that prevents secondary bleeding and cerebral infarction. To improve its therapeutic efficacy, this study aimed to employ a functionalized graphene oxide nanosheet (FGO) as a drug carrier loading pirfenidone to treat SAH. The graphene oxide nanosheet was introduced with transcription activator peptide (Tat), followed by functionalization with methoxy polyethylene glycol (mPEG) and loading with pirfenidone. The pirfenidone-loaded FGO (pirfenidone-FGO) exhibits better treatment efficacy than the single pirfenidone due to more effective loading and controlled release of the drug in tissue. The introduction of Tat and mPEG onto GO nanosheet contributes to the ability to cross the blood-brain barrier and the stability in blood circulation of the drug. At lower pH values, the highly efficient release of the drug from the pirfenidone-FGO exerts effective treatment to acidic inflammatory lesion after severe SAH. Besides its treatment function, FGO is also shown as a strong near infrared absorbing material which can be applied in photoacoustic imaging, allowing rapid real-time monitoring with deep resolution of brain tissues after SAH. The treatment efficacy of pirfenidone-FGO for central nervous system injuries is further demonstrated by hematoxylin and eosin staining of coronal brain slices, as well as measurements of brain water content and blood-brain barrier permeability. Our study supports the potential of FGO in clinical application in treatment of SAH. PMID:25819362

  16. Propolis as lipid bioactive nano-carrier for topical nasal drug delivery.

    PubMed

    Rassu, Giovanna; Cossu, Massimo; Langasco, Rita; Carta, Antonio; Cavalli, Roberta; Giunchedi, Paolo; Gavini, Elisabetta

    2015-12-01

    Propolis shows therapeutic properties ascribed to the presence of some flavonoids, phenolic acids, and their esters; it is a natural multifunctional material, solid at room temperature, and composed mainly of resin and waxes. We therefore used propolis as a lipid material to prepare solid lipid nanoparticles (SLNs); SLNs are proposed bioactive medications for topical intranasal therapy. Suitable formulation parameters were studied and the SLNs obtained by the high shear homogenization method were characterized; a selected formulation was viscosized to increase the residence time. Dimensional, morphological, and solid-state characterizations of the formulated SLNs were performed. In vitro and ex vivo permeation tests of diclofenac sodium, the model drug, and polyphenols were carried out. The propolis amount and surfactant concentration represent the key parameters that affect nanoparticle properties in terms of size, drug and polyphenol content, and physical stability. Size dispersions of about 600 nm and 0.4 PI were obtained, which do not change by increasing the viscosity. Drug is encapsulated in SLNs, as demonstrated by FTIR and DSC analyses. In vitro and ex vivo studies prove that drug and polyphenols do not cross the membranes; therefore, propolis-based SLNs could be used as delivery systems of diclofenac and flavonoids for the local treatment of nasal cavity diseases. Due to propolis composition, the proposed formulation could be used as a bioactive medication in which the carrier can exert a complementary effect with the loaded drug. PMID:26551868

  17. Vitamin B12-loaded solid lipid nanoparticles as a drug carrier in cancer therapy.

    PubMed

    Genç, Lütfi; Kutlu, H Mehtap; Güney, Gamze

    2015-05-01

    Nanostructure-mediated drug delivery, a key technology for the realization of nanomedicine, has the potential to improve drug bioavailability, ameliorate release deviation of drug molecules and enable precision drug targeting. Due to their multifunctional properties, solid lipid nanoparticles (SLNs) have received great attention of scientists to find a solution to cancer. Vitamin supplements may contribute to a reduction in the risk of cancer. Vitamin B12 has several characteristics that make it an attractive entity for cancer treatment and possible therapeutic applications. The aim of this study was to produce B12-loaded SLNs (B12-SLNs) and determine the cytotoxic effects of B12-SLNs on H-Ras 5RP7 and NIH/3T3 control cell line. Results obtained by MTT assay, transmission electron and confocal microscopy showed that B12-loaded SLNs are more effective than free vitamin B12 on cancer cells. In addition, characterization studies indicate that while the average diameter of the B12 was about 650 nm, B12-SLNs were about 200 nm and the drug release efficiency of vit. B12 by means of SLNs increased up to 3 h. These observations point to the fact that B12-SLNs could be used as carrier systems due to the therapeutic effects on cancer. PMID:24344935

  18. UV-curable gel formulations: Potential drug carriers for the topical treatment of nail diseases.

    PubMed

    Kerai, Laxmi Valji; Hilton, Stephen; Murdan, Sudaxshina

    2015-08-15

    Nail diseases are common, cause significant distress and treatments are far from successful. Our aim was to investigate the potential of UV-curable gels - currently used as cosmetics - as topical drug carriers for their treatment. These formulations have a long residence on the nail, which is expected to increase patient compliance and the success of topical therapy. The gels are composed of the diurethane dimethacrylate, ethyl methacrylate, 2-hydroxy-2-methylpropiophenone, an antifungal drug (amorolfine HCl or terbinafine HCl) and an organic liquid (ethanol or NMP) as drug solvent. Following its application to a substrate and exposure to a UVA lamp for 2 min, the gel polymerises and forms a smooth, glossy and amorphous film, with negligible levels of residual monomers. No drug-polymer interactions were found and drug loading did not affect the film's properties, such as thickness, crystallinity and transition temperatures. In contrast, the organic solvent did influence the film's properties; NMP-containing films had lower glass transition temperatures, adhesion and water resistance than ethanol-based ones. Water-resistance being a desired property, ethanol-based formulations were investigated further for stability, drug release and ungual permeation. The films were stable under accelerated stability testing conditions. Compared to terbinafine, amorolfine was released to a greater extent, had a higher ungual flux, but a lower concentration in the nailplate. However, both drugs were present at considerably high levels in the nail when their MICs are taken into account. We thus conclude that UV-curable gels are promising candidates as topical nail medicines. PMID:26187167

  19. Sorption of structurally different ionized pharmaceutical and illicit drugs to a mixed-mode coated microsampler.

    PubMed

    Peltenburg, Hester; Timmer, Niels; Bosman, Ingrid J; Hermens, Joop L M; Droge, Steven T J

    2016-05-20

    The mixed-mode (C18/strong cation exchange-SCX) solid-phase microextraction (SPME) fiber has recently been shown to have increased sensitivity for ionic compounds compared to more conventional sampler coatings such as polyacrylate and polydimethylsiloxane (PDMS). However, data for structurally diverse compounds to this (prototype) sampler coating are too limited to define its structural limitations. We determined C18/SCX fiber partitioning coefficients of nineteen cationic structures without hydrogen bonding capacity besides the charged group, stretching over a wide hydrophobicity range (including amphetamine, amitriptyline, promazine, chlorpromazine, triflupromazine, difenzoquat), and eight basic pharmaceutical and illicit drugs (pKa>8.86) with additional hydrogen bonding moieties (MDMA, atenolol, alprenolol, metoprolol, morphine, nicotine, tramadol, verapamil). In addition, sorption data for three neutral benzodiazepines (diazepam, temazepam, and oxazepam) and the anionic NSAID diclofenac were collected to determine the efficiency to sample non-basic drugs. All tested compounds showed nonlinear isotherms above 1mmol/L coating, and linear isotherms below 1mmol/L. The affinity for C18/SCX-SPME for tested organic cations without Hbond capacities increased with longer alkyl chains, ranging from logarithmic fiber-water distribution coefficients (log Dfw) of 1.8 (benzylamine) to 5.8 (triflupromazine). Amines smaller than benzylamine may thus have limited detection levels, while cationic surfactants with alkyl chain lengths >12 carbon atoms may sorb too strong to the C18/SCX sampler which hampers calibration of the fiber-water relationship in the linear range. The log Dfw for these simple cation structures closely correlates with the octanol-water partition coefficient of the neutral form (Kow,N), and decreases with increased branching and presence of multiple aromatic rings. Oxygen moieties in organic cations decreased the affinity for C18/SCX-SPME. Log Dfw values of

  20. Accuracy of drug advertisements in medical journals under new law regulating the marketing of pharmaceutical products in Switzerland

    PubMed Central

    Santiago, Macarena Gonzalez; Bucher, Heiner C; Nordmann, Alain J

    2008-01-01

    Background New legal regulations for the marketing of pharmaceutical products were introduced in 2002 in Switzerland. We investigated whether claims in drug advertisements citing published scientific studies were justified by these studies after the introduction of these new regulations. Methods In this cross-sectional study, two independent reviewers screened all issues of six major Swiss medical journals published in the year 2005 to identify all drug advertisements for analgesic, gastrointestinal and psychopharmacologic drugs and evaluated all drug advertisements referring to at least one publication. The pharmaceutical claim was rated as being supported, being based on a potentially biased study or not to be supported by the cited study according to pre-specified criteria. We also explored factors likely to be associated with supported advertisement claims. Results Of 2068 advertisements 577 (28%) promoted analgesic, psychopharmacologic or gastrointestinal drugs. Among them were 323 (56%) advertisements citing at least one reference. After excluding multiple publications of the same drug advertisement and advertisements with non-informative references, there remained 29 unique advertisements with at least one reference to a scientific study. These 29 advertisements contained 78 distinct pairs of claims of analgesic, gastrointestinal and psychopharmacologic drugs and referenced studies. Thirty-seven (47%) claims were supported, 16 (21%) claims were not supported by the corresponding reference, and 25 (32%) claims were based on potentially biased evidence, with no relevant differences between drug groups. Studies with conflict of interest and studies stating industry funding were more likely to support the corresponding claim (RR 1.52, 95% CI 1.07–2.17 and RR 1.50, 95% CI 0.98–2.28) than studies without identified conflict of interest and studies without information on type of funding. Conclusion Following the introduction of new regulations for drug

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

    PubMed Central

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

    2011-01-01

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

  2. RGD-modified lipid disks as drug carriers for tumor targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Gao, Jie; Xie, Cao; Zhang, Mingfei; Wei, Xiaoli; Yan, Zhiqiang; Ren, Yachao; Ying, Man; Lu, Weiyue

    2016-03-01

    Melittin, the major component of the European bee venom, is a potential anticancer candidate due to its lytic properties. However, in vivo applications of melittin are limited due to its main side effect, hemolysis, especially when applied through intravenous administration. The polyethylene glycol-stabilized lipid disk is a novel type of nanocarrier, and the rim of lipid disks has a high affinity to amphiphilic peptides. In our study, a c(RGDyK) modified lipid disk was developed as a tumor targeted drug delivery system for melittin. Cryo-TEM was used to confirm the shape and size of lipid disks with or without c(RGDyK) modification. In vitro and in vivo hemolysis analyses revealed that the hemolysis effect significantly decreased after melittin associated with lipid disks. Importantly, the results of our in vivo biodistribution and tumor growth inhibitory experiments showed that c(RGDyK) modification increased the distribution of lipid disks in the tumor and the anticancer efficacy of melittin loaded lipid disks. Thus, we successfully achieved a targeted drug delivery system for melittin and other amphiphilic peptides with a good therapeutic effect and low side effects.

  3. RGD-modified lipid disks as drug carriers for tumor targeted drug delivery.

    PubMed

    Gao, Jie; Xie, Cao; Zhang, Mingfei; Wei, Xiaoli; Yan, Zhiqiang; Ren, Yachao; Ying, Man; Lu, Weiyue

    2016-04-01

    Melittin, the major component of the European bee venom, is a potential anticancer candidate due to its lytic properties. However, in vivo applications of melittin are limited due to its main side effect, hemolysis, especially when applied through intravenous administration. The polyethylene glycol-stabilized lipid disk is a novel type of nanocarrier, and the rim of lipid disks has a high affinity to amphiphilic peptides. In our study, a c(RGDyK) modified lipid disk was developed as a tumor targeted drug delivery system for melittin. Cryo-TEM was used to confirm the shape and size of lipid disks with or without c(RGDyK) modification. In vitro and in vivo hemolysis analyses revealed that the hemolysis effect significantly decreased after melittin associated with lipid disks. Importantly, the results of our in vivo biodistribution and tumor growth inhibitory experiments showed that c(RGDyK) modification increased the distribution of lipid disks in the tumor and the anticancer efficacy of melittin loaded lipid disks. Thus, we successfully achieved a targeted drug delivery system for melittin and other amphiphilic peptides with a good therapeutic effect and low side effects. PMID:26972577

  4. Doxorubicin hydrochloride-oleic acid conjugate loaded nanostructured lipid carriers for tumor specific drug release.

    PubMed

    Zhao, Shuangni; Minh, Le Van; Li, Na; Garamus, Vasil M; Handge, Ulrich A; Liu, Jianwen; Zhang, Rongguang; Willumeit-Römer, Regine; Zou, Aihua

    2016-09-01

    The hydrophilic drug Doxorubicin hydrochloride (DOX) paired with oleic acid (OA) was successfully incorporated into nanostructured lipid carriers (NLCs) by a high-pressure homogenization (HPH) method. Drug nanovehicles with proper physico-chemical characteristics (less than 200nm with narrow size distribution, spherical shape, layered internal organization, and negative electrical charge) were prepared and characterized by dynamic light scattering, zeta potential measurements, transmission electron microscopy, small-angle X-ray scattering and differential scanning calorimetry. The drug loading and entrapment efficiency of DOX-OA/NLCs were 4.09% and 97.80%, respectively. A pH-dependent DOX release from DOX-OA/NLCs, i.e., fast at pH 3.8 and 5.7 and sustained at pH 7.4, was obtained. A cytotoxicity assay showed that DOX-OA/NLCs had comparable cytotoxicity to pure DOX and were favorably taken up by HCT 116 cells. The intracellular distribution of DOX was also studied using a confocal laser scanning microscope. All of these results demonstrated that DOX-OA/NLCs could be a promising drug delivery system with tumor-specific DOX release for cancer treatment. PMID:27137808

  5. Facile fabrication of single-phase multifunctional BaGdF5 nanospheres as drug carriers.

    PubMed

    Zhao, Qi; Lei, Zhen; Huang, Sa; Han, Xueli; Shao, Baiqi; Lü, Wei; Jia, Yongchao; Lv, Wenzhen; Jiao, Mengmeng; Wang, Zhenxin; You, Hongpeng

    2014-08-13

    Multifunctional BaGdF5 nanospheres with mesoporous, luminescent, and magnetic properties have been successfully synthesized with the assistance of trisodium citrate by a hydrothermal method. The mesoporous structure is revealed by scanning electron microscope and transmission electron microscope images as well as N2 adsorption-desorption isotherm. The as-synthesized BaGdF5 nanospheres exhibit an intense broad bluish emission (centered at 450 nm) under the excitation of 390 nm, which might originate from the CO2·(-) radical-related defect produced by Cit(3-) groups. It is also shown that these BaGdF5 nanospheres brightened the T1-weighted images, suggesting that they could act as T1 contrast agents for magnetic resonance imaging. Using metformin hydrochloride as the model drug, the luminescent porous spheres show good drug storage/release capability. Furthermore, the emission intensity varies as a function of the cumulative drug release, making the drug-carrying system easily trackable and monitorable by detecting the luminescence intensity. Additionally, the paramagnetic property, originating from the unpaired electrons of Gd(3+) ions, opens the possibility of directing the magnetic targeted carrier to the pathological site by magnetic field gradient. PMID:25007920

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

    PubMed

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

    2014-09-01

    Semifluorinated alkanes (SFA, e.g. perfluorobutylpentane F4H5, perfluorohexyloctane F6H8) are inert, non-toxic fluids capable of dissolving lipophilic drugs. The aim of this study to assess the bioavailability and safety of SFAs as drug solvents for the topical ocular application of Cyclosporin A (CsA). A commercially available CsA formulation (Restasis, 0.05% CsA in castor oil) was tested against two novel formulations of 0.05% CSA in (a) F4H5 containing Ethanol (0.5 w/w%) and (b) F6H8 containing Ethanol (0.5 w/w%) with 0.05% CsA. Formulations were tested on rabbit corneas cultured on an artificial anterior chamber with a constant flow of an aqueous humour supplement (Ex Vivo Eye Irritation Test (EVEIT) system). Anterior chamber fluids were sampled at multiple time points to analyse the CsA concentration following single and repeated application regimes by HPLC. Photographs of fluorescein sodium-stained corneas were recorded for corneal toxicity evaluation. The impact of the formulations on the integrity of the corneal barrier function was tested after drug application by fluorescein sodium corneal diffusion experiments. The influence on the corneal metabolism was evaluated by analysis of the metabolic markers glucose and lactate. Restasis did not pass the corneal barrier after short term application, CsA in ethanolic F4H6 reached a maximum of 152.95 ng/ml in anterior chamber fluid samples whilst CsA in ethanolic F6H8 reached a maximum of 15.12 ng/ml. After repeated applications for 8h, Restasis reached 21.07 ng/ml compared to 247.62 ng/ml and 174.5 ng/ml for F4H5 and F6H8, respectively. No corneal toxicity was observed in following application of any of the formulations. In contrast to the commercially available castor oil-based formulation, CsA dissolved in SFAs reached therapeutic inner ocular concentrations after topical administration, possibly leading to the replacement of systemic applications of CsA for inflammatory ocular disease. PMID:24844949

  7. Pharmaceutical lobbying under postcommunism: universal or country-specific methods of securing state drug reimbursement in Poland?

    PubMed

    Ozierański, Piotr; McKee, Martin; King, Lawrence

    2012-04-01

    This paper aims to fill in the gap in research on the effect of pharmaceutical lobbying on drug reimbursement policy, particularly in Poland, a post-communist country. To this end, we conducted in-depth, semi-structured, anonymous, elite interviews in Poland, supplemented by a review of legislation, policy documents, official reports and press articles, as well as observations. Overall, 109 representatives of stakeholders involved in reimbursement policy were interviewed. We identified two key lobbying methods: informal persuasion and third-party endorsements. These methods are coupled with two supplementary ones: lobbying through parliament and ministries, as well as diplomatic pressure. Pharmaceutical lobbying methods in Poland clearly resemble those used in other European countries. What is notable about the Polish case is extensive reliance on informal lobbying and diplomatic pressure. PMID:21819633

  8. Monodisperse Micro-Oil Droplets Stabilized by Polymerizable Phospholipid Coatings as Potential Drug Carriers.

    PubMed

    Park, Yoonjee; Pham, Tuan A; Beigie, Carl; Cabodi, Mario; Cleveland, Robin O; Nagy, Jon O; Wong, Joyce Y

    2015-09-15

    There is a critical need to formulate stable micron-sized oil droplets as hydrophobic drug carriers for efficient drug encapsulation, long-term storage, and sustained drug release. Microfluidic methods were developed to maximize the stability of micron-sized, oil-in-water (o/w) emulsions for potential use in drug delivery, using doxorubicin-loaded triacetin oil as a model hydrophobic drug formulation. Initial experiments examined multiple flow conditions for the dispersed (oil) and continuous (liposome aqueous) phases in a microfluidic device to establish the parameters that influenced droplet size. These data were fit to a mathematical model from the literature and indicate that the droplet sizes formed are controlled by the ratio of flow rates and the height of the device channel, rather than the orifice size. Next, we investigated effects of o/w emulsion production methods on the stability of the droplets. The stability of o/w emulsion produced by microfluidic flow-focusing techniques was found to be much greater (5 h vs 1 h) than for emulsions produced by mechanical agitation (vortexing). The increased droplet stability was attributed to the uniform size and lipid distribution of droplets generated by flow-focusing. In contrast, vortexed populations consisted of a wide size distribution that resulted in a higher prevalence of Ostwald ripening. Finally, the effects of shell polymerization on stability were investigated by comparing oil droplets encapsulated by a photopolymerizable diacetylene lipid shell to those with a nonpolymerizable lipid shell. Shell polymerization was found to significantly enhance stability against dissolution for flow-focused oil droplets but did not significantly affect the stability of vortexed droplets. Overall, results of these experiments show that flow-focusing is a promising technique for generating tunable, stable, monodisperse oil droplet emulsions, with potential applications for controlled delivery of hydrophobic drug

  9. Biomimetic synthesized chiral mesoporous silica: Structures and controlled release functions as drug carrier.

    PubMed

    Li, Jing; Xu, Lu; Yang, Baixue; Bao, Zhihong; Pan, Weisan; Li, Sanming

    2015-10-01

    This work initially illustrated the formation mechanism of chiral mesoporous silica (CMS) in a brand new insight named biomimetic synthesis. Three kinds of biomimetic synthesized CMS (B-CMS, including B-CMS1, B-CMS2 and B-CMS3) were prepared using different pH or stirring rate condition, and their characteristics were tested with transmission electron microscope and small angle X-ray diffraction. The model drug indomethacin was loaded into B-CMS and drug loading content was measured using ultraviolet spectroscopy. The result suggested that pH condition influenced energetics of self-assembly process, mainly packing energetics of the surfactant, while stirring rate was the more dominant factor to determine particle length. In application, indomethacin loading content was measured to be 35.3%, 34.8% and 35.1% for indomethacin loaded B-CMS1, indomethacin loaded B-CMS2 and indomethacin loaded B-CMS3. After loading indomethacin into B-CMS carriers, surface area, pore volume and pore diameter of B-CMS carriers were reduced. B-CMS converted crystalline state of indomethacin to amorphous state, leading to the improved indomethacin dissolution. B-CMS1 controlled drug release without burst-release, while B-CMS2 and B-CMS3 released indomethacin faster than B-CMS1, demonstrating that the particle length, the ordered lever of multiple helixes, the curvature degree of helical channels and pore diameter greatly contributed to the release behavior of indomethacin loaded B-CMS. PMID:26117767

  10. Plant lectins as carriers for oral drugs: is wheat germ agglutinin a suitable candidate?

    PubMed

    Dalla Pellegrina, Chiara; Rizzi, Corrado; Mosconi, Silvia; Zoccatelli, Gianni; Peruffo, Angelo; Chignola, Roberto

    2005-09-01

    Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed also by gastrointestinal epithelial cells. WGA is currently investigated as an anti-tumor drug and as a carrier for oral drugs. Information on whether it can cross the gastrointestinal epithelium and on its possible effects on the integrity of the epithelial layer is however scanty or lacking, and herein we address these issues. Differentiated Caco2 cells have been used as a model of polarized intestinal epithelium. WGA concentration at both the apical and the basolateral side of the epithelium has been quantified using a sensitive ELISA assay (sensitivity threshold 0.84 nM). Trans epithelial electrical resistance (TEER) has been measured to evaluate the integrity of the epithelium upon treatments with WGA. (3)H-Mannitol (182.2 Da) and FITC-dextran (3000 Da) have been used to measure the permeability of the epithelium. Cell viability has been measured by the MTT, by 7-AAD uptake, and Annexin-V binding assays. Up to a concentration of 5.6 microM, approximately 0.1% of intact WGA molecules only could cross the epithelial layer. WGA perturbed the integrity of the epithelium and increased the permeability of the tissue in a dose- and time-dependent manner. WGA did not induce cell death but increased the permeability of individual cells to 7-AAD which is normally not uptaken by viable cells. These data allowed us to define a toxicity threshold for WGA on epithelial cells. WGA suitability as a carrier for oral drugs can therefore be evaluated on a rational basis. PMID:16102568

  11. Influence of emulsifiers on the characteristics of polyurethane structures used as drug carrier

    PubMed Central

    2013-01-01

    Background Emulsifiers have a significant role in the emulsion polymerization by reducing the interfacial tension thus increasing the stability of colloidal dispersions of polymer nanostructures. This study evaluates the impact of four emulsifiers on the characteristics of polyurethane hollow structures used as drug delivery system. Results Polyurethane (PU) structures with high stability and sizes ranging from nano- to micro-scale were obtained by interfacial polyaddition combined with spontaneous emulsification. The pH of PU aqueous solutions (0.1% w/w) was slightly acidic, which is acceptable for products intended to be used on human skin. Agglomerated structures with irregular shapes were observed by scanning electron microscopy. The synthesized structures have melting points between 245-265°C and reveal promising results in different evaluations (TEWL, mexametry) on murine skin. Conclusions In this study hollow PU structures of reduced noxiousness were synthesized, their size and stability being influenced by emulsifiers. Such structures could be used in the pharmaceutical field as future drug delivery systems. PMID:23575277

  12. Synthesis, characterization and in vitro cytotoxicity analysis of a novel cellulose based drug carrier for the controlled delivery of 5-fluorouracil, an anticancer drug

    NASA Astrophysics Data System (ADS)

    Anirudhan, Thayyath S.; Nima, Jayachandran; Divya, Peethambaran L.

    2015-11-01

    The present investigation concerns the development and evaluation of a novel drug delivery system, aminated-glycidylmethacrylate grafted cellulose-grafted polymethacrylic acid-succinyl cyclodextrin (Cell-g-(GMA/en)-PMA-SCD) for the controlled release of 5-Fluorouracil, an anticancer drug. The prepared drug carrier was characterized by FT-IR, XRD and SEM techniques. Binding kinetics and isotherm studies of 5-FU onto Cell-g-(GMA/en)-PMA-SCD were found to follow pseudo-second-order and Langmuir model respectively. Maximum binding capacity of drug carrier was found to be 149.09 mg g-1 at 37 °C. Swelling studies, in vitro release kinetics, drug loading efficiency and encapsulation efficiency of Cell-g-(GMA/en)-PMA-SCD were studied. The release kinetics was analyzed using Ritger-Peppas equation at pH 7.4. Cytotoxicity analysis on MCF-7 (human breast carcinoma) cells indicated that the drug carrier shows sustained and controlled release of drug to the target site. Hence, it is evident from this investigation that Cell-g-(GMA/en)-PMA-SCD could be a promising carrier for 5-FU.

  13. Synthesis and characterization of DNA nano-meso-microspheres as drug delivery carriers for intratumoral chemotherapy

    NASA Astrophysics Data System (ADS)

    Enriquez Schumacher, Iris Vanessa

    Conventional cancer chemotherapy results in systemic toxicity which severely limits effectiveness and often adversely affects patient quality of life. There is a need to find new drugs and delivery methods for less toxic therapy. Previous studies concerning DNA complexing with chemotherapy drugs suggest unique opportunities for DNA as a mesosphere drug carrier. The overall objective of this research was devoted to the synthesis and evaluation of novel DNA-drug nano-mesospheres designed for localized chemotherapy via intratumoral injection. My research presents DNA nano-meso-microspheres (DNA-MS) that were prepared using a modified steric stabilization method originally developed in this lab for the preparation of albumin MS. DNA-MS were prepared with glutaraldehyde covalent crosslinking (genipin crosslinking was attempted) through the DNA base pairs. In addition, novel crosslinking of DNA-MS was demonstrated using chromium, gadolinium, or iron cations through the DNA phosphate groups. Covalent and ionic crosslinked DNA-MS syntheses yielded smooth and spherical particle morphologies with multimodal size distributions. Optimized DNA-MS syntheses produced particles with narrow and normal size distributions in the 50nm to 5mum diameter size range. In aqueous dispersions approximately 200% swelling was observed with dispersion stability for more than 48 hours. Typical process conditions included a 1550rpm initial mixing speed and particle filtration through 20mum filters to facilitate preparation. DNA-MS were in situ loaded during synthesis for the first time with mitoxantrone, 5-fluorouracil, and methotrexate. DNA-MS drug incorporation was 12%(w/w) for mitoxantrone, 9%(w/w) for methotrexate, and 5%(w/w) for 5-fluorouracil. In vitro drug release into phosphate buffered saline was observed for over 35 days by minimum sink release testing. The effect of gadolinium crosslink concentration on mitoxantrone release was evaluated at molar equivalences in the range of 20% to

  14. Pharmaceutical quality control of acid and neutral drugs based on competitive self-assembly in amphiphilic systems.

    PubMed

    Pedraza, Ana; Sicilia, María Dolores; Rubio, Soledad; Pérez-Bendito, Dolores

    2006-01-01

    An aggregation parameter-based methodology for determining acid and neutral drugs in pharmaceutical dosage forms is presented. The method is based on competitive self-assembly in ternary dye-surfactant-drug aqueous mixtures. Dyes bearing charge of opposite sign to that of surfactants bind to surfactant to form mixed dye-surfactant aggregates, which are monitored from changes in the spectra features of the dye. The drug competes with the dye to interact with the surfactant to form drug-surfactant aggregates, which results in a decrease in the surfactant to dye binding degree proportional to the drug concentration in the aqueous solution. Coomassie Brilliant Blue G (CBBG) and didodecyldimethylammonium bromide (DDABr) were the dye and surfactant reactant used, respectively. The suitability of the surfactant to dye binding degree (SDBD) method to determine drugs with very different molecular structure: propionic (flurbiprofen, ibuprofen, naproxen and ketoprofen) and acetic (diclofenac, felbinac and zomepirac) acids, indolines (indomethacin and sulindac), glycyrrhetinic acid derivatives (carbenoxolone and enoxolone), salicylates (diflunisal and phenyl salicylate), oxicams (meloxicam, piroxicam and tenoxicam), pyrazolones (phenylbutazone and sulfinpyrazone) and hydrocortisones (dexamethasone and prednisolone) has been proved. The proposed method was successfully applied to the determination of drugs in commercial formulates (effervescent granulates, tablets, suppositories, gels and blisters) with a minimum sample treatment (dilution of liquid samples and dissolution of solid samples). PMID:16365667

  15. Ready-to-use injectable calcium phosphate bone cement paste as drug carrier.

    PubMed

    Vorndran, E; Geffers, M; Ewald, A; Lemm, M; Nies, B; Gbureck, U

    2013-12-01

    Current developments in calcium phosphate cement (CPC) technology concern the use of ready-to-use injectable cement pastes by dispersing the cement powder in a water-miscible solvent, such that, after injection into the physiological environment, setting of cements occurs by diffusion of water into the cement paste. It has also been demonstrated recently that the combination of a water-immiscible carrier liquid combined with suitable surfactants facilitates a discontinuous liquid exchange in CPC, enabling the cement setting reaction to take place. This paper reports on the use of these novel cement paste formulations as a controlled release system of antibiotics (gentamicin, vancomycin). Cement pastes were applied either as a one-component material, in which the solid drugs were physically dispersed, or as a two-component system, where the drugs were dissolved in an aqueous phase that was homogeneously mixed with the cement paste using a static mixing device during injection. Drug release profiles of both antibiotics from pre-mixed one- and two-component cements were characterized by an initial burst release of ∼7-28%, followed by a typical square root of time release kinetic for vancomycin. Gentamicin release rates also decreased during the first days of the release study, but after ∼1 week, the release rates were more or less constant over a period of several weeks. This anomalous release kinetic was attributed to participation of the sulfate counter ion in the cement setting reaction altering the drug solubility. The drug-loaded cement pastes showed high antimicrobial potency against Staphylococcus aureus in an agar diffusion test regime, while other cement properties such as mechanical performance or phase composition after setting were only marginally affected. PMID:23954526

  16. Rod-shaped hydroxyapatite with mesoporous structure as drug carriers for proteins

    NASA Astrophysics Data System (ADS)

    Zhang, Wandong; Chai, Yamin; Xu, Xianghua; Wang, Yonglan; Cao, Nana

    2014-12-01

    Rod-shaped hydroxyapatite (HAp) with mesoporous structure was synthesized by a hydrothermal method using Pluronic block co-polymer F127 as the template. The rod-shaped HAp was then tested as protein drug carriers by investigating their protein adsorption/release properties. Bovine serum albumin (BSA) and lysozyme (LSZ) were used as the model drugs. Various instrumental methods were used to characterize the structure, morphology, texture and protein drug adsorption/release properties of the samples. The amounts of BSA or LSZ adsorbed onto the rod-shaped HAp and their release profiles were evaluated in a simulated body fluid (SBF). The synthesized rod-shaped HAp had irregular mesostructures with lengths of 75-125 nm and diameters of about 25 nm. The rod-shaped HAp exhibited a higher loading capacity for BSA than for LSZ in the SBF. This adsorption behavior can be explained by the morphology of the rod-shaped HAp, which grew along the c-axis, leading to an a(b)-plane area that is larger than the c-plane area. Consequently, the number of positive charges on the surface of the rod-shaped HAp increased relative to the number of negative charges. The BSA release rate in SBF was slower than that of LSZ which is a result of the HAp surface properties.

  17. Controllable fabrication and characterization of biocompatible core-shell particles and hollow capsules as drug carrier

    NASA Astrophysics Data System (ADS)

    Hao, Lingyun; Gong, Xinglong; Xuan, Shouhu; Zhang, Hong; Gong, Xiuqing; Jiang, Wanquan; Chen, Zuyao

    2006-10-01

    SiO 2@CdSe core-shell particles were fabricated by controllable deposition CdSe nanoparticles on silica colloidal spheres. Step-wise coating process was tracked by the TEM and XRD measurements. In addition, SiO 2@CdSe/polypyrrole(PPy) multi-composite particles were synthesized based on the as-prepared SiO 2@CdSe particles by cationic polymerization. The direct electrochemistry of myoglobin (Mb) could be performed by immobilizing Mb on the surface of SiO 2@CdSe particles. Immobilized with Mb, SiO 2@CdSe/PPy-Mb also displayed good bioelectrochemical activity. It confirmed the good biocompatible property of the materials with protein. CdSe hollow capsules were further obtained as the removal of the cores of SiO 2@CdSe spheres. Hollow and porous character of CdSe sub-meter size capsules made them becoming hopeful candidates as drug carriers. Doxorubicin, a typical an antineoplastic drug, was introduced into the capsules. A good sustained drug release behavior of the loading capsules was discovered via performing a release test in the PBS buffer (pH 7.4) solution at 310 k. Furthermore, SiO 2@CdSe/PPy could be converted to various smart hollow capsules via selectively removal of their relevant components.

  18. Cremophor RH40-PEG 400 microemulsions as transdermal drug delivery carrier for ketoprofen.

    PubMed

    Ngawhirunpat, Tanasait; Worachun, Narumon; Opanasopit, Praneet; Rojanarata, Theerasak; Panomsuk, Suwannee

    2013-01-01

    The aim of this study was to prepare novel microemulsion for transdermal drug delivery of ketoprofen (KP). The microemulsion composed of ketoprofen as model drug, isopropyl myristate (IPM) as oil phase, surfactant mixture consisting of polyoxyl 40 hydrogenated castor oil (Cremophor RH40) as surfactant and polyethylene glycol 400 (PEG400) as co-surfactant at the ratio 1:1, and water were prepared. The viscosity, droplet size, pH, conductivity of microemulsions, and skin permeation of KP through shed snake skin were evaluated. The particle size, pH, viscosity and conductivity of microemulsions were in the range of 114-210 nm, 6.3-6.8, 124-799 cPs and 1-45 µS/cm, respectively. The ratio of IPM, and surfactant mixture played the important role in the skin permeation of KP microemulsions. As the amount of surfactant mixture and IPM increased, the skin permeation of KP decreased. The formulation composed of 30% IPM, 45% surfactant mixture and 25% water showed the highest skin permeation flux. The incorporation of terpenes in the 2.5% KP microemulsions resulted in significant enhancement in skin permeation of KP. The rank order of enhancement ratio for skin permeation enhancement of terpenes was α-pinene > limonene > menthone. The results suggested that the novel microemulsion system containing IPM, water, Cremophor RH40:PEG400 and terpenes can be applied for using as a transdermal drug delivery carrier. PMID:22023398

  19. A novel strategy for encapsulating poorly soluble drug into nanostructured lipid carriers for intravenous administration.

    PubMed

    Zhao, Chunyan; Liu, Yan; Fan, Tingting; Zhou, Dan; Yang, Yang; Jin, Yun; Zhang, Zhirong; Huang, Yuan

    2012-01-01

    The present study aimed to formulate dexamethasone (DXM), a poorly soluble drug, into nanostructured lipid carriers (NLCs) for intravenous administration by employing a phospholipids complex. Initially, dexamethasone-phospholipids complex (DPC) was synthesized and characterized. Subsequently, DPC was entrapped into NLCs and the process was optimized using spherical symmetric design-surface response methodology. Then, the characteristics, in vitro release behavior and physical stability of the optimized DPC loaded NLCs (DPC-NLCs) were investigated. Comparison between DPC-NLCs and free DXM loaded NLCs was also conducted in the aspects of particle size, entrapment efficiency (EE), drug loading efficiency (DL), initial release and zeta potential. The results showed the optimized DPC-NLCs were prepared with an average size of 189.33 ± 0.58 nm, EE of 89.82 ± 1.64%, DL of 2.13 ± 0.13% and good physical stability for 30 days. In vitro release profile exhibited an initial burst release followed by a prolonged release. Compared with free DXM loaded NLCs, the EE and DL of DPC-NLCs were higher while the initial release was lower. These advantages of DPC-NLCs proved the phospholipids complex played an essential role in NLCs formulation and showed the potential for intravenous administration of poorly soluble drugs. PMID:21222507

  20. Auto-fluorescent mesoporous ZnO nanospheres for drug delivery carrier application.

    PubMed

    Bakrudeen, Haja Bava; Sugunalakshmi, Madurai; Reddy, Boreddy S R

    2015-11-01

    The zinc oxide (ZnO) nanostructures are very interesting materials because of their practical bio-applications in various areas such as drug delivery, construction of biomaterial, optical and acoustic devices as well as their bactericidal properties. Herein, we have prepared spheroidal mesoporous auto-fluorescent ZnO nanospheres by modified continuous distillation method, showed a blue emission in the concentration of 2mg/ml at 444nm. The auto-fluorescent property of ZnO nanospheres can be used in biomaterials for target sites of tissues/cells, thereby enabling site drug delivery especially in cancer therapy. Initially, the auto-fluorescent property of the ZnO material was characterized by different techniques like PXRD, FESEM with EDAX graph, TEM, ICP-OES, particle sizes, zeta potentials and BET analysis. The mesoporous ZnO nanospheres has attracted well for their crystalline, functionalized and intensified fluorescent properties. The surface of the ZnO nanospheres was porous, spherical and nanometric in size. The synthesized material has enormous potential as a nano-drug-carrier. Preliminary studies indicated that the material prepared has an excellent scope for detection and delivery at the site of therapeutic action. PMID:26249598

  1. Approaches to enhancing the quality of drug therapy. A joint statement by the CMA and the Canadian Pharmaceutical Association. Canadian Medical Association.

    PubMed Central

    1996-01-01

    This joint statement was developed by the CMA and the Canadian Pharmaceutical Association, a national association of pharmacists, and includes the goal of drug therapy, strategies for collaboration to optimize drug therapy and physicians' and pharmacists' responsibilities in drug therapy. The statement recognizes the importance of patients, physicians and pharmacists working in close collaboration and partnership to achieve optimal outcomes from drug therapy. PMID:8823225

  2. Temporal variability of pharmaceuticals and illicit drugs in wastewater and the effects of a major sporting event.

    PubMed

    Gerrity, Daniel; Trenholm, Rebecca A; Snyder, Shane A

    2011-11-01

    Diurnal variations in wastewater flows are common phenomena related to peak water use periods. However, few studies have examined high-resolution temporal variability in trace organic contaminant (TOrC) concentrations and loadings. Even fewer have assessed the impacts of a special event or holiday. This study characterizes the temporal variability associated with a major sporting event using flow data and corresponding mass loadings of a suite of prescription pharmaceuticals, potential endocrine disrupting compounds (EDCs), and illicit drugs. Wastewater influent and finished effluent samples were collected during the National Football League's Super Bowl, which is a significant weekend for tourism in the study area. Data from a baseline weekend is also provided to illustrate flows and TOrC loadings during "normal" operational conditions. Some compounds exhibited interesting temporal variations (e.g., atenolol), and several compounds demonstrated different loading profiles during the Super Bowl and baseline weekends (e.g., the primary cocaine metabolite benzoylecgonine). Interestingly, the influent mass loadings of prescription pharmaceuticals were generally similar in magnitude to those of the illicit drugs and their metabolites. However, conventional wastewater treatment was more effective in removing the illicit drugs and their metabolites. Total influent and effluent mass loadings are also provided to summarize treatment efficacy and environmental discharges. PMID:21920575

  3. Microfluidic interactions between red blood cells and drug carriers by image analysis techniques.

    PubMed

    D'Apolito, Rosa; Taraballi, Francesca; Minardi, Silvia; Liu, Xuewu; Caserta, Sergio; Cevenini, Armando; Tasciotti, Ennio; Tomaiuolo, Giovanna; Guido, Stefano

    2016-01-01

    Blood is a complex biological fluid composed of deformable cells and platelets suspended in plasma, a protein-rich liquid. The peculiar nature of blood needs to be considered when designing a drug delivery strategy based on systemically administered carriers. Here, we report on an in vitro fluid dynamic investigation of the influence of the microcapillary flow of red blood cells (RBCs) on micron-sized carriers by high-speed imaging methods. The experiments were carried out in a 50 µm diameter glass capillary that mimicked the hydrodynamic conditions of human microcirculation. Spherical μ-particles (μ-Ps), with sizes ranging between 0.5 and 3 µm, were tested. Images of the flowing RBCs and μ-Ps were acquired by a high- speed/high-magnification microscopy. The transport and distribution of rigid particles in a suspension of RBCs under shear flow were investigated by analyzing: (i) the velocity profile of both μ-Ps and RBCs in the capillary; (ii) the radial distribution of μ-Ps in the presence of RBCs; (iii) the migration of μ-Ps towards the vessel wall due to their hydrodynamic interactions with RBCs. This study suggests that the therapeutic efficacy of μ-Ps could be ultimately affected by their interactions with the flowing RBCs in the vasculature. PMID:26651215

  4. Zwitterionic Chitosan-Polyamidoamine Dendrimer Complex Nanoparticles as a pH-Sensitive Drug Carrier

    PubMed Central

    Liu, Karen C.; Yeo, Yoon

    2013-01-01

    Polyamidoamine (PAMAM) dendrimers have been widely explored as carriers of therapeutics and imaging agents. However, amine-terminated PAMAM dendrimers is rarely utilized in systemic applications due to its cytotoxicity and risk of opsonization, caused by its cationic charges. Such undesirable effects may be mitigated by shielding the PAMAM dendrimer surface with polymers that reduce the charges. However, this shielding may also interfere with PAMAM dendrimers’ ability to interact with target cells, thus reducing cellular uptake and overall efficacy of the delivery system. Therefore, we propose to use zwitterionic chitosan (ZWC), a new chitosan derivative, which has a unique pH-sensitive charge profile, as an alternative biomaterial to modify the cationic surface of PAMAM dendrimers. Stable electrostatic complex of ZWC and PAMAM dendrimers was formed at pH 7.4, where the PAMAM dendrimer surface was covered with ZWC, as demonstrated by fluorescence spectroscopy and transmission electron microscopy. The presence of ZWC coating protected red blood cells and fibroblast cells from hemolytic and cytotoxic activities of PAMAM dendrimers, respectively. Confocal microscopy showed that the protective effect of ZWC disappeared at low pH as the complex dissociated due to the charge conversion of ZWC, allowing PAMAM dendrimers to enter cells. These results demonstrate that ZWC is able to provide a surface coverage of PAMAM dendrimers in a pH-dependent manner and, thus, enhance the utility of PAMAM dendrimers as a drug carrier to solid tumors with acidifying microenvironment. PMID:23510114

  5. Harnessing the potential of bacterial ghost for the effective delivery of drugs and biotherapeutics

    PubMed Central

    Ganeshpurkar, Aditya; Ganeshpurkar, Ankit; Pandey, Vikas; Agnihotri, Abhishek; Bansal, Divya; Dubey, Nazneen

    2014-01-01

    It seems to be a necessary need to develop an effective drug carrier system for targeted delivery of pharmaceuticals. Bacterial ghosts are emerging drug delivery platform that are capable of delivery of proteins, antigens, nucleic acids, and pharmaceuticals. Bacterial ghosts are generally produced by lysis of gram-negative bacteria. Pharmaceutically, these ghosts could be utilized to deliver proteins peptides, vaccines, drugs effectively. However, this technology is at initial stage and systematic studies are required to implement such system over humans. PMID:24678455

  6. Places of pharmaceutical knowledge-making: global health, postcolonial science, and hope in South African drug discovery.

    PubMed

    Pollock, Anne

    2014-12-01

    This article draws on ethnographic research at iThemba Pharmaceuticals, a small South African startup pharmaceutical company with an elite international scientific board. The word 'iThemba' is Zulu for 'hope', and so far drug discovery at the company has been essentially aspirational rather than actual. Yet this particular place provides an entry point for exploring how the location of the scientific knowledge component of pharmaceuticals--rather than their production, licensing, or distribution--matters. The article explores why it matters for those interested in global health and postcolonial science, and why it matters for the scientists themselves. Consideration of this case illuminates limitations of global health frameworks that implicitly posit rich countries as the unique site of knowledge production, and thus as the source of unidirectional knowledge flows. It also provides a concrete example for consideration of the contexts and practices of postcolonial science, its constraints, and its promise. Although the world is not easily bifurcated, it still matters who makes knowledge and where. PMID:25608441

  7. Cathepsin B Cleavage of vcMMAE-Based Antibody-Drug Conjugate Is Not Drug Location or Monoclonal Antibody Carrier Specific.

    PubMed

    Gikanga, Benson; Adeniji, Nia S; Patapoff, Thomas W; Chih, Hung-Wei; Yi, Li

    2016-04-20

    Antibody-drug conjugates (ADCs) require thorough characterization and understanding of product quality attributes. The framework of many ADCs comprises one molecule of antibody that is usually conjugated with multiple drug molecules at various locations. It is unknown whether the drug release rate from the ADC is dependent on drug location, and/or local environment, dictated by the sequence and structure of the antibody carrier. This study addresses these issues with valine-citrulline-monomethylauristatin E (vc-MMAE)-based ADC molecules conjugated at reduced disulfide bonds, by evaluating the cathepsin B catalyzed drug release rate of ADC molecules with different drug distributions or antibody carriers. MMAE drug release rates at different locations on ADC I were compared to evaluate the impact of drug location. No difference in rates was observed for drug released from the VH, VL, or CH2 domains of ADC I. Furthermore, four vc-MMAE ADC molecules were chosen as substrates for cathepsin B for evaluation of Michaelis-Menten parameters. There was no significant difference in KM or kcat values, suggesting that different sequences of the antibody carrier do not result in different drug release rates. Comparison between ADCs and small molecules containing vc-MMAE moieties as substrates for cathepsin B suggests that the presence of IgG1 antibody carrier, regardless of its bulkiness, does not impact drug release rate. Finally, a molecular dynamics simulation on ADC II revealed that the val-cit moiety at each of the eight possible conjugation sites was, on average, solvent accessible over 50% of its maximum solvent accessible surface area (SASA) during a 500 ns trajectory. Combined, these results suggest that the cathepsin cleavage sites for conjugated drugs are exposed enough for the enzyme to access and that the drug release rate is rather independent of drug location or monoclonal antibody carrier. Therefore, the distribution of drug conjugation at different sites is not

  8. The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK.

    PubMed

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2008-07-01

    The presence and fate of 56 pharmaceuticals, personal care products, endocrine disruptors and illicit drugs (PPCPs) were investigated in the South Wales region of the UK. Two contrasting rivers: River Taff and River Ely were chosen for this investigation and were monitored for a period of 10 months. The impact of the factors affecting the levels of concentration of PPCPs and illicit drugs in surface water such as surrounding area, proximity to wastewater effluent and weather conditions, mainly rainfall was also investigated. Most PPCPs were frequently found in river water at concentrations reaching single microgL(-1) and their levels depended mainly on the extent of water dilution resulting from rainfall. Discharge of treated wastewater effluent into the river course was found to be the main cause of water contamination with PPCPs. The most frequently detected PPCPs represent the group of pharmaceuticals dispensed at the highest levels in the Welsh community. These were antibacterial drugs (trimethoprim, erythromycin-H(2)O and amoxicillin), anti-inflammatories/analgesics (paracetamol, tramadol, codeine, naproxen, ibuprofen and diclofenac) and antiepileptic drugs (carbamazepine and gabapentin). Only four PPCPs out of 56 (simvastatin, pravastatin, digoxin and digoxigenin) were not quantified over the course of the study. Several PPCPs were found to be both ubiquitous and persistent in the aqueous environment (e.g. erythromycin-H(2)O, codeine, carbamazepine, gabapentin and valsartan). The calculated average daily loads of PPCPs indicated that in total almost 6 kg of studied PPCPs are discharged daily into the studied rivers. The illicit drugs studied were found in rivers at low levels of ng L(-1). Average daily loads of amphetamine, cocaine and its main metabolite benzoylecgonine were as follows: 8, 1.2 and 39 gday(-1), respectively. Their frequent occurrence in surface water is primarily associated with their high illegal usage and is strongly associated with the

  9. Spatial and temporal occurrence of pharmaceuticals and illicit drugs in the aqueous environment and during wastewater treatment: new developments.

    PubMed

    Baker, David R; Kasprzyk-Hordern, Barbara

    2013-06-01

    This paper presents, for the first time, spatial and temporal occurrence of a comprehensive set of >60 pharmaceuticals, illicit drugs and their metabolites in wastewater (7 wastewater treatment plants utilising different treatment technologies) and a major river in the UK over a 12 month period. This paper also undertakes a comparison of the efficiency of processes utilised during wastewater treatment and it discusses under-researched aspects of pharmaceuticals and illicit drugs in the environment including sorption to solids and stereoselectivity in the fate of chiral drugs during wastewater treatment and in receiving waters. The removal efficiency of analytes strongly depended on the type of wastewater treatment technology employed and denoted <50% or >60% in the case of tricking filter and activated sludge respectively. It should be stressed, however, that the removal rate was highly variable for different groups of compounds. A clear increase in the cumulative concentration of all monitored compounds was observed in receiving waters; thus highlighting the impact of WWTP discharge on water quality and the importance of the removal efficiency of WWTPs. No seasonal variation was observed with regard to the total load of targeted compounds in the river each month. The concentration of each analyte was largely dependent on rainfall and the dilution factor of WWTP discharge. These results indicate that although the drugs of abuse are not present at very high concentrations in river water (typically low ng L(-1) levels), their occurrence and possible synergic action is of concern, and the study of multiple groups of drugs of abuse is of significant importance. PMID:23563258

  10. Solid self-emulsifying phospholipid suspension (SSEPS) with diatom as a drug carrier.

    PubMed

    Milović, Mladen; Simović, Spomenka; Lošić, Dušan; Dashevskiy, Andriy; Ibrić, Svetlana

    2014-10-15

    We report the application of diatom as a solid carrier for water insoluble drugs applied in oral drug delivery system based on the self-emulsifying drug delivery system (SEDDS) caprylocaproyl macrogol-8 glycerides/lecithin/propylene glycol/caprylic/capric triglyceride. Diatoms are fossilized skeletons of photosynthetic algae with complex 3-dimensional (3D), porous structure consisting of amorphous silica, obtained by purification of diatomaceous earth. Different solid samples of carbamazepine (CBZ) suspension in SEDDS, called solid self-emulsifying phospholipid suspension (SSEPS), were prepared using two methods: adsorption of CBZ dispersion in SEDDS by gentle mixing with diatoms in mortar with pestle (Method A) or dispersion of diatoms in ethanol solution of CBZ and SEDDS components, followed by ethanol evaporation (Method B). Release rate of CBZ from SSEPS was significantly higher in comparison to pure drug, physical mixture of diatoms and CBZ as well as solid dispersion of pure CBZ and diatoms obtained by ethanol evaporation. The dissolution of CBZ from SSEPS sample prepared using method B was faster than from the sample prepared by the method A. Higher dissolution for sample prepared by the method B can be attributed to the partial adsorption (deeper localization) of liquid material inside the pores of diatoms. Upon storage of the samples under accelerated conditions (40°C and 70% RH) for 10 weeks no significant changes in CBZ crystallinity and dissolution was in case of SSEPS, contrary to solid dispersion with increased crystallinity, indicating that diatoms with adsorbed liquid CBZ-loaded SEPS can maintain initial CBZ characteristics. PMID:25125211

  11. Red blood cell ghosts as promising drug carriers to target wound infections.

    PubMed

    Berikkhanova, Kulzhan; Omarbaev, Rustam; Gulyayev, Alexandr; Shulgau, Zarina; Ibrasheva, Dilbar; Adilgozhina, Gulsim; Sergazy, Shynggys; Zhumadilov, Zhaxybay; Askarova, Sholpan

    2016-09-01

    Autologous red blood cell ghosts (RBC ghosts) can carry cytokines to the sites of inflammation. The targeting moiety of the RBC ghosts is associated with the nature of purulent inflammation, where the erythrocytes are phagocyted and encapsulated drugs are released. In the present study we have investigated the healing potential of RBC ghosts loaded with cytokine IL-1β and antibiotic. Additionally, the pharmacokinetic properties of RBC ghosts loaded with IL-1β were studied. 35 Male Wistar rats (250-300g) were used in the pharmacokinetic study and in a wound infection model where a suspension of Staphylococcus aureus was placed into a surgical cut of the skin and subcutaneous tissue in the femoral region. In order to monitor progression of the wound repair processes, wound swabs or aspiration biopsies were taken for analyses on the 1st-6th days. Wound repair dynamics assessment was based on suppression of S. aureus growth, signs of pain, time of disappearance of pus and infiltration around the wound. Visual observations, as well as microbiological and cytological analysis of wound exudates demonstrated a significant acceleration of healing processes in a group of animals treated with a local injection of IL-1β and ceftriaxone encapsulated into RBC ghosts when compared to the animals treated either with a local or IM injection of free drugs. For the pharmacokinetic study, single IV injections of either free or encapsulated IL-1β were made and the concentration of IL-1β in serum samples and tissue homogenates were determined. Encapsulation in RBC ghosts improved pharmacokinetic profiles of IL-1β by increasing the half-life, reducing its clearance, and increasing the deposition of the drug in the liver, spleen and lungs. These data suggest that RBC ghosts are effective drug carriers for targeted delivery of cytokines to the sites of inflammation, and have a potential for improving the treatment outcomes of purulent diseases. PMID:27062487

  12. Synthesis and characterization of Zinc (II)-loaded Zeolite/Graphene oxide nanocomposite as a new drug carrier.

    PubMed

    Khatamian, M; Divband, B; Farahmand-Zahed, F

    2016-09-01

    Current research has focused on the preparation of Zinc-clinoptilolite/Graphene Oxide (Zn-Clin/GO) hybrid nanostructure and investigating its biocompatibility for the first time. As prepared samples were characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM), Thermo gravimetric analysis (TGA) and Fourier transform infrared (FT-IR). In order to use it as a drug carrier two important factors were investigated: cytocompatibility of nanocomposites and their drug loading capacity. The results showed that the prepared nanocomposite is cytocompatible and its high loading capacity and slow release performance for Doxorubicin (DOX), as a cancer drug, proved that it can be used as a drug carrier. At last in-vitro toxicity of DOX loaded nanocomposite was compared with pure DOX. PMID:27207061

  13. Chitosan Based Polyelectrolyte Complexes as Potential Carrier Materials in Drug Delivery Systems

    PubMed Central

    Hamman, Josias H.

    2010-01-01

    Chitosan has been the subject of interest for its use as a polymeric drug carrier material in dosage form design due to its appealing properties such as biocompatibility, biodegradability, low toxicity and relatively low production cost from abundant natural sources. However, one drawback of using this natural polysaccharide in modified release dosage forms for oral administration is its fast dissolution rate in the stomach. Since chitosan is positively charged at low pH values (below its pKa value), it spontaneously associates with negatively charged polyions in solution to form polyelectrolyte complexes. These chitosan based polyelectrolyte complexes exhibit favourable physicochemical properties with preservation of chitosan’s biocompatible characteristics. These complexes are therefore good candidate excipient materials for the design of different types of dosage forms. It is the aim of this review to describe complexation of chitosan with selected natural and synthetic polyanions and to indicate some of the factors that influence the formation and stability of these polyelectrolyte complexes. Furthermore, recent investigations into the use of these complexes as excipients in drug delivery systems such as nano- and microparticles, beads, fibers, sponges and matrix type tablets are briefly described. PMID:20479980

  14. Polydopamine-Based Simple and Versatile Surface Modification of Polymeric Nano Drug Carriers

    PubMed Central

    Park, Joonyoung; Brust, Tarsis F.; Lee, Hong Jae; Lee, Sang Cheon; Watts, Val J.; Yeo, Yoon

    2014-01-01

    The surface of a polymeric nanoparticle (NP) is often functionalized with cell-interactive ligands and/or additional polymeric layers to control NP interaction with cells and proteins. However, such modification is not always straightforward when the surface is not chemically reactive. For this reason, most NP functionalization processes employ reactive linkers or coupling agents or involve pre-functionalization of the polymer, which are complicated and inefficient. Moreover, pre-functionalized polymers can lose the ability to encapsulate and retain a drug if the added ligands change chemical properties of the polymer. To overcome this challenge, we use dopamine polymerization as a way of functionalizing NP surfaces. This method includes brief incubation of the pre-formed NPs in a weak alkaline solution of dopamine, followed by secondary incubation with desired ligands. Using this method, we have functionalized poly(lactic-co-glycolic acid) (PLGA) NPs with three representative surface modifiers: a small molecule (folate), a peptide (Arg-Gly-Asp), and a polymer [poly(carboxybetaine methacrylate)]. We confirmed that the modified NPs showed the expected cellular interactions with no cytotoxicity or residual bioactivity of dopamine. The dopamine polymerization method is a simple and versatile surface modification method, applicable to a variety of NP drug carriers irrespective of their chemical reactivity and the types of ligands. PMID:24628245

  15. miktoarm polymer: controlled synthesis, characterization, and application as anticancer drug carrier

    NASA Astrophysics Data System (ADS)

    Lin, Wenjing; Nie, Shuyu; Xiong, Di; Guo, Xindong; Wang, Jufang; Zhang, Lijuan

    2014-05-01

    Amphiphilic A2(BC)2 miktoarm star polymers [poly(ɛ-caprolactone)]2-[poly(2-(diethylamino)ethyl methacrylate)- b- poly(poly(ethylene glycol) methyl ether methacrylate)]2 [(PCL)2(PDEA- b-PPEGMA)2] were developed by a combination of ring opening polymerization (ROP) and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The critical micelle concentration (CMC) values were extremely low (0.0024 to 0.0043 mg/mL), depending on the architecture of the polymers. The self-assembled empty and doxorubicin (DOX)-loaded micelles were spherical in morphologies, and the average sizes were about 63 and 110 nm. The release of DOX at pH 5.0 was much faster than that at pH 6.5 and pH 7.4. Moreover, DOX-loaded micelles could effectively inhibit the growth of cancer cells HepG2 with IC50 of 2.0 μg/mL. Intracellular uptake demonstrated that DOX was delivered into the cells effectively after the cells were incubated with DOX-loaded micelles. Therefore, the pH-sensitive (PCL)2(PDEA- b-PPEGMA)2 micelles could be a prospective candidate as anticancer drug carrier for hydrophobic drugs with sustained release behavior.

  16. Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug

    PubMed Central

    Brunetti, Jlenia; Pillozzi, Serena; Falciani, Chiara; Depau, Lorenzo; Tenori, Eleonora; Scali, Silvia; Lozzi, Luisa; Pini, Alessandro; Arcangeli, Annarosa; Menichetti, Stefano; Bracci, Luisa

    2015-01-01

    Taxanes are highly effective chemotherapeutic drugs against proliferating cancer and an established option in the standard treatment of ovarian and breast cancer. However, treatment with paclitaxel is associated with severe side effects, including sensory axonal neuropathy, and its poor solubility in water complicates its formulation. In this paper we report the in vitro and in vivo activity of a new form of paclitaxel, modified for conjugation with a tumor-selective tetrabranched peptide carrier (NT4). NT4 selectively targets tumor cells by binding to membrane sulfated glycosaminoglycans (GAG) and to endocytic receptors, like LRP1 and LRP6, which are established tumor markers. Biological activity of NT4-paclitaxel was tested in vitro on MDA-MB 231 and SKOV-3 cell lines, representing breast and ovarian cancer, respectively, and in vivo in an orthotopic mouse model of human breast cancer. Using in vivo bioluminescence imaging, we found that conjugation of paclitaxel with the NT4 peptide led to increased therapeutic activity of the drug in vivo. NT4-paclitaxel induced tumor regression, whereas treatment with unconjugated paclitaxel only produced a reduction in tumor growth. Moreover, unlike paclitaxel, NT4-paclitaxel is very hydrophilic, which may improve its pharmacokinetic profile and allow the use of less toxic dilution buffers, further decreasing its general chemotherapic toxicity. PMID:26626158

  17. New amphiphilic derivatives of poly(ethylene glycol) (PEG) as surface modifiers of colloidal drug carriers. III. Lipoamino acid conjugates with carboxy- and amino-PEG(5000) polymers.

    PubMed

    Pignatello, Rosario; Impallomeni, Giuseppe; Pistarà, Venerando; Cupri, Sarha; Graziano, Adriana C E; Cardile, Venera; Ballistreri, Alberto

    2015-01-01

    Within a research directed to developing new polymeric materials, suitable for decorating the surface of colloidal drug carriers, PEG5000 polymers containing a free carboxyl or amine group at one end were conjugated to an α-lipoamino moiety (LAA). The conjugates were characterized by FT-IR, (1)H-NMR, and MALDI-TOF mass spectrometry. They showed the same profile of solubility as the parent PEGs in water and in some polar and apolar solvents of pharmaceutical use. Representative terms showed to be well tolerated when incubated with Caco-2 or L929 cell cultures. Dedicated differential scanning calorimetry (DSC) studies were performed to prove the interaction of increasing molar fractions of the PEG5000-LAA conjugates with dipalmitoylphosphatidylcholine (DPPC) bilayers, to gain information about their possible incorporation in drug nanocarriers. While the parent PEGs affected only the superficial structure of bilayers, the amphiphilic PEG-LAA conjugates induced a perturbing effect on the thermotropic behavior of DPPC liposomes, according to the structure of the linked LAA residue. A molar concentration of these PEG-LAA between 5 and 10% was individuated as the most suitable to produce stable vesicles. PMID:25492012

  18. A Novel Tumor Targeting Drug Carrier for Optical Imaging and Therapy

    PubMed Central

    Li, Rui; Zheng, Ke; Hu, Ping; Chen, Zhuo; Zhou, Shanyong; Chen, Jincan; Yuan, Cai; Chen, Song; Zheng, Wei; Ma, En; Zhang, Fengling; Xue, Jinping; Chen, Xueyuan; Huang, Mingdong

    2014-01-01

    Human serum albumin (HSA), a naturally abundant protein in blood plasma and tissue fluids, has an extraordinary ligand-binding capacity and is advocated as a drug carrier to facilitate drug delivery. To render it tumor targeting specificity, we generated a recombinant HSA fused with the amino-terminal fragment (ATF) of urokinase, allowing the fusion protein to bind to urokinase receptor (uPAR), which is shown to have a high expression level in many tumors, but not in normal tissues. To test the efficacy of this bifunctional protein (ATF-HSA), a hydrophobic photosensitizer (mono-substituted β-carboxy phthalocyanine zinc, CPZ) was chosen as a cytotoxic agent. A dilution-incubation-purification (DIP) strategy was developed to load the ATF-HSA with this CPZ, forming a 1:1 molecular complex (ATF-HSA:CPZ). We demonstrated that CPZ was indeed embedded inside ATF-HSA at the fatty acid binding site 1 (FA1) of HSA, giving a hydrodynamic radius of 7.5 nm, close to HSA's (6.5 nm). ATF-HSA:CPZ showed high stability and remarkable optical and photophysical properties in aqueous solution. In addition, the molecular complex ATF-HSA:CPZ can bind to recombinant uPAR in vitro and uPAR on tumor cell surfaces, and was efficient in photodynamic killing of tumor cells. The tumor-killing potency of this molecular complex was further demonstrated in a tumor-bearing mouse model at a dose of 0.080 μmol / kg, or 0.050 mg CPZ / kg of mouse body weight. Using fluorescent molecular tomography (FMT), ATF-HSA:CPZ was shown to accumulate specifically in tumors, and importantly, such tumor retention was higher than that of HSA:CPZ. Together, these results indicate that ATF-HSA:CPZ is not only an efficient tumor-specific cytotoxic agent, but also an useful tumor-specific imaging probe. This bifunctional protein ATF-HSA can also be used as a drug carrier for other types of cytotoxic or imaging agents to render them specificity for uPAR-expressing tumors. PMID:24723985

  19. Vitamin D: Pharmacokinetics and Safety When Used in Conjunction with the Pharmaceutical Drugs Used in Cancer Patients: A Systematic Review

    PubMed Central

    Kennedy, Deborah A.; Cooley, Kieran; Skidmore, Becky; Fritz, Heidi; Campbell, Tara; Seely, Dugald

    2013-01-01

    Vitamin D has reported anti-cancer and anti-inflammatory properties modulated through gene transcription and non-genomic signaling cascades. The purpose of this review was to summarize the available research on interactions and pharmacokinetics between vitamin D and the pharmaceutical drugs used in patients with cancer. Hypercalcemia was the most frequently reported side effect that occurred in high dose calcitriol. The half-life of 25(OH)D3 and/or 1,25(OH)2D3 was found to be impacted by cimetidine; rosuvastatin; prednisone and possibly some chemotherapy drugs. No unusual adverse effects in cancer patients; beyond what is expected from high dose 1,25(OH)2D3 supplementation, were revealed through this review. While sufficient evidence is lacking, supplementation with 1,25(OH)2D3 during chemotherapy appears to have a low risk of interaction. Further interactions with vitamin D3 have not been studied. PMID:24216707

  20. Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the stratum corneum

    PubMed Central

    Zaid Alkilani, Ahlam; McCrudden, Maelíosa T.C.; Donnelly, Ryan F.

    2015-01-01

    The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies. PMID:26506371

  1. Pharmaceutical companies vs. the State: who is responsible for post-trial provision of drugs in Brazil?

    PubMed

    Wang, Daniel Wei L; Ferraz, Octavio Luiz Motta

    2012-01-01

    This paper discusses the post-trial access to drugs for patients who participated in clinical trials in Brazil. The ethical guidance for clinical trials in Brazil is arguably one of the clearest in the world in attributing to research sponsors the responsibility for providing post-trial drugs to patients who participated in their experiments. The Federal Constitution recognizes health as a fundamental right to be fulfilled by the State. Based on the Brazilian constitution and on the National Health Council resolutions, courts have been accepting patients' claims and ordering the State and the pharmaceutical companies to provide these patients with the tested treatment in the quantity and duration they need it. This generous interpretation of the duties of the pharmaceutical companies and the State makes the Brazilian model for post-trial access unique when compared to the experience of other countries and thus should be followed with attention by future research in order to assess its consequences for patients, research sponsors, and the public health system. PMID:22789039

  2. A Review for the Analysis of Antidepressant, Antiepileptic and Quinolone Type Drugs in Pharmaceuticals and Environmental Samples.

    PubMed

    Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel

    2016-09-01

    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed. PMID:26939618

  3. Discrepancies in listed adverse drug reactions in pharmaceutical product information supplied by the regulatory authorities in Denmark and the USA.

    PubMed

    Eriksson, Robert; Aagaard, Lise; Jensen, Lars Juhl; Borisova, Liza; Hørlück, Dorte; Brunak, Søren; Hansen, Ebba Holme

    2014-06-01

    Pharmaceutical product information (PI) supplied by the regulatory authorities serves as a source of information on safe and effective use of drugs. The objectives of this study were to qualitatively and quantitatively compare PIs for selected drugs marketed in both Denmark and the USA with respect to consistency and discrepancy of listed adverse drug reaction (ADR) information. We compared individual ADRs listed in PIs from Denmark and the USA with respect to type and frequency. Consistency was defined as match of ADRs and of ADR frequency or match could not be ruled out. Discrepancies were defined as ADRs listed only in one country or listed with different frequencies. We analyzed PIs for 40 separate drugs from ten therapeutic groups and assigned the 4003 identified ADRs to System Organ Classes (Medical Dictionary for Regulatory Activities [MedDRA] terminology). Less than half of listed ADRs (n = 1874; 47%) showed consistency. Discrepancies (n = 2129; 53%) were split into ADRs listed only in the USA (n = 1558; 39%), ADRs listed only in Denmark (n = 325; 8%) and ADRs listed with different frequencies (n = 246; 6%). The majority of listed ADRs were of the type "gastrointestinal disorders" and "nervous system disorders". Our results show great differences in PIs for drugs approved in both Denmark and the USA illuminating concerns about the credibility of the publicly available PIs. The results also represent an argument for further harmonization across borders to improve consistency between authority-supplied information. PMID:25505588

  4. Secondary patenting of branded pharmaceuticals: a case study of how patents on two HIV drugs could be extended for decades.

    PubMed

    Amin, Tahir; Kesselheim, Aaron S

    2012-10-01

    Pharmaceutical manufacturers rely on patents to protect their intellectual property and often seek to extend market exclusivity for their products to maximize their return on investment. One method is by obtaining patents on features other than the original active drug ingredient, including secondary patents on alternate formulations of the drug or on methods of administration. This article examines how secondary patents can extend market exclusivity and thus delay generic competition, using as an example two key antiretroviral drugs for the management of HIV: ritonavir (Norvir) and lopinavir/ritonavir (Kaletra). We identified 108 patents, which together could delay generic competition until at least 2028--twelve years after the expiration of the patents on the drugs' base compounds and thirty-nine years after the first patents on ritonavir were filed. Some of the secondary patents that were reviewed were found to be of questionable inventiveness. We argue that increased transparency for existing patents, stricter patentability standards, and increased opportunities to challenge patent applications and patents could reduce inappropriate market exclusivity extensions on brand-name drugs and open the door to lower-cost generics. PMID:23048110

  5. Applicability of avidin protein coated mesoporous silica nanoparticles as drug carriers in the lung

    NASA Astrophysics Data System (ADS)

    van Rijt, S. H.; Bölükbas, D. A.; Argyo, C.; Wipplinger, K.; Naureen, M.; Datz, S.; Eickelberg, O.; Meiners, S.; Bein, T.; Schmid, O.; Stoeger, T.

    2016-04-01

    Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties and are thus considered as promising candidates for next generation nano-medicines. In particular, inhalation into the lungs represents a direct, non-invasive delivery route for treating lung disease. To assess MSN biocompatibility in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as well as aminated (uncoated) MSNs, after direct application into the lungs of mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and inflammatory responses to MSNs within one week after instillation. We show that amine-functionalized (MSN-NH2) particles are not taken up by lung epithelial cells, but induced a prolonged inflammatory response in the lung and macrophage cell death. In contrast, MSN-AVI co-localized with alveolar epithelial type 1 and type 2 cells in the lung in the absence of sustained inflammatory responses or cell death, and showed preferential epithelial cell uptake in in vitro co-cultures. Further, MSN-AVI particles demonstrated uniform particle distribution in mouse lungs and slow clearance rates. Thus, we provide evidence that avidin functionalized MSNs (MSN-AVI) have the potential to serve as versatile biocompatible drug carriers for lung-specific drug delivery.Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties and are thus considered as promising candidates for next generation nano-medicines. In particular, inhalation into the lungs represents a direct, non-invasive delivery route for treating lung disease. To assess MSN biocompatibility in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as well as aminated (uncoated) MSNs, after direct application into the lungs of mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and inflammatory responses to MSNs within one week after instillation. We show that amine-functionalized (MSN-NH2) particles are not taken up

  6. Assessment of PEG on polymeric particles surface, a key step in drug carrier translation.

    PubMed

    Rabanel, Jean-Michel; Hildgen, Patrice; Banquy, Xavier

    2014-07-10

    Injectable drug nanocarriers have greatly benefited in their clinical development from the addition of a superficial hydrophilic corona to improve their cargo pharmacokinetics. The most studied and used polymer for this purpose is poly(ethylene glycol), PEG. However, in spite of its wide use for over two decades now, there is no general consensus on the optimum PEG chain coverage-density and size required to escape from the mononuclear phagocyte system and to extend the circulation time. Moreover, cellular uptake and active targeting may have conflicting requirements in terms of surface properties of the nanocarriers which complicate even more the optimization process. These persistent issues can be largely attributed to the lack of straightforward characterization techniques to assess the coverage-density, the conformation or the thickness of a PEG layer grafted or adsorbed on a particulate drug carrier and is certainly one of the main reasons why so few clinical applications involving PEG coated particle-based drug delivery systems are under clinical trial so far. The objective of this review is to provide the reader with a brief description of the most relevant techniques used to assess qualitatively or quantitatively PEG chain coverage-density, conformation and layer thickness on polymeric nanoparticles. Emphasis has been made on polymeric particle (solid core) either made of copolymers containing PEG chains or modified after particle formation. Advantages and limitations of each technique are presented as well as methods to calculate PEG coverage-density and to investigate PEG chains conformation on the NP surface. PMID:24768790

  7. Size-exclusive effect of nanostructured lipid carriers on oral drug delivery.

    PubMed

    Li, Huipeng; Chen, Minglei; Su, Zhigui; Sun, Minjie; Ping, Qineng

    2016-09-10

    Nanostructured lipid carriers (NLCs) are generally recognized as safe (GRAS) to form a controlled nanostructure are a new generation of lipid nanoparticles. In addition to formulation and particle surface properties, particle size had great influence for overcoming gastrointestinal (GI) barriers on the oral drug delivery of lipid based nanoparticles. In the present study, we investigated the effect of size on oral drug delivery for NLCs. The NLCs with different particle sizes (NLCs100nm, NLCs200nm and NLCs300nm) were prepared by using solvent evaporation method and the coumarin-6 (C6) or DiO/DiI was loaded in the nanoparticles as the fluorescence probe. The MTT assay indicated that both blank NLCs and C6-loaded NLCs displayed relatively low toxicity towards Caco-2 cells. Cellular uptake mechanisms of NLCs with different sizes were found to be similar and governed by active endocytosis, clathrin- and caveolae-mediated process. However, the smaller nanoparticle (NLC-100nm) showed higher uptake efficiency in Caco-2 cell (P<0.05) as well as higher permeation ability in Caco-2 cell monolayer (P<0.01), compared with NLC-200nm and NLC-300nm. The fluorescence resonance energy transfer (FRET) assay indicated that all of three NLCs could maintained the structural integrity in blood circulation after oral administration. NLC-100nm exhibited the most stability according to the most stable FRET signal. In situ rat intestinal absorption experiments and in vitro ligated rat intestinal loops model demonstrated that all NLCs could rapidly penetrate duodenum versus jejunum, ileum and colon (P<0.01). Moreover, pharmacokinetic studies showed that NLC-100nm exhibited highest Cmax and AUC compared with the other two NLCs. In conclusion, the size of 100nm might be the most suitable size for oral drug delivery of lipid based nanoparticles. PMID:27452421

  8. Bio-derived poly(gamma-glutamic acid) nanogels as controlled anticancer drug delivery carriers.

    PubMed

    Bae, Hee Ho; Cho, Mi Young; Hong, Ji Hyeon; Poo, Haryoung; Sung, Moon-Hee; Lim, Yong Taik

    2012-12-01

    We have developed a novel type of polymer nanogel loaded with anticancer drug based on bio-derived poly(gamma- glutamic acid) (gamma-PGA). gamma-PGA is a highly anionic polymer that is synthesized naturally by microbial species, most prominently in various bacilli, and has been shown to have excellent biocompatibility. Thiolated gamma-PGA was synthesized by covalent coupling between the carboxyl groups of gamma-PGA and the primary amine group of cysteamine. Doxorubicin (Dox)-loaded gamma-PGA nanogels were fabricated using the following steps: (1) an ionic nanocomplex was formed between thiolated gamma-PGA as the negative charge component, and Dox as the positive charge component; (2) addition of poly(ethylene glycol) (PEG) induced hydrogen-bond interactions between thiol groups of thiolated gamma-PGA and hydroxyl groups of PEG, resulting in the nanocomplex; and (3) disulfide crosslinked gamma-PGA nanogels were fabricated by ultrasonication. The average size and surface charge of Dox-loaded disulfide cross-linked gamma-PGA nanogels in aqueous solution were 136.3 +/- 37.6 nm and -32.5 +/- 5.3 mV, respectively. The loading amount of Dox was approximately 38.7 microgram per mg of gamma-PGA nanogel. The Dox-loaded disulfide cross-linked gamma-PGA nanogels showed controlled drug release behavior in the presence of reducing agents, glutathione (GSH) (1- 10 mM). Through fluorescence microscopy and FACS, the cellular uptake of gamma-PGA nanogels into breast cancer cells (MCF-7) was analyzed. The cytotoxic effect was evaluated using the MTT assay and was determined to be dependent on both the concentration and treatment time of gamma-PGA nanogels. The bio-derived gamma-PGA nanogels are expected to be a well-designed delivery carrier for controlled drug delivery applications. PMID:23221543

  9. Transfer of PAMAM Dendrimers across Human Placenta: Prospects of Its Use as Drug Carrier During Pregnancy

    PubMed Central

    Menjoge, Anupa R.; Rinderknecht, Amber; Navath, Raghavendra S.; Faridnia, Masoud; Kim, Chong J.; Romero, Roberto; Miller, Richard K.; Kannan, Rangaramanujam M.

    2011-01-01

    Dendrimers offer significant potential as nanocarriers for targeted delivery of drugs and imaging agents. The objectives of this study were to evaluate the transplacental transport, kinetics and biodistribution of PAMAM dendrimers ex-vivo across the human placenta in comparison with antipyrine, a freely diffusible molecule, using dually perfused re-circulating term human placental lobules. The purpose of this study is to determine if dendrimers as drug carriers can be used to design drug delivery systems directed at selectively treating either the mother or the fetus. The transplacental transfers of fluorescently (Alexa 488) tagged PAMAM dendrimer (16 kDa) and antipyrine (188 Da) from maternal to fetal circulation were measured using HPLC/dual UV and fluorescent detector (sensitivity of 10 ng / mL for dendrimer and 100 ng /mL for antipyrine respectively). Cmax for the dendrimer-Alexa (DA) in maternal perfusate (Tmax = 15min) was 18 times higher than in the fetal perfusate and never equilibrated with the maternal perfusate during 5.5 hours of perfusion (n=4). DA exhibited a significant but low transplacental transport of ~2.26 ± 0.12 μg / mL during 5.5 hours, where the mean transplacental transfer was 0.84 ±0.11 % of the total maternal concentration and the feto-maternal ratio as percent was 0.073% ± 0.02. The biochemical and physiological analysis of the placentae perfused with DA demonstrated normal function throughout the perfusion. The immunofluorescence histochemistry confirmed that the biodistribution of DA in perfused placenta was sparsely dispersed, and when noted was principally seen in the inter-villous spaces and outer rim of the villous branches. In a few cases, DA was found internalized and localized in nuclei and cytoplasm of syncytiotrophoblast and inside the villous core; however, DA was mostly absent from the villous capillaries. In conclusion, the PAMAM dendrimers exhibited a low rate of transfer from maternal to the fetal side across the

  10. Feasibility of poly(ethylene glycol) derivatives as diagnostic drug carriers for tumor imaging.

    PubMed

    Kanazaki, Kengo; Sano, Kohei; Makino, Akira; Yamauchi, Fumio; Takahashi, Atsushi; Homma, Tsutomu; Ono, Masahiro; Saji, Hideo

    2016-03-28

    Poly(ethylene glycol) (PEG) is an artificial but biocompatible hydrophilic polymer that has been widely used in clinical products. To evaluate the feasibility of using PEG derivative itself as a tumor imaging carrier via an enhanced permeability and retention (EPR) effect, we prepared indium-111-labeled PEG ((111)In-DTPA-PEG) and indocyanine green (ICG)-labeled PEG (ICG-PEG) with PEG molecular weights of 5-40kDa and investigated their in vivo biodistribution in colon26 tumor-bearing mice. Thereafter, single-photon emission computed tomography (SPECT) and photoacoustic (PA) imaging studies were performed. The in vivo biodistribution studies demonstrated increased tumor uptake and a prolongation of circulation half-life as the molecular weight of PEG increased. Although the observed differences in in vivo biodistribution were dependent on the labeling method ((111)In or ICG), the tumor-to-normal tissue ratios were comparable. Because PEG-based probes with a molecular weight of 20kDa (PEG20) showed a preferable biodistribution (highest accumulation among tissues excised and relatively high tumor-to-blood ratios), an imaging study using (111)In-DTPA-PEG20 and ICG-PEG20 was performed. Colon26 tumors inoculated in the right shoulder were clearly visualized by SPECT 24h after administration. Furthermore, PA imaging using ICG-PEG20 also detected tumor regions, and the detected PA signals increased in proportion with the injected dose. These results suggest that PEG derivatives (20kDa) serve as robust diagnostic drug carriers for tumor imaging. PMID:26869546

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

    PubMed

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

    2016-06-01

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

  12. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... sponsor must require a pharmacy that dispenses a covered Part D drug to inform an enrollee of any... Part D drug that is therapeutically equivalent and bioequivalent and available at that pharmacy, unless... bioequivalent version of that drug available at that pharmacy. (b) Timing of notice. Subject to paragraph (d)...

  13. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... sponsor must require a pharmacy that dispenses a covered Part D drug to inform an enrollee of any... Part D drug that is therapeutically equivalent and bioequivalent and available at that pharmacy, unless... bioequivalent version of that drug available at that pharmacy. (b) Timing of notice. Subject to paragraph (d)...

  14. In silico predictions of gastrointestinal drug absorption in pharmaceutical product development: application of the mechanistic absorption model GI-Sim.

    PubMed

    Sjögren, Erik; Westergren, Jan; Grant, Iain; Hanisch, Gunilla; Lindfors, Lennart; Lennernäs, Hans; Abrahamsson, Bertil; Tannergren, Christer

    2013-07-16

    Oral drug delivery is the predominant administration route for a major part of the pharmaceutical products used worldwide. Further understanding and improvement of gastrointestinal drug absorption predictions is currently a highly prioritized area of research within the pharmaceutical industry. The fraction absorbed (fabs) of an oral dose after administration of a solid dosage form is a key parameter in the estimation of the in vivo performance of an orally administrated drug formulation. This study discloses an evaluation of the predictive performance of the mechanistic physiologically based absorption model GI-Sim. GI-Sim deploys a compartmental gastrointestinal absorption and transit model as well as algorithms describing permeability, dissolution rate, salt effects, partitioning into micelles, particle and micelle drifting in the aqueous boundary layer, particle growth and amorphous or crystalline precipitation. Twelve APIs with reported or expected absorption limitations in humans, due to permeability, dissolution and/or solubility, were investigated. Predictions of the intestinal absorption for different doses and formulations were performed based on physicochemical and biopharmaceutical properties, such as solubility in buffer and simulated intestinal fluid, molecular weight, pK(a), diffusivity and molecule density, measured or estimated human effective permeability and particle size distribution. The performance of GI-Sim was evaluated by comparing predicted plasma concentration-time profiles along with oral pharmacokinetic parameters originating from clinical studies in healthy individuals. The capability of GI-Sim to correctly predict impact of dose and particle size as well as the in vivo performance of nanoformulations was also investigated. The overall predictive performance of GI-Sim was good as >95% of the predicted pharmacokinetic parameters (C(max) and AUC) were within a 2-fold deviation from the clinical observations and the predicted plasma AUC

  15. Thermal, mechanical and drug release characteristics of an acrylic film using active pharmaceutical ingredient as non-traditional plasticizer.

    PubMed

    Wiranidchapong, Chutima; Kieongarm, Waraporn; Managit, Chittima; Phrompittayarat, Watoo

    2016-01-01

    The objective of this study was to investigate thermal and mechanical properties as well as in vitro drug release of Eudragit® RL (ERL) film using chlorpheniramine maleate (CPM) as either active pharmaceutical ingredient or non-traditional plasticizer. Differential scanning calorimeter was used to measure the glass transition temperature (Tg) of 0-100% w/w CPM in ERL physical mixture. Instron testing machine was used to investigate Young's modulus, tensile stress and tensile strain (%) of ERL film containing 20-60% w/w CPM. Finally, a Franz diffusion cell was used to study drug release from ERL films obtained from four formulations, i.e. CRHP0/0, CRHP0/5, CRHP2/0 and CRHP2/5. The Tg of ERL was decreased when the weight percentage of CPM increased. The reduction of the Tg could be described by Kwei equation, indicating the interaction between CPM and ERL. Modulus and tensile stress decreased whereas tensile strain (%) increased when weight percentage of CPM increased. The change of mechanical properties was associated with the reduction of the Tg when weight percentage of CPM increased. ERL films obtained from four formulations could release the drug in no less than 10 h. Cumulative amount of drug release per unit area of ERL film containing only CPM (CRHP0/0) was lower than those obtained from the formulations containing traditional plasticizer (CRHP0/5), surfactant (CRHP2/0) or both of them (CRHP2/5). The increase of drug release was a result of the increase of drug permeability through ERL film and drug solubility based on traditional plasticizer and surfactant, respectively. PMID:26133082

  16. Design and development of a multifunctional nano carrier system for imaging, drug delivery, and cell targeting in cancer research

    NASA Astrophysics Data System (ADS)

    Cho, Hoon-Sung

    There has been an increasing need in the last decade for early diagnosis and treatment of cancer prior to the tumor mass becoming evident as anatomical anomaly. A major challenge in cancer diagnosis is to distinguish cancer cells from the surrounding, normal tissue. For early cancer diagnosis and treatment, a nano carrier system was designed and developed with key components uniquely structured according to biomedical and clinical requirements: targeting, drug storage capabilities, fluorescent emissions near the infrared range for in vivo imaging, and magnetic hyperthermia. For in vivo imaging, quantum dots with emissions near infrared range (˜800 nm) were conjugated onto the surface of carbon nanotubes and nanospheres consisting of a spherical polystyrene matrix (˜100 nm) and high fraction of superparamagnetic Fe3O4 nanoparticles (˜10 nm) embedded. The QDs on these nano carriers exhibited intense visible emissions using fluorescent spectroscopy and successfully facilitated in vivo soft tissue imaging in mice. For drug storage, the chemotherapeutic agent, paclitaxel (PTX) was loaded onto the surfaces of these nano-carriers by using a layer of biodegradable poly(lactic-co-glycolic acid) (PLGA). A cell-based cytotoxicity assay was employed to verify successful loading of pharmacologically active drug, PTX. Cell viability of human, metastatic PC3mm2 prostate cancer cells was assessed in the presence and absence of various nano-carrier populations using the MTT assay. For hyperthermia, Fe3O 4 nanoparticles were conjugated onto the surfaces of carbon nanotubes (CNT) and embedded into the nanospheres. Magnetization measurements showed nearly reversible hysteresis curves from the Fe3O4-conjugated CNTs and the magnetic nanospheres (MNS). Application of an alternating electromagnetic field effectively induced heating the solution of the Fe3O 4-conjugated CNTs and the magnetic nanospheres (MNS) into temperature ranges (up to 55ºC) suitable for therapeutic hyperthermia

  17. Enhanced Loading and Release of Non-Steroidal Anti-Inflammatory Drugs from Silica-Based Nanoparticle Carriers.

    PubMed

    Mohammadzadeh, Mostafa; Nourbakhsh, Mohammad Sadegh; Khodaverdi, Elham; Hadizadeh, Farzin; Omid Malayeri, Sina

    2016-09-01

    Silica nanoparticles can be potentially considered the carriers of controlled drug systems. In this research, non-steroidal anti-inflammatory drugs were used. Diclofenac sodium and piroxicam were loaded on the considered nanosilica using solvent evaporation method. To prove drug encapsulation on the nanosilica and its rate, infrared spectroscopy, X-ray diffraction, and BET were used, and after proving the existence of the drug in the nanosilica matrix and determining the amount of loading, dissolution test was performed in an environment similar to that of stomach and intestine in terms of pH. Drug loading percentage showed that over 90% of drugs were loaded on nanosilica. Dissolution tests in stomach pH environment showed the control samples (drug without SBA-15) released considerable amount of drugs (about 90%) within first 15 min, when it was about 10-20% for the matrixes. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples. It was indicated nanosilica has the ability of retaining the drugs in acidic pH and prevented their release. Furthermore, the drugs were released in a controlled manner in small intestine, which is the main absorption site. PMID:27062095

  18. Biocompatibility, cellular uptake and biodistribution of the polymeric amphiphilic nanoparticles as oral drug carriers.

    PubMed

    Liu, Ya; Kong, Ming; Feng, Chao; Yang, Kui Kun; Li, Yang; Su, Jing; Cheng, Xiao Jie; Park, Hyun Jin; Chen, Xi Guang

    2013-03-01

    Oleoyl-carboxymethyl-chitosan (OCMCS) was synthesized and were soluble at neutral pH. The critical micelle concentration (CMC) of OCMCS in deionized water was 0.021 mg/ml. OCMCS nanoparticles were successfully prepared via self-assembly with mean diameter of 215.34 nm, zeta potential of 19.26 mV and an almost spherical shape as determined by electron microscopy. The OCMCS nanoparticles showed low erythrocyte membrane-damaging effect. The MTT survival assay indicated no significant cytotoxicity to Caco-2 cells and MEFs cells. The uptake of FITC labeled OCMCS nanoparticles by Caco-2 cells was confirmed via confocal laser scanning microscope (CLSM). In vivo toxicity assays were performed via histopathological evaluation, and no specific anatomical pathological changes or tissue damage was observed in the tissues of carps. The extent of tissue distribution and retention following oral administration of FITC-OCMCS nanoparticles was analyzed for 3 days. After 3 days, the nanoparticles remained detectable in the muscle, heart, kidney, liver, intestine, and spleen. The results showed that 34.32% of the particles were localized in the liver, 18.79% in the kidney, and 17.36% in the heart. The lowest percentage was observed in the muscle. These results implied that OCMCS nanoparticles had great potential to be applied as safe carriers for the oral administration of protein drugs. PMID:23247264

  19. Thermoresponsive Nanoparticles of Self-Assembled Block Copolymers as Potential Carriers for Drug Delivery and Diagnostics.

    PubMed

    Rahikkala, Antti; Aseyev, Vladimir; Tenhu, Heikki; Kauppinen, Esko I; Raula, Janne

    2015-09-14

    Thermally responsive hydrogel nanoparticles composed of self-assembled polystyrene-b-poly(N-isopropylacrylamide)-b-polystyrene block copolymers and fluorescent probe 1-anilinonaphthalene-8-sulfonic acid have been prepared by aerosol flow reactor method. We aimed exploring the relationship of intraparticle morphologies, that were, PS spheres and gyroids embedded in PNIPAm matrix, as well PS-PNIPAm lamellar structure, to probe release in aqueous solution below and above the cloud point temperature (CPT) of PNIPAm. The release was detected by fluorescence emission given by the probe binding to bovine serum albumin. Also, the colloidal behavior of hydrogel nanoparticles at varying temperatures were examined by scattering method. The probe release was faster below than above the CPT from all the morphologies of which gyroidal morphology showed the highest release. Colloidal behavior varied from single to moderately aggregated particles in order spheres-gyroids-lamellar. Hydrogel nanoparticles with tunable intra particle self-assembled morphologies can be utilized designing carrier systems for drug delivery and diagnostics. PMID:26207325

  20. Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA.

    PubMed

    Kissel, Maria; Peschke, Peter; Subr, Vladimir; Ulbrich, Karel; Strunz, Anke M; Kühnlein, Rainer; Debus, Jürgen; Friedrich, Eckhard

    2002-08-01

    Synthetic macromolecules such as copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(HPMA) was prepared for labelling by introducing biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of biotin-pHPMA was visualised using a streptavidin-alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated polymer could be easily detected in tissues fixed in 10% paraformaldehyde-phosphate buffer at 4 degrees C for 48 h. While biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate carcinoma (Dunning R3327-AT1). How biotin as a label influences the biodistribution of poly(HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(HPMA) with biotin-pHPMA. The organ distribution patterns of the two polymers correlated well, except with respect to kidney. It is assumed that the accumulation of biotin-pHPMA in the distal tubuli is due to a biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules. PMID:12173020

  1. Utilization of H-bond interaction of nucleobase Uralic with antitumor methotrexate to design drug carrier with ultrahigh loading efficiency and pH-responsive drug release

    PubMed Central

    Cai, Teng-Teng; Lei, Qi; Yang, Bin; Jia, Hui-Zhen; Cheng, Hong; Liu, Li-Han; Zeng, Xuan; Feng, Jun; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-01-01

    A novel Uralic (U)-rich linear-hyperbranched mono-methoxy poly (ethylene glycol)-hyperbranched polyglycerol-graft-Uralic (mPEG-HPG-g-U) nanoparticle (NP) was prepared as drug carrier for antitumor methotrexate (MTX). Due to the H-bond interaction of U with MTX and hydrophobic interaction, this NP exhibited high drug loading efficiency of up to 40%, which was significantly higher than that of traditional NPs based on U-absent copolymers (<15%). In addition, MTX-loaded mPEG-HPG-g-U NPs also demonstrated an acidity-accelerated drug release behavior. PMID:26816622

  2. Kitchen chemistry: A scoping review of the diversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions.

    PubMed

    Van Hout, Marie Claire

    2014-01-01

    Misuse of pharmaceuticals is of increasing drug policy and public health concern. A scoping review was conducted on the diversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions. The research question was broad: What is known from the existing literature about the diversion of pharmaceuticals for non-medicinal use and for home production of drug solutions? The scoping process centred on the systematic selection, collection, and summarization of extant knowledge within this broad thematic remit. One hundred and thirty-four records were grouped into discrete thematic categories namely: non medicinal use and tampering with pharmaceuticals, oral misuse of codeine cough syrups, homemade drug solutions, and home-produced drug-related harms in the narrative review design. Forms of abuse of codeine cough syrup include mixtures with alcohol or soft drinks ('Purple Drank'), with kratom leaves ('Kratom cocktails'), or chemically altered to extract dextromorphan ('Lemon Drop'). Production of homemade opiates ('Cheornaya', 'Kolyosa', Himiya', 'Braun', 'Krokodil'), methamphetamine ('Vint', 'Pervitin'), methcathinone ('Jeff'), and cathinone ('Boltushka') are described. Displacement patterns between the non-medical use of pharmaceuticals, commercial, and homemade drugs appear dependent on availability of opiates, prescribing practices, supervision of substitution drug dosing, availability of cheap ingredients, policing, and awareness of harms. Adverse health and social consequences relate to the use of unknown and contaminated (end) substances, injecting practices, redosing, medical complications, and death. The review highlights a public health imperative requiring a multidisciplinary approach to quantify potential impact and required integrated policy responses incorporating international regulation, enforcement, health surveillance and service delivery. PMID:24619569

  3. Ultrafast laser processing of drug particles in water for pharmaceutical discovery

    NASA Astrophysics Data System (ADS)

    Ding, Weimeng; Sylvestre, Jean-Philippe; Bouvier, Emmanuelle; Leclair, Grégoire; Meunier, Michel

    2014-01-01

    The laser fragmentation technique has been extensively used to produce inorganic nanoparticles, but its practice on organic materials, especially on drugs, is less common. Here, we briefly review the recent advances in laser micro-/nanonization of organic materials and the rationale of using laser fragmentation for drug discovery. We present our case studies of two drug models: fenofibrate and naproxen. Both drugs were fragmented in water with femtosecond (fs) laser and characterized in terms of particle size distribution and physicochemical properties. Effects of fs laser fragmentation were also compared with nanosecond (ns) laser fragmentation and with conventional media milling technique. Fs laser was more suitable to produce sub-micron size drug particles than ns laser, but degradation of drugs after nanonization was also more pronounced than micronization. Physicochemical transformations such as oxidation, hydration and amorphisation might occur during the laser-material interactions. Laser nanonization showed improved dissolution kinetics, similar to media milling. Unlike the conventional milling techniques, laser fragmentation enabled the treatment of minute amount (as small as several milligrams) of drugs with high efficiency, thus is a useful tool for particle size reduction during the early phases of drug discovery.

  4. Mixed micelles of Lecithin-Tyloxapol as pharmaceutical nanocarriers for anti-tubercular drug delivery.

    PubMed

    Mehta, S K; Jindal, Neha

    2013-10-01

    The equimolar mixed micellar system of Lecithin-Tyloxapol has been explored using physicochemical and spectroscopic measurements. Thermodynamic parameters have been computed for the prepared mixed micellar system. Interaction parameter, β, suggests synergistic interactions in the mixed systems. This has been further examined for the solubilization of anti-tuberculosis drugs (ATDs). In addition, the entrapment efficiency of the formulation has been evaluated for three ATDs. Micropolarity measurements indicate location of all the three drugs inside the mixed micellar systems. Fourier transform infrared spectroscopic and differential scanning calorimetric studies infer that the drugs are in harmony with the excipients since no visible interactions between the drugs and mixed micelles have been detected. In vitro release analyses exhibit sustained release of drugs from the formulation. Comparison of regression coefficients of different kinetic models reveal that release of ATDs from mixed micellar system follows first order exponential decay. PMID:23751420

  5. The Trial of Drug Discovery using the In-Silico Screening Methods Developed by Pharmaceutical Innovation Value Chain

    NASA Astrophysics Data System (ADS)

    Inoue, Tsuyoshi; Matsumura, Hiroyoshi; Adachi, Hiroaki; Mori, Yusuke; Takano, Kazufumi; Murakami, Satoshi; Fukunishi, Yoshifumi; Nakamura, Haruki; Kinoshita, Takayoshi; Nakanishi, Isao; Okuno, Yasushi; Minakata, Satoshi; Mikami, Yoshiaki; Sakuma, Toshihiro; Kitajima, Masato; Fukuoka, Yoshitada; Takada, Toshikazu; Sakata, Tsuneaki

    We have recently established Pharmaceutical Innovation Value Chain collaborated by The SOSHO project (http://www.so-sho.jp) and The BioGrid Project (http://www.biogrid.jp/) to accelerate new drug development. The in-silico group calculated the matrices on the interaction between the proteins and chemical compounds, and developed the novel in-silico screening methods, Multiple Target Screening (MTS) and Docking score index (DSI), improving the hit rate of screening a lead compound. We have applied these methods for the two target enzymes; human hematopoietic prostaglandin D synthase (H-PGDS) and orotidine 5’-monophosphate decarboxylase from human malaria parasite plasmodium falciparum (PfOMPDC). The optimizing of HQL-79, one of the known inhibitors for human H-PGDS and the screening of lead compounds for both enzymes are in study.

  6. Effect of particle size of calcium phosphate based bioceramic drug delivery carrier on the release kinetics of ciprofloxacin hydrochloride: an in vitro study

    NASA Astrophysics Data System (ADS)

    Sasikumar, Swamiappan

    2013-09-01

    Hydroxyapatite (HAP) is the constituent of calcium phosphate based bone cement and it is extensively used as a bone substitute and drug delivery vehicle in various biomedical applications. In the present study we investigated the release kinetics of ciprofloxacin loaded HAP and analyzed its ability to function as a targeted and sustained release drug carrier. Synthesis of HAP was carried out by combustion method using tartaric acid as a fuel and nitric acid as an oxidizer. Powder XRD and FTIR techniques were employed to characterize the phase purity of the drug carrier and to verify the chemical interaction between the drug and carrier. The synthesized powders were sieve separated to make two different drug carriers with different particle sizes and the surface topography of the pellets of the drug carrier was imaged by AFM. Surface area and porosity of the drug carrier was carried out using surface area analyzer. The in-vitro drug release kinetics was performed in simulated body fluid, at 37.3°C. The amount of ciprofloxacin released is measured using UV-visible spectroscopy following the characteristic λ max of 278 nm. The release saturates around 450 h which indicates that it can be used as a targeted and sustained release carrier for bone infections.

  7. Comparison of drug coverage in Canada before and after the establishment of the pan-Canadian Pharmaceutical Alliance

    PubMed Central

    Milliken, Debbie; Venkatesh, Jaya; Yu, Rebecca; Su, Zhuo; Thompson, Melissa; Eurich, Dean

    2015-01-01

    Objectives This study was conducted to determine whether establishment of the pan-Canadian Pharmaceutical Alliance (pCPA) was associated with significant changes in drug listing decisions across Canada. Analysis and results This study included drug indications that received a Common Drug Review or pan-Canadian Oncology Drug Review listing recommendation within 3 years before (‘pre-PCPA era’ group; n=79) and 3 years after (‘PCPA era’ group; n=91) the pCPA was established in August 2010. At the time of this study (30 April 2014), nine pCPA-participating jurisdictions had listed 35–59% of drug indications in the pre-pCPA era group and a nearly identical range, 36–59%, in the pCPA era group. Within the pCPA-era group, 31 drug indications (34%) had completed pCPA negotiations (‘pCPA negotiation’ subgroup); the jurisdictions had listed 39–77% of these drug indications. Comparison of the pCPA era group to the pre-pCPA era group indicated that the proportion listed did not change significantly in any jurisdiction, and time-to-listing increased significantly in New Brunswick and decreased significantly in Alberta, Manitoba, and Ontario. When the pCPA negotiation subgroup was compared to the pre-pCPA era group, the proportion listed increased significantly in British Columbia, Saskatchewan, Manitoba and Newfoundland and Labrador, and time-to-listing increased significantly in New Brunswick and Nova Scotia and decreased significantly in Manitoba and Ontario. A sensitivity analysis suggested more favourable results regarding the pCPA's impact. Conclusions While the pCPA might have had a varied effect on time-to-listing, this study's primary analysis did not observe a significant impact on the overall proportion of new drug indications listed across jurisdictions. This may be due to the fact that, at the time of this study, only a limited number of drug indications had completed pCPA negotiations. This study provides a framework for future evaluations of

  8. Dual Wavelength RP-HPLC Method for Simultaneous Determination of Two Antispasmodic Drugs: An Application in Pharmaceutical and Human Serum

    PubMed Central

    Hasan, Najmul; Chaiharn, Mathurot; Khan, Sauleha; Khalid, Hira; Sher, Nawab; Siddiqui, Farhan Ahmed; Siddiqui, Muhammad Zain

    2013-01-01

    A reverse phase stability indicating HPLC method for simultaneous determination of two antispasmodic drugs in pharmaceutical parenteral dosage forms (injectable) and in serum has been developed and validated. Mobile phase ingredients consist of Acetonitrile : buffer : sulfuric acid 0.1 M (50 : 50 : 0.3 v/v/v), at flow rate 1.0 mL/min using a Hibar μBondapak ODS C18 column monitored at dual wavelength of 266 nm and 205 nm for phloroglucinol and trimethylphloroglucinol, respectively. The drugs were subjected to stress conditions of hydrolysis (oxidation, base, acid, and thermal degradation). Oxidation degraded the molecule drastically while there was not so much significant effect of other stress conditions. The calibration curve was linear with a correlation coefficient of 0.9999 and 0.9992 for PG and TMP, respectively. The drug recoveries fall in the range of 98.56% and 101.24% with 10 pg/mL and 33 pg/mL limit of detection and limit of quantification for both phloroglucinol and trimethylphloroglucinol. The method was validated in accordance with ICH guidelines and was applied successfully to quantify the amount of trimethylphloroglucinol and phloroglucinol in bulk, injectable form and physiological fluid. Forced degradation studies proved the stability indicating abilities of the method. PMID:24286017

  9. Dual Wavelength RP-HPLC Method for Simultaneous Determination of Two Antispasmodic Drugs: An Application in Pharmaceutical and Human Serum.

    PubMed

    Hasan, Najmul; Chaiharn, Mathurot; Khan, Sauleha; Khalid, Hira; Sher, Nawab; Siddiqui, Farhan Ahmed; Siddiqui, Muhammad Zain

    2013-01-01

    A reverse phase stability indicating HPLC method for simultaneous determination of two antispasmodic drugs in pharmaceutical parenteral dosage forms (injectable) and in serum has been developed and validated. Mobile phase ingredients consist of Acetonitrile : buffer : sulfuric acid 0.1 M (50 : 50 : 0.3 v/v/v), at flow rate 1.0 mL/min using a Hibar μ Bondapak ODS C18 column monitored at dual wavelength of 266 nm and 205 nm for phloroglucinol and trimethylphloroglucinol, respectively. The drugs were subjected to stress conditions of hydrolysis (oxidation, base, acid, and thermal degradation). Oxidation degraded the molecule drastically while there was not so much significant effect of other stress conditions. The calibration curve was linear with a correlation coefficient of 0.9999 and 0.9992 for PG and TMP, respectively. The drug recoveries fall in the range of 98.56% and 101.24% with 10 pg/mL and 33 pg/mL limit of detection and limit of quantification for both phloroglucinol and trimethylphloroglucinol. The method was validated in accordance with ICH guidelines and was applied successfully to quantify the amount of trimethylphloroglucinol and phloroglucinol in bulk, injectable form and physiological fluid. Forced degradation studies proved the stability indicating abilities of the method. PMID:24286017

  10. Potentiometric sensors enabling fast screening of the benign prostatic hyperplasia drug alfuzosin in pharmaceuticals, urine and serum.

    PubMed

    Gupta, Vinod K; Singh, Ashok K; Gupta, Barkha

    2007-08-01

    The construction and characterization of potentiometric membrane electrodes are described for the quantification of alfuzosin, a drug used in a mono- and combined therapy of benign prostatic hyperplasia (BPH). The membranes of these electrodes consist of alfuzosin hydrochloride-tetraphenyl borate, (Az-TPB), chlorophenyl borate (Az-ClPB), and phosphotungstate (Az(3)-PT) ion associations as molecular recognition reagent dispersed in PVC matrix with dioctylpthalate as plasticizer. The performance characteristics of these electrodes, which were evaluated according to IUPAC recommendations, revealed a fast, stable and liner response for alfuzosin over the concentration ranges of 8.3 x 10(-6) to 1.0 x 10(-2) M, 3.8 x 10(-6) to 1.0 x 10(-2) M, 7.5 x 10(-7) to 1.0 x 10(-2) M AzCl with cationic slopes of 57.0, 56.0 and 58.5 mV/decade, respectively. The solubility product of the ion-pair and the formation constant of the precipitation reaction leading to the ion-pair formation were determined conductometrically. The electrodes, fully characterized in terms of composition, life span and usable pH range, were applied to the potentiometric determination of alfuzosin hydrochloride ion in different pharmaceutical preparations and biological fluids without any interference from excipients or diluents commonly used in drug formulations. The potentiometric method was also used in the determination of alfuzosin hydrochloride in pharmaceutical preparations in four batches with different expiration dates. Validation of the method showed suitability of the proposed electrodes for use in the quality control assessment of alfuzosin hydrochloride. This potentiometric method offers the advantages of high-throughput determination, simplicity, accuracy, automation feasibility, and applicability to turbid and colored sample solutions. PMID:17979639

  11. Preparation of luminescent and mesoporous Eu3+/Tb3+ doped calcium silicate microspheres as drug carriers via a template route.

    PubMed

    Kang, Xiaojiao; Huang, Shanshan; Yang, Piaoping; Ma, Ping'an; Yang, Dongmei; Lin, Jun

    2011-03-01

    Luminescent and mesoporous Eu(3+)/Tb(3+) doped calcium silicate microspheres (LMCS) were synthesized by using mesoporous silica spheres as the templates. The LMCS and drug-loaded samples were characterized by means of X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), N(2) adsorption/desorption, and photoluminescence (PL) spectra. The results reveal that the LMCS have uniform spherical morphology with a diameter around 400 nm and the mesopore size of 6 nm. The prepared samples exhibit little cytotoxicity at concentrations below 5 mg mL(-1) via MTT assay. In addition, drug storage/release properties of the LMCS were demonstrated for ibuprofen (IBU). The obtained LMCS can be used to encapsulate drugs and release them. Under excitation by UV light, the IBU-loaded samples still show the characteristic (5)D(0)-(7)F(1-3) emission lines of Eu(3+) and the characteristic (5)D(4)-(7)F(3-6) emission lines of Tb(3+). The PL intensity of Eu(3+) in the drug carrier system increases with the cumulative released amount of IBU, making the drug release able to be tracked or monitored by the change of luminescence of Eu(3+). The LMCS reported here with mesoporous structure, good biocompatibility and luminescent property can be a promising drug delivery carrier. PMID:21183970

  12. [Incentives and disincentives for research and development of new drugs by the pharmaceutical industry].

    PubMed

    Curcio, Pasqualina Curcio

    2008-10-01

    The authors present a model with factors that influence research and development decisions by the pharmaceutical industry: risk of disease transmission and possibility of control; case-fatality and the presence of cure or treatments; income; number of persons who demand the medicine; and opportunity costs for the company. Companies tend to invest in markets with inelastic demand (highly contagious diseases with no possibility of controlling transmission and/or very lethal diseases without treatment) and/or where there is a large population or high per capita income. Companies tend not to invest in markets where marginal costs exceed marginal income, particularly when costs increase permanently as a consequence of rising opportunity costs generated by foregoing profit in other markets. In such cases, policies to subsidize R&D are not effective, and policies must be orientated towards strengthening basic and applied research by public institutions. PMID:18949238

  13. Pharmaceutical Applications of Nanoparticle Carriers

    NASA Astrophysics Data System (ADS)

    Heurtault, B.; Schuber, F.; Frisch, B.

    Once it has been administered, an active principle still has to face many physiological barriers on the way to its target, and this may significantly affect its efficiency. These different barriers depend to a great extent on the active ingredient itself and on the way it is administered. They may be constituted by enzymes, an acidic or basic pH, or cell membranes that must be crossed. As a consequence, the active principle may be degraded or distributed to organs other than the therapeutic target. This can reduce the efficiency of the administered dose, or even lead to toxicity with regard to organs other than the target. For example, this situation is observed in trials for the oral administration of insulin (for treating type I diabetes). One point is that this molecule is weakly absorbed by the digestive epithelium (first barrier). Secondly, it undergoes enzymatic degradation by gastric proteases (second barrier). As a consequence, the free form of the molecule cannot be administered orally. This is why insulin is mainly administered subcutaneously, so that it attains the blood circulation directly. However, such a means of administration requires specific training of the patient. This example shows that lack of efficiency and/or difficulties in using certain molecules are not necessarily due to their pharmacology, but rather in some cases to their physicochemical properties.

  14. Detained and drugged: a brief overview of the use of pharmaceuticals for the interrogation of suspects, prisoners, patients, and POWs in the US.

    PubMed

    Calkins, Laura

    2010-01-01

    Using medical literature citations, Congressional hearings, and declassified documents this paper examines the uses of pharmaceuticals in the interrogation of vulnerable populations. From the use of IV relaxants on criminal suspects during the 1920s to the Global War on Terror, the nexus of drugs, testing, and interrogations will be explored in both the domestic and international contexts. PMID:20017745

  15. New drug regulations in France: what are the impacts on market access? Part 2 – impacts on market access and impacts for the pharmaceutical industry

    PubMed Central

    Rémuzat, Cécile; Toumi, Mondher; Falissard, Bruno

    2013-01-01

    Access to the French drug market is being impacted by an ongoing dramatic shift in practice as well as by two laws that came into force in December 2011. This new environment has been described and analyzed in two separate articles. This second article analyzes how this new environment will actually impact the access to French drug market. French drug market access will be increasingly driven by comparative-effectiveness and cost-effectiveness data, and an increased role of postmarketing studies in the years to come. This access is evolving in a more complex environment for stakeholders due to the uncertainties surrounding these changes and it will be more complex and difficult for the pharmaceutical industry to address. The main issue faced by the pharmaceutical companies will be to minimize uncertainty at the time of a drug's launch to narrow the decision window. This is a major change of paradigm for the pharmaceutical business, in which pre- and postlaunch risks are directed toward the pharmaceutical industry. PMID:27226829

  16. The delayed luminescence spectroscopy as tool to investigate the cytotoxic effect on human cancer cells of drug-loaded nanostructured lipid carrier

    NASA Astrophysics Data System (ADS)

    Grasso, R.; Gulino, M.; Scordino, A.; Musumeci, F.; Campisi, A.; Bonfanti, R.; Carbone, C.; Puglisi, G.

    2016-05-01

    The first results concerning the possibility to use Delayed Luminescence spectroscopy to evaluate the in vitro induction of cytotoxic effects on human glioblastoma cells of nanostructured lipid carrier and drug-loaded nanostructured lipid carrier are showed in this contribution. We tested the effects of nanostructured lipid carrier, ferulic acid and ferulic acidloaded nanostructured lipid carrier on U-87MG cell line. The study seems to confirm the ability of Delayed Luminescence to be sensible indicator of alterations induced on functionality of the mitochondrial respiratory chain complex I in U-87MG cancer cells when treated with nanostructured lipid carriers.

  17. Towards MR-navigable Nanorobotic Carriers for Drug Delivery into the Brain

    PubMed Central

    Tabatabaei, Seyed Nasrollah; Duchemin, Sonia; Girouard, Helene

    2013-01-01

    Magnetic Resonance Navigation (MRN) relies on Magnetic Nanoparticles (MNPs) embedded in microcarriers or microrobots to allow the induction of a directional propelling force by 3-D magnetic gradients. These magnetic gradients are superposed on a sufficiently high homogeneous magnetic field (e.g. the Bo field of a MR scanner) to achieve maximum propelling force through magnetization saturation of the MNPs. As previously demonstrated by our group, such technique was successful at maintaining microcarriers along a planned trajectory in the blood vessels based on tracking information gathered using Magnetic Resonance Imaging (MRI) sequences from artifacts caused by the same MNPs. Besides propulsion and tracking, the same MNPs can be synthesized with characteristics that can allow for the diffusion of therapeutic cargo carried by these MR-navigable carriers through the Blood Brain Barrier (BBB) using localized hyperthermia without compromising the MRN capabilities. In the present study, localized hyperthermia induced by an alternating magnetic field (AC field) is investigated for the purpose of transient controlled disruption of the BBB and hence local delivery of therapeutic agents into the brain. Here, an external heating apparatus was used to impose a regional heat shock on the skull of a living mouse model. The effect of heat on the permeability of the BBB was assessed using histological observation and tissue staining by Evans blue dye. Results show direct correlation between hyperthermia and BBB leakage as well as its recovery from thermal damage. Therefore, in addition to on-command propulsion and remote tracking, the proposed navigable agents could be suitable for controlled opening of the BBB by hyperthermia and selective brain drug delivery. PMID:23518572

  18. Dextran-coated superparamagnetic nanoparticles as potential cancer drug carriers in vivo

    NASA Astrophysics Data System (ADS)

    Peng, Mingli; Li, Houli; Luo, Zhiyi; Kong, Jian; Wan, Yinsheng; Zheng, Lemin; Zhang, Qinlu; Niu, Hongxin; Vermorken, Alphons; van de Ven, Wim; Chen, Chao; Zhang, Xikun; Li, Fuqiang; Guo, Lili; Cui, Yali

    2015-06-01

    Dextran-coated superparamagnetic iron oxide nanoparticles (DSPIONs) have gained considerable interest, because of their biocompatibility and biosafety in clinics. Doxorubicin (Dox), a widely used chemotherapeutic drug, always has limited applications in clinical therapy due to its serious side effects of dose-limiting irreversible cardiotoxicity and myelo suppression. Herein, DSPIONs were synthesized and developed as magnetic carriers for doxorubicin. The Dox-DSPION conjugates were evaluated in the in vitro test of Dox release, which showed pH-dependence with the highest release percentage of 50.3% at pH 5.0 and the lowest release percentage of 11.8% in a physiological environment. The cytotoxicity of DSPIONs and Dox-DSPIONs evaluated by the MTT assay indicated that DSPIONs had no cytotoxicity and the conjugates had significantly reduced the toxicity (IC50 = 1.36 μg mL-1) compared to free Dox (IC50 = 0.533 μg mL-1). Furthermore, confocal microscopic data of cell uptake suggest that less cytotoxicity of Dox-DSPIONs may be attributed to the cellular internalization of the conjugates and sustainable release of Dox from the formulation in the cytoplasm. More importantly, the results from the rabbit VX2 liver tumor model test under an external magnetic field showed that the conjugates had approximately twice the anti-tumor activity and two and a half times the animal survival rate, respectively, compared to free Dox. Collectively, our data have demonstrated that Dox-DSPIONs have less toxicity with better antitumor effectiveness in in vitro and in vivo applications, suggesting that the conjugates have potential to be developed into chemo-therapeutic formulations.

  19. A tumor mRNA-dependent gold nanoparticle-molecular beacon carrier for controlled drug release and intracellular imaging.

    PubMed

    Qiao, Guangming; Zhuo, Linhai; Gao, Yuan; Yu, Lijuan; Li, Na; Tang, Bo

    2011-07-14

    We demonstrate a tumor mRNA-dependent drug carrier for controlled release of doxorubicin (Dox) and intracellular imaging based on gold nanoparticle-molecular beacon. Fluorescent Dox is released effectively and induces apoptosis in breast cancer cells but not in normal cells. Significantly, the release of Dox is correlated positively with the quantities of tumor mRNA, which is according to various stages of tumor progression, and so can decrease effectively side effects of Dox. PMID:21589964

  20. Functionalized single-walled carbon nanotube (5, 0) as a carrier for isoniazid — A tuberculosis drug

    NASA Astrophysics Data System (ADS)

    Rajarajeswari, M.; Iyakutti, K.; Lakshmi, I.; Rajeswarapalanichamy, R.; Kawazoe, Y.

    2015-06-01

    Nanostructures functionalized with amino acid are able to penetrate the cell wall. In this first principle study, we have demonstrated that the amino acid alanine functionalized carbon nanotubes (CNTs) (5, 0) can be a drug carrier for the tuberculosis drug isoniazid. Isoniazid is binding with both the non-covalently and covalently functionalized CNTs through the π-π stacking and NH⋯π interactions. The planar structure of isoniazid and hydrophobic nature of CNT promote the π-π stacking interactions. The amine group present in the isoniazid enables the NH⋯π interaction with the delocalized π electron cloud of CNT.

  1. Enhancing the value delivered by the statistician throughout drug discovery and development: putting statistical science into regulated pharmaceutical innovation.

    PubMed

    Enas, G G; Andersen, J S

    With the dawn of the 21st century, the pharmaceutical industry faces a dramatically different constellation of business and scientific predictors of success than those of just a few years ago. Significant advances in science at the genetic, molecular and cellular levels, combined with progress demonstrated around the globe with drug regulations, have increased business and competitive opportunities. This has occurred in search of better and cheaper medicines that reach patients with unmet medical needs as quickly as possible. Herein lie new opportunities for those who can help business and regulatory leaders make good decisions about drug development and market authorization as quickly and efficiently as possible in the presence of uncertainty. The statistician is uniquely trained and qualified to render such value. We show how the statistician can contribute to the process of drug innovation from the very early stages of drug discovery until patients, payers and regulators are satisfied. Indeed, the very nature of regulated innovation demands that efficient and effective processes are implemented which yield the right information for good decision making. The statistician can take the lead in setting a strategy that directs such processes in the direction of greatest value. This demands skills that enable one to identify important sources of variability and uncertainty and then leverage those skills to make decisions. If such decisions call for more information, then the statistician can render experimental designs which generate the right information needed to make the decision in an efficient, timely manner. To add value to the enterprise, statisticians will have to become more intimately associated with business and regulatory decisions by building on their traditional roles (for example, numerical analyst, tactician) and unique skill sets (for example, analysis, computation, logical thought and work process, precision, accuracy). Business and regulatory savvy

  2. Completeness assessment of type II active pharmaceutical ingredient drug master files under generic drug user fee amendment: review metrics and common incomplete items.

    PubMed

    Zhang, Huyi; Li, Haitao; Song, Wei; Shen, Diandian; Skanchy, David; Shen, Kun; Lionberger, Robert A; Rosencrance, Susan M; Yu, Lawrence X

    2014-09-01

    Under the Generic Drug User Fee Amendments (GDUFA) of 2012, Type II active pharmaceutical ingredient (API) drug master files (DMFs) must pay a user fee and pass a Completeness Assessment (CA) before they can be referenced in an Abbreviated New Drug Application (ANDA), ANDA amendment, or ANDA prior approval supplement (PAS). During the first year of GDUFA implementation, from October 1, 2012 to September 30, 2013, approximately 1,500 Type II API DMFs received at least one cycle of CA review and more than 1,100 Type II DMFs were deemed complete and published on FDA's "Available for Reference List". The data from CA reviews were analyzed for factors that influenced the CA review process and metrics, as well as the areas of DMF submissions which most frequently led to an incomplete CA status. The metrics analysis revealed that electronic DMFs appear to improve the completeness of submission and shorten both the review and response times. Utilizing the CA checklist to compile and proactively update the DMFs improves the chance for the DMFs to pass the CA in the first cycle. However, given that the majority of DMFs require at least two cycles of CA before being deemed complete, it is recommended that DMF fees are paid 6 months in advance of the ANDA submissions in order to avoid negatively impacting the filling status of the ANDAs. PMID:25034968

  3. Illicit drugs and pharmaceuticals in the environment--forensic applications of environmental data. Part 1: Estimation of the usage of drugs in local communities.

    PubMed

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2009-06-01

    Pharmaceuticals and recently also illicit drugs have been recognised as emerging environmental contaminants due to their potential environmental impact: frequent occurrence, persistence and risk to aquatic life and humans. This manuscript is part one of the two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. An attempt to use wastewater data is made in order to verify patterns of the usage of drugs (in particular illicit) in local communities. The average usage of cocaine in South Wales was estimated at 0.9 g day(-1) 1000 people(-1), which equals 1 tonne of this drug used or disposed of to sewage annually in Wales. The calculated usage of amphetamine denoted 2.5 g day(-1) 1000 people(-1) and is suspected to be an overestimate. Because no analysis of enantiomers of amphetamine was undertaken, no distinction between amphetamine's legal and illicit usage could be made. PMID:19324480

  4. Poly(ethylene glycol)-conjugated multi-walled carbon nanotubes as an efficient drug carrier for overcoming multidrug resistance

    SciTech Connect

    Cheng Jinping; Meziani, Mohammed J.; Sun Yaping; Cheng, Shuk Han

    2011-01-15

    The acquisition of multidrug resistance poses a serious problem in chemotherapy, and new types of transporters have been actively sought to overcome it. In the present study, poly(ethylene glycol)-conjugated (PEGylated) multi-walled carbon nanotubes (MWCNTs) were prepared and explored as drug carrier to overcome multidrug resistance. The prepared PEGylated MWCNTs penetrated into mammalian cells without damage plasma membrane, and its accumulation did not affect cell proliferation and cell cycle distribution. More importantly, PEGylated MWCNTs accumulated in the multidrug-resistant cancer cells as efficient as in the sensitive cancer cells. Intracellular translocation of PEGylated MWCNTs was visualized in both multidrug-resistant HepG2-DR cells and sensitive HepG2 cells, as judged by both fluorescent and transmission electron microscopy. PEGylated MWCNTs targeted cancer cells efficiently and multidrug-resistant cells failed to remove the intracellular MWCNTs. However, if used in combination with drugs without conjugation, PEGylated MWCNTs prompted drug efflux in MDR cells by stimulating the ATPase activity of P-glycoprotein. This study suggests that PEGylated MWCNTs can be developed as an efficient drug carrier to conjugate drugs for overcoming multidrug resistance in cancer chemotherapy.

  5. A novel composite matrix based on polymeric micelle and hydrogel as a drug carrier for the controlled release of dual drugs.

    PubMed

    Anirudhan, T S; Parvathy, J; Nair, Anoop S

    2016-01-20

    In the present work, we present a system of hydrogel/micelle composite as dual-drug release vehicle. The hydrogel is prepared from poly(ethyleneglycol) PEG and poly(vinyl alcohol) PVA. Polymeric micelles are enjoying high resurgence of interest in biomedical field as promising candidates for the stabilization and delivery of water insoluble drugs. This property was used to design and synthesize oleic acid-g-chitosan (OA-g-CS) copolymer micelles. Dual drugs, an analgesic, Tramadol (TMD) and an antibiotic, Cefixime trihydrate (CFX) were used as model drugs. The drug release behaviors of the micelle and PEG-PVA/micelle DDDS were studied as functions of pH and temperature. The release profiles were analyzed by a power law equation to reveal the release mechanism of drugs. The drug carrier vehicle was characterized and studies including swelling, effect of ionic strength, anti-oxidant, antimicrobial and in vitro drug release were carried out. The release of the two drugs was much more pronounced in the basic medium than in the acidic medium. PMID:26572454

  6. Pharmaceutical formulation of HSA hybrid coated iron oxide nanoparticles for magnetic drug targeting.

    PubMed

    Zaloga, Jan; Pöttler, Marina; Leitinger, Gerd; Friedrich, Ralf P; Almer, Gunter; Lyer, Stefan; Baum, Eva; Tietze, Rainer; Heimke-Brinck, Ralph; Mangge, Harald; Dörje, Frank; Lee, Geoffrey; Alexiou, Christoph

    2016-04-01

    In this work we present a new formulation of superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic drug targeting. The particles were reproducibly synthesized from current good manufacturing practice (cGMP) - grade substances. They were surface coated using fatty acids as anchoring molecules for human serum albumin. We comprehensively characterized the physicochemical core-shell structure of the particles using sophisticated methods. We investigated biocompatibility and cellular uptake of the particles using an established flow cytometric method in combination with microwave-plasma assisted atomic emission spectroscopy (MP-AES). The cytotoxic drug mitoxantrone was adsorbed on the protein shell and we showed that even in complex media it is slowly released with a close to zero order kinetics. We also describe an in vitro proof-of-concept assay in which we clearly showed that local enrichment of this SPION-drug conjugate with a magnet allows site-specific therapeutic effects. PMID:26854862

  7. Dielectric study of the molecular mobility and the isothermal crystallization kinetics of an amorphous pharmaceutical drug substance.

    PubMed

    Alie, J; Menegotto, J; Cardon, P; Duplaa, H; Caron, A; Lacabanne, C; Bauer, M

    2004-01-01

    During the development of new pharmaceutical products based on drug substances in their amorphous form, the molecular mobility of an amorphous active ingredient was characterized in detail within a very broad time-temperature range. The relation between the isothermal crystallization kinetics and the dynamics of this amorphous substance was investigated. First, dynamic dielectric spectroscopy (DDS) and the thermostimulated current (TSC) techniques were used to analyze the molecular mobility of the amorphous drug substance over a wide frequency and temperature range (the drug substance is referred to as SSR in this text and was chosen as a model glass-forming system). Two relaxation processes, corresponding to different molecular motions, were identified. The beta(a)-relaxation process, associated with intramolecular oscillation of small dipolar groups, followed Arrhenius temperature behavior over the entire time-temperature domain that was studied. However, the main alpha(a)-relaxation process, assigned to the dielectric manifestation of the dynamic glass transition of the amorphous phase, was described by Vogel-Fulcher-Tammann (VFT) and Arrhenius behavior above and below the glass transition temperature (T(g)) respectively. The physical meaning of these complex dynamics is explained in the context of the Adam and Gibbs (AG) model, by the temperature dependence of the size of cooperatively rearranging regions (CRR) that govern the time scale of delocalized molecular motions. The distinction between the molecular mobility and the structural relaxation of amorphous systems below T(g) is discussed. This work shows that the complementary nature of both DDS and TSC techniques is essential to directly analyze the intramolecular and molecular motions of disordered phases over a wide time-temperature range above and below the T(g). Second, real-time dielectric measurements were carried out to determine the isothermal crystallization kinetics of the SSR amorphous drug

  8. Japan-China Joint Medical Workshop on Drug Discoveries and Therapeutics 2008: The need of Asian pharmaceutical researchers' cooperation.

    PubMed

    Nakata, M; Tang, W

    2008-10-01

    The Japan-China Joint Medical Workshop on Drug Discoveries and Therapeutics 2008 (JCMWDDT 2008) was held from September 29 to October 1, 2008 at The University of Tokyo, Tokyo, Japan. JCMWDDT is an international workshop that is mainly organized by Asian editorial members of Drug Discoveries & Therapeutics (http://www.ddtjournal.com/home) for the purpose of promoting research exchanges in the field of drug discovery and therapeutic. This year's JCMWDDT is the second workshop and focused particularly on novel development and technological innovation of anti-influenza agents. The workshop began with an announcement by the Japanese Co-chairperson, Dr. Sekimizu (Department of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan; Editorin- Chief of Drug Discoveries & Therapeutics, DDT) followed by a speech by the Chinese Co-chairperson, Dr. Wenfang Xu (School of Pharmaceutical Sciences, Shandong University, Shandong, China; Editor in China Office of DDT), with additional speeches by Dr. Norio Matsuki (The University of Tokyo, Japan; Editor of DDT) and Dr. Guanhua Du (Chinese Academy of Medical Science, China; Editor of DDT). Fifty-nine titles were presented in 6 specialized sessions (Research Advances in Drug Discoveries and Therapeutics, Drug Synthesis/Clinical Therapeutics, Medicinal Chemistry/Natural Products, Anti-influenza Drugs, Anti-infection/antiviral Drugs, Biochemistry/Molecular Biology /Pharmacology) and a poster session (Drug Discov Ther 2008; 2, Suppl; available at http://www.ddtjournal.com/Announce/index.htm). An annual outbreak of avian influenza in Asian countries including China and Japan has sparked fears that the virus will mutate and then cause an epidemic in humans. Therefore, Asian researchers need to work together to control this infection. This year's JCMWDDT helped provide an

  9. Comprehensive summary--Predict-IV: A systems toxicology approach to improve pharmaceutical drug safety testing.

    PubMed

    Mueller, Stefan O; Dekant, Wolfgang; Jennings, Paul; Testai, Emanuela; Bois, Frederic

    2015-12-25

    This special issue of Toxicology in Vitro is dedicated to disseminating the results of the EU-funded collaborative project "Profiling the toxicity of new drugs: a non animal-based approach integrating toxicodynamics and biokinetics" (Predict-IV; Grant 202222). The project's overall aim was to develop strategies to improve the assessment of drug safety in the early stage of development and late discovery phase, by an intelligent combination of non animal-based test systems, cell biology, mechanistic toxicology and in silico modeling, in a rapid and cost effective manner. This overview introduces the scope and overall achievements of Predict-IV. PMID:25450741

  10. Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened

    PubMed Central

    Friedman, Gary D.; Udaltsova, Natalia; Chan, James; Quesenberry, Charles P; Habel, Laurel A.

    2010-01-01

    Objective We screened commonly used prescription drugs for possible carcinogenic effects. Methods In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12½ years for incident cancer. Nested case-control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least two years between drug dispensing and cancer. Positive associations entailed a relative risk (RR) of 1.50, with p≤ 0.01 and higher risk for three or more, than for one prescription. Evaluation included further analyses, searches of the literature, and clinical judgment. Results There were 101 associations of interest for 61 drugs. Sixty-six associations were judged to have involved substantial confounding. We found evidence that of the remaining 35, the following associations may not be due to chance: sulindac with gallbladder cancer and leukemia, hyoscyamine with non-Hodgkin lymphoma, nortriptyline with esophageal and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine with testicular cancer, hydrochlorothiazide with renal and lip cancer, and nifedipine with lip cancer. Conclusions These preliminary findings suggest that further studies are indicated regarding sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide and nifedipine. PMID:19582585

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

    PubMed

    Seo, Youn Gee; Kim, Dong-Wuk; Cho, Kwan Hyung; Yousaf, Abid Mehmood; Kim, Dong Shik; Kim, Jeong Hoon; Kim, Jong Oh; Yong, Chul Soon; Choi, Han-Gon

    2015-02-01

    The purpose of this study was to develop a novel tacrolimus-loaded solid self-emulsifying drug delivery system (SEDDS) using Labrafac as an oil phase. The ternary phase diagram was plotted with Labrafac, Labrasol and Lauroglycol used as an oil, surfactant and co-surfactant, respectively. The liquid SEDDS formulated with Labrasol, Lauroglycol and Labrafac (70:15:15, volume ratio) furnished the smallest emulsion globule size. The solid SEDDS was obtained by spray-drying the liquid mixture containing the liquid SEDDS with 5 % tacrolimus and silicon dioxide. Furthermore, dissolution of tacrolimus from the solid SEDDS and pharmacokinetics in rats was studied compared to the commercial product. The solid SEDDS produced relatively larger emulsion globule size than that exhibited by the corresponding liquid SEDDS. However, this size variation was not significantly different. The solid SEDDS with approximately 280 nm emulsion droplet size improved the dissolution of the drug compared to drug power and the commercial product. It resulted in significantly higher plasma concentration, AUC and Cmax, and shorter Tmax values than did the commercial product (p < 0.05). The enormously enhanced oral bioavailability of tacrolimus in rats was attributed to relatively faster absorption due to accelerated dissolution of the drug from the solid SEDDS. Therefore, this novel solid SEDDS prepared with Labrafac as an oil phase is an excellent way to achieve better bioavailability of tacrolimus given via the oral route. PMID:25134927

  12. 77 FR 26768 - Food and Drug Administration/International Society for Pharmaceutical Engineering Cosponsorship...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... manufacturing operations with information on a number of topics concerning FDA requirements and expectations related to current good manufacturing practice (CGMP). The joint public workshop offers the opportunity... Network; (4) IT Strategies--Cloud Computing, RFID, and Beyond; (5) The Future of Drug Manufacturing....

  13. Drug repurposing in pharmaceutical industry and its impact on market access: market access implications

    PubMed Central

    Murteira, Susana; Millier, Aurélie; Toumi, Mondher

    2014-01-01

    Background Drug repurposing is a group of development strategies employed in order to overcome some of the hurdles innate to drug research and development. Drug repurposing includes drug repositioning, reformulation and combination. Objective This study aimed to identify the determinants of successful market access outcome for drug repurposing in the United States of America (USA) and in Europe. Methods The case studies of repurposing strategies were identified through a systematic review of the literature. Price information and reimbursement conditions for all the case studies were collected mainly through access of public datasources. A list of attributes that could be associated with market access outcome (price level and reimbursement conditions) was developed, discussed, and validated by an external expert group. Detailed information for all attributes was researched and collected for each case study. Bivariate regression models were conducted to identify factors associated with price change for all repurposing cases. A similar analysis was performed for reformulation and repositioning cases, in the USA and in Europe, separately. A significance level of 5% was used for all analyses. Results A total of 144 repurposing case studies were included in the statistical analysis for evaluation of mean price change. Combination cases (the combination of two or more individual drug components) were excluded from the statistical analysis due to the low number of cases retrieved. The main attributes associated with a significant price increase for overall repurposing cases were ‘change in administration setting to hospital’ (374%, p<0.0001), ‘addressing unmet needs’ (69%, p<0.05), ‘reformulations belonging to Group 3’—that is, change in administration route (117%, p<0.001), and being a repurposed product with the ‘same brand name’ as the original product (65%, p<0.05). Conclusion We found that the ability of the repurposed product to address unmet needs

  14. Preparation of microspheres of water-soluble pharmaceuticals.

    PubMed

    Huang, H P; Ghebre-Sellassie, I

    1989-01-01

    An emulsion-solvent evaporation procedure involving the dispersion of an alcoholic solution of an active in liquid paraffin was used to prepare microspheres of water-soluble pharmaceuticals using ethylcellulose as a carrier. The effects of surfactant, plasticizer, drug loading, and agitation speed on drug release rate from the microspheres were evaluated. The release rates of water-soluble drugs from microspheres, ranging from 100 and 500 microns in diameter, were sustained over an extended time and were found to be related to the ratio of drug to polymer in the final product. PMID:2723966

  15. Stability-Indicating HPTLC Determination of Imatinib Mesylate in Bulk Drug and Pharmaceutical Dosage

    NASA Astrophysics Data System (ADS)

    Musmade, P.; Vadera, N.; Subramanian, G.

    A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of imatinib mesylate both as a bulk drug and in formulations was developed and validated. The method employed HPTLC aluminum plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of chloroform:methanol (6:4, v/v). The system was found to give compact spot for imatinib mesylate (R f value of 0.53 ± 0.02). Densitometric analysis of imatinib mesylate was carried out in the absorbance mode at 276 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r 2 = 0.9966 ± 0.0013 with respect to peak area in the concentration range 100-1,000 ng per spot. The mean value ± SD of slope and intercept were 164.85 ± 0.72 and 1168.3 ± 8.26, respectively, with respect to peak area. The method was validated for precision, recovery, and robustness. The limits of detection and quantitation were 10 and 30 ng per spot, respectively. Imatinib mesylate was subjected to acid and alkali hydrolysis, and oxidation and thermal degradation. The drug undergoes degradation under acidic, basic, oxidation, and heat conditions. This indicates that the drug is susceptible to acid, base hydrolysis, oxidation, and heat. Statistical analysis proves that the method is repeatable, selective, and accurate for the estimation of the said drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of imatinib mesylate in bulk drug and dosage forms.

  16. Evaluation of drug-carrier interactions in quaternary powder mixtures containing perindopril tert-butylamine and indapamide.

    PubMed

    Voelkel, Adam; Milczewska, Kasylda; Teżyk, Michał; Milanowski, Bartłomiej; Lulek, Janina

    2016-04-30

    Interactions occurring between components in the quaternary powder mixtures consisting of perindopril tert-butylamine, indapamide (active pharmaceutical ingredients), carrier substance and hydrophobic colloidal silica were examined. Two grades of lactose monohydrate: Spherolac(®) 100 and Granulac(®) 200 and two types of microcrystalline cellulose: M101D+ and Vivapur(®) 102 were used as carriers. We determined the size distribution (laser diffraction method), morphology (scanning electron microscopy) and a specific surface area of the powder particles (by nitrogen adsorption-desorption). For the determination of the surface energy of powder mixtures the method of inverse gas chromatography was applied. Investigated mixtures were characterized by surface parameters (dispersive component of surface energy, specific interactions parameters, specific surface area), work of adhesion and cohesion as well as Flory-Huggins parameter χ23('). Results obtained for all quaternary powder mixtures indicate existence of interactions between components. The strongest interactions occur for both blends with different types of microcrystalline cellulose (PM-1 and PM-4) while much weaker ones for powder mixtures with various types of lactose (PM-2 and PM-3). PMID:26924356

  17. Stability-Indicating HPLC Determination of Trandolapril in Bulk Drug and Pharmaceutical Dosage Forms

    PubMed Central

    Al-Hawash, Leena A.; Shakya, Ashok K.; Saleem, Maher L.

    2015-01-01

    A rapid, simple, accurate, precise, economical, robust, and stability indicating reverse phase HPLC-PDA procedure has been developed and validated for the determination of trandolapril. The trandolapril was separated isocratically on Hypersil-Gold C18 column (250 mm × 4.6 mm, 5 μm) with a mobile phase consisting of 50% acetonitrile and 50% water (containing 0.025% triethylamine, pH 3.0 ± 0.1), at 25 ± 2°C. Retention time of the drug was ~4.6 min. The eluted compounds were monitored and identified at 210 nm. The linearity of the method was excellent (r2 > 0.9999) over the concentration range of 1–24 μg/mL; the limit of detection (LOD) and limit of quantitation (LOQ) were 0.0566 μg/mL and 0.1715 μg/mL, respectively. The overall precision was less than 2%. Mean recovery of trandolapril was more than 99%; no interference was found from the component present in the preparation. Stability studies indicate that the drug was stable to sunlight and UV light. The drug gives 6 different oxidative products on exposure to hydrogen peroxide. Slight degradation was observed in acidic condition. Degradation was higher in the alkaline condition compared to other conditions. The robustness of the method was studied using factorial design experiment. PMID:25802524

  18. Physical enhancement of transdermal drug application: is delivery technology keeping up with pharmaceutical development?

    PubMed

    Cross, S E; Roberts, M S

    2004-01-01

    Advances in molecular biology have given us a wide range of protein and peptide-based drugs that are unsuitable for oral delivery because of their high degree of first-pass metabolism. Though parenteral delivery is the obvious answer, for the successful development of commercial chronic and self-administration usage formulations it is not the ideal choice. Transdermal delivery is emerging as the biggest application target for these agents, however, the skin is extremely efficient at keeping out such large molecular weight compounds and therapeutic levels are never going to be realistically achieved by passive absorption. Physical enhancement mechanisms including: iontophoresis, electroporation, ultrasound, photomechanical waves, microneedles and jet-propelled particles are emerging as solutions to this topical delivery dilemma. Adding proteins and peptides to the list of other large molecular weight drugs with insufficient passive transdermal fluxes to be therapeutically useful, we have a collection of pharmacological agents waiting for efficient delivery methods to be introduced. This article reviews the current state of physical transdermal delivery technology, assesses the pros and cons of each technique and summarises the evidence-base of their drug delivery capabilities. PMID:16305373

  19. Stability-indicating HPLC determination of trandolapril in bulk drug and pharmaceutical dosage forms.

    PubMed

    Al-Hawash, Leena A; Shakya, Ashok K; Saleem, Maher L

    2015-01-01

    A rapid, simple, accurate, precise, economical, robust, and stability indicating reverse phase HPLC-PDA procedure has been developed and validated for the determination of trandolapril. The trandolapril was separated isocratically on Hypersil-Gold C18 column (250 mm × 4.6 mm, 5 μm) with a mobile phase consisting of 50% acetonitrile and 50% water (containing 0.025% triethylamine, pH 3.0 ± 0.1), at 25 ± 2°C. Retention time of the drug was ~4.6 min. The eluted compounds were monitored and identified at 210 nm. The linearity of the method was excellent (r (2) > 0.9999) over the concentration range of 1-24 μg/mL; the limit of detection (LOD) and limit of quantitation (LOQ) were 0.0566 μg/mL and 0.1715 μg/mL, respectively. The overall precision was less than 2%. Mean recovery of trandolapril was more than 99%; no interference was found from the component present in the preparation. Stability studies indicate that the drug was stable to sunlight and UV light. The drug gives 6 different oxidative products on exposure to hydrogen peroxide. Slight degradation was observed in acidic condition. Degradation was higher in the alkaline condition compared to other conditions. The robustness of the method was studied using factorial design experiment. PMID:25802524

  20. [Strategy and collaboration between medicinal chemists and pharmaceutical scientists for drug delivery systems].

    PubMed

    Mano, Takashi

    2013-01-01

    In order to successfully apply drug delivery systems (DDS) to new chemical entities (NCEs), collaboration between medicinal chemists and formulation scientists is critical for efficient drug discovery. Formulation scientists have to use 'language' that medicinal chemists understand to help promote mutual understanding, and medicinal chemists and formulation scientists have to set up strategies to use suitable DDS technologies at the discovery phase of the programmes to ensure successful transfer into the development phase. In this review, strategies of solubilisation formulation for oral delivery, inhalation delivery, nasal delivery and bioconjugation are all discussed. For example, for oral drug delivery, multiple initiatives can be proposed to improve the process to select an optimal delivery option for an NCE. From a technical perspective, formulation scientists have to explain the scope and limitations of formulations as some DDS technologies might be applicable only to limited chemical spaces. Other limitations could be the administered dose and, cost, time and resources for formulation development and manufacturing. Since DDS selection is best placed as part of lead-optimisation, formulation scientists need to be involved in discovery projects at lead selection and optimisation stages. The key to success in their collaboration is to facilitate communication between these two areas of expertise at both a strategic and scientific level. Also, it would be beneficial for medicinal chemists and formulation scientists to set common goals to improve the process of collaboration and build long term partnerships to improve DDS. PMID:23292022

  1. Novel flower-shaped albumin particles as controlled-release carriers for drugs to penetrate the round-window membrane

    PubMed Central

    Yu, Zhan; Yu, Min; Zhou, Zhimin; Zhang, Zhibao; Du, Bo; Xiong, Qingqing

    2014-01-01

    Controlled-release carriers for local drug delivery have attracted increasing attention for inner-ear treatment recently. In this paper, flower-shaped bovine serum albumin (FBSA) particles were prepared by a modified desolvation method followed by glutaraldehyde or heat denaturation. The size of the FBSA particles varied from 10 μm to 100 μm, and most were 50–80 μm. Heat-denatured FBSA particles have good cytocompatibility with a prolonged survival time for L929 cells. The FBSA particles were utilized as carriers to investigate the release behaviors of the model drug – rhodamine B. Rhodamine B showed a sustained-release effect and penetrated the round-window membrane of guinea pigs. We also confirmed the attachment of FBSA particles onto the round-window membrane by microscopy. The FBSA particles, with good biocompatibility, drug-loading capacity, adhesive capability, and biodegradability, may have potential applications in the field of local drug delivery for inner-ear disease treatment. PMID:25061296

  2. Magnetic targeted drug delivery carriers encapsulated with pH-sensitive polymer: synthesis, characterization and in vitro doxorubicin release studies.

    PubMed

    Wu, Juan; Shen, Yueqing; Jiang, Wei; Jiang, Wei; Shen, Yewen

    2016-09-01

    Targeted and efficient delivery of drug to tumor is one of the crucial issues in cancer therapy. In this work, we have successfully designed and prepared the pH-sensitive magnetic nanoparticles (MNPs) as targeted anticancer drug carriers, in which the MNPs were coated by poly(acrylic acid) (PAA) and the obtained PAA@MNPs exhibited a size within 100 nm, good stability, and superparamagnetic responsibility (Ms 45.97 emu/g). Doxorubicin (DOX) can be successfully loaded onto MNPs via electrostatic interaction, and the drug loading content and loading efficiency are 26.4 and 88.1%, respectively. Moreover, the release studies showed that the drug-loaded carriers (MNPs-DOX) had excellent pH sensitivity, 75.6% of the loaded DOX was released at pH 4.0 within 48 h. Importantly, MTT assays in HUVEC and MCF-7 cells demonstrated that MNPs-DOX exhibited high anti-tumor activity, while the PAA@MNPs were practically nontoxic. Thus, our results revealed that PAA@MNPs would be a competitive candidate for biomedical application and MNPs-DOX could be used in targeted cancer therapy. PMID:27252073

  3. Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases.

    PubMed

    Bulaj, Grzegorz; Ahern, Margaret M; Kuhn, Alexis; Judkins, Zachary S; Bowen, Randy C; Chen, Yizhe

    2016-01-01

    Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or α-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their additional clinical benefits include reducing levels of TNFα and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. The incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products

  4. A study of purified montmorillonite intercalated with 5-fluorouracil as drug carrier.

    PubMed

    Lin, F H; Lee, Y H; Jian, C H; Wong, Jau-Min; Shieh, Ming-Jium; Wang, Cheng-Yi

    2002-05-01

    Since its introduction over 40 years ago, 5-fluorouracil (5-FU) has remained the only effective chemotherapy option available for the treatment of colorectal cancer (CRC). However, this cytotoxic anticancer drug often causes severe side effects because it does not act selectively on the tumor. It has been reported that the 5-FU showed considerable toxicity when administered by intravenous injections or via alimentary tract. Although, many materials have been developed for carrying 5-FU, there has been no clinically acceptable carrier for 5-FU till now. Montmorillonite, one of the clay minerals, consists of hydrated aluminum silicates with fine grains and large spaces between the layers. Isomorphous substitution of cations is common. In the study, we attempt to intercalate 5-FU into interlayers of montmorillonite through ion exchange. Montmorillonite was purified from crude clays of bentonite in Tai-dong, Taiwan by filtration and sedimentation. Solutions of 5-FU with different concentrations were prepared by dissolving various amounts of 5-FU into 10 ml NaOH solution. Purified montmorillonite powder was soaked in 5-FU solution for a period of time with different pH values and temperatures. In this study, we try to intercalate 5-FU into interlayers of montmorillonite to find out optimum conditions, such as soaking time, temperature, pH value, initial 5-FU concentration, etc., to prepare composites of 5-FU and montmorillonite (5-FU/mont). UV, SDT, FTIR, XRD are used to characterize the 5-FU/mont composite. From the results. 5-FU was successfully intercalated into the interlayer of montmorillonite both by free surface absorption and OH replacement. The optimum condition for 5-FU/mont preparations is 1.185 wt% of 5-FU as initial concentration under a pH value of 11.6 at a temperature of 80 degrees C and a soaking time of 2 h. The total amount of 5-FU in montmorillonite is about 87.5 mg for each gram of montmorillonite, which can be proved by thermal gravimetric analysis

  5. FDA pharmaceutical quality oversight.

    PubMed

    Yu, Lawrence X; Woodcock, Janet

    2015-08-01

    The launch of the Center for Drug Evaluation and Research (CDER) Office of Pharmaceutical Quality (OPQ) is a milestone in FDA's efforts to assure that quality medicines are available to the American public. As a new super-office within CDER, OPQ is strategically organized to streamline regulatory processes, advance regulatory standards, align areas of expertise, and originate surveillance of drug quality. Supporting these objectives will be an innovative and systematic approach to product quality knowledge management and informatics. Concerted strategies will bring parity to the oversight of innovator and generic drugs as well as domestic and international facilities. OPQ will promote and encourage the adoption of emerging pharmaceutical technology to enhance pharmaceutical quality and potentially reinvigorate the pharmaceutical manufacturing sector in the United States. With a motto of "One Quality Voice," OPQ embodies the closer integration of review, inspection, surveillance, policy, and research for the purpose of strengthening pharmaceutical quality on a global scale. PMID:26027494

  6. Mesoporous silica aerogel as a drug carrier for the enhancement of the sunscreen ability of benzophenone-3.

    PubMed

    Li, C C; Chen, Y T; Lin, Y T; Sie, S F; Chen-Yang, Y W

    2014-03-01

    In the present study, about 45 and 34 wt% of benzophenone-3 (BP-3), an organic UV filter, was adsorbed on a high surface area mesoporous silica (MS) drug carrier to prepare BP-3-bearing MS (MSBP) sunscreen materials MSBP-1 and MSBP-2, respectively. The effect of the adsorption of BP-3 by MS on the UV protection ability of MSBP was demonstrated and a synergistic UV protection effect was observed in the as-prepared MSBP UV filters. Compared with free BP-3, adsorbed BP-3 had greatly reduced crystallinity and the dispersion of MSBP was significantly improved in the sunscreen. The in vitro sun protection factor (SPF) and in vitro UV-A values of the MSBP-2-based sunscreen was about 17.3% and 17.0% higher than that of free BP-3-based sunscreen, respectively, indicating that the ability of the sunscreen to protect against UV-B and UV-A improved because of the BP-3 content of the MS matrix. In addition, the decrease in SPF and UV-A values over time was significantly less in the MSBP-based sunscreens than in free BP-3-based sunscreen. Results of this study reveal that MS is a promising organic sunscreen carrier as well as a potential carrier for other topical drugs. PMID:24362058

  7. Impulsion of nanoparticles as a drug carrier for the theoretical investigation of stenosed arteries with induced magnetic effects

    NASA Astrophysics Data System (ADS)

    Nadeem, S.; Ijaz, S.

    2016-07-01

    In this paper hemodynamics of stenosis are discussed to predict effect of atherosclerosis by means of mathematical models in the presence of uniform transverse magnetic field. The analysis is carried out using silver and copper nanoparticles as a drug carrier. Exact solution for the fluid temperature, velocity, axial induced magnetic field and current density distribution are obtained under mild stenosis approximation. The results indicate that with an increase in the concentration of nanoparticle hemodynamics effects of stenosis reduces throughout the inclined composite stenosed arteries. The considered analysis also summarizes that the drug silver nanoparticles is more efficient to reduce hemodynamics of stenosis when compare to the drug copper nanoparticle. In future this model could be helpful to predict important properties in some biomedical applications.

  8. Influence of a lipophilic drug on the stability of emulsions: an important approach on the development of lipidic carriers.

    PubMed

    Formiga, F R; Fonseca, I A A; Souza, K B; Silva, A K A; Macedo, J P F; Araújo, I B; Soares, L A L; Egito, E Socrates T

    2007-11-01

    The aim of this work was to investigate the influence of a lipophilic drug, Ibuprofen, on the stability of o/w emulsions. Five formulations were prepared by the phase inversion temperature (PIT) method, and Ibuprofen was incorporated into their oil phase. Emulsion stability was evaluated by short- and long-term studies. Concerning the former, stability under centrifugation showed an improved profile for Ibuprofen-loaded emulsions. The latter confirmed such findings. In conclusion, a rather resistant interfacial film may take place when Ibuprofen was incorporated into the emulsions. Therefore, the critical hydrophilic-lipophilic-balance (HLB) of o/w emulsions can be affected by a lipophilic drug into their oil phase. Such approach is of great importance on the development of lipid carriers for therapeutic drug targeting. PMID:17614224

  9. Radiation preparation of drug carriers based polyacrylic acid (PAAc) using poly(vinyl pyrrolidone) (PVP) as a template polymer

    NASA Astrophysics Data System (ADS)

    Abd El-Rehim, H. A.; Hegazy, E. A.; Khalil, F. H.; Hamed, N. A.

    2007-01-01

    The present study deals with the radiation synthesis of stimuli response hydrophilic polymers from polyacrylic acid (PAAc). To maintain the property of PAAc and control the water swellibility for its application as a drug delivery system, radiation polymerization of AAc in the presence of poly(vinyl pyrrolidone) (PVP) as a template polymer was carried out. Characterization of the prepared PAA/PVP inter-polymer complex was investigated by determining gel content, swelling property, hydrogel microstructure and the release rate of caffeine as a model drug. The release rate of caffeine from the PAA/PVP inter-polymer complexes showed pH-dependency, and seemed to be mainly controlled by the dissolution rate of the complex above a p Ka of PAAc. The prepared inter-polymer complex could be used for application as drug carriers.

  10. Gender bias in clinical research, pharmaceutical marketing, and the prescription of drugs

    PubMed Central

    Chilet-Rosell, Elisa

    2014-01-01

    This thesis is part of the studies of gender bias in health which together with the paradigm of evidence-based medicine shares the empirical assumption that there are inaccuracies in medical practice, in addition to a lack of rigour and transparency. It worked with the distinction between the concepts of sex and gender and between the concepts of sex-related differences and gender inequalities, in terms of applying a gender perspective in the study design and the subsequent analysis. This PhD review presents the research process conducted in Spain, which can provide an example for future research. Study I described a review of 58 clinical trials (CTs) of etoricoxib to assess its compliance with the Recommendations of Evaluation of Gender Differences in the Clinical Evaluation of Drugs. In Study II, key informants from professions related to different areas in drug development and pharmacovigilance held a working meeting to reach a consensus document on recommendations for the study and evaluation of gender differences in CTs in Spain. In Study III, the websites of the eight best-selling hormone replacement therapy drugs in Spain on Google first page of results were analysed. In Study IV, a logistic regression analysis was performed to compare analgesic prescription by sex in regions with a higher or lower Gender Development Index (GDI) than the Spanish average. Gender biases identified in this thesis limited the legitimacy of medicine, which is not based on the best possible evidence. The results also demonstrate the existence of inequalities between men and women that are not due merely to biological differences, but are gender inequalities stemming from the social differences that exist between both sexes. PMID:25498360

  11. Gender bias in clinical research, pharmaceutical marketing, and the prescription of drugs.

    PubMed

    Chilet-Rosell, Elisa

    2014-01-01

    This thesis is part of the studies of gender bias in health which together with the paradigm of evidence-based medicine shares the empirical assumption that there are inaccuracies in medical practice, in addition to a lack of rigour and transparency. It worked with the distinction between the concepts of sex and gender and between the concepts of sex-related differences and gender inequalities, in terms of applying a gender perspective in the study design and the subsequent analysis. This PhD review presents the research process conducted in Spain, which can provide an example for future research. Study I described a review of 58 clinical trials (CTs) of etoricoxib to assess its compliance with the Recommendations of Evaluation of Gender Differences in the Clinical Evaluation of Drugs. In Study II, key informants from professions related to different areas in drug development and pharmacovigilance held a working meeting to reach a consensus document on recommendations for the study and evaluation of gender differences in CTs in Spain. In Study III, the websites of the eight best-selling hormone replacement therapy drugs in Spain on Google first page of results were analysed. In Study IV, a logistic regression analysis was performed to compare analgesic prescription by sex in regions with a higher or lower Gender Development Index (GDI) than the Spanish average. Gender biases identified in this thesis limited the legitimacy of medicine, which is not based on the best possible evidence. The results also demonstrate the existence of inequalities between men and women that are not due merely to biological differences, but are gender inequalities stemming from the social differences that exist between both sexes. PMID:25498360

  12. Drug reformulations and repositioning in the pharmaceutical industry and their impact on market access: regulatory implications

    PubMed Central

    Murteira, Susana; Millier, Aurélie; Ghezaiel, Zied; Lamure, Michel

    2014-01-01

    Background Repurposing has become a mainstream strategy in drug development, but it faces multiple challenges, amongst them the increasing and ever changing regulatory framework. This is the second study of a series of three-part publication project with the ultimate goal of understanding the market access rationale and conditions attributed to drug repurposing in the United States and in Europe. The aim of the current study to evaluate the regulatory path associated with each type of repurposing strategy according to the previously proposed nomenclature in the first article of this series. Methods From the cases identified, a selection process retrieved a total of 141 case studies in all countries, harmonized for data availability and common approval in the United States and in Europe. Regulatory information for each original and repurposed drug product was extracted, and several related regulatory attributes were also extracted such as, designation change and filing before or after patent expiry, among others. Descriptive analyses were conducted to determine trends and to investigate potential associations between the different regulatory paths and attributes of interest, for reformulation and repositioning cases separately. Results Within the studied European countries, most of the applications for reformulated products were filed through national applications. In contrast, for repositioned products, the centralized procedure was the most frequent regulatory pathway. Most of the repurposing cases were approved before patent expiry, and those cases have followed more complex regulatory pathways in the United States and in Europe. For new molecular entities filed in the United States, a similar number of cases were developed by serendipity and by a hypothesis-driven approach. However, for the new indication's regulatory pathway in the United States, most of the cases were developed through a hypothesis-driven approach. Conclusion The regulations in the United

  13. Pharmaceutical Education in Poland

    ERIC Educational Resources Information Center

    Furmanowa, Miroslawa; Borke, Mitchell L.

    1978-01-01

    The content and organization of Poland's system of pharmaceutical education is described. Tables are presented of the subjects of the basic studies curriculum and the following areas of specialization: applied pharmacy, pharmaceutical analysis, clinical analysis, drug technology, herbal pharmacy, and bioanalysis and environmental studies. (SW)

  14. A survey of the syntheses of active pharmaceutical ingredients for antiretroviral drug combinations critical to access in emerging nations.

    PubMed

    Pinheiro, Eloan Dos Santos; Antunes, Octavio Augusto Ceva; Fortunak, Joseph M D

    2008-09-01

    irrelevant, except for "advanced salvage" drugs such as enfuvirtide. In resource-poor settings cost is a huge factor that limits drug access, resulting in high rates of new infection and subsequent mortality. IP coverage, where granted, can keep access prices for essential ARVs higher than would otherwise be the case. Large, innovator companies have made drugs available at prices very close to the cost of manufacturing for "lowest income" countries. Generic providers in India and elsewhere provide the largest supply of drugs for the developing world. The recent issuance of Voluntary and Compulsory Licenses (VLs, CLs) through the World Trade Organization's TRIP (Treaty Respecting Intellectual Property) provisions arguably contribute to bringing down access prices. The utilization of improved science, pooled purchasing and intelligent procurement practices all definitely contribute to access. This work surveys the production processes for several critical ARVs. These are discussed in terms of scale up, raw material/intermediates and active pharmaceutical ingredient (API) costs. In some cases new routes to APIs or critical intermediates are needed. Based on potential new chemistries, there are significant opportunities to reduce cost for a number of critical ARVs. PMID:18571246

  15. Phytochemicals as Prototypes for Pharmaceutical Leads Towards Drug Development Against Diabetic Cardiomyopathy.

    PubMed

    Ojha, Shreesh; Kurdi, Amani; Sadek, Bassem; Kaleem, M; Cai, Lu; Kamal, M A; Rajesh, Mohanraj

    2016-01-01

    Globally diabetes mellitus (DM) is swiftly reaching epidemic proportions and impose major health care and socio-economic challenges that are associated with its complications. DM is considered as the major risk factor for the development of debilitating micro & macro vascular complications. Clinical studies have revealed that development of diabetic cardiomyopathy (DCM) in subjects with diabetes can occur both- dependent and independent of pre-existing increased risk factors such as poor glycemic control, hyperlipidemia, and or hypertension. Therefore, DCM represents as a major challenge for the clinical community for the prompt diagnosis and devising the treatment paradigm to combat the diabetes induced cardiac dysfunction. In Chinese traditional medical practice, heart ailments have been coped with herbal extracts. Phytochemicals bioavailability and pharmacokinetic properties are to yet be established completely in human subjects. However, tremendous progress has been made to isolate, purify the phytochemicals and characterize their effects on mitigating the development of DCM in pre-clinical models. Currently there are no approved drugs available for the treatment of DCM. In this review, we have discussed the progress made in understanding the mechanisms for the phytochemicals cardio-protective actions in the diabetic milieu and their caveats and provide future perspectives for proposing these agents to serve as prototypes in the development of drugs for the management of DCM. PMID:27000825

  16. Mechanistic Modeling Identifies Drug-Uptake History as Predictor of Tumor Drug Resistance and Nano-Carrier-Mediated Response

    PubMed Central

    Brocato, Terisse A.; Butner, Joseph D.; Carnes, Eric C.; Koay, Eugene J.; Brinker, C. Jeffrey; Cristini, Vittorio

    2013-01-01

    A quantitative understanding of the advantages of nanoparticle-based drug delivery vis-à-vis conventional free drug chemotherapy has yet to be established for cancer or other disease despite numerous investigations. Here, we employ first-principles cell biophysics, drug pharmaco-kinetics and drug pharmaco-dynamics to model the delivery of doxorubicin (DOX) to hepatocellular carcinoma (HCC) tumor cells and predict the resultant experimental cytotoxicity data. The fundamental, mechanistic hypothesis of our mathematical model is that the integrated history of drug uptake by the cells over time of exposure, which sets the cell death rate parameter, and the uptake rate are the sole determinants of dose response relationship. A universal solution of the model equations is capable of predicting the entire, nonlinear dose response of the cells to any drug concentration based on just two separate measurements of these cellular parameters. This analysis reveals that nanocarrier-mediated delivery overcomes resistance to free drug because of improved cellular uptake rates, and that dose response curves to nanocarrier mediated drug delivery are equivalent to those for free-drug, but “shifted to the left,” i.e., lower amounts of drug achieve the same cell kill. We then demonstrate the model’s general applicability to different tumor and drug types, and cell-exposure time courses by investigating HCC cells exposed to cisplatin and 5-fluorouracil, breast cancer MCF-7 cells exposed to DOX, and pancreatic adenocarcinoma PANC-1 cells exposed to gemcitabine. The model will help in the optimal design of nanocarriers for clinical applications and improve the current, largely empirical understanding of in vivo drug transport and tumor response. PMID:24187963

  17. 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. PMID:26545484

  18. Preparation of hierarchical mesoporous CaCO3 by a facile binary solvent approach as anticancer drug carrier for etoposide

    PubMed Central

    2013-01-01

    To develop a nontoxic system for targeting therapy, a new highly ordered hierarchical mesoporous calcium carbonate nanospheres (CCNSs) as small drug carriers has been synthesized by a mild and facile binary solvent approach under the normal temperature and pressure. The hierarchical structure by multistage self-assembled strategy was confirmed by TEM and SEM, and a possible formation process was proposed. Due to the large fraction of voids inside the nanospheres which provides space for physical absorption, the CCNSs can stably encapsulate the anticancer drug etoposide with the drug loading efficiency as high as 39.7 wt.%, and etoposide-loaded CCNS (ECCNS) nanoparticles can dispersed well in the cell culture. Besides, the drug release behavior investigated at three different pH values showed that the release of etoposide from CCNSs was pH-sensitive. MTT assay showed that compared with free etoposide, ECCNSs exhibited a higher cell inhibition ratio against SGC-7901 cells and also decreased the toxicity of etoposide to HEK 293 T cells. The CLSM image showed that ECCNSs exhibited a high efficiency of intracellular delivery, especially in nuclear invasion. The apoptosis test revealed that etoposide entrapped in CCNSs could enhance the delivery efficiencies of drug to achieve an improved inhibition effect on cell growth. These results clearly implied that the CCNSs are a promising drug delivery system for etoposide in cancer therapy. PMID:23849350

  19. Induced circular dichroism as a tool to investigate the binding of drugs to carrier proteins: Classic approaches and new trends.

    PubMed

    Tedesco, Daniele; Bertucci, Carlo

    2015-09-10

    Induced circular dichroism (ICD) is a spectroscopic phenomenon that provides versatile and useful methods for characterizing the structural and dynamic properties of the binding of drugs to target proteins. The understanding of biorecognition processes at the molecular level is essential to discover and validate new pharmacological targets, and to design and develop new potent and selective drugs. The present article reviews the main applications of ICD to drug binding studies on serum carrier proteins, going from the classic approaches for the derivation of drug binding parameters and the identification of binding sites, to an overview of the emerging trends for the characterization of binding modes by means of quantum chemical (QC) techniques. The advantages and limits of the ICD methods for the determination of binding parameters are critically reviewed; the capability to investigate the binding interactions of drugs and metabolites to their target proteins is also underlined, as well as the possibility of characterizing the binding sites to obtain a complete picture of the binding mechanism and dynamics. The new applications of ICD methods to identify stereoselective binding modes of drug/protein complexes are then reviewed with relevant examples. The combined application of experimental ICD spectroscopy and QC calculations is shown to identify qualitatively the bound conformations of ligands to target proteins even in the absence of a detailed structure of the binding sites, either obtained from experimental X-ray crystallography and NMR measurements or from computational models of the complex. PMID:25769668

  20. The impacts of pharmaceutical drugs under ocean acidification: New data on single and combined long-term effects of carbamazepine on Scrobicularia plana.

    PubMed

    Freitas, Rosa; Almeida, Ângela; Calisto, Vânia; Velez, Cátia; Moreira, Anthony; Schneider, Rudolf J; Esteves, Valdemar I; Wrona, Frederick J; Figueira, Etelvina; Soares, Amadeu M V M

    2016-01-15

    Ocean acidification and increasing discharges of pharmaceutical contaminants into aquatic systems are among key and/or emerging drivers of environmental change affecting marine ecosystems. A growing body of evidence demonstrates that ocean acidification can have direct and indirect impacts on marine organisms although combined effects with other stressors, namely with pharmaceuticals, have received very little attention to date. The present study aimed to evaluate the impacts of the pharmaceutical drug Carbamazepine and pH 7.1, acting alone and in combination, on the clam Scrobicularia plana. For this, a long-term exposure (28 days)was conducted and a set of oxidative stress markers was investigated. The results obtained showed that S. plana was able to develop mechanisms to prevent oxidative damage when under low pH for a long period, presenting higher survival when exposed to this stressor compared to CBZ or the combination of CBZ with pH 7.1. Furthermore, the toxicity of CBZ on S. plana was synergistically increased under ocean acidification conditions (CBZ + pH 7.1): specimens survival was reduced and oxidative stress was enhanced when compared to single exposures. These findings add to the growing body of evidence that ocean acidification will act to increase the toxicity of CBZ to marine organisms,which has clear implications for coastal benthic ecosystems suffering chronic pollution from pharmaceutical drugs. PMID:26473700

  1. ¹³C solid-state NMR analysis of the most common pharmaceutical excipients used in solid drug formulations, Part I: Chemical shifts assignment.

    PubMed

    Pisklak, Dariusz Maciej; Zielińska-Pisklak, Monika Agnieszka; Szeleszczuk, Łukasz; Wawer, Iwona

    2016-04-15

    Solid-state NMR is an excellent and useful method for analyzing solid-state forms of drugs. In the (13)C CP/MAS NMR spectra of the solid dosage forms many of the signals originate from the excipients and should be distinguished from those of active pharmaceutical ingredient (API). In this work the most common pharmaceutical excipients used in the solid drug formulations: anhydrous α-lactose, α-lactose monohydrate, mannitol, sucrose, sorbitol, sodium starch glycolate type A and B, starch of different origin, microcrystalline cellulose, hypromellose, ethylcellulose, methylcellulose, hydroxyethylcellulose, sodium alginate, magnesium stearate, sodium laurilsulfate and Kollidon(®) were analyzed. Their (13)C CP/MAS NMR spectra were recorded and the signals were assigned, employing the results (R(2): 0.948-0.998) of GIPAW calculations and theoretical chemical shifts. The (13)C ssNMR spectra for some of the studied excipients have not been published before while for the other signals in the spectra they were not properly assigned or the assignments were not correct. The results summarize and complement the data on the (13)C ssNMR analysis of the most common pharmaceutical excipients and are essential for further NMR studies of API-excipient interactions in the pharmaceutical formulations. PMID:26845204

  2. Stress Studies of Tenofovir Disoproxil Fumarate by HPTLC in Bulk Drug and Pharmaceutical Formulation

    PubMed Central

    Havele, Shweta; Dhaneshwar, Sunil R.

    2012-01-01

    A stability-indicating high-performance thin-layer chromatographic (HPTLC) method for determination of tenofovir disoproxil fumarate in bulk drug and in tablet has been developed and validated. The mobile phase selected was chloroform : methanol (9.0 : 1.0, v/v) with ultraviolet (UV) detection at 260 nm. The retention factor was found to be 0.49 ± 0.03 with correlation coefficients of 0.9994 in the range 300–1500 ng/spot and with an accuracy of 99.25%. Method had the potential to determine tenofovir disoproxil fumarate from tablet without any interference, and it was a stability-indicating one. PMID:22606065

  3. Modified Release and Improved Stability of Unstable BCS II Drug by Using Cyclodextrin Complex as Carrier To Remotely Load Drug into Niosomes.

    PubMed

    Chi, Liandi; Wu, Delin; Li, Zhuo; Zhang, Minmin; Liu, Hongchun; Wang, Caifen; Gui, Shuangying; Geng, Meiyu; Li, Haiyan; Zhang, Jiwen

    2016-01-01

    In answering to the challenge of enzymatic unstability of Biopharmaceutics Classification System (BCS) class II drugs, an effective remote loading strategy was developed to successfully incorporate the drug-cyclodextrin (CD) complex into niosomes to modify the release and stability of a drug candidate, pseudolaric acid B (PAB). Judged by binding constants, and combined solubilization effects of pH and CD complexation on PAB at different pH, the complex internalization driven by a transmembrane pH gradient (from 2.0 to 7.4) and the dynamic shifting of PAB-CD complexation equilibrium at this gradient were introduced. The transfer of PAB-CD complex into the internal aqueous phase of niosomes at 60 °C was primarily verified by synchrotron radiation Fourier transform infrared spectroscopy. The remote loading samples behaved as retarded release at pH 5.8, 6.8, and 7.4, for which the stability of PAB in rat plasma was significantly enhanced (about 8.1-fold), in comparison with niosomes prepared by the passive and lipid bilayer loading of PAB. The drug-carrier interaction based release modeling was further fitted, and the convection rate constant (ks) and free energy difference between free and bound states (ΔG) indicated the strongest PAB-carrier interactions in remote loading niosomes. The remote loading strategy also reduced the CD-cholesterol interaction and provided better physical stability of the system. In conclusion, the remote loading of drug-CD complex into niosomes provides advantages to modify the release and enhance the stability of unstable BCS class II drug. PMID:26569615

  4. A novel use of oxidative coupling reactions for determination of some statins (cholesterol-lowering drugs) in pharmaceutical formulations

    NASA Astrophysics Data System (ADS)

    Ashour, Safwan; Bahbouh, Mahmoud; Khateeb, Mouhammed

    2011-03-01

    New, accurate and reliable spectrophotometric methods for the assay of three statin drugs, atorvastatin calcium (AVS), fluvastatin sodium (FVS) and pravastatin sodium (PVS) in pure form and pharmaceutical formulations have been described. All methods involve the oxidative coupling reaction of AVS, FVS and PVS with 3-methyl-2-benzothiazolinone hydrazone hydrochloride monohydrate (MBTH) in the presence of Ce(IV) in an acidic medium to form colored products with λmax at 566, 615 and 664 nm, respectively. Beer's law was obeyed in the ranges of 2.0-20.0, 4.9-35.4 and 7.0-30.0 μg mL -1 for AVS-MBTH, FVS-MBTH and PVS-MBTH, respectively. Molar absorptivities for the above three methods were found to be 3.24 × 10 4, 1.05 × 10 4 and 0.68 × 10 4 L mol -1 cm -1, respectively. Statistical treatment of the experimental results indicates that the methods are precise and accurate. The proposed methods have been applied to the determination of the components in commercial forms with no interference from the excipients. A comparative study between the suggested procedures and the official methods for these compounds in the commercial forms showed no significant difference between the two methods.

  5. Formulation of Biologically-Inspired Silk-Based Drug Carriers for Pulmonary Delivery Targeted for Lung Cancer.

    PubMed

    Kim, Sally Yunsun; Naskar, Deboki; Kundu, Subhas C; Bishop, David P; Doble, Philip A; Boddy, Alan V; Chan, Hak-Kim; Wall, Ivan B; Chrzanowski, Wojciech

    2015-01-01

    The benefits of using silk fibroin, a major protein in silk, are widely established in many biomedical applications including tissue regeneration, bioactive coating and in vitro tissue models. The properties of silk such as biocompatibility and controlled degradation are utilized in this study to formulate for the first time as carriers for pulmonary drug delivery. Silk fibroin particles are spray dried or spray-freeze-dried to enable the delivery to the airways via dry powder inhalers. The addition of excipients such as mannitol is optimized for both the stabilization of protein during the spray-freezing process as well as for efficient dispersion using an in vitro aerosolisation impactor. Cisplatin is incorporated into the silk-based formulations with or without cross-linking, which show different release profiles. The particles show high aerosolisation performance through the measurement of in vitro lung deposition, which is at the level of commercially available dry powder inhalers. The silk-based particles are shown to be cytocompatible with A549 human lung epithelial cell line. The cytotoxicity of cisplatin is demonstrated to be enhanced when delivered using the cross-linked silk-based particles. These novel inhalable silk-based drug carriers have the potential to be used as anti-cancer drug delivery systems targeted for the lungs. PMID:26234773

  6. Formulation of Biologically-Inspired Silk-Based Drug Carriers for Pulmonary Delivery Targeted for Lung Cancer

    PubMed Central

    Kim, Sally Yunsun; Naskar, Deboki; Kundu, Subhas C.; Bishop, David P.; Doble, Philip A.; Boddy, Alan V.; Chan, Hak-Kim; Wall, Ivan B.; Chrzanowski, Wojciech

    2015-01-01

    The benefits of using silk fibroin, a major protein in silk, are widely established in many biomedical applications including tissue regeneration, bioactive coating and in vitro tissue models. The properties of silk such as biocompatibility and controlled degradation are utilized in this study to formulate for the first time as carriers for pulmonary drug delivery. Silk fibroin particles are spray dried or spray-freeze-dried to enable the delivery to the airways via dry powder inhalers. The addition of excipients such as mannitol is optimized for both the stabilization of protein during the spray-freezing process as well as for efficient dispersion using an in vitro aerosolisation impactor. Cisplatin is incorporated into the silk-based formulations with or without cross-linking, which show different release profiles. The particles show high aerosolisation performance through the measurement of in vitro lung deposition, which is at the level of commercially available dry powder inhalers. The silk-based particles are shown to be cytocompatible with A549 human lung epithelial cell line. The cytotoxicity of cisplatin is demonstrated to be enhanced when delivered using the cross-linked silk-based particles. These novel inhalable silk-based drug carriers have the potential to be used as anti-cancer drug delivery systems targeted for the lungs. PMID:26234773

  7. Soft condensed matter in pharmaceutical design.

    PubMed

    Paradossi, Gaio; Cavalieri, Francesca; Chiessi, Ester

    2006-01-01

    In recent years pharmaceutical design has been facing the needs expressed by new therapeutic methodologies such as gene therapy, targeted delivery and closely related diagnostic fields as contrast enhancing agents for ultrasonic investigations. In this context pharmaceutical research has diversified the efforts toward a more integrated approach where the efficacy of an active molecule is enhanced and assisted by the surrounding carrier. Usually this drug platform is a hydrogel matrix, a multicomponent system constituted by an aqueous solution and a polymeric moiety imparting different functions to the matrix, as responsiveness to external stimuli, affinity to receptors, controlled drug release. Such devices represent one of the leading topics of the soft condensed matter recent research, a domain where physics, chemistry and bioengineering cross each other with the aim to achieve an integrated description of these materials. In this respect modern drug design will make use more and more of concepts proper of soft condensed polymer and colloidal sciences. In this review we will describe the state-of-art in the field of the matrices used in innovative drug formulations with a particular emphasis on the implications to pharmaceutical design along with the experimental and theoretical investigation tools worked out in the last decade. PMID:16611124

  8. Intratympanic delivery of oligoarginine-conjugated nanoparticles as a gene (or drug) carrier to the inner ear.

    PubMed

    Yoon, Ji Young; Yang, Keum-Jin; Kim, Da Eun; Lee, Kyu-Yup; Park, Shi-Nae; Kim, Dong-Kee; Kim, Jong-Duk

    2015-12-01

    A drug delivery system to the inner ear using nanoparticles consisting of oligoarginine peptide (Arg8) conjugated to poly(amino acid) (poly(2-hydroxyethyl L-aspartamide; PHEA) was investigated to determine whether the limitations of low drug transport levels across the round window membrane (RWM) and poor transport into inner ear target cells, including hair cells and spiral ganglion, could be overcome. Three types of carrier materials, PHEA-g-C18, PHEA-g-Arg8, and PHEA-g-C18-Arg8, were synthesized to examine the effects of oligoarginine and morphology of the synthesized carriers. Nile red (NR) was used as a fluorescent indicator as well as to model a hydrophobic drug. Compared with PHEA-g-C18-NR nanoparticles, the oligoarginine-conjugated nanoparticles of PHEA-g-C18-Arg8-NR and PHEA-g-Arg8-NR entered into HEI-OC1 cells at significant levels. Furthermore, the strongest fluorescence intensity was observed in nuclei when PHEA-g-C18-Arg8 nanoparticles were used. The high uptake rates of PHEA-g-C18 and PHEA-g-C18-Arg8 nanoparticles were observed in ex vivo experiments using hair cells. After the delivery of PHEA-g-C18-Arg8 nanoparticles with reporter gene transfer, EGFP (enhanced green fluorescent protein) expression was monitored as an indicator of gene delivery. In the inner ear cells, PHEA-g-C18-Arg8 nanoparticles showed comparable or better transfection capabilities than the commercially available Lipofectamine reagent. PHEA-g-C18-Arg8 penetrated in vivo across the RWM of C57/BL6 mice with Nile red staining and GFP expression in various inner ear tissues. In conclusion, PHEA-g-C18-Arg8 nanoparticles were successfully transported into the inner ear through the intratympanic route and are proposed as promising candidates as delivery carriers to address inner ear diseases. PMID:26414408

  9. Direct analysis of pharmaceutical drug formulations using ion mobility spectrometry/quadrupole-time-of-flight mass spectrometry combined with desorption electrospray ionization.

    PubMed

    Weston, Daniel J; Bateman, Robert; Wilson, Ian D; Wood, Tim R; Creaser, Colin S

    2005-12-01

    A novel approach to the rapid analysis of pharmaceutical drug formulations using hyphenated ion mobility spectrometry (IMS) and time-of-flight mass spectrometry (ToF-MS) that requires no sample pretreatment or chromatographic separation is described. A modified quadrupole time-of-flight mass spectrometer containing an ion mobility drift cell was used for gas-phase electrophoretic separation of ions prior to ToF-MS detection. The generation of sample ions directly from tablets and cream formulations was effected by desorption electrospray ionization (DESI) using a modified electrospray ion source. The analysis of a range of over-the-counter and prescription tablet formulations is described, including histamine H2 receptor antagonist (ranitidine), analgesic (paracetamol), opiate (codeine), and aromatase inhibitor anticancer (anastrozole) drugs. The successful determination of active drugs from soft formulations, such as an antiseptic cream (chlorhexidine) and a nicotine-containing skin patch, is also presented. Limits of detection for the active drugs using the DESI/IMS/ToF-MS method fell within the high-picomole to nanomole range. In all cases, the use of ion mobility drift tube separation showed increased selectivity for active drug responses (present as low as 0.14% w/w) over excipient responses such as poly(ethylene glycol). Tandem mass spectrometric analysis of precursor ions separated by IMS allowed positive confirmation of active drugs with little loss of ion mobility efficiency. The ability to analyze hard or soft pharmaceutical formulations directly by DESI combined with ion mobility spectrometry/mass spectrometry in approximately 2 min demonstrates the potential applicability of this novel method to pharmaceutical screening of low-molecular-weight drug formulations with high selectivity over the formulation vehicle. PMID:16316164

  10. Hollow superparamagnetic iron oxide nanoshells as a hydrophobic anticancer drug carrier: intracelluar pH-dependent drug release and enhanced cytotoxicity

    NASA Astrophysics Data System (ADS)

    Zhu, Xiao-Ming; Yuan, Jing; Leung, Ken Cham-Fai; Lee, Siu-Fung; Sham, Kathy W. Y.; Cheng, Christopher H. K.; Au, Doris W. T.; Teng, Gao-Jun; Ahuja, Anil T.; Wang, Yi-Xiang J.

    2012-08-01

    With curcumin and doxorubicin (DOX) base as model drugs, intracellular delivery of hydrophobic anticancer drugs by hollow structured superparamagnetic iron oxide (SPIO) nanoshells (hydrodynamic diameter: 191.9 +/- 2.6 nm) was studied in glioblastoma U-87 MG cells. SPIO nanoshell-based encapsulation provided a stable aqueous dispersion of the curcumin. After the SPIO nanoshells were internalized by U-87 MG cells, they localized at the acidic compartments of endosomes and lysosomes. In endosome/lysosome-mimicking buffers with a pH of 4.5-5.5, pH-dependent drug release was observed from curcumin or DOX loaded SPIO nanoshells (curcumin/SPIO or DOX/SPIO). Compared with the free drug, the intracellular curcumin content delivered via curcumin/SPIO was 30 fold higher. Increased intracellular drug content for DOX base delivered via DOX/SPIO was also confirmed, along with a fast intracellular DOX release that was attributed to its protonation in the acidic environment. DOX/SPIO enhanced caspase-3 activity by twofold compared with free DOX base. The concentration that induced 50% cytotoxic effect (CC50) was 0.05 +/- 0.03 μg ml-1 for DOX/SPIO, while it was 0.13 +/- 0.02 μg ml-1 for free DOX base. These results suggested SPIO nanoshells might be a promising intracellular carrier for hydrophobic anticancer drugs.

  11. Rattle-type hollow CaWO4:Tb(3+)@SiO2 nanocapsules as carriers for drug delivery.

    PubMed

    Zhai, Xuefeng; Yu, Min; Cheng, Ziyong; Hou, Zhiyao; Ma, Ping'an; Yang, Dongmei; Kang, Xiaojiao; Dai, Yunlu; Wang, Dong; Lin, Jun

    2011-12-28

    Rattle-type hollow nanocapsules are among of the most promising candidates as drug carriers owing to their huge inner space and multifunctional material combination. In this paper, rattle-type hollow CaWO(4):Tb(3+)@SiO(2) nanocapsules with a diameter of 100-110 nm and a wall thickness around 10 nm were fabricated. The hollow silica nanospheres were used as nano-reactors and the luminescent core of CaWO(4):Tb(3+) was post-filled into the nano-reactors by a vacuum nano-casting route combined with a Pechini-type sol-gel method. Subsequently, doxorubicin hydrochloride (DOX), a model of an anti-cancer drug, is loaded into the CaWO(4):Tb(3+)@SiO(2) nanocapsules and their cell cytotoxicity, cancer cell uptake and drug release behavior are investigated in vitro. The prepared multifunctional inorganic nanocapsules show a loading capacity for DOX as high as 124 mg g(-1) and sustained-release properties. The release profile of the drug from DOX-loaded nanocapsules can last over five days. Besides, the blank CaWO(4):Tb(3+)@SiO(2) shows very low cytotoxicity against cancer cell lines (HeLa cell) while the DOX-loaded nanocapsules exhibit relatively high efficiency for killing of HeLa cells. The rapid cancer cell uptake process is observed by confocal laser scanning microscopy. The results indicate that a rattle-type hollow CaWO(4):Tb(3+)@SiO(2) nanocapsule has the potential to be used as drug carrier in therapy. Moreover, it is possible to extend the synthetic strategy in this study to other rattle-type multifunctional composites to meet various demands. PMID:21879092

  12. Chitins and Chitosans as Immunoadjuvants and Non-Allergenic Drug Carriers

    PubMed Central

    Muzzarelli, Riccardo A. A.

    2010-01-01

    amplified during many infections and diseases, the common feature of chitinase-like proteins and chitinase activity in all organisms appears to be the biochemical defense of the host. Unfortunately, conceptual and methodological errors are present in certain recent articles dealing with chitin and allergy, i.e., (1) omitted consideration of mammalian chitinase and/or chitotriosidase secretion, accompanied by inactive chitinase-like proteins, as an ancestral defensive means against invasion, capable to prevent the insurgence of allergy; (2) omitted consideration of the fact that the mammalian organism recognizes more promptly the secreted water soluble chitinase produced by a pathogen, rather than the insoluble and well protected chitin within the pathogen itself; (3) superficial and incomplete reports and investigations on chitin as an allergen, without mentioning the potent allergen from crustacean flesh, tropomyosine; (4) limited perception of the importance of the chemical/biochemical characteristics of the isolated chitin or chitosan for the replication of experiments and optimization of results; and (5) lack of interdisciplinarity. There is quite a large body of knowledge today on the use of chitosans as biomaterials, and more specifically as drug carriers for a variety of applications: the delivery routes being the same as those adopted for the immunological studies. Said articles, that devote attention to the safety and biocompatibility aspects, never reported intolerance or allergy in individuals and animals, even when the quantities of chitosan used in single experiments were quite large. Therefore, it is concluded that crab, shrimp, prawn and lobster chitins, as well as chitosans of all grades, once purified, should not be considered as “crustacean derivatives”, because the isolation procedures have removed proteins, fats and other contaminants to such an extent as to allow them to be classified as chemicals regardless of their origin. PMID:20390107

  13. Nano-pharmaceutical formulations for targeted drug delivery against HER2 in breast cancer.

    PubMed

    Sadat, Sams M A; Saeidnia, Soodabeh; Nazarali, Adil J; Haddadi, Azita

    2015-01-01

    Nanotechnology has revolutionized fundamental opportunities for higher specific drug delivery with minimum side effects. Since its inception, the goal of nanotechnology has been to advance effective and reliable systems for precise anti-cancer therapy and diagnosis. To accomplish this goal, bio-conjugation strategies of therapeutic agents loaded nanoparticles with monoclonal antibodies or their analogues have demonstrated a targeted approach both in vitro and in vivo. In this review, we primarily focus on the specific recognition of HER2 receptors of HER2 overexpressed tumor cells, and evaluate anti-HER2 monoclonal antibody as an effective tool for active targeting. Currently, a variety of nanoparticle systems are under both preclinical and clinical trials for targeting to HER2 positive breast cancer. Different nanotechnology scaffolds including liposomes, dendrimers, micelles, polymeric and inorganic nanoparticles that have higher flexibility for macromolecular synthesis and versatile functionalizing properties have been reviewed in this study. Continuing advances in anti-HER2 functionalized nanoparticles have good potential to lead to the development of nano-therapy against HER2 positive breast cancer. PMID:25564255

  14. Diffusion of pharmaceuticals: cross-country evidence of anti-TNF drugs.

    PubMed

    Brekke, Kurt Richard; Dalen, Dag Morten; Holmås, Tor Helge

    2014-12-01

    This article studies the diffusion of biopharmaceuticals across European countries, focusing on anti-TNF drugs, which are used to treat autoimmune diseases (e.g., rheumatism, psoriasis). We use detailed sales information on the three brands Remicade, Enbrel and Humira for nine European countries covering the period from the first launch in 2000 until becoming blockbusters in 2009. Descriptive statistics reveal large variations across countries in per-capita consumption and price levels both overall and at the brand level. We explore potential sources for the cross-country consumption differences by estimating several multivariate regression models. Our results show that large parts of the cross-country variation are explained by time-invariant country-specific factors (e.g., disease prevalence, demographics, health care system). We also find that differences in income [gross domestic product (GDP) per capita] and health spending (share of GDP) explain the cross-country variation in consumption, while relative price differences seem to have limited impact. PMID:24146261

  15. [Findings from a questionnaire survey on new guidelines for preparing Drug Guide for Patients and a perspective from a pharmaceutical company as the information provider].

    PubMed

    Asada, Kazuhiro

    2015-01-01

    Draft versions of two products of based on a "Drug Guide for Patients" have been prepared the guidelines proposed in "Research on risk communication between patients and healthcare professionals regarding information on safety measures for drugs, etc." by Health and Labour Sciences Research Grants. We conducted a questionnaire survey on the draft to identify issues regarding the contents and their preparation from the viewpoint of pharmaceutical companies as authors. The questionnaire results indicated that, the segments of the contents of the "Drug Guide for Patients" based on the new guidelines are generally acceptable. In this paper, the author offers proposals to address issues regarding the preparation of easy-to-read contents for patients and strategies to promote the overall understanding recognition of Drug Guide for Patients. Drug Guide for Patients are expected to be utilized as materials providing information to be used for routine risk minimization activities of the Risk Management Plan in the future. PMID:25747228

  16. Implications of In-Use Photostability: Proposed Guidance for Photostability Testing and Labeling to Support the Administration of Photosensitive Pharmaceutical Products, Part 3. Oral Drug Products.

    PubMed

    Allain, Leonardo; Baertschi, Steven W; Clapham, David; Foti, Chris; Lantaff, Wendy M; Reed, Robert A; Templeton, Allen C; Tønnesen, Hanne Hjorth

    2016-05-01

    The ICH Q1B guidance and additional clarifying manuscripts provide the essential information needed to conduct photostability testing for pharmaceutical drug products in the context of manufacturing, packaging, and storage. As the previous 2 papers in this series highlight for drug products administered by injection (part 1) and drug products administered via topical application (part 2), there remains a paucity of guidance and methodological approaches to conducting photostability testing to ensure effective product administration. Part 3 in the series is presented here to provide a similar approach and commentary for photostability testing for oral drug products. The approach taken, as was done previously, is to examine "worst case" photoexposure scenarios in combination with ICH-defined light sources to derive a set of practical experimental approaches to support the safe and effective administration of photosensitive oral drug products. PMID:27056630

  17. A review of melanized (black) fungal contamination in pharmaceutical products-incidence, drug recall and control measures.

    PubMed

    Vijayakumar, R; Saleh Al-Aboody, M; Sandle, T

    2016-04-01

    The aim of this study was to describe the incidence of contamination of pharmaceutical products by melanized fungi and to consider control measures in relation to bioburden and cleanrooms. This study reviews and analyses pharmaceutical product recalls and offers incidence rates of fungal detection from a typical cleanrooms. The recalls include some serious cases which resulted in the loss of life. Of different types of fungal contamination incidences some of the most damaging have been due to melanized fungi ('black mould'), such as Exserohilum rostratum. The focus of the article is with melanized fungi. The study concludes that, from the review of recent pharmaceutical product recalls, fungal contamination is either increasingly common within cleanroom environments or the accuracy of sampling and the level of reporting has risen. The prevalence of melanized fungi in pharmaceutical facilities rests on specific virulence factors particular to these types of fungi, which are outlined. The article identifies a gap in the way that such fungi are screened for using available cultural methods. The article provides some control strategies, including assessing the suitability of disinfectants and biocides, for reducing the risk of melanized fungal incidences within the pharmaceutical facility. Understanding the fungal risk to pharmaceutical products remains a poorly understood and often overlooked aspect of pharmaceutical microbiology. This article helps to identify this risk and offer some guidance to those involved with pharmaceutical products manufacture in relation to bio-contamination control strategies. PMID:26119714

  18. Powerful inner/outer controlled multi-target magnetic nanoparticle drug carrier prepared by liquid photo-immobilization

    PubMed Central

    Guan, Yan-Qing; Zheng, Zhe; Huang, Zheng; Li, Zhibin; Niu, Shuiqin; Liu, Jun-Ming

    2014-01-01

    Nanomagnetic materials offer exciting avenues for advancing cancer therapies. Most researches have focused on efficient delivery of drugs in the body by incorporating various drug molecules onto the surface of nanomagnetic particles. The challenge is how to synthesize low toxic nanocarriers with multi-target drug loading. The cancer cell death mechanisms associated with those nanocarriers remain unclear either. Following the cell biology mechanisms, we develop a liquid photo-immobilization approach to attach doxorubicin, folic acid, tumor necrosis factor-α, and interferon-γ onto the oleic acid molecules coated Fe3O4 magnetic nanoparticles to prepare a kind of novel inner/outer controlled multi-target magnetic nanoparticle drug carrier. In this work, this approach is demonstrated by a variety of structural and biomedical characterizations, addressing the anti-cancer effects in vivo and in vitro on the HeLa, and it is highly efficient and powerful in treating cancer cells in a valuable programmed cell death mechanism for overcoming drug resistance. PMID:24845203

  19. Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug

    NASA Astrophysics Data System (ADS)

    Hsu, Shu-Hui; Wen, Chih-Jen; Al-Suwayeh, S. A.; Chang, Hui-Wen; Yen, Tzu-Chen; Fang, Jia-You

    2010-10-01

    Nanostructured lipid carriers (NLCs) were prepared to investigate whether the duration of brain targeting and accumulation of drugs in the brain can be improved by intravenous delivery. NLCs were developed using cetyl palmitate as the lipid matrix, squalene as the cationic surfactant, and Pluronic F68, polysorbate 80 and polyethylene glycol as the interfacial additives. Solid lipid nanoparticles (SLNs) and lipid emulsions (LEs) were also prepared for comparison. An anti-Parkinson's drug, apomorphine, was used as the model drug. Nuclear magnetic resonance and differential scanning calorimetry showed possible interactions between the solid and liquid lipids in the inner core. The lipid nanoparticles with different compositions were characterized by mean size, zeta potential, apomorphine encapsulation and in vitro drug release. NLCs were 370-430 nm in size, which was between the sizes of the SLNs and LEs. A cationic surfactant was used to produce a positive surface charge of 42-50 mV. The base form of apomorphine was successfully entrapped by NLCs with an entrapment percentage of > 60%. The loading of apomorphine in nanoparticles resulted in a slower release behavior compared to the aqueous solution, with LEs showing the lowest release. In vivo real-time bioluminescence imaging of the rat brain revealed that NLCs could be targeted, through certain vessels, to selected brain regions. This effect was further confirmed by imaging the entire brain and brain slices. The results indicated that NLCs with moderate additives are a promising controlled-release and drug-targeting system.

  20. Powerful inner/outer controlled multi-target magnetic nanoparticle drug carrier prepared by liquid photo-immobilization

    NASA Astrophysics Data System (ADS)

    Guan, Yan-Qing; Zheng, Zhe; Huang, Zheng; Li, Zhibin; Niu, Shuiqin; Liu, Jun-Ming

    2014-05-01

    Nanomagnetic materials offer exciting avenues for advancing cancer therapies. Most researches have focused on efficient delivery of drugs in the body by incorporating various drug molecules onto the surface of nanomagnetic particles. The challenge is how to synthesize low toxic nanocarriers with multi-target drug loading. The cancer cell death mechanisms associated with those nanocarriers remain unclear either. Following the cell biology mechanisms, we develop a liquid photo-immobilization approach to attach doxorubicin, folic acid, tumor necrosis factor-α, and interferon-γ onto the oleic acid molecules coated Fe3O4 magnetic nanoparticles to prepare a kind of novel inner/outer controlled multi-target magnetic nanoparticle drug carrier. In this work, this approach is demonstrated by a variety of structural and biomedical characterizations, addressing the anti-cancer effects in vivo and in vitro on the HeLa, and it is highly efficient and powerful in treating cancer cells in a valuable programmed cell death mechanism for overcoming drug resistance.

  1. Nano-assembly of Surfactants with Interfacial Drug-Interactive Motifs as Tailor-Designed Drug Carriers

    PubMed Central

    Gao, Xiang; Huang, Yixian; Makhov, Alexander M.; Epperly, Michael; Lu, Jianqin; Grab, Sheila; Zhang, Peijun; Rohan, Lisa; Xie, Xiang-qun (Sean); Wipf, Peter; Greenberger, Joel; Li, Song

    2012-01-01

    PEGylated lipopeptide surfactants carrying drug-interactive motifs specific for a peptide-nitroxide antioxidant, JP4-039, were designed and constructed to facilitate the solubilization of this drug candidate as micelles and emulsion nanoparticles. A simple screening process based on the ability that prevents the formation of crystals of JP4-039 in aqueous solution was used to identify agents that have potential drug-interactive activities. Several protected lysine derivatives possessing this activity were identified, of which α-Fmoc-ε-tBoc lysine is the most potent, followed by α-Cbz- and α-iso-butyloxycarbonyl-ε-tBoc-lysine. Using polymer-supported liquid-phase synthesis approach, a series of synthetic lipopeptide surfactants with PEG head group, varied numbers and geometries of α-Fmoc or α-Cbz-lysyl groups located at interfacial region as the drug-interactive domains, and oleoyl chains as the hydrophobic tails were synthesized. All α-Fmoc-lysyl-containing lipopeptide surfactants were able to solubilize JP4-039 as micelles, with enhanced solubilizing activity for surfactants with increased numbers of α-Fmoc groups. The PEGylated lipopeptide surfactants with α-Fmoc-lysyl groups alone tend to form filamentous or worm-like micelles. The presence of JP4-039 transformed α-Fmoc-containing filamentous micelles into dots and bar-like mixed micelles with substantially reduced sizes. Fluorescence quenching and NMR studies revealed that the drug and surfactant molecules were in a close proximity in the complex. JP4-039-loaded emulsion carrying α-Cbz-containing surfactants demonstrated enhanced stability over drug loaded emulsion without lipopeptide surfactants. JP4-039-emulsion showed significant mitigation effect on mice exposed to a lethal dose of radiation. PEGylated lipopeptides with an interfacially located drug-interactive domain are therefore tailor-designed formulation materials potentially useful for drug development. PMID:23244299

  2. Microparticles as controlled drug delivery carrier for the treatment of ulcerative colitis: A brief review.

    PubMed

    Nidhi; Rashid, Muzamil; Kaur, Veerpal; Hallan, Supandeep Singh; Sharma, Saurabh; Mishra, Neeraj

    2016-07-01

    Ulcerative colitis is the chronic relapsing multifactorial gastrointestinal inflammatory bowel disease, which is characterized by bloody or mucus diarrhea, tenesmus, bowel dystension, anemia. The annual incidence of ulcerative colitis in Asia, North America and Europe was found to be 6.3, 19.2 and 24.3 per 100,000 person-years. The major challenge in the treatment of ulcerative colitis is appropriate local targeting and drug related side-effects. To overcome these challenges, microparticulate systems seem to be a promising approach for controlled and sustained drug release after oral administration. The main goal of this article is to explore the role of microparticles in ulcerative colitis for the appropriate targeting of drugs to colon. There are different approaches which have been studied over the last decade, including prodrugs, polymeric approach, time released system, pH sensitive system, which show the site specific drug delivery to colon. Among these approaches, microparticulate drug delivery system has been gaining an immense importance for local targeting of drug to colon at a controlled and sustained rate. Combined approaches such as pH dependent and time dependent system provide the maximum release of drug into colon via oral route. This article embraces briefly about pathophysiology, challenges and polymeric approaches mainly multiparticulate systems for site specific drug delivery to colon in sustained and controlled manner so that drug related side-effects by reducing dosage frequency can be minimized. PMID:27330377

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

    PubMed

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

    2012-11-01

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

  4. Examination of nanoparticles as a drug carrier on blood flow through catheterized composite stenosed artery with permeable walls.

    PubMed

    Ijaz, S; Nadeem, S

    2016-09-01

    In this paper, we have discussed the influence of copper nanoparticles on a blood flow through composite stenosed artery with permeable walls. The nature of blood is discussed mathematically by considering it as viscous nanofluid. The study is carried out for a blood vessel under mild stenosis approximations and expressions of the temperature, velocity, resistance impedance to flow, wall shear stress and the pressure gradient is obtained by using corresponding boundary conditions. Results for the effects of permeability on blood flow through composite stenosis have been discussed graphically. The considered analysis also summarizes that the drug copper nanoparticles are efficient to reduce hemodynamics of stenosis and could be helpful to predict important uses for biomedical applications. Results indicate that nanoparticles are helpful as drug carriers to minimize the effects of resistance impedance to blood flow or coagulation factors due to stenosis. PMID:27393802

  5. The absorptive flux of the anti-epileptic drug substance vigabatrin is carrier-mediated across Caco-2 cell monolayers.

    PubMed

    Nøhr, Martha Kampp; Hansen, Steen Honoré; Brodin, Birger; Holm, René; Nielsen, Carsten Uhd

    2014-01-23

    Vigabatrin is an anti-epileptic drug substance. The oral bioavailability of vigabatrin is high (60-70%), however, little is known about the mechanism(s) mediating the intestinal absorption. The aim of the present study was to identify which solute carrier(s) are involved in the absorption of vigabatrin in Caco-2 cells, a cell culture model of the small intestinal epithelium. The uptake and transepithelial flux of vigabatrin was measured using an LC-MS method for quantification. Transepithelial transport of vigabatrin was shown to be proton-dependent and polarized in the apical-to-basolateral (A-B) direction. The A-B flux of vigabatrin had a saturable component and a passive component, indicating the presence of a carrier system in parallel with a passive permeability. The Michaelis constant, Km, of the transepithelial A-B flux of vigabatrin was estimated to be 32.8±7.4 mM (n=3-5), whereas the Km of the apical uptake was found to be 12.7±3.7 mM (n=3). The carrier-mediated transepithelial A-B flux of vigabatrin accounted for 80-95% (50.0-1.0mM) of the total A-B flux. The transepithelial A-B flux (as well as apical uptake) of vigabatrin was significantly decreased upon addition of substrates or inhibitors of the human proton-coupled amino acid transporter (hPAT1) to the apical solution. The present study indicates that the transepithelial A-B flux of vigabatrin is mainly mediated by hPAT1 in Caco-2 cells at dose-relevant concentrations. PMID:24008184

  6. Synthesis and Anchoring of Antineoplastic Ferrocene and Phthalocyanine Derivatives on Water-Soluble Polymeric Drug Carriers Derived from Lysine and Aspartic Acid

    PubMed Central

    Maree, M. David; Neuse, Eberhard W.; Erasmus, Elizabeth; Swarts, Jannie C.

    2008-01-01

    The general synthetic strategy towards water-soluble biodegradable drug carriers and the properties that they must have are discussed. The syntheses of water-soluble biodegradable copolymers of lysine and aspartic acid as potential drug-delivering devices, having amine-functionalised side chains are then described. Covalent anchoring of carboxylic acid derivatives of the antineoplastic ferrocene and photodynamically active phthalocyanine moieties to the amine-containing drug carrier copolymers under mild coupling conditions has been achieved utilising the coupling reagent O-benzotriazolyl-N,N,N′,N′-tetramethyluronium hexafluorophosphate to promote formation of the biodegradable amide bond. Even though the parent antineoplastic ferrocene and phthalocyanine derivatives are themselves insoluble in water at pH < 7, the new carrier-drug conjugates that were obtained are well water-soluble. PMID:18288243

  7. Preparation and characterization of L-Leucine-modified amphiprotic bifunctional mesoporous SBA-15 molecular sieve as a drug carrier for ribavirin

    NASA Astrophysics Data System (ADS)

    Xu, Zhigang; Ji, Yongsheng; Guan, Min; Huang, Huayu; Zhao, Chuande; Zhang, Haixia

    2010-03-01

    In this study, an amphiphilic bifunctional mesoporous SBA-15 material (AMPBIF-SBA-15) was synthesized through post-synthesis method as a drug carrier. Ribavirin was selected as the model drug and whose release from both unmodified and functionalized SBA-15 was evaluated in four media solutions with different pH or ionic strength. The release process indicated that AMPBIF-SBA-15 was a pH-sensitive drug carrier, which showed a phased low-release effect to ribavirin in the simulated body fluid (PBS, pH 7.4) solution. The materials were further characterized by Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen adsorption-desorption measurements and elemental analysis. This study provided a novel drug carrier for ribavirin to improve curative effect of ribavirin.

  8. The Impact of Variables on Particle Size of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers; A Comparative Literature Review

    PubMed Central

    Azhar Shekoufeh Bahari, Leila; Hamishehkar, Hamed

    2016-01-01

    During the past decade, pharmaceutical science has seen rapid growth in interest for nanoscale materials. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are popular research topics recently introduced as nano-scale drug carriers; they have shown numerous merits in drug delivery. Size is the most important index in a nanocarrier affecting its drug delivery efficiency. The influence of preparation conditions and type of lipidic components on the size of SLN and NLC in comparable states seems to be interesting for researchers who investigate these types of carriers. This review highlights the results of SLN and NLC particle size and size distribution comparisons. PMID:27478775

  9. Inorganically modified diatomite as a potential prolonged-release drug carrier.

    PubMed

    Janićijević, Jelena; Krajišnik, Danina; Calija, Bojan; Dobričić, Vladimir; Daković, Aleksandra; Krstić, Jugoslav; Marković, Marija; Milić, Jela

    2014-09-01

    Inorganic modification of diatomite was performed with the precipitation product of partially neutralized aluminum sulfate solution at three different mass ratios. The starting and the modified diatomites were characterized by SEM-EDS, FTIR, thermal analysis and zeta potential measurements and evaluated for drug loading capacity in adsorption batch experiments using diclofenac sodium (DS) as a model drug. In vitro drug release studies were performed in phosphate buffer pH6.8 from comprimates containing: the drug adsorbed onto the selected modified diatomite sample (DAMD), physical mixture of the drug with the selected modified diatomite sample (PMDMD) and physical mixture of the drug with the starting diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite samples was performed on mice. High adsorbent loading of the selected modified diatomite sample (~250mg/g in 2h) enabled the preparation of comprimates containing adsorbed DS in the amount near to its therapeutic dose. Drug release studies demonstrated prolonged release of DS over a period of 8h from both DAMD comprimates (18% after 8h) and PMDMD comprimates (45% after 8h). The release kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer-Peppas and Bhaskar models, indicating that the release mechanism was a combination of non-Fickian diffusion and ion exchange process. PMID:25063135

  10. Designer nanoparticles: Incorporating size, shape, and triggered release into nanoscale drug carriers

    PubMed Central

    Caldorera-Moore, Mary; Guimard, Nathalie; Shi, Li; Roy, Krishnendu

    2009-01-01

    Importance of the field Although significant progress has been made in delivering therapeutic agents through micro and nanocarriers, precise control over in vivo biodistribution and disease-responsive drug release has been difficult to achieve. This is critical for the success of next generation drug delivery devices, since newer drugs, designed to interfere with cellular functions, must be efficiently and specifically delivered to diseased cells. The major constraint in achieving this has been our limited repertoire of particle synthesis methods, especially at the nanoscale. Recent developments in generating shape-specific nanocarriers and the potential to combine stimuli-responsive release with nanoscale delivery devices show great promise in overcoming these limitations. Areas covered in this review Here we discuss how recent advancements in fabrication technology allow synthesis of highly monodisperse, stimuli-responsive, drug-carrying nanoparticles of precise geometries. We also review how particle properties, specifically shape and stimuli responsiveness, affect biodistribution, cellular uptake, and drug release. What the reader will gain The reader is introduced to recent developments in intelligent drug nanocarriers and new nanofabrication approaches that can be combined with disease-responsive biomaterials. This will provide insight into the importance of controlling particle geometry and incorporating stimuli responsive materials into drug delivery. PMID:20331355

  11. 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

  12. Nanodrug-Enhanced Radiofrequency Tumor Ablation: Effect of Micellar or Liposomal Carrier on Drug Delivery and Treatment Efficacy

    PubMed Central

    Moussa, Marwan; Goldberg, S. Nahum; Kumar, Gaurav; Sawant, Rupa R.; Levchenko, Tatyana; Torchilin, Vladimir P.; Ahmed, Muneeb

    2014-01-01

    Purpose To determine the effect of different drug-loaded nanocarriers (micelles and liposomes) on delivery and treatment efficacy for radiofrequency ablation (RFA) combined with nanodrugs. Materials/Methods Fischer 344 rats were used (n = 196). First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of IV fluorescent beads (20, 100, and 500 nm), with fluorescent intensity measured at 4–24 hr. Next, to study carrier type on drug efficiency, RFA was combined with micellar (20 nm) or liposomal (100 nm) preparations of doxorubicin (Dox; targeting HIF-1α) or quercetin (Qu; targeting HSP70). Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg IV, 15 min post-RFA), and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min post-RFA (0.3 mg IV). Tumor coagulation and HIF-1α orHSP70 expression were assessed 24 hr post-RFA. Third, the effect of RFA combined with IV Lipo-Dox, Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA) compared to RFA alone on tumor growth and animal endpoint survival was evaluated. Finally, drug uptake was compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4–72 hr. Results Smaller 20 nm beads had greater deposition and deeper tissue penetration in both tumor (100 nm/500 nm) and liver (100 nm) (p<0.05). Mic-Dox and Mic-Qu suppressed periablational HIF-1α or HSP70 rim thickness more than liposomal preparations (p<0.05). RFA/Mic-Dox had greater early (4 hr) intratumoral doxorubicin, but RFA/Lipo-Dox had progressively higher intratumoral doxorubicin at 24–72 hr post-RFA (p<0.04). No difference in tumor growth and survival was seen between RFA/Lipo-Qu and RFA/Mic-Qu. Yet, RFA/Lipo-Dox led to greater animal endpoint survival compared to RFA/Mic-Dox (p<0.03). Conclusion With RF ablation, smaller particle micelles have superior penetration and more effective local molecular modulation. However, larger long-circulating liposomal carriers can result in greater intratumoral drug accumulation over

  13. Preparation of solid lipid nanoparticles as drug carriers for levothyroxine sodium with in vitro drug delivery kinetic characterization.

    PubMed

    Rostami, E; Kashanian, S; Azandaryani, A H

    2014-05-01

    The aim of this work was to produce and characterize solid lipid nanoparticles (SLN) containing levothyroxine sodium for oral administration, and to evaluate the kinetic release of these colloidal carriers. SLNs were prepared by microemulsion method. The particle size and zeta potential of levothyroxine sodium-loaded SLNs were determined to be around 153 nm,-43 mV (negatively charged), respectively by photon correlation spectroscopy. The levothyroxine entrapment efficiency was over 98%. Shape and surface morphology were determined by TEM and SEM. They revealed fairly spherical shape of nanoparticles.SLN formulation was stable over a period of 6 months. There were no significant changes in particle size, zeta potential and polydispersity index and entrapment efficiency, indicating that the developed SLNs were fairly stable. PMID:24515386

  14. [Cancer: Is it really so different? Particularities of oncologic drugs from the perspective of the pharmaceutical regulatory agency].

    PubMed

    Enzmann, Harald; Broich, Karl

    2013-01-01

    For innovative oncological medicines the centralised procedure at the European Medicines Agency is mandatory for a marketing authorisation application for the European Union. As with other medical drugs, the marketing authorisation decision is based on the assessment of its efficacy, safety and pharmaceutical quality but does not consider price or reimbursement. More sophisticated diagnostic methods drive an increasing stratification of cancer into a multitude of different diseases. Regardless of their different pathogenesis and therapeutic options the most relevant clinical endpoints remain cure, overall survival and progression free survival. These endpoints include both efficacy and safety, as patient survival reflects the sum of the beneficial anti-tumour effects (increasing survival) AND the adverse effects (decreasing survival). The benefit of an anticancer medicine should be evident from both overall survival and progression free survival (e.g. used as primary and secondary endpoints). Mature data on overall survival may not be needed for marketing authorisation if a clear increase in progression free survival convincingly predicts a beneficial effect on overall survival. In these exceptional cases treatment of patients with an obviously beneficial medicine must not be delayed - possibly for years - until the exact size of the benefit has been established. The continued stratification of the disease cancer results in a lower prevalence for each of the newly distinguished disease entities and an ever increasing number of orphan designations for medicines for rare diseases. Incentives for the development of orphan medicines include market exclusivity for up to ten years. In specific circumstances, however, the orphan legislation may restrict the authorisation and marketing of competing generic products even beyond these ten years. Conditional approval and approval under exceptional circumstances may accelerate patients' access to a new medicine. Both postulate

  15. Inhalable chitosan nanoparticles as antitubercular drug carriers for an effective treatment of tuberculosis.

    PubMed

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

    2016-05-01

    The aim of this study was to prepare and characterize spray dried inhalable chitosan nanoparticles (CNPs) for sustained delivery of anti-tubercular drugs, isoniazid (INH) and rifampicin (RIF), to the lungs. CNPs were prepared by ionic gelation technique followed spray drying. Results showed that the CNPs obtained had a smooth spherical shape with an average size of 230 ± 4.5 nm, with a poly dispersity index of 0.180 ± 0.021. Both drugs, were detected in various organs (lungs, liver, spleen and kidney) until 24 h post nebulization. The chemotherapeutic efficacy of a single dose of drug-loaded CNPs suggested that they are more effective against the mycobacterium than free drugs. PMID:25682840

  16. Phase-shift, stimuli-responsive drug carriers for targeted delivery

    PubMed Central

    O’Neill, Brian E; Rapoport, Natalya

    2011-01-01

    The intersection of particles and directed energy is a rich source of novel and useful technology that is only recently being realized for medicine. One of the most promising applications is directed drug delivery. This review focuses on phase-shift nanoparticles (that is, particles of submicron size) as well as micron-scale particles whose action depends on an external-energy triggered, first-order phase shift from a liquid to gas state of either the particle itself or of the surrounding medium. These particles have tremendous potential for actively disrupting their environment for altering transport properties and unloading drugs. This review covers in detail ultrasound and laser-activated phase-shift nano- and micro-particles and their use in drug delivery. Phase-shift based drug-delivery mechanisms and competing technologies are discussed. PMID:22059114

  17. Guar gum succinate-sodium alginate beads as a pH-sensitive carrier for colon-specific drug delivery.

    PubMed

    Seeli, D Sathya; Dhivya, S; Selvamurugan, N; Prabaharan, M

    2016-10-01

    Guar gum succinate - sodium alginate (GGS-SA) beads cross-linked with barium ions were prepared and characterized as a pH sensitive carrier for colon-specific drug delivery. The structure of GGS-SA beads was confirmed by FT-IR spectroscopy. Scanning Electron Microscope (SEM) studies revealed that the drug loaded GGS-SA beads prepared using 2:2 (w/v) weight percent of GGS and SA had a diameter about 1.4mm and roughly spherical in shape. X-ray diffraction (XRD) studies showed that the peaks corresponding to GGS and SA at 13.5°, 17.5°, 20.2° and 13.5°, 22°, 24.1°, respectively were destroyed in GGS-SA beads which show that these beads are more amorphous in nature. Swelling studies demonstrated the pH-dependent swelling behavior of GGS-SA beads. The beads showed higher swelling degrees in pH 7.4 than that in pH 1.2 due to the existence of anionic groups in the polymer chains. The drug release study showed that the amount of model drug, ibuprofen, released from the GGS-SA beads was higher in pH 7.4 than that in pH 1.2 due to the pH-dependent swelling behavior of the beads. MTT assay revealed that GGS-SA beads at a concentration range of 0-30μg/ml had no cytotoxic effect on the cultured mouse mesenchymal stem cells (C3H10T1/2). These results suggest that GGS-SA beads can be used as effective colon-specific drug delivery system with pH-dependent drug release ability. PMID:27212216

  18. 75 FR 42455 - Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 27 New Drug Applications and 58...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-21

    ...., Chadds Tablets Ford, PA 19317 ] NDA 16-023 Symmetrel (amantadine hydrochloride Do. (HCl) USP) Syrup NDA... (amantadine HCl USP) Syrup Endo Pharmaceuticals NDA 17-255 MPI DTPA Chelate multidose (kit for...

  19. The use of LC/MS, GC/MS, and LC/NMR hyphenated techniques to identify a drug degradation product in pharmaceutical development.

    PubMed

    Pan, Changkang; Liu, Frances; Ji, Qin; Wang, Wei; Drinkwater, Donald; Vivilecchia, Richard

    2006-02-24

    Understanding drug degradation in the formulated product is critical in pharmaceutical development as it has significant impacts on drug efficacy, safety profile and storage conditions. As a result, identification of degradation compounds has taken an important role in the drug development process. In this study, various hyphenated analytical techniques, such as liquid chromatography mass spectrometry (LC/MS), gas chromatography mass spectrometry (GC/MS), and liquid chromatography nuclear magnetic resonance with a solid phase extraction interface (LC/SPE/NMR), have been applied to the identification of a drug degradation product which grew over time in the stability study of the drug product. The target unknown is less polar and more unsaturated than the drug substance based upon reverse phase HPLC relative retention time and UV spectra. It is not ionizable by electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI) in either a positive or a negative mode. The unknown was isolated by an HPLC fraction collector and enriched by solid phase extraction. GC/MS with chemical ionization (CI) was employed to determine the molecular weight of this compound. Its fragmentation pattern was determined by CI-MS/MS using an ion trap mass spectrometer. The isolated material was also analyzed by LC/SPE/NMR, from which the structure of this compound was further characterized. The study utilizes a combination of various hyphenated analytical techniques to obtain complimentary information for structure elucidation of the unknown. The combination approach is critical for unambiguous impurity structure elucidation in drug degradation studies of pharmaceutical drug products. PMID:16242883

  20. Europium-doped amorphous calcium phosphate porous nanospheres: preparation and application as luminescent drug carriers.

    PubMed

    Chen, Feng; Zhu, Ying-Jie; Zhang, Kui-Hua; Wu, Jin; Wang, Ke-Wei; Tang, Qi-Li; Mo, Xiu-Mei

    2011-01-01

    Calcium phosphate is the most important inorganic constituent of biological tissues, and synthetic calcium phosphate has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of amorphous calcium phosphate (ACP)/polylactide-block-monomethoxy(polyethyleneglycol) hybrid nanoparticles and ACP porous nanospheres. Europium-doping is performed to enable photoluminescence (PL) function of ACP porous nanospheres. A high specific surface area of the europium-doped ACP (Eu3+:ACP) porous nanospheres is achieved (126.7 m2/g). PL properties of Eu3+:ACP porous nanospheres are investigated, and the most intense peak at 612 nm is observed at 5 mol% Eu3+ doping. In vitro cytotoxicity experiments indicate that the as-prepared Eu3+:ACP porous nanospheres are biocompatible. In vitro drug release experiments indicate that the ibuprofen-loaded Eu3+:ACP porous nanospheres show a slow and sustained drug release in simulated body fluid. We have found that the cumulative amount of released drug has a linear relationship with the natural logarithm of release time (ln(t)). The Eu3+:ACP porous nanospheres are bioactive, and can transform to hydroxyapatite during drug release. The PL properties of drug-loaded nanocarriers before and after drug release are also investigated. PMID:21711603

  1. Europium-doped amorphous calcium phosphate porous nanospheres: preparation and application as luminescent drug carriers

    PubMed Central

    2011-01-01

    Calcium phosphate is the most important inorganic constituent of biological tissues, and synthetic calcium phosphate has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of amorphous calcium phosphate (ACP)/polylactide-block-monomethoxy(polyethyleneglycol) hybrid nanoparticles and ACP porous nanospheres. Europium-doping is performed to enable photoluminescence (PL) function of ACP porous nanospheres. A high specific surface area of the europium-doped ACP (Eu3+:ACP) porous nanospheres is achieved (126.7 m2/g). PL properties of Eu3+:ACP porous nanospheres are investigated, and the most intense peak at 612 nm is observed at 5 mol% Eu3+ doping. In vitro cytotoxicity experiments indicate that the as-prepared Eu3+:ACP porous nanospheres are biocompatible. In vitro drug release experiments indicate that the ibuprofen-loaded Eu3+:ACP porous nanospheres show a slow and sustained drug release in simulated body fluid. We have found that the cumulative amount of released drug has a linear relationship with the natural logarithm of release time (ln(t)). The Eu3+:ACP porous nanospheres are bioactive, and can transform to hydroxyapatite during drug release. The PL properties of drug-loaded nanocarriers before and after drug release are also investigated. PMID:21711603

  2. Semi-fluorinated alkanes as carriers for drug targeting in acute respiratory failure.

    PubMed

    Dembinski, Rolf; Bensberg, Ralf; Marx, Gernot; Rossaint, Rolf; Quintel, Michael; Vohmann, Cathrin; Kuhlen, Ralf

    2010-10-01

    Partial liquid ventilation (PLV) with perfluorocarbons may cause pulmonary recruitment in acute lung injury (ALI). Semi-fluorinated alkanes (SFAs) provide biochemical properties similar to perfluorocarbons. Additionally, SFAs are characterized by increased lipophilicity. Therefore, SFA-PLV may be considered for deposition of certain therapeutic drugs into atelectatic lung areas. In this experimental study SFA-PLV was evaluated to demonstrate feasibility, pulmonary recruitment, and efficacy of drug deposition. Feasibility of SFA-PLV was determined in pigs with and without experimental ALI. Animals were randomized to PLV with SFAs up to a cumulative amount of 30 mL x kg⁻¹ or to conventional mechanical ventilation. Pulmonary recruitment effects were determined by analyzing ventilation-perfusion distributions. Efficacy of intrapulmonary drug deposition was evaluated in further experiments by measuring drug serum concentrations in the course of PLV with SFA-dissolved α-tocopherol and ibuprofen. Increasing SFA doses caused progressive reduction of intrapulmonary shunt in animals with ALI, indicating pulmonary recruitment. PLV with SFA-dissolved α-tocopherol had no effect on serum levels of α-tocopherol, whereas PLV with SFA-dissolved ibuprofen caused a rapid increase of serum levels of ibuprofen. The authors conclude that SFA-PLV is feasible and causes pulmonary recruitment in ALI. Effectiveness of drug deposition in the lung obviously depends on the partitioning drugs out of the SFA phase into blood. PMID:20939753

  3. Sodium alginate as a potential carrier in solid dispersion formulations to enhance dissolution rate and apparent water solubility of BCS II drugs.

    PubMed

    Borba, Paola Aline Amarante; Pinotti, Marihá; de Campos, Carlos Eduardo Maduro; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

    2016-02-10

    The solid dispersion technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs, however it depends on a suitable carrier selection. The work explored the use of the biopolymer sodium alginate (SA) as a potential carrier in solid dispersions (SD). The data demonstrated that SA was able to improve the biopharmaceutical properties of the BCS II drug telmisartan (TEL) of low solubility even using relative small drug:polymer ratio. A solid state grinding process was used to prepare the solid dispersions (SD) during 45 min. The SD were prepared in different proportions of drug and carrier of 1:1, 1:3, 1:5, 1:7 and 1:9 (mass/mass). DSC, XRPD, FTIR and Raman confirmed the presence of molecular interactions between TEL and the carrier. FTIR supports the presence of hydrogen bonds between TEL and the carrier. SD_1:5, SD_1:7 and SD_1:9 enhanced the dissolution rate of the drug releasing more than 80% of the drug in just 30 min (83%, 84% and 87%). The the t-test results demonstrated equal dissolution efficiency values for SD_1:7 and Micardis(®), however the similarity (f2) and difference (f1) fit factors showed that the SD and Micardis(®) are statistically different. The physical stability studies demonstrated that SD using sodium alginate as a carrier remained unchanged during the period of 90 days at room temperature, showing that the sodium alginate acts as a good anti plasticizer agent, preventing the drug recrystallization. PMID:26686139

  4. Pharmaceuticals and Related Drugs.

    ERIC Educational Resources Information Center

    Gilpin, R. K.; Pachla, L. A.

    1989-01-01

    This review is divided into these topics: alkaloids, antibiotics, inorganics, nitrogen and oxygen containing compounds, steroids, sulfur containing compounds, vitamins, techniques, and miscellaneous methods. The review covers from November 1986, to October 1988. (MVL)

  5. Delivery of drugs bound to erythrocytes: new avenues for an old intravascular carrier.

    PubMed

    Villa, Carlos H; Pan, Daniel C; Zaitsev, Sergei; Cines, Douglas B; Siegel, Donald L; Muzykantov, Vladimir R

    2015-07-01

    For several decades, researchers have used erythrocytes for drug delivery of a wide variety of therapeutics in order to improve their pharmacokinetics, biodistribution, controlled release and pharmacodynamics. Approaches include encapsulation of drugs within erythrocytes, as well as coupling of drugs onto the red cell surface. This review focuses on the latter approach, and examines the delivery of red blood cell (RBC)-surface-bound anti-inflammatory, anti-thrombotic and anti-microbial agents, as well as RBC carriage of nanoparticles. Herein, we discuss the progress that has been made in surface loading approaches, and address in depth the issues relevant to surface loading of RBC, including intrinsic features of erythrocyte membranes, immune considerations, potential surface targets and techniques for the production of affinity ligands. PMID:26228773

  6. Mechanism of erosion of nanostructured porous silicon drug carriers in neoplastic tissues

    NASA Astrophysics Data System (ADS)

    Tzur-Balter, Adi; Shatsberg, Zohar; Beckerman, Margarita; Segal, Ester; Artzi, Natalie

    2015-02-01

    Nanostructured porous silicon (PSi) is emerging as a promising platform for drug delivery owing to its biocompatibility, degradability and high surface area available for drug loading. The ability to control PSi structure, size and porosity enables programming its in vivo retention, providing tight control over embedded drug release kinetics. In this work, the relationship between the in vitro and in vivo degradation of PSi under (pre)clinically relevant conditions, using breast cancer mouse model, is defined. We show that PSi undergoes enhanced degradation in diseased environment compared with healthy state, owing to the upregulation of reactive oxygen species (ROS) in the tumour vicinity that oxidize the silicon scaffold and catalyse its degradation. We further show that PSi degradation in vitro and in vivo correlates in healthy and diseased states when ROS-free or ROS-containing media are used, respectively. Our work demonstrates that understanding the governing mechanisms associated with specific tissue microenvironment permits predictive material performance.

  7. Self-assembled penetratin-deferasirox micelles as potential carriers for hydrophobic drug delivery.

    PubMed

    Goswami, Dibakar; Vitorino, Hector Aguilar; Machini, M Teresa; Espósito, Breno P

    2015-11-01

    There has been a growing interest in the use of micelles with nanofiber geometry as nanocarriers for hydrophobic drugs. Here we show that the conjugate of penetratin, a cell-penetrating peptide (CPP) with blood-brain barrier (BBB) permeability, and deferasirox (DFX), a hydrophobic iron chelator, self-assembles to form micelles at a very low concentration (∼15 mg/L). The critical micelle concentration (CMC) was determined, and the micelles were used for solubilizing curcumin, a hydrophobic anti-neurodegenerative drug, for successful delivery across RBE4 cells, a BBB model. Transmission Electron Microscope images of the curcumin-loaded micelles confirmed the formation of nanofibers. These results indicate the potential of CPP-drug conjugates for use as nanocarriers. PMID:25973759

  8. Cross-linked sodium carboxymethylcellulose as a carrier for dissolution rate improvement of drugs.

    PubMed

    Sangalli, M E; Giunchedi, P; Colombo, P; Conte, U; Gazzaniga, A; La Manna, A

    1989-01-01

    The dissolution rate is often the limiting step in gastrointestinal absorption of water insoluble drugs from solid oral dosage forms. The aim of this work was to use a swellable polymer chosen among superdisintegrants, for improving the dissolution rate of a sparingly soluble drug, loaded on its surface. Nifedipine, which has a very low water solubility, was chosen as a model drug, while cross-linked sodium carboxymethylcellulose (Ac-Di-Sol) was chosen as the swellable polymer. The Nifedipine/Ac-Di-Sol systems were prepared using two different techniques: evaporation and spraying; in some preparations polyethylene glycol (PEG 1500), or sucrose palmitate (Sucrodet), or dioctyl sodium sulfosuccinate (Aerosol OT) were added. The results of the dissolution tests showed that the dissolution rate of Nifedipine from the systems prepared increases, particularly in the case of the preparation composed of Ac-Di-Sol plus surfactant agents. PMID:2611009

  9. Carboxymethyl functionalization of amylopectin and its evaluation as a nanometric drug carrier.

    PubMed

    Thakur, Kanika; Ahuja, Munish; Kumar, Ashok

    2013-11-01

    Carboxymethylation of amylopectin was accomplished by reacting it with monochloroacetic acid. The results of characterization study confirmed the carboxymethyl functionalization with degree of substitution of 1.25. Carboxymethyl amylopectin was found to be slightly more crystalline, appearing morphologically as polyhedral flakes with striated surface. Further, carboxymethylation of amylopectin modified its compression characteristic from fragmentary to plastic. Interaction of carboxymethyl amylopectin (0.001-0.005%, w/v) with chitosan (0.05-0.075% w/v) using ibuprofen (0.05%, w/v) as a model drug provided polyelectrolyte nanoparticles of size 182.7-353.3 nm and 75-92% drug entrapment. The polyelectrolyte nanoparticles showed a sustained release of drug following zero-order kinetics with mechanism of release being combination of matrix erosion and diffusion through the matrix. PMID:23973491

  10. Mechanism of erosion of nanostructured porous silicon drug carriers in neoplastic tissues

    PubMed Central

    Tzur-Balter, Adi; Shatsberg, Zohar; Beckerman, Margarita; Segal, Ester; Artzi, Natalie

    2015-01-01

    Nanostructured porous silicon (PSi) is emerging as a promising platform for drug delivery owing to its biocompatibility, degradability and high surface area available for drug loading. The ability to control PSi structure, size and porosity enables programming its in vivo retention, providing tight control over embedded drug release kinetics. In this work, the relationship between the in vitro and in vivo degradation of PSi under (pre)clinically relevant conditions, using breast cancer mouse model, is defined. We show that PSi undergoes enhanced degradation in diseased environment compared with healthy state, owing to the upregulation of reactive oxygen species (ROS) in the tumour vicinity that oxidize the silicon scaffold and catalyse its degradation. We further show that PSi degradation in vitro and in vivo correlates in healthy and diseased states when ROS-free or ROS-containing media are used, respectively. Our work demonstrates that understanding the governing mechanisms associated with specific tissue microenvironment permits predictive material performance. PMID:25670235

  11. Delivery of drugs bound to erythrocytes: new avenues for an old intravascular carrier

    PubMed Central

    Villa, Carlos H; Pan, Daniel C; Zaitsev, Sergei; Cines, Douglas B; Siegel, Donald L; Muzykantov, Vladimir R

    2015-01-01

    For several decades, researchers have used erythrocytes for drug delivery of a wide variety of therapeutics in order to improve their pharmacokinetics, biodistribution, controlled release and pharmacodynamics. Approaches include encapsulation of drugs within erythrocytes, as well as coupling of drugs onto the red cell surface. This review focuses on the latter approach, and examines the delivery of red blood cell (RBC)-surface-bound anti-inflammatory, anti-thrombotic and anti-microbial agents, as well as RBC carriage of nanoparticles. Herein, we discuss the progress that has been made in surface loading approaches, and address in depth the issues relevant to surface loading of RBC, including intrinsic features of erythrocyte membranes, immune considerations, potential surface targets and techniques for the production of affinity ligands. PMID:26228773

  12. Biodegradable nanoparticles of amphiphilic triblock copolymers based on poly(3-hydroxybutyrate) and poly(ethylene glycol) as drug carriers.

    PubMed

    Chen, Cheng; Yu, Chung Him; Cheng, Yin Chung; Yu, Peter H F; Cheung, Man Ken

    2006-09-01

    New amorphous amphiphilic triblock copolymers of poly(3-hydroxybutyrate)-poly(ethylene glycol)-poly(3-hydroxybutyrate) (PHB-PEG-PHB) were synthesized using the ring-opening copolymerization of beta-butyrolactone monomer. They were characterized by fluorescence, SEM and (1)H NMR. These triblock copolymers can form biodegradable nanoparticles with core-shell structure in aqueous solution. Comparing to the poly(ethylene oxide)-PHB-poly(ethylene oxide) (PEO-PHB-PEO) copolymers, these nanoparticles exhibited much smaller critical micelle concentrations and better drug loading properties, which indicated that the nanoparticles were very suitable for delivery carriers of hydrophobic drugs. The drug release profile monitored by fluorescence showed that the release of pyrene from the PHB-PEG-PHB nanoparticles exhibited the second-order exponential decay behavior. The initial biodegradation rate of the PHB-PEG-PHB nanoparticles was related to the enzyme amount, the initial concentrations of nanoparticle dispersions and the PHB block length. The biodegraded products detected by (1)H NMR contained 3HB monomer, dimer and minor trimer, which were safe to the body. PMID:16740306

  13. Soluplus Graft Copolymer: Potential Novel Carrier Polymer in Electrospinning of Nanofibrous Drug Delivery Systems for Wound Therapy

    PubMed Central

    Tamm, Ingrid; Laidmäe, Ivo; Lust, Andres; Kirsimäe, Kalle

    2014-01-01

    Electrospinning is an effective method in preparing polymeric nanofibrous drug delivery systems (DDSs) for topical wound healing and skin burn therapy applications. The aim of the present study was to investigate a new synthetic graft copolymer (Soluplus) as a hydrophilic carrier polymer in electrospinning of nanofibrous DDSs. Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PCL-PVAc-PEG)) was applied in the nonwoven nanomats loaded with piroxicam (PRX) as a poorly water-soluble drug. Raman spectroscopy, X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy (SEM) were used in the physical characterization of nanofibrous DDSs. According to the SEM results, the drug-loaded PCL-PVAc-PEG nanofibers were circular in cross-section with an average diameter ranging from 500 nm up to 2 µm. Electrospinning stabilized the amorphous state of PRX. In addition, consistent and sustained-release profile was achieved with the present nanofibrous DDSs at the physiologically relevant temperature and pH applicable in wound healing therapy. In conclusion, electrospinning can be used to prepare nanofibrous DDSs of PCL-PVAc-PEG graft copolymer (Soluplus) and to stabilize the amorphous state of a poorly water-soluble PRX. The use of this synthetic graft copolymer can open new options to formulate nanofibrous DDSs for wound healing. PMID:24575414

  14. Polymeric nanoparticles based on chitooligosaccharide as drug carriers for co-delivery of all-trans-retinoic acid and paclitaxel.

    PubMed

    Zhang, Jing; Han, Jian; Zhang, Xiuli; Jiang, Jing; Xu, Maolei; Zhang, Daolai; Han, Jingtian

    2015-09-20

    An amphiphilic all-trans-retinoic acid (ATRA)-chitooligosaccharide (RCOS) conjugate was synthesized to form self-assembled polymeric nanoparticles to facilitate the co-delivery of ATRA and paclitaxel (PTX). The blank RCOS nanoparticles possessed low hemolytic activity and cytotoxicity, and could efficiently load PTX with a drug loading of 22.2% and a high encapsulation efficiency of 71.3%. PTX-loaded RCOS nanoparticles displayed a higher cytotoxicity to HepG2 cells compared to PTX plus ATRA solution when corrected by the accumulated drug release. Cellular uptake profiles of RCOS nanoparticles were evaluated via confocal laser scanning microscope and flow cytometry with FITC as a fluorescent mark. The RCOS nanoparticles could be rapidly and continuously taken up by HepG2 cells via endocytosis and transported into the nucleus, and the uptake rates increased with particle concentration. These results revealed the promising potential of RCOS nanoparticles as drug carriers for co-delivery of ATRA and PTX or other hydrophobic therapeutic agents. PMID:26050884

  15. Carbon nanotubes part II: a remarkable carrier for drug and gene delivery

    PubMed Central

    Karimi, Mahdi; Solati, Navid; Ghasemi, Amir; Estiar, Mehrdad Asghari; Hashemkhani, Mahshid; Kiani, Parnian; Mohamed, Elmira; Saeidi, Ahad; Taheri, Mahdiar; Avci, Pinar; Aref, Amir R; Amiri, Mohammad; Baniasadi, Fazel; Hamblin, Michael R

    2015-01-01

    Introduction Carbon nanotubes (CNT) have recently been studied as novel and versatile drug and gene delivery vehicles. When CNT are suitably functionalized, they can interact with various cell types and are taken up by endocytosis. Areas covered Anti-cancer drugs cisplatin and doxorubicin have been delivered by CNT, as well as methotrexate, taxol and gemcitabine. The delivery of the antifungal compound amphotericin B and the oral administration of erythropoietin have both been assisted using CNT. Frequently, targeting moieties such as folic acid, epidermal growth factor or various antibodies are attached to the CNT-drug nanovehicle. Different kinds of functionalization (e.g., polycations) have been used to allow CNT to act as gene delivery vectors. Plasmid DNA, small interfering RNA and micro-RNA have all been delivered by CNT vehicles. Significant concerns are raised about the nanotoxicology of the CNT and their potentially damaging effects on the environment. Expert opinion CNT-mediated drug delivery has been studied for over a decade, and both in vitro and in vivo studies have been reported. The future success of CNTs as vectors in vivo and in clinical application will depend on achievement of efficacious therapy with minimal adverse effects and avoidance of possible toxic and environmentally damaging effects. PMID:25613837

  16. Coatless alginate pellets as sustained-release drug carrier for inflammatory bowel disease treatment.

    PubMed

    Md Ramli, Siti Hajar; Wong, Tin Wui; Naharudin, Idanawati; Bose, Anirbandeep

    2016-11-01

    Conventional alginate pellets underwent rapid drug dissolution and failed to exert colon targeting unless subjected to complex coating. This study designed coatless delayed-release oral colon-specific alginate pellets for ulcerative colitis treatment. Alginate pellets, formulated with water-insoluble ethylcellulose and various calcium salts, were prepared using solvent-free melt pelletization technique which prevented reaction between processing materials during agglomeration and allowed reaction to initiate only in dissolution. Combination of acid-soluble calcium carbonate and highly water-soluble calcium acetate did not impart colon-specific characteristics to pellets due to pore formation in fragmented matrices. Combination of moderately water-soluble calcium phosphate and calcium acetate delayed drug release due to rapid alginate crosslinking by soluble calcium from acetate salt followed by sustaining alginate crosslinking by calcium phosphate. The use of 1:3 ethylcellulose-to-alginate enhanced the sustained drug release attribute. The ethylcellulose was able to maintain the pellet integrity without calcium acetate. Using hydrophobic prednisolone as therapeutic, hydrophilic alginate pellets formulated with hydrophobic ethylcellulose and moderately polar calcium phosphate exhibited colon-specific in vitro drug release and in vivo anti-inflammatory action. Coatless oral colon-specific alginate pellets can be designed through optimal formulation with melt pelletization as the processing technology. PMID:27516284

  17. Delivery of hydrophilic drug doxorubicin hydrochloride-targeted liver using apoAI as carrier.

    PubMed

    Yuan, Yuan; Wang, Weina; Wang, Baolong; Zhu, Haiyan; Zhang, Boheng; Feng, Meiqing

    2013-05-01

    High-density lipoprotein (HDL) particles can deliver cholesterol from peripheral tissues to the liver through apolipoprotein A1 (Apo A1), which specifically binds to the scavenger receptor class B type 1 (SR-B1) receptor on the surface of hepatocytes. Therefore, ApoA1 can be potentially used to target drugs to the liver. In this study, we successfully loaded doxorubicin hydrochloride (Dox or Dox-HCl), which is a hydrophilic drug used in a wide variety of clinical applications, into the core of reconstituted HDL (rHDL prepared by apoAI and egg phospholipids) to form a doxorubicin-HDL complex (rHDL-Dox). The MTT assays showed that rHDL-Dox particles also had higher cytotoxicity against several cells lines compared to free drug or Dox encapsulated into liposomes. A cellular uptake assay demonstrated that rHDL-Dox had higher absorption in SR-BI receptor positive liver cells. Importantly, in vivo experiments showed that rHDL-Dox can reduce tumor growth more effectively than liposomes. In addition, an in vitro hemolysis assay showed that rHDL-Dox caused only limited hemolysis in the case of high doses. Taken together, our findings indicate that rHDL is a safe and effective drug delivery system for targeting liver. PMID:23600747

  18. Chitosan–pectin polyelectrolyte complex as a carrier for colon targeted drug delivery

    PubMed Central

    Pandey, Sonia; Mishra, Ashish; Raval, Pooja; Patel, Hetal; Gupta, Arti; Shah, Dinesh

    2013-01-01

    Objective The objective of present work was to prepare a polyelectrolyte complex (PEC) between chitosan (polycation) & pectin (polyanion) and to develop enteric coated tablets for colon delivery using the PEC. Methodology The PECs were prepared using different concentrations of chitosan and pectin. Drug loaded enteric coated tablets were prepared by wet granulation method using PEC to sustain the release at colon and coating was done with Eudragit S 100 to prevent the early release of the drug in stomach and intestine. Two independent variable, % PEC (chitosan/pectin) and % coating were optimized by 32 full factorial design. Statistical model were also used to supplement the optimization. DSC was performed to confirm the interaction between the polyions. Developed formulations were evaluated for physical appearance, weight variation, thickness, hardness, friability, % swelling, assay, in-vitro and ex-vivo drug release studies to investigate the PEC's ability to deliver the drug to colon. Ex-vivo release study using rat caecal content was also carried out on optimized formulation. Results and discussion DSC results confirmed chitosan/pectin interaction and subsequent formation of PEC. The optimized formulation containing 1.1% of PEC and 3% of coating showed highest swelling and release in alkaline pH mechanism of which was found to be microbial enzyme dependent degradation established by ex-vivo study using rat caecal content. PMID:24563596

  19. Synthesis and Evaluation of Thermo-Sensitive, Magnetic Fluorescent Nanocomposite as Trifunctional Drug Delivery Carrier.

    PubMed

    Jiang, Wei; Chen, Binhua; Wu, Juan; Xu, Shanshan; Tian, Renbing

    2016-01-01

    The thermo-sensitive magnetic fluorescent trifunctional nanocomposite (Fe₃O₄/ZnS@PNIPAM) has been synthesized via a facile route. The obtained biocompatible nanocomposite was composed of monodisperse heterostructural Fe₃O₄/ZnS core and a thermo-sensitive poly(N-isopropyl acrylamide) (PNIPAM) shell. Fe₃O₄/ZnS acted as magnetic response and fluorescence luminous body, PNIPAM acted as drug loaded platform which can adsorb and release drug controllably. Fe₃O₄/ZnS@PNIPAM was characterized and all of the results showed that it had excellent magnetic response, photostability and thermo-sensitivity. Moreover, the drug release studies in vitro showed that the release rate increased with increasing temperature. MTT assays in model HepG2 cells demonstrated that Fe₃O₄/ZnS@PNIPAM was practically non-toxic. Thus, our results revealed that Fe₃O₄/ZnS@PNIPAM would be used in biomedical fields such as targeted drug delivery, as well as cancer diagnosis and treatment in the nearly future. PMID:27398451

  20. The Role of Polydimethylsiloxane in the Molecular Structure of Silica Xerogels Intended for Drug Carriers

    PubMed Central

    Czarnobaj, Katarzyna

    2015-01-01

    The aim of this study was to prepare and examine polymer/oxide xerogels with metronidazole (MT) as delivery systems for the local application of a drug to a bone. The nanoporous SiO2-CaO and PDMS-modified SiO2-CaO xerogel materials with different amounts of the polymer, polydimethylsiloxane (PDMS), were prepared by the sol-gel method. Characterization assays comprised the analysis of the composite materials by using Fourier transform infrared spectroscopy (FTIR), determining the specific surface area of solids (BET), using X-ray powder diffraction (XRD) and scanning electron microscope (SEM) techniques, and further monitoring in the ultraviolet and visible light regions (UV-Vis) of the in vitro release of the drug (metronidazole) over time. According to these results, the bioactive character and chemical stability of PDMS-modified silica xerogels have been proven. The release of MT from xerogels was strongly correlated with the composition of the matrix. In comparison with the pure oxide matrix, PDMS-modified matrices accelerated the release of the drug through its bigger pores, and additionally, on account of weaker interactions with the drug. The obtained results for the xerogel composites suggest that the metronidazole-loaded xerogels could be promising candidates for formulations in local delivery systems particularly to bone. PMID:26839836

  1. Aerodynamic Factors Responsible for the Deaggregation of Carrier-Free Drug Powders to form Micrometer and Submicrometer Aerosols

    PubMed Central

    Longest, P. Worth; Son, Yoen-Ju; Holbrook, Landon; Hindle, Michael

    2013-01-01

    Purpose The objective of this study was to employ in vitro experiments combined with computational fluid dynamics (CFD) analysis to determine which aerodynamic factors were most responsible for deaggregating carrier-free powders to form micrometer and submicrometer aerosols from a capsule-based platform. Methods Eight airflow passages were evaluated for deaggregation of the aerosol including a standard constricted tube, impaction surface, 2D mesh, inward radial jets, and newly proposed 3D grids and rod arrays. CFD simulations were implemented to evaluate existing and new aerodynamic factors for deaggregation and in vitro experiments were used to evaluate performance of each inhaler. Results For the carrier-free formulation considered, turbulence was determined to be the primary deaggregation mechanism. A strong quantitative correlation was established between the mass median diameter (MMD) and newly proposed non-dimensional specific dissipation (NDSD) factor, which accounts for turbulent energy, inverse of the turbulent length scale, and exposure time. A 3D rod array design with unidirectional elements maximized NDSD and produced the best deaggregation with MMD<1μm. Conclusions The new NDSD parameter can be used to develop highly effective dry powder inhalers like the 3D rod array that can efficiently produce submicrometer aerosols for next-generation respiratory drug delivery applications. PMID:23471640

  2. N-malonyl-1,2-dihydroisoquinoline as a novel carrier for specific delivery of drugs to the brain.

    PubMed

    Abdel-Aziz, Mohamed; Abuo-Rahma, Gamal El-Din A A; Hassan, Heba A; Farag, Hassan H

    2010-01-01

    N-Malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as a novel carrier system for site-specific and sustained delivery of drugs to the brain. Such carriers are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydroisoquinoline. Reduction of the prepared isoquinolinium quaternary derivatives with sodium dithionite afforded a novel group of N-malonyl-1,2-dihydroisoquinoline chemical delivery systems (CDS). The synthesized N-malonyl-1,2-dihydroisoquinoline chemical delivery systems were subjected to various chemical and biological investigations to evaluate their ability to cross the blood-brain barrier (BBB), and to be oxidized biologically into their corresponding quaternary derivatives. The in-vitro oxidation studies showed that the designed N-malonyl-1,2-dihydroisoquinoline chemical delivery system could be oxidized into its corresponding quaternary derivatives at an adequate rate. The in-vivo distribution studies showed that these N-malonyl-1,2-dihydroisoquinoline chemical delivery systems were able to cross the blood-brain barrier at detectable concentrations. PMID:19899103

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

    PubMed Central

    2012-01-01

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

  4. Design Considerations for Developing Hyperbranched Polyglycerol Nanoparticles as Systemic Drug Carriers.

    PubMed

    Wong, Nelson K Y; Misri, Ripen; Shenoi, Rajesh A; Chafeeva, Irina; Kizhakkedathu, Jaya