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Sample records for pharmaceutical drug carriers

  1. Immunomicelles: Targeted pharmaceutical carriers for poorly soluble drugs

    PubMed Central

    Torchilin, Vladimir P.; Lukyanov, Anatoly N.; Gao, Zhonggao; Papahadjopoulos-Sternberg, Brigitte

    2003-01-01

    To prepare immunomicelles, new targeted carriers for poorly soluble pharmaceuticals, a procedure has been developed to chemically attach mAbs to reactive groups incorporated into the corona of polymeric micelles made of polyethylene glycol–phosphatidylethanolamine conjugates. Micelle-attached antibodies retained their ability to specifically interact with their antigens. Immunomicelles with attached antitumor mAb 2C5 effectively recognized and bound various cancer cells in vitro and showed an increased accumulation in experimental tumors in mice when compared with nontargeted micelles. Intravenous administration of tumor-specific 2C5 immunomicelles loaded with a sparingly soluble anticancer agent, taxol, into experimental mice bearing Lewis lung carcinoma resulted in an increased accumulation of taxol in the tumor compared with free taxol or taxol in nontargeted micelles and in enhanced tumor growth inhibition. This family of pharmaceutical carriers can be used for the solubilization and enhanced delivery of poorly soluble drugs to various pathological sites in the body. PMID:12716967

  2. 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

  3. 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

  4. 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

  5. Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic.

    PubMed

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

    2009-01-01

    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 nanoemulsions, 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

  6. Nanoscale Polymersomes as Anti-Cancer Drug Carriers Applied for Pharmaceutical Delivery.

    PubMed

    Tuguntaev, Ruslan G; Okeke, Chukwunweike Ikechukwu; Xu, Jing; Li, Chan; Wang, Paul C; Liang, Xing-Jie

    2016-01-01

    Polymersomes are self-assembled nano-vesicles composed of amphiphilic block copolymers. These building blocks can be selected from a large number of hydrophilic and hydrophobic polymers in order to achieve required properties of the final system, such as biodegradability, sustainable and multiple stimuli-response drug release, long blood circulation, and low toxicity. Moreover, the surface of polymersomes can be functionalized to induce targeting character. Polymersomes are able to encapsulate a broad range of hydrophilic or/and hydrophobic molecules either in the aqueous core or membrane bilayer, respectively. In addition, colloidal stability and low membrane fluidity make polymersomes attractive nano-sized drug carriers. The review describes polymersomes compositions, their applications in pharmaceutical delivery, and preparation methods.

  7. Nanostructured lipid carriers: a potential drug carrier for cancer chemotherapy.

    PubMed

    Selvamuthukumar, Subramanian; Velmurugan, Ramaiyan

    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

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

    PubMed

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

    2012-12-01

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

  9. Nanoparticulate carriers (NPC) for oral pharmaceutics and nutraceutics.

    PubMed

    Lopes, C M; Martins-Lopes, P; Souto, E B

    2010-02-01

    The introduction of nanoparticulate carriers (NPC) in the pharmaceutic and nutraceutic fields has changed the definitions of disease management and treatment, diagnosis, as well as the supply food chain in the agri-food sector. NPC composed of synthetic polymers, proteins or polysaccharides gather interesting properties to be used for oral administration of pharmaceutics and nutraceutics. Oral administration remains the most convenient way of delivering drugs (e.g. peptides, proteins and nucleic acids) since these suffer similar metabolic pathways as food supply. Recent advances in biotechnology have produced highly potent new molecules however with low oral bioavailability. A suitable and promising approach to overcome their sensitivity to chemical and enzymatic hydrolysis as well as the poor cellular uptake, would be their entrapment within suitable gastrointestinal (GI) resistant NPC. Increasing attention has been paid to the potential use of NPC for peptides, proteins, antioxidants (carotenoids, omega fatty acids, coenzyme Q10), vitamins, probiotics, for oral administration. This review focuses on the most important materials to produce NPC for oral administration, and the most recent achievements in the production techniques and bioactives successfully delivered by these means. PMID:20225647

  10. Drug information residency rotation with pharmaceutical industry.

    PubMed

    Cramer, R L

    1986-01-01

    A drug information rotation in pharmaceutical industry may be elected as a component of a hospital pharmacy residency program. Program objectives include improving communication between the pharmaceutical industry and hospital pharmacy/academia, exposing the resident to the challenges the pharmaceutical industry encounters, improving proficiency in drug information practice, and providing insight into the working relationships of various departments within the company. During the rotation, the resident serves as a member of the Drug Information Service. Resident activities include participating in interviews with corporate professionals, updating pharmacokinetic profiles, responding to drug information requests and participating in other information projects. This rotation enables the resident to better understand pharmaceutical industry's concerns and relate these concerns to clinical pharmacy practice. PMID:10277398

  11. Porous Carriers for Controlled/Modulated Drug Delivery

    PubMed Central

    Ahuja, G.; Pathak, K.

    2009-01-01

    Considerable research efforts have been directed in recent years towards the development of porous carriers as controlled drug delivery matrices because of possessing several features such as stable uniform porous structure, high surface area, tunable pore size and well-defined surface properties. Owing to wide range of useful properties porous carriers have been used in pharmaceuticals for many purposes including development of floating drug delivery systems, sustained drug delivery systems. Various types of pores like open, closed, transport and blind pores in the porous solid allow them to adsorb drugs and release them in a more reproducible and predictable manner. Pharmaceutically exploited porous adsorbents includes, silica (mesoporous), ethylene vinyl acetate (macroporous), polypropylene foam powder (microporous), titanium dioxide (nanoporous). When porous polymeric drug delivery system is placed in contact with appropriate dissolution medium, release of drug to medium must be preceded by the drug dissolution in the water filled pores or from surface and by diffusion through the water filled channels. The porous carriers are used to improve the oral bioavailability of poorly water soluble drugs, to increase the dissolution of relatively insoluble powders and conversion of crystalline state to amorphous state. PMID:20376211

  12. Porous carriers for controlled/modulated drug delivery.

    PubMed

    Ahuja, G; Pathak, K

    2009-11-01

    Considerable research efforts have been directed in recent years towards the development of porous carriers as controlled drug delivery matrices because of possessing several features such as stable uniform porous structure, high surface area, tunable pore size and well-defined surface properties. Owing to wide range of useful properties porous carriers have been used in pharmaceuticals for many purposes including development of floating drug delivery systems, sustained drug delivery systems. Various types of pores like open, closed, transport and blind pores in the porous solid allow them to adsorb drugs and release them in a more reproducible and predictable manner. Pharmaceutically exploited porous adsorbents includes, silica (mesoporous), ethylene vinyl acetate (macroporous), polypropylene foam powder (microporous), titanium dioxide (nanoporous). When porous polymeric drug delivery system is placed in contact with appropriate dissolution medium, release of drug to medium must be preceded by the drug dissolution in the water filled pores or from surface and by diffusion through the water filled channels. The porous carriers are used to improve the oral bioavailability of poorly water soluble drugs, to increase the dissolution of relatively insoluble powders and conversion of crystalline state to amorphous state.

  13. 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…

  14. 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

  15. 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

  16. 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

  17. 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

  18. Driving forces for drug loading in drug carriers.

    PubMed

    Li, Yang; Yang, Li

    2015-01-01

    The loading capacity of a drug carrier is determined essentially by intermolecular interactions between drugs and carrier materials. In this review, the process of drug loading is described in detail based on the differences in the driving force for drug incorporation, including hydrophobic interaction, electrostatic interaction, hydrogen bonding, Pi-Pi stacking and van der Waals force. Modifying drug-loading sites of carrier materials with interacting groups aiming at tailoring drug-carrier interactions is reviewed by highlighting its importance for improving in vitro properties such as the loading capacity, release behaviour and stability. Other factors affecting drug loading, methods employed to predict the encapsulation capacity and the techniques to verify intermolecular interactions are also discussed to inform the readers of all-sided information on drug-loading processes and theories. The drug carriers can be designed more reasonably with the better understanding of the nature and interacting mechanism of intermolecular interactions.

  19. 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

  20. 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.

  1. Pharmaceutical technology, biopharmaceutics and drug delivery.

    PubMed

    Youn, Yu Seok; Lee, Beom-Jin

    2011-03-01

    The 40th annual international conference of the Korean Society of Pharmaceutical Sciences and Technology on Pharmaceutical Technology, Biopharmaceutics and Drug Delivery was held on 2-3 December 2010 in Jeju Special Self-Governing Providence, Korea, to celebrate its 40th anniversary. A comprehensive review of a wide spectrum of recent topics on pharmaceutical technology, biopharmaceutics and drug delivery was presented. Invited lectures and poster presentations over 2 days were divided into six parallel sessions covering areas such as biotechnology, biopharmaceutics, drug delivery, formulation/manufacture, regulatory science and frontier science. Among these, there were two sessions related to regulatory science and biopharmaceutics that were co-sponsored by the Korea Food and Drug Administration. In fact, this conference provided an opportunity for many investigators to discuss their research, collect new information and to promote the advancement of knowledge in each pharmaceutical area. This conference report summarizes the keynote podium presentations provided by many distinguished speakers, including Gordon L Amidon of the University of Michigan.

  2. 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.

  3. 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

  4. Halloysite - interesting nanotubular carrier for drugs.

    PubMed

    Rabišková, Miloslava

    2012-12-01

    Halloysite is a naturally occurring mineral similar to kaolin, possessing a special particle shape in the form of ultramicroscopic multi-layered hollow cylinders. It is utilizable in many industrial branches and due to its advantages, e.g. biocompatibility, drug entrapment, high mechanical strength and easy natural availability also on the pharmaceutical field and in medicine. It can bind drugs on the surface or inside of tubules and increase drug stability or change its release. Surface of the tubules can be readily modified for the application in drug delivery systems. Halloysite was reported as promising material for bone implants and controlled delivery of biomacromolecules. This review is dealing with pharmaceutical and biomedical usage of this interesting material and is including original experimental work published recently.

  5. 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

  6. 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

  7. Interview with Vladimir P Torchilin: liposomal carriers for drug delivery.

    PubMed

    Torchilin, Vladimir P

    2013-05-01

    Vladimir P Torchilin is a University Distinguished Professor and Director at the Center for Pharmaceutical Biotechnology and Nanomedicine at the School of Pharmacy, Northeastern University (MA, USA). He has published over 350 original research papers and among many other awards was the recent recipient of the 2012 Bangham Award, for his contributions to the study of liposomes. Professor Torchilin spoke to Therapeutic Delivery about the progress and challenges of the field of liposomal carriers for drug delivery as well as his own career in science to date. Interview conducted by James Potticary, Assistant Commissioning Editor. PMID:23647271

  8. Organized polysaccharide fibers as stable drug carriers.

    PubMed

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

    2013-04-15

    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.

  9. 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

  10. Synthetic biology for pharmaceutical drug discovery.

    PubMed

    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

  11. 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

  12. Advancing drug discovery: a pharmaceutics perspective.

    PubMed

    Kwong, Elizabeth

    2015-03-01

    Current industry perspective of how discovery is conducted seems to be fragmented and does not have a unified overall outlook of how discovery challenges are being addressed. Consequently, well-defined processes and drug-likeness criteria are being viewed as "broken" and will not maintain future R&D productivity. In this commentary, an analysis of existing practices for defining successful development candidates resulted in a 5 "must do" list to help advance Drug Discovery as presented from a Pharmaceutics perspective. The 5 "must do" list includes: what an ideal discovery team model should look like, what criteria should be considered for the desired development candidate profile, what the building blocks of the development candidate should look like, and how to assess the development risks of the candidate.

  13. 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

  14. 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

  15. Nanostructured lipid carriers (NLCs) for drug delivery and targeting.

    PubMed

    Fang, Chia-Lang; Al-Suwayeh, Saleh A; Fang, Jia-You

    2013-01-01

    Nanostructured lipid carriers (NLCs) are drug-delivery systems composed of both solid and liquid lipids as a core matrix. It was shown that NLCs reveal some advantages for drug therapy over conventional carriers, including increased solubility, the ability to enhance storage stability, improved permeability and bioavailability, reduced adverse effect, prolonged half-life, and tissue-targeted delivery. NLCs have attracted increasing attention in recent years. This review describes recent developments in drug delivery using NLCs strategies. The structures, preparation techniques, and physicochemical characterization of NLCs are systematically elucidated in this review. The potential of NLCs to be used for different administration routes is highlighted. Special attention is paid to parenteral injection and topical delivery since these are the most common routes for investigating NLCs. Relevant issues for the introduction of NLCs to market, including pharmaceutical and cosmetic applications, are discussed. The related patents of NLCs for drug delivery are also reviewed. Finally, the future development and current obstacles needing to be resolved are elucidated. PMID:22946628

  16. 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

  17. China: current trends in pharmaceutical drug discovery.

    PubMed

    Luo, Ying

    2008-04-01

    Pharmaceutical discovery and development is expensive and highly risky, even for multinational corporations. As a developing country with limited financial resources, China has been seeking the most cost-effective means to reach the same level of innovation and productivity as Western countries in the pharmaceutical industry sector. After more than 50 years of building up talent and experience, the time for China to become a powerhouse in pharmaceutical innovation is finally approaching. Returnee scientists to China are one of the reasons for the wave of new discovery and commercialization occurring within the country. The consolidation of local Chinese pharmaceutical companies and foreign investment is also providing an agreeable environment for the evolution of a new generation of biotechnology. The opportunity for pharmaceutical innovation is also being expedited by the entry of multinational companies into the Chinese pharmaceutical market, and by the outsourcing of research from these companies to China. PMID:18379963

  18. 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

  19. Target Nanoparticles for Therapy - SANS and DLS of Drug Carrier Liposomes and Polymer Nanoparticles

    NASA Astrophysics Data System (ADS)

    Nawroth, T.; Johnson, R.; Krebs, L.; Khoshakhlagh, P.; Langguth, P.; Hellmann, N.; Goerigk, G.; Boesecke, P.; Bravin, A.; Le Duc, G.; Szekely, N.; Schweins, R.

    2016-09-01

    T arget Nano-Pharmaceutics shall improve therapy and diagnosis of severe diseases, e.g. cancer, by individual targeting of drug-loaded nano-pharmaceuticals towards cancer cells, and drug uptake receptors in other diseases. Specific ligands, proteins or cofactors, which are recognized by the diseased cells or cells of food and drug uptake, are bound to the nanoparticle surface, and thus capable of directing the drug carriers. The strategy has two branches: a) for parenteral cancer medicine a ligand set (2-5 different, surface-linked) are selected according to the biopsy analysis of the patient tissue e.g. from tumor.; b) in the oral drug delivery part the drug transport is enforced by excipients/ detergents in combination with targeting materials for cellular receptors resulting in an induced drug uptake. Both targeting nanomaterials are characterized by a combination of SANS + DLS and SAXS or ASAXS in a feedback process during development by synthesis, nanoparticle assembly and formulation.

  20. 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

  1. Liposomes as drug carriers for oral ulcers.

    PubMed

    Harsanyi, B B; Hilchie, J C; Mezei, M

    1986-09-01

    The aim of this study was to test the potential of liposomes as drug carriers to the ulcerated oral mucosa. Radioactive triamcinolone acetonide palmitate (3H-TRMAp) was encapsulated in large multilamellar lipid vesicles and served as the test lotion. 3H-TRMAp in solution served as control. Forty-six hamsters were divided into three groups. In group I, multiple confluent ulcers in both cheek pouches were treated by topical application. In group II, single ulcers on the cheeks were treated by intramucosal injection. In group III, multiple confluent ulcers were produced in the cheek pouch on one side, with a single ulcer in the contralateral cheek pouch; no drug was applied, and the tissues were prepared for histology. Hamsters were killed at three and 24 hours, respectively, after treatment. Pouches were divided into ulcerated and intact adjacent mucosa. Cheeks were divided into ulcerated mucosa and distant mucosa. Drug levels in the four mucosal portions as well as in the blood, liver, spleen, brain, and thalamic region were determined by radioactive tracer technique. At three hours, liposomal drug concentrations were lower than in control animals in the brain and the thalamic region. At 24 hours, liposomal drug values were higher than in control animals in the ulcerated mucosa and lower than in control animals in the thalamic region. Mean drug concentrations in the ulcerated mucosa were higher in group II than group I. The results parallel those of Mezei and Gulasekharam (1980, 1982); liposomes increase local and decrease systemic drug concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. 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

  3. The pharmaceutical biochemistry group: where pharmaceutical chemistry meets biology and drug delivery.

    PubMed

    Kalia, Yogeshvar N; Perozzo, Remo; Scapozza, Leonardo

    2012-01-01

    Successful drug discovery and development of new therapeutics is a long, expensive multidisciplinary process needing innovation and the integration of smart cutting edge science and technology to overcome the challenges in taking a drug from the bench to the bedside. The research activities of the Pharmaceutical Biochemistry group span the drug discovery and development process, providing an interface that brings together pharmaceutical chemistry, biochemistry, structural biology, computational chemistry and biopharmaceutics. Formulation and drug delivery are brought into play at an earlier stage when facing the perennial challenge of transforming a potent molecule in vitro into a therapeutic agent in vivo. Concomitantly, drug delivery results can be understood at a molecular level. This broad range of interdisciplinary research activities and competences enables us to address key challenges in modern drug discovery and development, provides a powerful collaborative platform for other universities and the pharmaceutical industry and an excellent training platform for pharmacists and pharmaceutical scientists who will later be involved in drug discovery and development.

  4. HDL drug carriers for targeted therapy.

    PubMed

    Liu, Xing; Suo, Rong; Xiong, Sheng-Lin; Zhang, Qing-Hai; Yi, Guang-Hui

    2013-01-16

    Plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are strongly and inversely associated with cardiovascular risk. HDL is not a simple lipid transporter, but possesses multiple anti-atherosclerosis activities because it contains special proteins, signaling lipid, and microRNAs. Natural or recombinant HDLs have emerged as potential carriers for delivering a drug to a specified target. However, HDL function also depends on enzymes that alter its structure and composition, as well as cellular receptors and membrane micro-domains that facilitate interactions with the microenvironment. In this review, four mechanisms predicted to enhance functions or targeted therapy of HDL in vivo are discussed. The first involves caveolae-mediated recruitment of HDL signal to bind their receptors. The second involves scavenger receptor class B type I (SR-BI) mediating anchoring and fluidity for signal-lipid of HDL. The third involves lecithin-cholesterol acyltransferase (LCAT) concentrating the signaling lipid at the surface of the HDL particle. The fourth involves microRNAs (miRNAs) being delivered in the blood to special targets by HDL. Exploitation of these four mechanisms will promote HDL to carry targeted drugs and increase HDL's clinical value. PMID:23063777

  5. Pharmaceutical cocrystals: the coming wave of new drug substances.

    PubMed

    Brittain, Harry G

    2013-02-01

    Solid crystalline phases containing two cocrystallized components offer a new development pathway whereby one can potentially improve the physical characteristics (i.e., equilibrium solubility, dissolution rate, solid-state stability, etc.) of a drug substance that exhibits a profile that is less than desirable. In this commentary, the topic of pharmaceutical cocrystals will be briefly explored, and a short exposition of the solubility and dissolution rate advantages that have been realized in various systems will be provided. The Guidance for Industry document recently proposed by United States Food and Drug Administration will be outlined, and its requirements explained. Finally, the subset of pharmaceutical cocrystals that consist of a drug substance and a salt of that substance (termed a salt cocrystal) will be examined to illustrate this additional class of pharmaceutical cocrystals that may offer significant scientific and regulatory advantages.

  6. 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.

  7. 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

  8. [X-ray diffractometry in the analysis of drugs and pharmaceutical forms].

    PubMed

    Bettinetti, G P

    1989-05-01

    As a consequence of the importance of solid drug substance characterization, analytical tools such as X-ray diffractometry (powder and single crystal methods) are usually employed in the pharmaceutical field. The diagnostic power of X-ray powder diffraction in identifying crystalline compounds, even in multicomponent mixtures, and in showing the non-crystalline ones, has brought about the usual characterization through the X-ray powder diffraction pattern of polymorphic, pseudopolymorphic, and amorphous drugs and of some drug-carrier systems such as solid dispersions, glass dispersions, solid surface dispersions, physical mixtures, eutectics, solid solutions, addition and inclusion compounds, etc. Moreover this technique is also used in the qualitative and quantitative analysis both of drug mixtures and dosage forms, and also in the study of relationships between crystal habit and technological characteristics of pharmaceutical formulations. Single crystal methods are employed for calculating the unit cell lenghts and angles, for indexing powder diffraction patterns, and for demonstrating the crystal and molecular structure of the drug. After a picture of the solid state properties and the X-ray characteristics, as well as of the interaction between X-rays and solid matter, the main pharmaceutical applications of X-ray diffraction are described.

  9. Two Important Polysaccharides as Carriers for Drug Delivery.

    PubMed

    Huang, Gangliang; Chen, Yingli; Li, Yue; Huang, Dan; Han, Jie; Yang, Min

    2015-01-01

    Chitosan can be used to prepare the carriers, such as nanoparticles (NPs), intelligent gels, microspheres, nano/microencapsulation, and so on. Its applications in the drug delivery are more broad. Dextran can be combined with drugs by non-covalent crosslinking method or covalent modification mode in the course of delivery. The applications of chitosan and dextran as carriers for drug delivery were summed up herein. PMID:26156418

  10. 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.

  11. 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

  12. 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.…

  13. Including carrier-mediated transport in oral uptake prediction of nutrients and pharmaceuticals in humans.

    PubMed

    O'Connor, Isabel A; Veltman, Karin; Huijbregts, Mark A J; Ragas, Ad M J; Russel, Frans G M; Hendriks, A Jan

    2014-11-01

    Most toxicokinetic models consider passive diffusion as the only mechanism when modeling the oral uptake of chemicals. However, the overall uptake of nutrients and xenobiotics, such as pharmaceuticals and environmental pollutants, can be increased by influx transport proteins. We incorporated carrier-mediated transport into a one-compartment toxicokinetic model originally developed for passive diffusion only. The predictions were compared with measured oral uptake efficiencies of nutrients and pharmaceuticals, i.e. the fraction of the chemical reaching systemic circulation. Including carrier-mediated uptake improved model predictions for hydrophilic nutrients (RMSE=10% vs. 56%, Coefficient of Efficiency CoE=0.5 vs. -9.6) and for pharmaceuticals (RMSE=21% vs. 28% and CoE=-0.4 vs. -1.1). However, the negative CoE for pharmaceuticals indicates that further improvements are needed. Most important in this respect is a more accurate estimation of vMAX and KM as well as the determination of the amount of expressed and functional transport proteins both in vivo and in vitro.

  14. 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

  15. Core competencies for pharmaceutical physicians and drug development scientists.

    PubMed

    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.

  16. 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

  17. 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.

  18. [Progress in the research of carbon nanotubes as drug carriers].

    PubMed

    Yu, Jin-gang; Huang, Ke-long; Yang, Qiao-qin; Liu, Su-qin; Tang, Jin-chun

    2008-10-01

    Research and development of new drug carriers are crucial to the research of drugs. Due to their unique hollow structure and nano-diameter, carbon nanotubes (CNTs) can be used as drug carriers. Functionalization of CNTs with peptides, proteins, nucleic acids or even drug molecules, the so obtained functionalized CNTs can be used as carriers to deliver bioactive molecules into cells without causing any toxicity. The research progress of CNTs as drug carriers in recent years is summarized, and the CNTs' cytotoxicity and their ability to penetrate cells are discussed, and the methods of functionalizing carbon nanotubes are also mentioned in the paper. Along with the advancement of CNTs in drug carriers system, the relationship between the way to functionalize CNTs and the so obtained modified CNTs' ability to penetrate into cells, including the effect of dimension, should be further studied. Preparation of functionalized CNTs with high solubility and low toxicity as drug carriers will be the main research areas in the near future. PMID:19127860

  19. Direct Analysis of Pharmaceutical Drugs Using Nano-DESI MS

    PubMed Central

    Cardoso-Palacios, Carlos

    2016-01-01

    Counterfeit pharmaceutical drugs imply an increasing threat to the global public health. It is necessary to have systems to control the products that reach the market and to detect falsified medicines. In this work, molecules in several pharmaceutical tablets were directly analyzed using nanospray desorption electrospray ionization mass spectrometry (nano-DESI MS). Nano-DESI is an ambient surface sampling technique which enables sampling of molecules directly from the surface of the tablets without any sample pretreatment. Both the active pharmaceutical ingredients (APIs) and some excipients were detected in all analyzed tablets. Principal component analysis was used to analyze mass spectral features from different tablets showing strong clustering between tablets with different APIs. The obtained results suggest nano-DESI MS as future tool for forensic analysis to discern APIs present in unknown tablet samples. PMID:27766177

  20. 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

  1. [Strategies for pharmaceutical research and development. II. Generic drugs].

    PubMed

    Kuchar, M

    1996-07-01

    When the patent protection is terminated, the original registered-mark preparation becomes a generic drug, which results in a decrease in its price as compared with the original pharmaceutical. The effects of changes in price relation are discussed from the viewpoint of the generic firms and the manufacturers of original preparations. The differences in the insurance system and legislative regulations of the registration of generic preparations can markedly the size influence of the share of generic drugs in the total consumption of drugs. The future development of generic drugs from a general viewpoint is discussed in relation to the contemporary extensive expiration of patent protection of drugs. The hitherto results are summed up and the topics for the present strategy of the development of generic drugs in the Research Institute for Pharmacy and Biochemistry, or in the Czech Republic, respectively are discussed.

  2. 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

  3. 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

  4. 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.

  5. [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.

  6. Drug-related hospital admissions in a generic pharmaceutical system.

    PubMed

    Zargarzadeh, A H; Emami, M H; Hosseini, F

    2007-01-01

    1. Generically based pharmaceutical systems exist in a few countries of the world, such as Iran. Most developed countries have free market pharmaceutical systems. Drug-related problems (DRP) have been reported mostly in the Western world but few data are available for generic systems. In this study, we tried to measure the prevalence of drug-related problems leading to hospital admissions in Isfahan, Iran. 2. One thousand consecutive hospital admissions in three major teaching hospitals were studied for a period of 6 months for the presence of DRP as a cause of hospital admissions. Two subcategories of DRP were considered: (i) drug therapy failure; and (ii) adverse drug reactions. Preventability and outcome measures were also assessed. Medications responsible for DRP were classified according to the Anatomic Therapeutic Chemical (ATC) classification of the World Health Organization. 3. Of the 1000 admissions studied, 115 (11.5%) were owing to DRP, 81% as a result of drug therapy failure and 19% as adverse drug reactions. A total of 106 out of the 115 DRP cases (92%) were either preventable or probably preventable, most of which had to do with either prescriber or patient error. An overview of DRP showed that 58.3% resulted in complete recovery, 33.9% in relative recovery and 7.8% in death. Close to 1% of hospital admissions resulted in DRP-related deaths. 4. The overall prevalence of hospital admissions caused by DRP is similar to that in free market pharmaceutical systems. The high preventability rate of these problems should alert clinicians and policy makers to design strategies to curtail this. Also, reasons for differences in subtypes of DRP between the results of this study and those of the literature from free market systems needs to be investigated further.

  7. 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.

  8. 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

  9. Drug delivery to the brain--realization by novel drug carriers.

    PubMed

    Müller, Rainer H; Keck, Cornelia M

    2004-05-01

    Delivery of drugs to the brain is still a major challenge. Successful delivery across the bloodbrain barrier has only been achieved in some cases, e.g., using pro-drugs. The review describes the delivery to the brain using nanoparticulate drug carriers in combination with the novel targeting principle of "differential protein adsorption" (PathFinder technology). The PathFinder technology exploits proteins in the blood which adsorb onto the surface of intravenously injected carriers for targeting. Apolipoprotein E is the targeting moiety for the delivery of particles to the endothelials of the blood-brain barrier. To reach therapeutic drug level in the brain, nanoparticulate drug carriers with sufficiently high loading capacity are reviewed, including drug nanocrystals (nanosuspensions), lipid drug conjugate (LDC) nanoparticles and lipid nanoparticles (solid lipid nanoparticles-SLN, nanostructured lipid carriers-NLC). The features are described, including regulatory aspects and large scale production. PMID:15503432

  10. Drug delivery to the brain--realization by novel drug carriers.

    PubMed

    Müller, Rainer H; Keck, Cornelia M

    2004-05-01

    Delivery of drugs to the brain is still a major challenge. Successful delivery across the bloodbrain barrier has only been achieved in some cases, e.g., using pro-drugs. The review describes the delivery to the brain using nanoparticulate drug carriers in combination with the novel targeting principle of "differential protein adsorption" (PathFinder technology). The PathFinder technology exploits proteins in the blood which adsorb onto the surface of intravenously injected carriers for targeting. Apolipoprotein E is the targeting moiety for the delivery of particles to the endothelials of the blood-brain barrier. To reach therapeutic drug level in the brain, nanoparticulate drug carriers with sufficiently high loading capacity are reviewed, including drug nanocrystals (nanosuspensions), lipid drug conjugate (LDC) nanoparticles and lipid nanoparticles (solid lipid nanoparticles-SLN, nanostructured lipid carriers-NLC). The features are described, including regulatory aspects and large scale production.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Application of hydroxyapatite-sol as drug carrier.

    PubMed

    Kano, S; Yamazaki, A; Otsuka, R; Ohgaki, M; Akao, M; Aoki, H

    1994-01-01

    The application of hydroxyapatite-sol as a drug carrier is being developed. Hydroxyapatite-sol which is a suspension consisting of hydroxyapatite nano-crystals, was synthesized using an ultrasonic homogenizer. The size of the crystals was 40 x 15 x 10 mm3 on average and their specific surface area was 100 m2/g. An amount of a glycoside antibiotics adsorbed onto hydroxyapatite nano-crystals was measured. The drug adsorbed 0.2 mg per 1 mg of hydroxyapatite. The affect of the drug adsorbed onto the hydroxyapatite was investigated using cancer cells. The drug, adsorbed onto the hydroxyapatite nano-crystals, inhibited cancer cell growth.

  18. 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

  19. 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

  20. Amphiphilogels as drug carriers: effects of drug incorporation on the gel and on the active drug.

    PubMed

    Jibry, Nadeen; Sarwar, Tanzeem; Murdan, Sudaxshina

    2006-02-01

    Amphiphilogels (a subset of organogels) are being studied as drug carriers in our laboratories. In this paper, the effects of drug incorporation on the drugs and the gels are discussed. Amphiphilogels were prepared by heating a mixture of the gelator (sorbitan monostearate or sorbitan monopalmitate) and the liquid (e.g. Tweens or liquid Spans) to form a solution/dispersion, which was cooled to the gel state. Drugs were dissolved by heating a mixture of the drug and the gel and cooling the resulting solution. Hydrophilic gels (composed of hydrophilic Tweens as the liquid) were more effective solvents than hydrophobic ones (composed of hydrophobic Span 20 or 80 liquids). The latter's solvent capacity could, however, be increased by the inclusion of co-solvents, such as propylene glycol and ethanol. Drug incorporation at 10% w/w did not cause any detrimental changes in gel stability, while the drug's release rate was dependent on its concentration and on the nature of the gel's liquid component (which influences drug solubility), but not on gelator concentration or on the method of drug incorporation. This study shows the importance of the nature of the gels' liquid component and the possibility of using hydrophilic amphiphilogels as solvents for poorly water-soluble drugs.

  1. Nanoparticles: Emerging carriers for drug delivery

    PubMed Central

    Mudshinge, Sagar R.; Deore, Amol B.; Patil, Sachin; Bhalgat, Chetan M.

    2011-01-01

    The core objective of nanoparticles is to control and manipulate biomacromolecular constructs and supramolecular assemblies that are critical to living cells in order to improve the quality of human health. By definition, these constructs and assemblies are nanoscale and include entities such as drugs, proteins, DNA/RNA, viruses, cellular lipid bilayers, cellular receptor sites and antibody variable regions critical for immunology and are involved in events of nanoscale proportions. The emergence of such nanotherapeutics/diagnostics will allow a deeper understanding of human longevity and human ills that include cancer, cardiovascular disease and genetic disorders. A technology platform that provides a wide range of synthetic nanostructures that may be controlled as a function of size, shape and surface chemistry and scale to these nanotechnical dimensions will be a critical first step in developing appropriate tools and a scientific basis for understanding nanoparticles. PMID:23960751

  2. 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

  3. Injectable nanomaterials for drug delivery: carriers, targeting moieties, and therapeutics.

    PubMed

    Webster, David M; Sundaram, Padma; Byrne, Mark E

    2013-05-01

    Therapeutics such as nucleic acids, proteins/peptides, vaccines, anti-cancer, and other drugs have disadvantages of low bio-availability, rapid clearance, and high toxicity. Thus, there is a significant need for the development of efficient delivery methods and carriers. Injectable nanocarriers have received much attention due to their vast range of structures and ability to contain multiple functional groups, both within the bulk material and on the surface of the particles. Nanocarriers may be tailored to control drug release and/or increase selective cell targeting, cellular uptake, drug solubility, and circulation time, all of which lead to a more efficacious delivery and action of therapeutics. The focus of this review is injectable, targeted nanoparticle drug delivery carriers highlighting the diversity of nanoparticle materials and structures as well as highlighting current therapeutics and targeting moieties. Structures and materials discussed include liposomes, polymersomes, dendrimers, cyclodextrin-containing polymers (CDPs), carbon nanotubes (CNTs), and gold nanoparticles. Additionally, current clinical trial information and details such as trial phase, treatment, active drug, carrier sponsor, and clinical trial identifier for different materials and structures are presented and discussed.

  4. 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

  5. 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

  6. Anionic cyclodextrins as versatile hosts for pharmaceutical nanotechnology: Synthesis, drug delivery, enantioselectivity, contrast agents for MRI.

    PubMed

    Mavridis, Irene M; Yannakopoulou, Konstantina

    2015-08-15

    The review presents a full library of single-isomer primary rim per-carboxylate- and per-sulfate-α-, -β- and -γ-cyclodextrin (CD) derivatives and their potential for pharmaceutical nanotechnology. Recent advances in cyclodextrin chemistry have enabled robust methods for the synthesis of single-isomer anionic CDs. Numerous nanobio-applications have been already reported for these negatively charged derivatives, which alone or in combination with other biodegradable molecular platforms can become important carriers for targeted drug delivery and release. Specialized applications are also discussed, such as chiral separations, as well as the ability of per-6-carboxylated-cyclodextrins to coordinate with metal cations and especially with lanthanide cations that makes them candidates as contrast agents for Magnetic Resonance Imaging.

  7. New, highly efficient formulation of diclofenac for the topical, transdermal administration in ultradeformable drug carriers, Transfersomes.

    PubMed

    Cevc, G; Blume, G

    2001-10-01

    Transfenac, a lotion-like formulation of diclofenac, is described. It consists of pharmaceutically acceptable ingredients and mediates the agent transport through intact skin and into the target tissues. Therapeutically meaningful drug concentrations in the target tissue are reached even when the administered drug dose in Transfenac is below 0.5 mg/kg body weight. Ultradeformable agent carriers, called Transfersomes, form the basis of Transfenac. These Transfersomes are proposed to cross the skin spontaneously under the influence of transepidermal water activity gradient (see [Biochim. Biophys. Acta 1104 (1992) 226]). Diclofenac association with ultradeformable carriers permits it to have a longer effect and to reach 10-times higher concentrations in the tissues under the skin in comparison with the drug from a commercial hydrogel. For example, Transfenac achieves intramuscular agent concentrations between 0.5 and 2 microg/g and 2 and 20 microg/g at t=12 h, depending on the tissue depth, when it is administered in the dose range 0.25-2 mg/kg of rat body weight. A much higher drug concentration in a hydrogel (1.25-10 mg/kg body weight) creates the drug level of only <0.5 microg/g in the muscle. The drug concentration in the rat patella for these two types of formulation is between 1 microg/g and 5 microg/g or 0.4 microg/g, respectively. The relative advantage of diclofenac delivery by means of ultradeformable carriers increases with the treated muscle thickness and with decreasing drug dose, as seen in mice, rats and pigs; this can be explained by assuming that the drug associated with carriers is cleared less efficiently by the dermal capillary plexus. In pigs it suffices to use 0.3 mg of diclofenac in highly deformable vesicles per kg body weight, spread over an area of 25 cm(2), to ensure therapeutic drug concentration in a 5-cm thick muscle specimen, collected under the agent application site. When the drug is used in a hydrogel at 8 times higher dose, the

  8. 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

  9. [Liposomes as non-viral carriers for genetic drugs].

    PubMed

    Meissner, Justyna M; Toporkiewicz, Monika; Matusewicz, Lucyna; Machnicka, Beata

    2016-01-01

    Methods in cancer therapy particularly in recent years, are rapidly changing, due to the need of design of new, more effective therapeutic strategies. Very promising approach to treatment of the neoplastic diseases is antisense gene therapy. Due to the low toxicity of treatment and eliminating not only the symptoms but also the molecular causes of the disease it may represent a breakthrough in cancer therapies. Delivery of a therapeutic DNA or RNA oligonucleotides to the target cells in vivo requires suitable carrier system. Non-viral drug carriers are increasingly used in new systems of targeted gene therapy. This review presents new generation of non-viral carriers, and is focused on immunoliposomes finding potential application in targeted gene therapy.

  10. 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

  11. Molecular Mechanisms of Pharmaceutical Drug Binding into Calsequestrin

    PubMed Central

    Subra, Arun K.; Nissen, Mark S.; Lewis, Kevin M.; Muralidharan, Ashwin K.; Sanchez, Emiliano J.; Milting, Hendrik; Kang, ChulHee

    2012-01-01

    Calsequestrin (CASQ) is a major Ca2+-storage/buffer protein present in the sarcoplasmic reticulum of both skeletal (CASQ1) and cardiac (CASQ2) muscles. CASQ has significant affinity for a number of pharmaceutical drugs with known muscular toxicities. Our approach, with in silico molecular docking, single crystal X-ray diffraction, and isothermal titration calorimetry (ITC), identified three distinct binding pockets on the surface of CASQ2, which overlap with 2-methyl-2,4-pentanediol (MPD) binding sites observed in the crystal structure. Those three receptor sites based on canine CASQ1 crystal structure gave a high correlation (R2 = 0.80) to our ITC data. Daunomycin, doxorubicin, thioridazine, and trifluoperazine showed strong affinity to the S1 site, which is a central cavity formed between three domains of CASQ2. Some of the moderate-affinity drugs and some high-affinity drugs like amlodipine and verapamil displayed their binding into S2 sites, which are the thioredoxin-like fold present in each CASQ domain. Docking predictions combined with dissociation constants imply that presence of large aromatic cores and less flexible functional groups determines the strength of binding affinity to CASQ. In addition, the predicted binding pockets for both caffeine and epigallocatechin overlapped with the S1 and S2 sites, suggesting competitive inhibition by these natural compounds as a plausible explanation for their antagonistic effects on cardiotoxic side effects. PMID:23203067

  12. Novel pectin-based carriers for colonic drug delivery.

    PubMed

    Zhang, Wujie; Mahuta, Kirsten Mary; Mikulski, Brandon Anthony; Harvestine, Jenna Nicole; Crouse, James Zachary; Lee, Jung Chull; Kaltchev, Matey Georgiev; Tritt, Charles Samuel

    2016-01-01

    Pectin-based hydrogel carriers have been studied and shown to have promising applications for drug delivery to the lower GI tract, especially to the colonic region. However, making sure these hydrogel carriers can pass through the upper GI tract and reach the targeted regions, after oral administration, still remains a challenge to overcome. A solution to this problem is to promote stronger cross-linking interactions within the pectin-based hydrogel network. The combined usage of a divalent cation (Ca(2+)) and the cationic biopolymer oligochitosan has shown to improve the stability of pectin-based hydrogel systems - suggesting that these two cross-linkers may be used to eventually help improve pectin-based hydrogel systems for colonic drug delivery methods.

  13. Drug carrier systems for solubility enhancement of BCS class II drugs: a critical review.

    PubMed

    Kumar, Sumit; Bhargava, Deepak; Thakkar, Arti; Arora, Saahil

    2013-01-01

    Poor aqueous solubility impedes a drug's bioavailability and challenges its pharmaceutical development. Pharmaceutical development of drugs with poor water solubility requires the establishment of a suitable formulation layout among various techniques. Various approaches have been investigated extensively to improve the aqueous solubility and poor dissolution rate of BCS class II and IV drugs. In this literature review, novel formulation options, particularly for class II drugs designed for applications such as micronization, self-emulsification, cyclodextrin complexation, co-crystallisation, super critical fluid technology, solubilisation by change in pH, salt formation, co-solvents, melt granulation, and solid dispersion, liposomal/niosomal formulations, are discussed in detail to introduce biopharmaceutical challenges and recent approaches to facilitate more efficient drug formulation and development. PMID:23614647

  14. 76 FR 72955 - Wyeth Pharmaceuticals, Inc.; Withdrawal of Approval of a New Drug Application for MYLOTARG

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... HUMAN SERVICES Food and Drug Administration Wyeth Pharmaceuticals, Inc.; Withdrawal of Approval of a New Drug Application for MYLOTARG AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of a new drug application (NDA) for...

  15. Encapsulation of cannabinoid drugs in nanostructured lipid carriers.

    PubMed

    Esposito, Elisabetta; Drechsler, Markus; Cortesi, Rita; Nastruzzi, Claudio

    2016-05-01

    This study describes the development and optimization of a method to encapsulate the potent and expensive cannabinoids drugs in nanostructured lipid carriers; namely, URB597, AM251 and rimonabant have been considered. NLC production by melt and ultrasonication protocol has been specifically designed to optimize nanoparticle recovery and drug encapsulation efficiency. Special care has been devoted to the modality of oil and water phase emulsification and the entire production has been studied and discussed. NLC recovery, morphology, dimensional distribution and encapsulation efficiency are presented. PMID:26952905

  16. 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.

  17. 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

  18. Biodegradable Particulate Carrier Formulation and Tuning for Targeted Drug Delivery.

    PubMed

    Tammam, Salma N; Azzazy, Hassan M E; Lamprecht, Alf

    2015-04-01

    Biodegradable micro- and nanoparticles have the potential to reform the drug development landscape by improving drug solubility, changing undesirable pharmacokinetics, realizing the benefits of new molecules arising from genomic and proteomic research, and increasing drug localization in target organs and tissues; i.e., drug targeting. This review provides an overview of the in vivo fate of biodegradable particulate carriers following administration via several routes, as well as how the patient's health state, disease pathophysiology and particle physicochemical properties affect such fates. It also discusses some of the widely used biodegradable polymers, their in vivo biochemical degradation, methods of nanoparticle formulation from such polymers and finally, how such methods could be tailored to achieve targeted delivery to specified tissues both passively and actively.

  19. Porous hydroxyapatite tablets as carriers for low-dosed drugs.

    PubMed

    Cosijns, A; Vervaet, C; Luyten, J; Mullens, S; Siepmann, F; Van Hoorebeke, L; Masschaele, B; Cnudde, V; Remon, J P

    2007-09-01

    The present study evaluated an innovative technique for the manufacturing of low-dosed tablets. Tablets containing hydroxyapatite and a pore forming agent (50% (w/w) Avicel PH 200/20, 37.5% and 50% corn starch/37.5% sorbitol) were manufactured by direct compression followed by sintering. The influence of pore forming agent (type and concentration), sinter temperature and sinter time on tablet properties was investigated. Sintering (1250 degrees C) revealed tablets with an acceptable friability (<1%). Using 50% (w/w) Avicel PH 200 as pore forming agent resulted in tablets combining the highest porosity (50%) and the highest median pore diameter (5 microm). Aqueous drug solutions (metoprolol tartrate, riboflavin sodium phosphate) were spiked on the tablet surface. The maximum volume of drug solution absorbed was limited (2x100 microl), revealing that these porous carriers were ideal for low dosed formulations. Drug release from the tablets was slow, independent of the drug. To accelerate drug release, tablets were manufactured using a modified gelcasting technique yielding tablets with a median pore size of 60 and 80 microm. Release from these tablets was drastically increased indicating that the permeability of the tablets was influenced by the pore size, shape and connectivity of the porous network. Changing and controlling these parameters made it possible to obtain drug delivery systems providing different drug delivery behaviour.

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

    PubMed

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

    2016-01-01

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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. Thermally Responsive Hydrogel Blends: A General Drug Carrier Model for Controlled Drug Release.

    PubMed

    Ma, Chongbo; Shi, Ye; Pena, Danilo A; Peng, Lele; Yu, Guihua

    2015-06-15

    Thermally responsive hydrogels have drawn significant research attention recently because of their simple use as drug carrier at human body temperature. Here we design a hybrid hydrogel that incorporates a hydrophilic polymer, polyethyleneimine (PEI), into the thermally responsive hydrogel poly(N-isopropylacrylamide) (PNIPAm), as a general drug carrier model for controlled drug release. In this work, on one hand, PEI modifies the structure and the size of the pores in the PNIPAm hydrogel. On the other hand, PEI plays an important role in tuning the water content in the hydrogel and controls the water release rate of the hydrogel below the lower critical solution temperature (LCST), resulting in a tunable release rate of the drugs at human body temperature (37 °C). Different release rates are shown as different amounts of PEI are incorporated. PEI controls the release rate, dependent on the charge characteristics of the drugs. The hydrogel blends described in this work extend the concept of a general drug carrier for loading both positively and negatively charged drugs, as well as the controlled release effect.

  6. [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.

  7. [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.

  8. [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

  9. 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

  10. 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

  11. 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.

  12. 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).

  13. 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

  14. 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

  15. The effect of pharmaceutical patent term length on research and development and drug expenditures in Canada.

    PubMed

    Grootendorst, Paul; Matteo, Livio Di

    2007-02-01

    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.

  16. Preparation of bovine serum albumin nanospheres as drug targeting carriers.

    PubMed

    Nakagawa, Y; Takayama, K; Ueda, H; Machida, Y; Nagai, T

    1987-12-01

    Bovine serum albumin nanospheres (BSA-NS) of mean diameter about 170 nm were prepared by means of the tanning method with glutaraldehyde, and their efficacy as drug targeting carriers was evaluated. To gain insight of biodegradability, BSA microspheres (BSA-MS) were first administered to rats and their distributions in the lungs and liver were observed by a scanning electron microscope. A large amount of BSA-MS was found in the lungs and their surface was slightly degraded at 1 week after the administration. For investigating biocompatibility, the weight increase of the spleen and liver was measured after the administration of the BSA-NS to mice. The spleen weight of the group receiving BSA-NS was equivalent to that of the control group, though the liver weight was significantly increased. It was observed that conjugates of BSA-NS with antibody selectively concentrated on the surface of Sepharose beads which were coated with antigen.

  17. 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

  18. 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

  19. Peering into the pharmaceutical "pipeline": investigational drugs, clinical trials, and industry priorities.

    PubMed

    Fisher, Jill A; Cottingham, Marci D; Kalbaugh, Corey A

    2015-04-01

    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 2477 different drugs in 4182 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 was 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.

  20. 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

  1. 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.

  2. Natural attenuation of pharmaceuticals and an illicit drug in a laboratory column experiment.

    PubMed

    Greenhagen, Andrew M; Lenczewski, Melissa E; Carroll, Monica

    2014-11-01

    Trace amounts of pharmaceutical compounds have been detected in waters across the United States. Many compounds are released as the result of human ingestion and subsequent excretion of over-the-counter and prescription medications, and illicit drugs. This research utilized columns (30×30cm) of sand and undisturbed fine-grained sediments to simulate injection of wastewater containing pharmaceuticals and an illicit drug, such as would be found in a septic system, leaky sewer, or landfill. The columns were placed in a temperature-controlled laboratory and each was injected with natural groundwater containing known concentrations of caffeine, methamphetamine, and acetaminophen. Natural attenuation of each chemical was observed in all columns. The highest amount removed (approximately 90%) occurred in the undisturbed column injected with methamphetamine, compared with little reduction in the sand column. When the suite of drugs was injected, loss of methamphetamine was less than when methamphetamine was injected alone. The subsurface sediments exhibit the ability to remove a substantial amount of the injected pharmaceuticals and illicit drug; however, complete removal was not achieved. There was little attenuation of injected pharmaceuticals in the sand column which demonstrates a concern for water quality in the environment if pharmaceuticals were to contaminate a sandy aquifer. Understanding the transport of pharmaceuticals in the subsurface environment is an important component of protecting drinking water supplies from contamination.

  3. 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

  4. [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

  5. 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

  6. 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

  7. Polymeric vesicles: from drug carriers to nanoreactors and artificial organelles.

    PubMed

    Tanner, Pascal; Baumann, Patric; Enea, Ramona; Onaca, Ozana; Palivan, Cornelia; Meier, Wolfgang

    2011-10-18

    One strategy in modern medicine is the development of new platforms that combine multifunctional compounds with stable, safe carriers in patient-oriented therapeutic strategies. The simultaneous detection and treatment of pathological events through interactions manipulated at the molecular level offer treatment strategies that can decrease side effects resulting from conventional therapeutic approaches. Several types of nanocarriers have been proposed for biomedical purposes, including inorganic nanoparticles, lipid aggregates, including liposomes, and synthetic polymeric systems, such as vesicles, micelles, or nanotubes. Polymeric vesicles--structures similar to lipid vesicles but created using synthetic block copolymers--represent an excellent candidate for new nanocarriers for medical applications. These structures are more stable than liposomes but retain their low immunogenicity. Significant efforts have been made to improve the size, membrane flexibility, and permeability of polymeric vesicles and to enhance their target specificity. The optimization of these properties will allow researchers to design smart compartments that can co-encapsulate sensitive molecules, such as RNA, enzymes, and proteins, and their membranes allow insertion of membrane proteins rather than simply serving as passive carriers. In this Account, we illustrate the advances that are shifting these molecular systems from simple polymeric carriers to smart-complex protein-polymer assemblies, such as nanoreactors or synthetic organelles. Polymeric vesicles generated by the self-assembly of amphiphilic copolymers (polymersomes) offer the advantage of simultaneous encapsulation of hydrophilic compounds in their aqueous cavities and the insertion of fragile, hydrophobic compounds in their membranes. This strategy has permitted us and others to design and develop new systems such as nanoreactors and artificial organelles in which active compounds are simultaneously protected and allowed to

  8. 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.

  9. 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

  10. 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

  11. [PHARMACEUTICAL INDUSTRY AND PERSONALIZED MEDICINE: A PARADIGM SHIFT IN THE DEVELOPMENT OF NEW DRUGS].

    PubMed

    Scheen, A J

    2015-01-01

    The cost of pharmacotherapy is increasing in the health care budget. The pharmaceutical industry is facing the exhaustion of medications that are largely prescribed and have a high profitability (blockbusters). Because of patient heterogeneity, there is a great interindividual variability of the responses to drug therapy. Thus, it is essential to better detect potential to avoid waste of resources resulting from the prescription of expensive drugs to poor responders. The development of personalized medicine, or precision medicine, certainly offers opportunities to the pharmaceutical industry, but also exposes it to new big challenges.

  12. 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

  13. Synthetic biology approaches in drug discovery and pharmaceutical biotechnology

    PubMed Central

    2010-01-01

    Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology. PMID:20396881

  14. 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

    2016-01-01

    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

  15. Effectiveness of various drug carriers in controlled release formulations of raloxifene HCl prepared by melt mixing.

    PubMed

    Bikiaris, Dimitrios; Karavelidis, Vassilios; Karavas, Evangelos

    2009-10-01

    In the present study solid dispersions of Raloxifene HCl were prepared by melt mixing. As drug carriers, biodegradable/biocompatible aliphatic polyesters were used. These formulations were compared to those based on extensively used drug carriers such as PEG and Gelucire 50/13. The used aliphatic polyesters namely poly(propylene succinate) (PPSu) and poly(propylene adipate) (PPAd) were prepared by melt polycondensation. The polyesters have melting points close to human body temperature and were used for first time as drug carries. Polymer cytocompatibility based on HUVEC cells viability in the presence of increasing concentrations of polymer was investigated and it was found that PPSu and PPAd exhibit comparable cytocompatibility with poly(dl-lactide). The physical state of solid dispersions was evaluated by FTIR, SEM and XRD techniques. In all cases the interactions between drug and carriers are limited and thus the dispersed drug was mainly in the crystalline state. SEM revealed that the particles size of the dispersed drug increases with increasing the drug amount. The release behavior of the drug is affected from both the drug amount and the kind of the used carrier. The drug is released almost immediately from PEG formulations while Gelucire results in sustained release. In formulations that polyesters were used as drug carriers the release is slower. PMID:19751201

  16. 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

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

    PubMed

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

    2005-01-01

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

  18. 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

  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

    ... HUMAN SERVICES Food and Drug Administration Wyeth Pharmaceuticals, Inc.; Withdrawal of Approval of a New Drug Application for DURACT Capsules AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of a new drug application (NDA)...

  20. 76 FR 59144 - Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 27 New Drug Applications and 58...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-23

    ... HUMAN SERVICES Food and Drug Administration Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 27 New Drug Applications and 58 Abbreviated New Drug Applications; Correction AGENCY: Food and... document withdrew approval of 27 new drug applications (NDAs) and 58 abbreviated new drug...

  1. 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

    ... HUMAN SERVICES Food and Drug Administration AstraZeneca Pharmaceuticals LP; Withdrawal of Approval of a New Drug Application for IRESSA AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of a new drug application (NDA)...

  2. [Drugs and pharmaceutical episodes in "Sazae-San": Japanese comic strips in 1940s-1970s].

    PubMed

    Goino, Masahiko

    2009-01-01

    This is a report on episodes with references to drugs and pharmaceuticals in one of the most famous Japanese comic strips, "Sazae-san", in the period from 1945 to 1974. There were 111 episodes of "Sazae-san" including references to drugs and pharmaceuticals in this period. In the period from 1945 to 1954, there were some references to pharmacists and pharmacies but only a small number of references in the period from 1965 to 1974. In the period from 1945 to 1954, there were references to disinfectants and insecticides in the hygienic chemistry field. However, in the period from 1965 to 1974, there were references to environmental problems, food additives and agricultural chemicals. As drug development has progressed, the number of references to practical drugs in "Sazae-san" has decreased over the period from 1945-1974.

  3. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... provided after the drug is dispensed at the point of sale or, in the case of dispensing by mail order, at... 42 Public Health 3 2012-10-01 2012-10-01 false Public disclosure of pharmaceutical prices for... OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) VOLUNTARY MEDICARE...

  4. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... provided after the drug is dispensed at the point of sale or, in the case of dispensing by mail order, at... 42 Public Health 3 2014-10-01 2014-10-01 false Public disclosure of pharmaceutical prices for... OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) VOLUNTARY MEDICARE...

  5. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... provided after the drug is dispensed at the point of sale or, in the case of dispensing by mail order, at... 42 Public Health 3 2013-10-01 2013-10-01 false Public disclosure of pharmaceutical prices for... OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) VOLUNTARY MEDICARE...

  6. Coexistence of passive and carrier-mediated processes in drug transport.

    PubMed

    Sugano, Kiyohiko; Kansy, Manfred; Artursson, Per; Avdeef, Alex; Bendels, Stefanie; Di, Li; Ecker, Gerhard F; Faller, Bernard; Fischer, Holger; Gerebtzoff, Grégori; Lennernaes, Hans; Senner, Frank

    2010-08-01

    The permeability of biological membranes is one of the most important determinants of the pharmacokinetic processes of a drug. Although it is often accepted that many drug substances are transported across biological membranes by passive transcellular diffusion, a recent hypothesis speculated that carrier-mediated mechanisms might account for the majority of membrane drug transport processes in biological systems. Based on evidence of the physicochemical characteristics and of in vitro and in vivo findings for marketed drugs, as well as results from real-life discovery and development projects, we present the view that both passive transcellular processes and carrier-mediated processes coexist and contribute to drug transport activities across biological membranes.

  7. 'Pro et contra' ionic liquid drugs - Challenges and opportunities for pharmaceutical translation.

    PubMed

    Balk, Anja; Holzgrabe, Ulrike; Meinel, Lorenz

    2015-08-01

    Ionic liquids (ILs) are organic salts with a melting point below 100°C. Active pharmaceutical ingredients (APIs) are transformed into ILs by combining them with typically large yet charged counterions. ILs hold promise to build a large design space for relevant pharmaceutical parameters, particularly for poorly water soluble drugs. It is for this wide design space that ILs may be the entry into the fascinating vision of modifying physico-chemical properties without the need to structurally modify the active pharmaceutical ingredient itself. This extremely intriguing pharmaceutical option is critically discussed including its potential and limitations. The review is starting off with an introduction to the metathesis and characterization of ILs, and leads over to examples for pharmaceutical application, including enhancement of dissolution rate and kinetic solubility and hygroscopicity adaptation, respectively. Tuning biopharmaceutics and toxicology by proper IL design is another focus. The review connects the interrelated chemical, physical, pharmaceutical, and toxicological outcome of API-ILs, serving as guidance for the formulation scientist who aims at expanding ones armamentarium for poorly water soluble APIs while avoiding structural modification, thereof.

  8. 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

  9. 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

  10. Dental gel viscosity parameters and pharmaceutical availability of non-steroidal anti-inflammatory drugs.

    PubMed

    Kołodziejska, Justyna; Zgoda, Marian Mikołaj

    2004-01-01

    Model prescription for dental anti-inflammatory gels with carboxymethylcellulose sodium salt and non-ionic surfactants have been worked out. Viscosity parameters of 10 variant gel forms were investigated and an attempt on their interpretation was undertaken in relation to pharmaceutical availability of non-steroidal anti-inflammatory drugs (diclofenac, ibuprofen sodium). Viscosity tests demonstrated higher pharmaceutical availability of ibuprofen sodium than of diclofenac sodium particularly from model gels with surfactants of low number of oxyethylene segments in the structure. The above has been confirmed by in vitro studies on the kinetics of therapeutic agent penetration into external compartment.

  11. A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development.

    PubMed

    Robinson, Sally; Delongeas, Jean-Luc; Donald, Elizabeth; Dreher, David; Festag, Matthias; Kervyn, Sophie; Lampo, Ann; Nahas, Kamil; Nogues, Vicente; Ockert, Deborah; Quinn, Kirsty; Old, Sally; Pickersgill, Nigel; Somers, Kev; Stark, Claudia; Stei, Peter; Waterson, Lynne; Chapman, Kathryn

    2008-04-01

    Regulatory guidelines indicate acute toxicity studies in animals are considered necessary for pharmaceuticals intended for human use. This is the only study type where lethality is mentioned as an endpoint. The studies are carried out, usually in rodents, to support marketing of new drugs and to identify the minimum lethal dose. A European initiative including 18 companies has undertaken an evidence-based review of acute toxicity studies and assessed the value of the data generated. Preclinical and clinical information was shared on 74 compounds. The analysis indicated acute toxicity data was not used to (i) terminate drugs from development (ii) support dose selection for repeat dose studies in animals or (iii) to set doses in the first clinical trials in humans. The conclusion of the working group is that acute toxicity studies are not needed prior to first clinical trials in humans. Instead, information can be obtained from other studies, which are performed at more relevant doses for humans and are already an integral part of drug development. The conclusions have been discussed and agreed with representatives of regulatory bodies from the US, Japan and Europe.

  12. 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

  13. Ceramic-based nanoparticles entrapping water-insoluble photosensitizing anticancer drugs: a novel drug-carrier system for photodynamic therapy.

    PubMed

    Roy, Indrajit; Ohulchanskyy, Tymish Y; Pudavar, Haridas E; Bergey, Earl J; Oseroff, Allan R; Morgan, Janet; Dougherty, Thomas J; Prasad, Paras N

    2003-07-01

    A novel nanoparticle-based drug carrier for photodynamic therapy is reported which can provide stable aqueous dispersion of hydrophobic photosensitizers, yet preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. A multidisciplinary approach is utilized which involves (i) nanochemistry in micellar cavity to produce these carriers, (ii) spectroscopy to confirm singlet oxygen production, and (iii) in vitro studies using tumor cells to investigate drug-carrier uptake and destruction of cancer cells by photodynamic action. Ultrafine organically modified silica-based nanoparticles (diameter approximately 30 nm), entrapping water-insoluble photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide, have been synthesized in the nonpolar core of micelles by hydrolysis of triethoxyvinylsilane. The resulting drug-doped nanoparticles are spherical, highly monodispersed, and stable in aqueous system. The entrapped drug is more fluorescent in aqueous medium than the free drug, permitting use of fluorescence bioimaging studies. Irradiation of the photosensitizing drug entrapped in nanoparticles with light of suitable wavelength results in efficient generation of singlet oxygen, which is made possible by the inherent porosity of the nanoparticles. In vitro studies have demonstrated the active uptake of drug-doped nanoparticles into the cytosol of tumor cells. Significant damage to such impregnated tumor cells was observed upon irradiation with light of wavelength 650 nm. Thus, the potential of using ceramic-based nanoparticles as drug carriers for photodynamic therapy has been demonstrated.

  14. Interfacing materials science and biology for drug carrier design.

    PubMed

    Such, Georgina K; Yan, Yan; Johnston, Angus P R; Gunawan, Sylvia T; Caruso, Frank

    2015-04-01

    Over the last ten years, there has been considerable research interest in the development of polymeric carriers for biomedicine. Such delivery systems have the potential to significantly reduce side effects and increase the bioavailability of poorly soluble therapeutics. The design of carriers has relied on harnessing specific variations in biological conditions, such as pH or redox potential, and more recently, by incorporating specific peptide cleavage sites for enzymatic hydrolysis. Although much progress has been made in this field, the specificity of polymeric carriers is still limited when compared with their biological counterparts. To synthesize the next generation of carriers, it is important to consider the biological rationale for materials design. This requires a detailed understanding of the cellular microenvironments and how these can be harnessed for specific applications. In this review, several important physiological cues in the cellular microenvironments are outlined, with a focus on changes in pH, redox potential, and the types of enzymes present in specific regions. Furthermore, recent studies that use such biologically inspired triggers to design polymeric carriers are highlighted, focusing on applications in the field of therapeutic delivery.

  15. 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

  16. Analysis of pharmaceutical preparations containing antihistamine drugs by micellar liquid chromatography.

    PubMed

    Martínez-Algaba, C; Bermúdez-Saldaña, J M; Villanueva-Camañas, R M; Sagrado, S; Medina-Hernández, M J

    2006-02-13

    Rapid chromatographic procedures for analytical quality control of pharmaceutical preparations containing antihistamine drugs, alone or together with other kind of compounds are proposed. The method uses C18 stationary phases and micellar mobile phases of cetyltrimethylammonium bromide (CTAB) with either 1-propanol or 1-butanol as organic modifier. The proposed procedures allow the determination of the antihistamines: brompheniramine, chlorcyclizine, chlorpheniramine, diphenhydramine, doxylamine, flunarizine, hydroxyzine, promethazine, terfenadine, tripelennamine and triprolidine, in addition to caffeine, dextromethorphan, guaifenesin, paracetamol and pyridoxine in different pharmaceutical presentations (tablets, capsules, suppositories, syrups and ointments). The methods require minimum handling sample and are rapid (between 3 and 12 min at 1 mLmin(-1) flow rate) and reproducible (R.S.D. values<5%). Limits of detection are lower than 1 microgmL(-1) and the recoveries of the analytes in the pharmaceutical preparations are in the range 100+/-10%.

  17. Spectrophotometric determination of dopaminergic drugs used for Parkinson's disease, cabergoline and ropinirole, in pharmaceutical preparations.

    PubMed

    Onal, Armağan; Cağlar, Sena

    2007-04-01

    Simple and reproducible spectrophotometric methods have been developed for determination of dopaminergic drugs used for Parkinson's disease, cabergoline (CAB) and ropinirole hydrochloride (ROP), in pharmaceutical preparations. The methods are based on the reactions between the studied drug substances and ion-pair agents [methyl orange (MO), bromocresol green (BCG) and bromophenol blue (BPB)] producing yellow colored ion-pair complexes in acidic buffers, after extracting in dichloromethane, which are spectrophotometrically determined at the appropriate wavelength of ion-pair complexes. Beer's law was obeyed within the concentration range from 1.0 to 35 microg ml(-1). The developed methods were applied successfully for the determination of these drugs in tablets.

  18. 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

  19. 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.

  20. 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

  1. 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

    ... HUMAN SERVICES Food and Drug Administration Generic Drug User Fee--Active Pharmaceutical Ingredient and Finished Dosage Form Facility Fee Rates for Fiscal Year 2013 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the rate for the...

  2. 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.

  3. 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

  4. 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.

  5. Pharmaceutical cocrystals: a novel approach for oral bioavailability enhancement of drugs.

    PubMed

    Chadha, Renu; Saini, Anupam; Arora, Poonam; Bhandari, Swati

    2012-01-01

    Solid dosage forms are by far the preferred drug delivery systems. However, these often face the problem of poor and erratic bioavailability during the drug development process. Numerous formulation strategies for drug delivery are currently under development, among which the solid forms such as polymorphs, solvates, salts, and cocrystals have been considered to be the most important for improving dissolution rate and bioavailability. Cocrystallization is a fairly new approach in pharmaceutical industry that can improve the solubility and, consequently, the bioactivity of the active pharmaceutical ingredient (API) without compromising its structural integrity. Pharmaceutical cocrystals have found their place in drug delivery, primarily due to their ability to produce alternative, viable solid forms when a more standard approach of salt and polymorph formation fails to deliver the desired objectives. Over the past few years, a number of papers have been published focusing on a broad range of subjects, from traditional crystal engineering to structure-property relationships of cocrystals. The present review, however, illustrates how the cocrystalline forms of APIs have improved their in vitro dissolution rate and in vivo bioavailability, often correlating well with their improved solubility as well.

  6. 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

  7. 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

  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. 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.

  11. 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.

  12. 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.

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

    PubMed

    Jaiswal, Piyush; Gidwani, Bina; Vyas, Amber

    2016-01-01

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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. [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

  20. Cardiovascular drug discovery: a perspective from a research-based pharmaceutical company.

    PubMed

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

    2014-06-02

    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.

  1. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs.

    PubMed

    1997-02-01

    Because of an increasing number of reports of adverse reactions associated with pharmaceutical excipients, in 1985 the Committee on Drugs issued a position statement recommending that the Food and Drug Administration mandate labeling of over-the-counter and prescription formulations to include a qualitative list of inactive ingredients. However, labeling of inactive ingredients remains voluntary. Adverse reactions continue to be reported, although some are no longer considered clinically significant, and other new reactions have emerged. The original statement, therefore, has been updated and its information expanded.

  2. [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

  3. [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.

  4. Biocompatible hydrodispersible magnetite nanoparticles used as antibiotic drug carriers.

    PubMed

    Bolocan, Alexandra; Mihaiescu, Dan Eduard; Andronescu, Ecaterina; Voicu, Georgeta; Grumezescu, Alexandru Mihai; Ficai, Anton; Vasile, Bogdan Ştefan; Bleotu, Coralia; Chifiriuc, Mariana Carmen; Pop, Corina Silvia

    2015-01-01

    Here we report a newly synthesized vectorizing nanosystem, based on hydrodispersible magnetite nanoparticles (HMNPs) with an average size less than 10 nm, obtained by precipitation of Fe(II) and Fe(III) in basic solution of p-aminobenzoic acid (PABA), characterized by high-resolution transmission electron microscopy (HR-TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), differential thermal analysis coupled with thermogravimetric analysis (DTA-TGA) and bioevaluated for cytotoxicity and antibiotic delivery in active forms. The obtained data demonstrate that HMNPs can be used as an efficient drug delivery system, for clinically relevant antimicrobial drugs. HMNPs antimicrobial activity depended on the loaded drug structure and the tested microbial strain, being more efficient against Pseudomonas aeruginosa, comparing with the Escherichia coli strain. The novel HMNPs demonstrated an acceptable biocompatibility level, being thus a very good candidate for biomedical applications, such as drug delivery or targeting.

  5. 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.

  6. 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

  7. 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

  8. Evidence-based approach to assess passive diffusion and carrier-mediated drug transport.

    PubMed

    Di, Li; Artursson, Per; Avdeef, Alex; Ecker, Gerhard F; Faller, Bernard; Fischer, Holger; Houston, J Brian; Kansy, Manfred; Kerns, Edward H; Krämer, Stefanie D; Lennernäs, Hans; Sugano, Kiyohiko

    2012-08-01

    Evidence supporting the action of passive diffusion and carrier-mediated (CM) transport in drug bioavailability and disposition is discussed to refute the recently proposed theory that drug transport is CM-only and that new transporters will be discovered that possess transport characteristics ascribed to passive diffusion. Misconceptions and faulty speculations are addressed to provide reliable guidance on choosing appropriate tools for drug design and optimization.

  9. 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

  10. 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.

  11. 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

  12. Drug production with a social conscience, the experience of Gonoshasthaya Pharmaceuticals.

    PubMed

    Chetley, A

    1985-01-01

    In many 3rd World countries, people face shortages of the most essential drugs for primary health care and an excess of drugs which are inappropriate to their basic needs. In Bangladesh, a grassroots primary health care project has established its own pharmaceuticals factory--Gonoshasthaya Pharmaceuticals Limited (GPL)--to challenge the situation. The author of this article, a journalist, visited GPL and found that the technology to produce drugs was accessible to a poor, rural workforce with little or no formal education. Because the factory grew out of the health care project, it has been integrated into the surrounding community, and supported by the local people. GPL has played a prominent role in transforming the drug production and supply system in Bangladesh, and its example could have future impact in other 3rd World countries. The management team at GPL recognized that at all costs, the drugs produced by GPL would have to be of the very highest quality. GPL focuses on basic health and development needs rather than simply on production of drugs. GPL gave the government confidence that, even if all the transnational companies withdrew from the country, local firms could meet high standards of quality and produce at least the essential drugs. GPL's survival is largely due to its relationship with the local community. GPL is clear proof that business can operate with a social conscience. It can interact with the community around it and play a major role in fulfilling the community's needs. GPL provides essential drugs as well as employment, education, and a sense of achievement.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. [Role of pharmaceutical company pharmacist in provision of drug information for cancer chemotherapy].

    PubMed

    Koshida, Iori; Kubota, Kenichi; Yamashita, Masaki; Katayanagi, Hideya; Noda, Kohei; Terada, Hakaru; Yoshioka, Shinichi; Sekine, Nobuyuki; Kameda, Toshikazu; Terada, Kiyoshi

    2009-04-01

    Recently, oxaliplatin(L-OHP)and irinotecan hydrochloride hydrate(CPT-11)have gained recognition as key drugs in the treatment of advanced colorectal cancer. In this article, we describe the results of a survey of medical institutions by pharmacists working at a pharmaceutical company. First, questions from medical institutions on L-OHP and CPT-11 were totaled and analyzed. The results showed that most of these questions concerned safety, with many of these addressing side effects. Next, a questionnaire on FOLFOX and FOLFIRI regimens was administered to medical institutions. The results indicated that staff are interested in the safety and critical path of these regimens. These results suggest that a lot of medical institutions require more information from pharmaceutical companies. This indicates that pharmacists should do more to take the needs of medical institutions into account in providing improved customer support.

  1. Human in vivo regional intestinal permeability: importance for pharmaceutical drug development.

    PubMed

    Lennernäs, Hans

    2014-01-01

    Both the development and regulation of pharmaceutical dosage forms have undergone significant improvements and development over the past 25 years, due primarily to the extensive application of the biopharmaceutical classification system (BCS). The Biopharmaceutics Drug Disposition Classification System, which was published in 2005, has also been a useful resource for predicting the influence of transporters in several pharmacokinetic processes. However, there remains a need for the pharmaceutical industry to develop reliable in vitro/in vivo correlations and in silico methods for predicting the rate and extent of complex gastrointestinal (GI) absorption, the bioavailability, and the plasma concentration-time curves for orally administered drug products. Accordingly, a more rational approach is required, one in which high quality in vitro or in silico characterizations of active pharmaceutical ingredients and formulations are integrated into physiologically based in silico biopharmaceutics models to capture the full complexity of GI drug absorption. The need for better understanding of the in vivo GI process has recently become evident after an unsuccessful attempt to predict the GI absorption of BCS class II and IV drugs. Reliable data on the in vivo permeability of the human intestine (Peff) from various intestinal regions is recognized as one of the key biopharmaceutical requirements when developing in silico GI biopharmaceutics models with improved predictive accuracy. The Peff values for human jejunum and ileum, based on historical open, single-pass, perfusion studies are presented in this review. The main objective of this review is to summarize and discuss the relevance and current status of these human in vivo regional intestinal permeability values.

  2. 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

  3. Barrier or carrier? Pulmonary surfactant and drug delivery.

    PubMed

    Hidalgo, Alberto; Cruz, Antonio; Pérez-Gil, Jesús

    2015-09-01

    To consider the lung as a target for drug delivery and to optimise strategies directed at the pulmonary route, it is essential to consider the role of pulmonary surfactant, a thin lipid-protein film lining the respiratory surface of mammalian lungs. Membrane-based surfactant multilayers are essential for reducing the surface tension at the respiratory air-liquid interface to minimise the work of breathing. Different components of surfactant are also responsible for facilitating the removal of potentially pathological entities such as microorganisms, allergens or environmental pollutants and particles. Upon inhalation, drugs or nanoparticles first contact the surfactant layer, and these interactions critically affect their lifetime and fate in the airways. This review summarises the current knowledge on the possible role and effects of the pulmonary surfactant system in drug delivery strategies. It also summarises the evidence that suggests that pulmonary surfactant is far from being an insuperable barrier and could be used as an efficient shuttle for delivering hydrophobic and hydrophilic compounds deep into the lung and the organism.

  4. [Rising attention to the market to ratio meet demand of improving efficiency of pharmaceutical circulation--based on complicated variety and specification of drugs].

    PubMed

    Chen, Zhaoxing; Sun, Lihua

    2010-05-01

    Analyzing the complicated variety and specification of drugs and the objective demand of pharmaceutical circulation, to seek out the key factors in improving the efficiency of pharmaceutical circulation, for putting forward suggestions to promote the development of pharmaceutical circulation in China. The conclusion is drawed from industrial organization theory and successful experience of foreign countries, high market attention met with the demand of complicated variety and specification of drugs in pharmaceutical circulation.

  5. 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

  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. 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.

  8. 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.

  9. Molecular Aspects of Mucoadhesive Carrier Development for Drug Delivery and Improved Absorption

    PubMed Central

    Peppas, Nicholas A; Thomas, J. Brock; McGinity, James

    2011-01-01

    Although the oral route remains the most favored route of drug administration, major scientific obstacles prevent the effective and efficient delivery of low-molecular-mass drugs, peptides and proteins that exhibit poor solubility and permeability. Mucoadhesive dosage forms and the associated drug carriers have the ability to interact at a molecular level with the mucus gel layer that lines the epithelial surfaces of the major absorptive regions of the body. This interaction provides an increased residence time of the therapeutic formulation while localizing the drug at the site of administration. Such local, non-specific targeting leads to an increase in both oral absorption and bioavailability. Fundamental understanding of the biological processes encountered along the gastrointestinal tract can provide a sufficient engineer of carriers that are capable to provide this increase in residence time. Here we discuss the theoretical framework for achieving mucoadhesive systems as related to biomaterials science and the structure of the biomaterials used. PMID:19105897

  10. Methods for methotrexate determination in macromolecular conjugates drug carrier.

    PubMed

    Ciekot, Jarosław; Goszczyński, Tomasz; Boratyńskit, Janusz

    2012-01-01

    In this paper, two simple, cost-effective and fast methods for quantification of methotrexate (MTX) in the macromolecular conjugates are presented. The method for analysis of total MTX in preparations was based on absorption spectrophotometry. Validation was performed by measuring absorbance at 372 nm of the sodium bicarbonate solution. Curve describing drug concentration against absorption had a linear character in the range of 1.204-40.13 microM. The reproducibility and precision of method was 0.1558 to 3.086%. The recovery of the method was between 99.56 and 104.7%. The limit of quantitation method was 1.050 microM. The method for free MTX determination was based on size exclusion chromatography and UV-VIS detection at the wavelength of 302 nm. Superdex Peptide column (150 x 4.6 mm) and a mobile phase 0.1 M sodium bicarbonate with a flow rate of 0.4 mL/min was used. In the free drug determination method, the curve had a linear character in the range of 2.006-200.6 microM. The reproducibility and precision of method was 0.3761 to 2.452%. The recovery of the method was between 93.18 and 104.5%. The limit of quantitation method was 0.9203 microM. PMID:23285700

  11. 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

  12. High-Capacity Drug Carriers from Common Polymer Amphiphiles.

    PubMed

    Zhou, Zhun; Munyaradzi, Oliver; Xia, Xin; Green, Da'Sean; Bong, Dennis

    2016-09-12

    We report herein a dual-purpose role for polyacidic domains in an aqueous-phase polymer amphiphile assembly. In addition to their typical role as ionized water-solubilizing and self-repulsive motifs, we find that polycarboxylic acid domains uniquely enable high levels of hydrophobic drug encapsulation. By attenuated total reflectance infrared spectroscopy, we find significant differences in the carbonyl stretching region of the nanoparticles formed by polyacidic amphiphiles relative to those in soluble, single-domain poly(acrylic acid), suggesting that stabilization may be derived from limited ionization of the carboxylate groups upon assembly. Acidic-hydrophobic diblock polyacrylates were prepared and coassembled with up to 60 wt % camptothecin (CPT) into nanoparticles, the highest loading reported to date. Controlled release of bioactive CPT from polymer nanoparticles is observed, as well as protection from human serum albumin-induced hydrolysis. Surface protection with PEG limits uptake of the CPT-loaded nanoparticles by MCF-7 breast cancer cells, as expected. Acidic-hydrophobic polymer amphiphiles thus have the hallmarks of a useful and general drug delivery platform and are readily accessible from living radical polymerization of cheap, commercially available monomers. We highlight here the potential utility of this common polymer design in high-capacity, controlled-release polymer nanoparticle systems. PMID:27476544

  13. Are pharmaceuticals with evolutionary conserved molecular drug targets more potent to cause toxic effects in non-target organisms?

    PubMed

    Furuhagen, Sara; Fuchs, Anne; Lundström Belleza, Elin; Breitholtz, Magnus; Gorokhova, Elena

    2014-01-01

    The ubiquitous use of pharmaceuticals has resulted in a continuous discharge into wastewater and pharmaceuticals and their metabolites are found in the environment. Due to their design towards specific drug targets, pharmaceuticals may be therapeutically active already at low environmental concentrations. Several human drug targets are evolutionary conserved in aquatic organisms, raising concerns about effects of these pharmaceuticals in non-target organisms. In this study, we hypothesized that the toxicity of a pharmaceutical towards a non-target invertebrate depends on the presence of the human drug target orthologs in this species. This was tested by assessing toxicity of pharmaceuticals with (miconazole and promethazine) and without (levonorgestrel) identified drug target orthologs in the cladoceran Daphnia magna. The toxicity was evaluated using general toxicity endpoints at individual (immobility, reproduction and development), biochemical (RNA and DNA content) and molecular (gene expression) levels. The results provide evidence for higher toxicity of miconazole and promethazine, i.e. the drugs with identified drug target orthologs. At the individual level, miconazole had the lowest effect concentrations for immobility and reproduction (0.3 and 0.022 mg L-1, respectively) followed by promethazine (1.6 and 0.18 mg L-1, respectively). At the biochemical level, individual RNA content was affected by miconazole and promethazine already at 0.0023 and 0.059 mg L-1, respectively. At the molecular level, gene expression for cuticle protein was significantly suppressed by exposure to both miconazole and promethazine; moreover, daphnids exposed to miconazole had significantly lower vitellogenin expression. Levonorgestrel did not have any effects on any endpoints in the concentrations tested. These results highlight the importance of considering drug target conservation in environmental risk assessments of pharmaceuticals.

  14. 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.

  15. The Impact of Chemical Probes in Drug Discovery: A Pharmaceutical Industry Perspective.

    PubMed

    Garbaccio, Robert M; Parmee, Emma R

    2016-01-21

    Chemical probes represent an important component of both academic and pharmaceutical drug discovery research. As a complement to prior reviews that have defined this scientific field, we aim to provide an industry perspective on the value of having high-quality chemical probes throughout the course of preclinical research. By studying examples from the internal Merck pipeline, we recognize that these probes require significant collaborative investment to realize their potential impact in clarifying the tractability and translation of a given therapeutic target. This perspective concludes with recommendations for chemical probe discovery aimed toward maximizing their potential to identify targets that result in the successful delivery of novel therapeutics.

  16. 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.

  17. Patent issues in drug development: perspectives of a pharmaceutical scientist-attorney.

    PubMed

    Melethil, Srikumaran

    2005-10-27

    The major purpose of this article is to emphasize the need for pharmaceutical scientists to have a better understanding of patent fundamentals. This need is illustrated by analyses of key scientific and legal issues that arose during recent patent infringement cases involving Prozac, Prilosec, and Buspar. Economic incentives for drug discovery and development clash with societal needs for low-cost pharmaceuticals in the United States and all over the world. The Hatch-Waxman Act of 1984 was enacted to promote public health by balancing the interests of brand name and generic companies. Patent protection, which provides a monopoly for a limited time, is aimed to provide such incentives. Creation of patents requires the interaction between scientists and lawyers, an endeavor made difficult by the differing intellectual spheres of their respective disciplines. Therefore, in the first place, a thorough understanding of patent fundamentals among pharmaceutical scientists will help them work more efficiently with patent attorneys. Second, it will enable them to appreciate the strengths and weaknesses of individual patents, which is critical in developing strategies amidst the ongoing patent tug-of-war between brand-name and generic companies.

  18. Electrochemical Analysis of Antichemotherapeutic Drug Zanosar in Pharmaceutical and Biological Samples by Differential Pulse Polarography

    PubMed Central

    Reddy, Chennupalle Nageswara; ReddyPrasad, Puthalapattu; Sreedhar, NeelamYughandhar

    2013-01-01

    The electrochemical reduction of zanosar was investigated systematically by direct current polarography, cyclic voltammetry, and differential pulse polarography (DPP). A simple DPP technique was proposed for the direct quantitative determination of anticancer drug zanosar in pharmaceutical formulation and spiked human urine samples for the first time. The reduction potential was −0.28 V versus Ag/AgCl with a hanging mercury drop electrode in Britton-Robinson buffer as supporting electrolyte. The dependence of the intensities of currents and potentials on pH, concentration, scan rate, deposition time, and nature of the supporting electrolyte was investigated. The calibration curve was found to be linear with the following equation: y = 0.4041x + 0.012, with a correlation coefficient of 0.992 (R2) over a concentration range from 1.0 × 10−7 M to 1.0 × 10−3 M. In the present investigation, the achieved limit of detection (LOD) and limit of quantization (LQD) were 7.42 × 10−8 M and 2.47 × 10−8 M; respectively. Excipients did not interfere with the determination of zanosar in pharmaceutical formulation and spiked urine samples. Precision and accuracy of the developed method were checked by recovery studies in pharmaceutical formulation and spiked human urine samples. PMID:24455423

  19. Preparation, characterization and physico-chemical properties of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): their benefits as colloidal drug carrier systems.

    PubMed

    Uner, M

    2006-05-01

    Solid lipid nanoparticles (SLN) have attracted increasing attention by various research groups and companies since the early 1990s. Their advantages over existing traditional carriers have been clearly documented. In addition, modified SLN have been described which are nanostructured lipid carriers (NLC) composed of liquid lipid blended with a solid lipid to form a nanostructured solid particle matrix. NLC combine controlled release characteristics with some advantages over SLN. This paper reviews the production techniques, characterization and physical stability of these systems including destabilizing factors and principles of drug loading, then considers aspects and benefits of SLN and NLC as colloidal drug carriers. PMID:16724531

  20. 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.

  1. 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

  2. Drug information pharmacists at health-care facilities, universities, and pharmaceutical companies.

    PubMed

    Gong, S D; Millares, M; VanRiper, K B

    1992-05-01

    A national survey was conducted to provide a profile of drug information pharmacists. Questionnaires were mailed to 436 drug information pharmacists whose names were obtained from directors of drug information centers (DICs) at health-care facilities, universities, and pharmaceutical companies. The net response rate was 64% (278 usable replies). Most respondents were 30 to 39 years of age and had practiced in drug information for four years or less. There were equal numbers of male and female respondents. More than half had a doctor of pharmacy (Pharm.D.) degree, and about half had completed a postgraduate residency or fellowship. Respondents with a Pharm.D. degree or postgraduate training reported a more favorable professional outcome, including position, income, and job satisfaction. Respondents reported a high level of professional involvement, including faculty appointment, publishing, and professional membership. Common reasons cited for choosing a career in drug information were an opportunity to continually learn, job satisfaction, and regular work hours. More than 70% of respondents were either very satisfied or extremely satisfied with their current job position. The most frequently reported income range was $40,000-44,999; distribution of income differed significantly among geographic regions. Drug information pharmacists report a high level of job satisfaction and involvement in professional activities; they often have completed advanced pharmacy education or postgraduate training.

  3. 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.

  4. Data-mining for sulfur and fluorine: an evaluation of pharmaceuticals to reveal opportunities for drug design and discovery.

    PubMed

    Ilardi, Elizabeth A; Vitaku, Edon; Njardarson, Jon T

    2014-04-10

    Among carbon, hydrogen, oxygen, and nitrogen, sulfur and fluorine are both leading constituents of the pharmaceuticals that comprise our medicinal history. In efforts to stimulate the minds of both the general public and expert scientist, statistics were collected from the trends associated with therapeutics spanning 12 disease categories (a total of 1969 drugs) from our new graphical montage compilation: disease focused pharmaceuticals posters. Each poster is a vibrant display of a collection of pharmaceuticals (including structural image, Food and Drug Administration (FDA) approval date, international nonproprietary name (INN), initial market name, and a color-coded subclass of function) organized chronologically and classified according to an association with a particular clinical indication. Specifically, the evolution and structural diversity of sulfur and the popular integration of fluorine into drugs introduced over the past 50 years are evaluated. The presented qualitative conclusions in this article aim to promote innovative insights into drug development. PMID:24102067

  5. Nanoparticles of hydrophobically modified dextrans as potential drug carrier systems.

    PubMed

    Aumelas, A; Serrero, A; Durand, A; Dellacherie, E; Leonard, M

    2007-09-01

    Nanoparticles combining a hydrophobically modified dextran core and a polysaccharide surface coverage were elaborated. Their suitability for applications like drug delivery was evaluated. The selected polysaccharide, dextran, was chemically modified by the covalent attachment of hydrocarbon groups (aliphatic or aromatic) via the formation of ether links. According to the extent of modification, either water-soluble or water-insoluble dextran derivatives were obtained. The latter exhibited solubility in organic solvents like tetrahydrofuran or dichloromethane saturated with water. Water-soluble dextran derivatives were used as polymeric surfactants for the control of nanoparticles surface characteristics. Nanoparticles were prepared either by o/w emulsion or solvent-diffusion methods. The size and surface properties of dextran nanoparticles were correlated to processing conditions. The stability of colloidal suspensions was examined as a function of ionic strength and related to the particle surface characteristics. The redispersability of freeze-dried suspensions without the addition of cryoprotectant was demonstrated. Finally, the degradability of modified dextrans was compared to that of starting dextran, after enzymatic hydrolysis in the presence of dextranase.

  6. Drug solubility in phospholipid carrier as a predictive parameter for drug recovery in microparticles produced by the aerosol solvent extraction system (ASES) process.

    PubMed

    Sarisuta, Narong; Kunastitchai, Sarinnate; Pichert, Lars; Müller, Bernd W

    2007-09-01

    The solubility of various drugs in a constant ratio of phosphatidylcholine-cholesterol carrier were studied to investigate their influence on drug recovery in drug-lipid microparticles produced by the aerosol solvent extraction system (ASES) process. Solubility of the drugs in such lipid carrier were determined by using differential scanning calorimetry and confirmed by X-ray powder diffraction study. The results showed that drug possessing relatively high solubility in the lipid carrier used could lead to a higher amount of drug recovered in the drug-lipid microparticles produced. However, too high amount of dissolved drug imposed an adverse effect on the solidification of the lipid carrier during ASES processing, which led to partial film formation in the production column and hence a lower yield of microparticles. Such adverse effect was not the case for the drugs with low solubility in the carrier but there was an incomplete recovery of drug in the produced microparticles due to the partial extraction by the supercritical gas instead. The maximum amount of drug recovered in the ASES-prepared microparticles was found to correlate to the solubility of drug in the lipid carrier so that it might be utilized as a predictive parameter for determining the amount of drug to be incorporated into the microparticles.

  7. The politics of pharmaceutical reform: the case of the Philippine National Drug Policy.

    PubMed

    Lee, M B

    1994-01-01

    A national drug policy was formulated in the Philippines after the rise of the Aquino government in 1986. In this article, the author discusses the pharmaceutical situation before the policy was announced, and argues that the major push for a policy came from the confluence of four factors: a change in the structures of political power, especially the rise of a new government and the empowerment of health non-governmental organizations as new participants in the policy process; members of the Department of Health who pushed for a policy; a more conductive social and political climate, both locally and internationally; and a growing body of knowledge about the drug issue. The author discusses the policy's achievements as well as the limitations that have beset the policy from 1987 to 1992.

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

    PubMed

    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 lambda(max) 470nm. 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 426nm 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 5-70microgmL(-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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. Drug-conjugated polymers as gene carriers for synergistic therapeutic effect.

    PubMed

    Pofali, P A; Singh, B; Dandekar, P; Jain, R D; Maharjan, S; Choi, Y J; Arote, R B; Cho, C S

    2016-05-01

    The ability to safely and effectively transfer gene into cells is the fundamental goal of gene delivery. In spite of the best efforts of researchers around the world, gene therapy has limited success. This may be because of several limitations of delivering gene which is one of the greatest technical challenges in the modern medicine. To address these issues, many efforts have been made to bind drugs and genes together by polymers for co-delivery to achieve synergistic effect. Usually, binding interaction of drugs with polymers is either physical or chemical. In case of drug-polymer physical interaction, the efficiency of drugs generally decreases because of separation of drugs from polymers in vivo whenever it comes in contact with charged biofluid/s or cells. While chemical interaction of drug-polymer overcomes the aforementioned obstacle, several problems such as steric hindrance, solubility, and biodegradability hinder it to develop as gene carrier. Considering these benefits and pitfalls, the objective of this review is to discuss the possible extent of drug-conjugated polymers as safe and efficient gene delivery carriers for achieving synergistic effect to combat various genetic disorders.

  14. Drug-conjugated polymers as gene carriers for synergistic therapeutic effect.

    PubMed

    Pofali, P A; Singh, B; Dandekar, P; Jain, R D; Maharjan, S; Choi, Y J; Arote, R B; Cho, C S

    2016-05-01

    The ability to safely and effectively transfer gene into cells is the fundamental goal of gene delivery. In spite of the best efforts of researchers around the world, gene therapy has limited success. This may be because of several limitations of delivering gene which is one of the greatest technical challenges in the modern medicine. To address these issues, many efforts have been made to bind drugs and genes together by polymers for co-delivery to achieve synergistic effect. Usually, binding interaction of drugs with polymers is either physical or chemical. In case of drug-polymer physical interaction, the efficiency of drugs generally decreases because of separation of drugs from polymers in vivo whenever it comes in contact with charged biofluid/s or cells. While chemical interaction of drug-polymer overcomes the aforementioned obstacle, several problems such as steric hindrance, solubility, and biodegradability hinder it to develop as gene carrier. Considering these benefits and pitfalls, the objective of this review is to discuss the possible extent of drug-conjugated polymers as safe and efficient gene delivery carriers for achieving synergistic effect to combat various genetic disorders. PMID:26471335

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  2. 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

  3. Controlled release formulations of risperidone antipsychotic drug in novel aliphatic polyester carriers: Data analysis and modelling.

    PubMed

    Siafaka, Panoraia I; Barmpalexis, Panagiotis; Lazaridou, Maria; Papageorgiou, George Z; Koutris, Efthimios; Karavas, Evangelos; Kostoglou, Margaritis; Bikiaris, Dimitrios N

    2015-08-01

    In the present study a series of biodegradable and biocompatible poly(ε-caprolactone)/poly(propylene glutarate) (PCL/PPGlu) polymer blends were investigated as controlled release carriers of Risperidone drug (RISP), appropriate for transdermal drug delivery. The PCL/PPGlu carriers were prepared in different weight ratios. Miscibility studies of blends were evaluated through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolysis studies were performed at 37°C using a phosphate buffered saline solution. The prepared blends have been used for the preparation of RISP patches via solvent evaporation method, containing 5, 10 and 15wt% RISP. These formulations were characterized using FT-IR spectroscopy, DSC and WAXD in order to evaluate interactions taking place between polymer matrix and drug, as well as the dispersion and the physical state of the drug inside the polymer matrix. In vitro drug release studies were performed using as dissolution medium phosphate buffered saline simulating body fluids. It was found that in all cases controlled release formulations were obtained, while the RISP release varies due to the properties of the used polymer blend and the different levels of drug loading. Artificial Neural Networks (ANNs) were used for dissolution behaviour modelling showing increased correlation efficacy compared to Multi-Linear-Regression (MLR). PMID:26159838

  4. 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

  5. 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.

  6. Drug delivery via lipoprotein-based carriers: answering the challenges in systemic therapeutics.

    PubMed

    Sabnis, Nirupama; Lacko, Andras G

    2012-05-01

    Plasma lipoproteins are transporters of lipids and other hydrophobic molecules in the mammalian circulation. Lipoproteins also have a strong potential to serve as drug-delivery vehicles due to their small size, long residence time in the circulation and high-drug payload. Consequently, lipoproteins and synthetic/reconstituted lipoprotein preparations have been evaluated with increasing interest towards clinical applications, particularly for cancer diagnostics/imaging and chemotherapy. In this review, past and current studies on lipoproteins and similar alternative drug carriers are discussed regarding their suitability as agents to deliver drugs, primarily to cancer cells and tumors. A lipoprotein-based delivery strategy may also provide a novel platform for improving the therapeutic efficacy of drugs that have previously been judged unsuitable or had only limited application due to poor solubility. An additional, and perhaps the most important aspect of the drug-delivery process via lipoprotein-type carriers, is the receptor-mediated uptake of the payload from the lipoprotein complex. Monitoring the expression of specific receptors prior to treatment could, thus, give rise to efficient selection of optimally responsive patients, resulting in a successful personalized therapy regimen.

  7. 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

  8. 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).

  9. 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

  10. 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.

  11. Micellar nanocarriers: pharmaceutical perspectives.

    PubMed

    Torchilin, V P

    2007-01-01

    Micelles, self-assembling nanosized colloidal particles with a hydrophobic core and hydrophilic shell are currently successfully used as pharmaceutical carriers for water-insoluble drugs and demonstrate a series of attractive properties as drug carriers. Among the micelle-forming compounds, amphiphilic copolymers, i.e., polymers consisting of hydrophobic block and hydrophilic block, are gaining an increasing attention. Polymeric micelles possess high stability both in vitro and in vivo and good biocompatibility, and can solubilize a broad variety of poorly soluble pharmaceuticals many of these drug-loaded micelles are currently at different stages of preclinical and clinical trials. Among polymeric micelles, a special group is formed by lipid-core micelles, i.e., micelles formed by conjugates of soluble copolymers with lipids (such as polyethylene glycol-phosphatidyl ethanolamine conjugate, PEG-PE). Polymeric micelles, including lipid-core micelles, carrying various reporter (contrast) groups may become the imaging agents of choice in different imaging modalities. All these micelles can also be used as targeted drug delivery systems. The targeting can be achieved via the enhanced permeability and retention (EPR) effect (into the areas with the compromised vasculature), by making micelles of stimuli-responsive amphiphilic block-copolymers, or by attaching specific targeting ligand molecules to the micelle surface. Immunomicelles prepared by coupling monoclonal antibody molecules to p-nitrophenylcarbonyl groups on the water-exposed termini of the micelle corona-forming blocks demonstrate high binding specificity and targetability. This review will discuss some recent trends in using micelles as pharmaceutical carriers. PMID:17109211

  12. 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

  13. Oxidative effects of the pharmaceutical drug paracetamol on the edible clam Ruditapes philippinarum under different salinities.

    PubMed

    Correia, Bárbara; Freitas, Rosa; Figueira, Etelvina; Soares, Amadeu M V M; Nunes, Bruno

    2016-01-01

    Paracetamol, a drug with analgesic and antipyretic properties, is one of the most used substances in human therapeutics, being also frequently detected in aquatic environments. Recent studies report its toxicity towards aquatic species, but the overall amount of data concerning its effects is still scarce. Global changes, likely alterations in abiotic conditions, including salinity, can modulate the interactions of contaminants with biota, conditioning the toxicological responses elicited also by pharmaceuticals. The present article describes the oxidative toxic effects posed by paracetamol on the clam species Ruditapes philippinarum under different salinity conditions. The results demonstrated the establishment of an oxidative-based effect, with significant alteration of several parameters, such as superoxide dismutase (SOD) and the ratio of reduced/oxidized glutathione (GSH/GSSG). Water salinity influenced the response of clams exposed to different paracetamol concentrations, showing the importance of studying physiological traits under realistic test conditions, which are likely to vary in great extent as a result of climate change. PMID:26409706

  14. 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

  15. 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

  16. 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.

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

    PubMed

    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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. [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.

  7. [Advances in the use of instrumental measurement of colour in the development, production and quality control of drugs, medicinal preparations and pharmaceutical auxiliary substances I ].

    PubMed

    Subert, Jan; Cižmárik, Jozef

    2013-04-01

    Colour is one of the important indices of the quality of drugs, medicinal preparations and pharmaceutical auxiliary substances. The paper summarizes the development and use of instrumental measurement of colour in pharmacy in recent ten years focusing on the drugs of synthetic origin and pharmaceutical auxiliary substances including their control.

  8. Magnetic nanoparticles-loaded PLA/PEG microspheres as drug carriers.

    PubMed

    Frounchi, Masoud; Shamshiri, Soodeh

    2015-05-01

    Surface-modified magnetite (Fe3 O4 ) nanoparticles with an average size of 22 nm were prepared. The nanoparticles had a saturation magnetization of 50.7 emu g(-1) . Then magnetite and drug-loaded microspheres of poly (lactic acid)/poly (ethylene glycol) were prepared at various compositions. The microspheres were spherical in shape and had smooth surface. The diameter size of the microspheres ranged between about 0.2 and 4 μm. Doxorubicin hydrochloride for cancer treatment was the drug that loaded into the microspheres. The prepared microspheres were characterized by FTIR, XRD, VSM, SEM and drug-release measurements. It was found that the drug cumulative release percentage was proportional to (time) (n) where 0.61 < n < 0.75 depending on PEG and Fe3 O4 contents. The drug release was controlled through a combination of diffusion and PLA hydrolysis and obeyed a non-fickian mechanism. The drug release was facilitated by presence of poly (ethylene glycol) as PLA plasticizer and was higher under applied external magnetic field. The obtained magnetic microspheres could be used as drug carriers for targeted drug delivery purposes. PMID:25203941

  9. Magnetic nanoparticles-loaded PLA/PEG microspheres as drug carriers.

    PubMed

    Frounchi, Masoud; Shamshiri, Soodeh

    2015-05-01

    Surface-modified magnetite (Fe3 O4 ) nanoparticles with an average size of 22 nm were prepared. The nanoparticles had a saturation magnetization of 50.7 emu g(-1) . Then magnetite and drug-loaded microspheres of poly (lactic acid)/poly (ethylene glycol) were prepared at various compositions. The microspheres were spherical in shape and had smooth surface. The diameter size of the microspheres ranged between about 0.2 and 4 μm. Doxorubicin hydrochloride for cancer treatment was the drug that loaded into the microspheres. The prepared microspheres were characterized by FTIR, XRD, VSM, SEM and drug-release measurements. It was found that the drug cumulative release percentage was proportional to (time) (n) where 0.61 < n < 0.75 depending on PEG and Fe3 O4 contents. The drug release was controlled through a combination of diffusion and PLA hydrolysis and obeyed a non-fickian mechanism. The drug release was facilitated by presence of poly (ethylene glycol) as PLA plasticizer and was higher under applied external magnetic field. The obtained magnetic microspheres could be used as drug carriers for targeted drug delivery purposes.

  10. 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

  11. Nanostructured lipid carrier-based hydrogel formulations for drug delivery: a comprehensive review.

    PubMed

    Doktorovova, Slavomira; Souto, Eliana B

    2009-02-01

    The scientific literature today provides several systems that can deliver active pharmaceutical ingredients (APIs) across the skin. These include reservoir matrices, matrix diffusion-controlled devices, multiple polymer devices and multilayer matrix assemblies. Among these, nanostructured lipid carriers (NLC) have emerged as novel systems composed of physiological lipid materials suitable for topical, dermal and transdermal administration. This review focuses on the design characteristics, production and composition of semi-solid formulations containing NLC as API carriers. One of the useful semi-solid systems are hydrogels, which can be used as vehicles to provide appropriate consistency for NLC formulations to be applied onto the skin. In the present review recent developments in the field are highlighted, including examples of APIs successfully entrapped within NLC now amenable for delivery via the skin. Further innovations in NLC composition and formulation, as well as in semi-solid hydrogel assemblies, are likely to expand the number of APIs available for topical, dermal and transdermal delivery. PMID:19239388

  12. 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

  13. Resuscitation and rescue of the pharmaceutical detail: a prescriber-drug representative collaboration.

    PubMed

    Kale, Scott A; Barkin, Robert L

    2009-01-01

    The traditional pharmaceutical detail must be revised to meet current prescriber presentation and interaction needs. Best practice and evidence-based clinical strategies demands, an expanded database describing prescribable pharmaceutical therapies. We present a format for the structure of a functional database for pharmaceuticals and a means by which the data can be introduced, updated and instituted. PMID:19618754

  14. 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

  15. Strategies to reduce the risk of drug-induced QT interval prolongation: a pharmaceutical company perspective.

    PubMed

    Pollard, C E; Valentin, J-P; Hammond, T G

    2008-08-01

    Drug-induced prolongation of the QT interval is having a significant impact on the ability of the pharmaceutical industry to develop new drugs. The development implications for a compound causing a significant effect in the 'Thorough QT/QTc Study' -- as defined in the clinical regulatory guidance (ICH E14) -- are substantial. In view of this, and the fact that QT interval prolongation is linked to direct inhibition of the hERG channel, in the early stages of drug discovery the focus is on testing for and screening out hERG activity. This has led to understanding of how to produce low potency hERG blockers whilst retaining desirable properties. Despite this, a number of factors mean that when an integrated risk assessment is generated towards the end of the discovery phase (by conducting at least an in vivo QT assessment) a QT interval prolongation risk is still often apparent; inhibition of hERG channel trafficking and partitioning into cardiac tissue are just two confounding factors. However, emerging information suggests that hERG safety margins have high predictive value and that when hERG and in vivo non-clinical data are combined, their predictive value to man, whilst not perfect, is >80%. Although understanding the anomalies is important and is being addressed, of greater importance is developing a better understanding of TdP, with the aim of being able to predict TdP rather than using an imperfect surrogate marker (QT interval prolongation). Without an understanding of how to predict TdP risk, high-benefit drugs for serious indications may never be marketed.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Computational Study of Nanosized Drug Delivery from Cyclodextrins, Crown Ethers and Hyaluronan in Pharmaceutical Formulations.

    PubMed

    Torrens, Francisco; Castellano, Gloria

    2015-01-01

    The problem in this work is the computational characterization of cyclodextrins, crown ethers and hyaluronan (HA) as hosts of inclusion complexes for nanosized drug delivery vehicles in pharmaceutical formulations. The difficulty is addressed through a computational study of some thermodynamic, geometric and topological properties of the hosts. The calculated properties of oligosaccharides of D-glucopyranoses allow these to act as co-solvents of polyanions in water. In crown ethers, the central channel is computed. Mucoadhesive polymer HA in formulations releases drugs in mucosas. Geometric, topological and fractal analyses are carried out with code TOPO. Reference calculations are performed with code GEPOL. From HA to HA·3Ca and hydrate, the hydrophilic solvent-accessible surface varies with the count of H-bonds. The fractal dimension rises. The dimension of external atoms rises resulting 1.725 for HA. It rises going to HA·3Ca and hydrate. Nonburied minus molecular dimension rises and decays. Hydrate globularity is lower than O(water), Ca(2+) and O(HA). Ca(2+) rugosity is smaller than for hydrate, O(HA) and O(water). Ca(2+) and O(water) accessibilities are greater than hydrate. Conclusions are drawn on: (1) the relative stability of linear/cyclic and shorter/larger polymers; (2) the atomic analysis of properties allows determining the atoms with maximum reactivity.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. Solid lipid nanoparticles of guggul lipid as drug carrier for transdermal drug delivery.

    PubMed

    Gaur, Praveen Kumar; Mishra, Shikha; Purohit, Suresh

    2013-01-01

    Diclofenac sodium loaded solid lipid nanoparticles (SLNs) were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG) and plain carbopol gel containing drug (CG) for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1) and stearic acid nanoparticle 1 (SAN-1) gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3) showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher C(max) than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile.

  8. Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

    PubMed Central

    Gaur, Praveen Kumar; Mishra, Shikha; Purohit, Suresh

    2013-01-01

    Diclofenac sodium loaded solid lipid nanoparticles (SLNs) were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG) and plain carbopol gel containing drug (CG) for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1) and stearic acid nanoparticle 1 (SAN-1) gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3) showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher Cmax than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile. PMID:24058913

  9. 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.

  10. 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

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

    PubMed

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

    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.

  12. In vitro evaluation of proniosomes as a drug carrier for flurbiprofen.

    PubMed

    Ibrahim, Mahmoud Mokhtar Ahmed; Sammour, Omaima A; Hammad, Mohamed A; Megrab, Nagia A

    2008-01-01

    The purpose of the present investigation is to formulate and evaluate proniosomal transdermal carrier systems for flurbiprofen. Proniosomes were prepared using various non-ionic surfactants, namely span 20 (Sp 20), span 40 (Sp 40), span 60 (Sp 60) and span 80 (Sp 80) without and with cholesterol at percentages ranging from 0% to 50%. The effect of surfactant type and cholesterol content on drug release was investigated. Drug release was tested by diffusion through cellophane membrane and rabbit skin. Drug release from the prepared systems was compared to that from flurbiprofen suspensions in distilled water and HPMC (hydroxypropylmethylcellulose) gels. In case of Sp 20 and Sp 80, the added amount of cholesterol affected the preparation type to be either proniosomal alcoholic solutions or liquid crystalline gel systems. On the other hand, both Sp 40 and Sp 60 produced gel systems in presence or absence of cholesterol. Microscopic observations showed that either proniosomal solutions or gel formulations immediately converted to niosomal dispersions upon hydration. Due to the skin permeation barrier, rabbit skin showed lower drug diffusion rates compared to cellophane membrane. The proniosomal composition controlled drug diffusion rates to be either faster or slower than the prepared flurbiprofen suspensions in HPMC gels or distilled water, respectively. In conclusion, this study demonstrated the possibility of using proniosomal formulations for transdermal drug delivery.

  13. 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

  14. 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

  15. Hydroxypropyl-β-cyclodextrin-graphene oxide conjugates: Carriers for anti-cancer drugs.

    PubMed

    Tan, Jingting; Meng, Na; Fan, Yunting; Su, Yutian; Zhang, Ming; Xiao, Yinghong; Zhou, Ninglin

    2016-04-01

    A novel drug carrier based on hydroxypropyl-β-cyclodextrin (HP-β-CD) modified carboxylated graphene oxide (GO-COOH) was designed to incorporate anti-cancer drug paclitaxel (PTX). The formulated nanomedicines were characterized by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Results showed that PTX can be incorporated into GO-COO-HP-β-CD nanospheres successfully, with an average diameter of about 100 nm. The solubility and stability of PTX-loaded GO-COO-HP-β-CD nanospheres in aqueous media were greatly enhanced compared with the untreated PTX. The results of hemolysis test demonstrated that the drug-loaded nanospheres were qualified with good blood compatibility for intravenous use. In vitro anti-tumor activity was measured and results demonstrated that the incorporation of PTX into the newly developed GO-COO-HP-β-CD carrier could confer significantly improved cytotoxicity to the nanosystem against tumor cells than single application of PTX. GO-COO-HP-β-CD nanospheres may represent a promising formulation platform for a broad range of therapeutic agent, especially those with poor solubility. PMID:26838897

  16. 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.

  17. 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

  18. Recent advances in the assessment of the antioxidant capacity of pharmaceutical drugs: from in vitro to in vivo evidence.

    PubMed

    Beretta, Giangiacomo; Facino, Roberto Maffei

    2010-09-01

    In this review, some well-established assays and more recent markers developed for the understanding of the biological activity of pharmaceutical drugs belonging to different pharmacological classes (nonsteroidal anti-inflammatory drugs, cardiovascular drugs, and central-nervous-system-acting drugs) are considered. The results of in vitro studies are reviewed and critically compared with those available from clinical trials, and their relevance for the elucidation of the mechanism of action of the drugs is discussed. Although from this examination a positive correlation between the in vitro and in vivo data seems to emerge, the small number of clinical trials available, their low number of patients enrolled, and sometimes the arbitrary or inappropriate choice of the biomarker(s) used highlight the need for (1) more standardized protocols to allow a reliable comparison of the results from different studies and (2) the development of new and more appropriate and specific biomarkers for the evaluation of oxidative stress before and after drug intervention.

  19. 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

  20. The international pharmaceutical market as a source of low-cost prescription drugs for U.S. patients.

    PubMed

    Kesselheim, Aaron S; Choudhry, Niteesh K

    2008-04-15

    In response to increasing prescription drug costs, more U.S. patients and policymakers are importing less-expensive pharmaceutical products from other countries. Large-scale prescription drug importation is currently illegal, but the U.S. Food and Drug Administration permits individuals to bring in 90-day supplies of drugs for personal use. As patient use of foreign-bought drugs has increased, federal legislators have continued to debate the full legalization of importation. Three factors help guide whether U.S. patients and policymakers can rely on other countries as sources of imported prescription drugs: whether the safety of the product can be ensured, how the import price compares with domestic prices, and how importation might affect the exporting country's pharmaceutical market. In wealthier countries with active regulatory systems, drug safety can be adequately ensured, and brand-name products are usually less expensive than in the United States (although generic drugs may be more expensive). However, implementing large-scale importation can negatively impact the originating country's market and can diminish the long-term cost savings for U.S. consumers. In low- and middle-income countries, prices may be reduced for both brand-name and generic drugs, but the prevalence of unauthorized products on the market makes ensuring drug safety more difficult. It may be reasonable for individual U.S. consumers to purchase essential medicines from certain international markets, but the most effective way to decrease drug costs overall is the appropriate use of domestic generic drugs, which are available for almost every major therapeutic class.

  1. 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.

  2. Optimization of the THP-1 activation assay to detect pharmaceuticals with potential to cause immune mediated drug reactions.

    PubMed

    Corti, Daniele; Galbiati, Valentina; Gatti, Nicolò; Marinovich, Marina; Galli, Corrado L; Corsini, Emanuela

    2015-10-01

    Despite important impacts of systemic hypersensitivity induced by pharmaceuticals, for such endpoint no reliable preclinical approaches are available. We previously established an in vitro test to identify contact and respiratory allergens based on interleukin-8 (IL-8) production in THP-1 cells. Here, we challenged it for identification of pharmaceuticals associated with systemic hypersensitivity reactions, with the idea that drug sensitizers share common mechanisms of cell activation. Cells were exposed to drugs associated with systemic hypersensitivity reactions (streptozotocin, sulfamethoxazole, neomycin, probenecid, clonidine, procainamide, ofloxacin, methyl salicylate), while metformin was used as negative drug. Differently to chemicals, drugs tested were well tolerated, except clonidine and probenecid, with no signs of cytotoxicity up to 1-2mg/ml. THP-1 activation assay was adjusted, and conditions, that allow identification of all sensitizing drugs tested, were established. Next, using streptozotocin and selective inhibitors of PKC-β and p38 MAPK, two pathways involved in chemical allergen-induced cell activation, we tested the hypothesis that similar pathways were also involved in drug-induced IL-8 production and CD86 upregulation. Results indicated that drugs and chemical allergens share similar activation pathways. Finally, we made a structure-activity hypothesis related to hypersensitivity reactions, trying to individuate structural requisite that can be involved in immune mediated adverse reactions. PMID:26028146

  3. Lipid vesicles and other colloids as drug carriers on the skin.

    PubMed

    Cevc, Gregor

    2004-03-27

    lipid micelles, solid (nano)particles, nano-droplets, biphasic vesicles, etc. Such colloids, therefore, merely enter the skin through the rare wide gaps between groups of skin cells near the organ surface. Transdermal drug delivery systems based on corresponding drug formulations, therefore, rely on simple drug diffusion through the skin; the colloid then, at best, can modulate drug transport through the barrier. In contrast, the adaptability-and stability-optimised mixed lipid vesicles (Transfersomes, a trademark of IDEA AG) can trespass much narrower pathways between most cells in the skin; such highly adaptable colloids thus mediate drug transport through the skin. Sufficiently stable ultra-adaptable carriers, therefore, can ensure targeted drug delivery deep below the application site. This has already been shown in numerous preclinical tests and several phase I and phase II clinical studies. Drug delivery by means of highly adaptable drug carriers, moreover, allows highly efficient and well-tolerated drug targeting into the skin proper. Sustained drug release through the skin into systemic blood circulation is another field of ultradeformable drug carrier application.

  4. [Pharmaceutical assistance in the basic units of health: from the national drug policy to the basic attention to health].

    PubMed

    de Oliveira, Luciane Cristina Feltrin; Assis, Marluce Maria Araújo; Barboni, André René

    2010-11-01

    This study of theoretical revision discuss the Pharmaceutical Assistance in the Basic Units of Health, rescuing briefly the history of the National Drug Policy, the mechanisms of financing in the process of health decentralization and Pharmaceutical Assistance on the Basic Attention to Health. The expansion of the population access to the health system has demanded changes on drug distribution in order to increase the coverage and at the same time to reduce costs. It was identified advances in legal and institutional structures: the management decentralization of actions on pharmaceutical assistance; the expansion of the population access to essential medicines; and the establishment of the pharmaceutical assistance in some cities. However, it still persists priority actions in relation to the financing and population coverage, in detriment of quality processes. The conclusion is that, many Brazilian cities has low availability and discontinuity of essential medicine offer; dispensation by workers without qualification; inadequate conditions of storage that compromise the quality of medicines; medicine prescription that does not belong to the National Reference of Essential Medicines; and problems related to the access of users to the pharmacotherapy.

  5. [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

  6. [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

  7. 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.

  8. 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.

  9. 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

  10. Determination of aromatic hydrotropic drugs in pharmaceutical preparations by the surfactant-binding degree method.

    PubMed

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

    2005-07-01

    An aggregation parameter-based analytical approach, the surfactant-dye binding degree (SDBD) method, was used, for the first time, to determine aromatic hydrotropic compounds. The anionic dye Coomassie Brilliant Blue G (CBBG) was used as inductor of didodecyldimethylammonium bromide (DDABr) aggregates, whose formation was monitored from changes in the spectral features of the dye. Interactions between hydrotrope and DDABr molecules resulted in a decrease of the degree of binding of the cationic surfactant to CBBG, which was proportional to the concentration of hydrotrope in the aqueous solution. The CBBG-DDABr-hydrotrope chemical system was found to fit to the mathematical expression previously derived for the determination of amphiphilic compounds. The hydrotrope-surfactant bond strength determined the sensitivity achieved for the determination of hydrotropic compounds, which was highly dependent on the molecular structure of the analyte. The high precision (the relative standard deviation for 7 mg l(-1) of salicylic acid was 0.8%), rapidity (measurements were performed in a few minutes) and low cost (in both instrumentation and reactants) of the proposed method, made it especially suitable for quality control. The practical analytical applicability of the SDBD method for the control of hydrotropic drugs in pharmaceutical preparations was demonstrated by quantifying salicylic acid and acetyl salicylic acid in liquid (solutions) and solid (tablets, granulates, unguents, gels and creams) samples, which were directly analyzed after dissolution of the samples.

  11. Nanocarriers for dermal drug delivery: influence of preparation method, carrier type and rheological properties.

    PubMed

    Schwarz, Julia C; Weixelbaum, Angelika; Pagitsch, Elisabeth; Löw, Monika; Resch, Guenter P; Valenta, Claudia

    2012-11-01

    Nanocarriers are highly interesting delivery systems for the dermal application of drugs. Based on a eudermic alkylpolyglycosid nanoemulsions, solid lipid nanoparticles (SLN) and nano-structured lipid carriers (NLC) were prepared by ultrasonic dispersion. The ultrasound preparation technique turned out to be convenient and rapid. For reasons of comparison, nanoemulsions were also prepared by high-pressure homogenisation with highly similar physicochemical properties. Cryo electron microscopy was employed to elucidate the microstructure of the ultrasound-engineered nanocarriers. Furthermore, in vitro skin experiments showed excellent skin permeation and penetration properties for flufenamic acid from all formulations. Moreover, ATR-FTIR studies revealed barrier-restorative properties for NLC and SLN. Furthermore, the rheological characteristics of all nanocarriers were determined. In order to increase the viscosity, three different polymers were employed to also prepare semi-solid NLC drug delivery systems. All of them exhibited comparable skin diffusion properties, but may offer improved dermal applicability.

  12. Tamoxifen-loaded nanostructured lipid carrier as a drug delivery system: characterization, stability assessment and cytotoxicity.

    PubMed

    How, Chee Wun; Rasedee, Abdullah; Manickam, Sivakumar; Rosli, Rozita

    2013-12-01

    Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as carrier for Tamoxifen (TAM). The TAM-loaded NLC (TAM-NLC) developed with 200mg of TAM showed a spherical particle with the size of 46.6nm, polydispersity index of 0.267, entrapment efficiency of 99.74% and with the zeta potential of -23.78mV. Besides, the equivalent cytotoxicity of TAM and TAM-NLC to human (MCF-7) and mice (4T1) mammary breast cancer cell lines were observed. Incubating the formulation at the physiological pH resulted into reduced Ostwald ripening rate but without any significant change in the absorptivity. When coupled with the measurements of zeta potential and Ostwald ripening rate, the absorbance assay may be used to predict the long-term stability of drug-loaded nanoparticle formulations. The results of the study also suggest that TAM-NLC is a promising drug delivery system for breast cancer therapy. This is the first encouraging report on the in vitro effect of TAM-NLC against human and mouse mammary adenocarcinoma cell lines. PMID:24036474

  13. Fate and removal of pharmaceuticals and illicit drugs in conventional and membrane bioreactor wastewater treatment plants and by riverbank filtration.

    PubMed

    Petrovic, Mira; de Alda, Maria Jose Lopez; Diaz-Cruz, Silvia; Postigo, Cristina; Radjenovic, Jelena; Gros, Meritxell; Barcelo, Damià

    2009-10-13

    Pharmaceutically active compounds (PhACs) and drugs of abuse (DAs) are two important groups of emerging environmental contaminants that have raised an increasing interest in the scientific community. A number of studies revealed their presence in the environment. This is mainly due to the fact that some compounds are not efficiently removed during wastewater treatment processes, being able to reach surface and groundwater and subsequently, drinking waters. This paper reviews the data regarding the levels of pharmaceuticals and illicit drugs detected in wastewaters and gives an overview of their removal by conventional treatment technologies (applying activated sludge) as well as advanced treatments such as membrane bioreactor. The paper also gives an overview of bank filtration practices at managed aquifer recharge sites and discusses the potential of this approach to mitigate the contamination by PhACs and DAs.

  14. 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.

  15. 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.

  16. Paclitaxel-liposome-microbubble complexes as ultrasound-triggered therapeutic drug delivery carriers.

    PubMed

    Yan, Fei; Li, Lu; Deng, Zhiting; Jin, Qiaofeng; Chen, Juanjuan; Yang, Wei; Yeh, Chih-Kuang; Wu, Junru; Shandas, Robin; Liu, Xin; Zheng, Hairong

    2013-03-28

    Liposome-microbubble complexes (LMC) have become a promising therapeutic carrier for ultrasound-triggered drug delivery to treat malignant tumors. However, the efficacy for ultrasound-assisted chemotherapy in vivo and the underlying mechanisms remain to be elucidated. Here, we investigated the feasibility of using paclitaxel-liposome-microbubble complexes (PLMC) as possible ultrasound (US)-triggered targeted chemotherapy against breast cancer. PTX-liposomes (PL) were conjugated to the microbubble (MB) surface through biotin-avidin linkage, increasing the drug-loading efficiency of MBs. The significant increased release of payloads from liposome-microbubble complexes was achieved upon US exposure. We used fluorescent quantum dots (QDs) as a model drug to show that released QDs were taken up by 4T1 breast cancer cells treated with QD-liposome-microbubble complexes (QLMC) and US, and uptake depended on the exposure time and intensity of insonication. We found that PLMC plus US inhibited tumor growth more effectively than PL plus US or PLMC without US, not only in vitro, but also in vivo. Histologically, the inhibition of tumor growth appeared to result from increased apoptosis and reduced angiogenesis in tumor xenografts. In addition, a significant increase of drug concentration in tumors was observed in comparison to treatment with non-conjugated PL or PLMC without US. The significant increase in an antitumor efficacy of PLMC plus US suggests their potential use as a new targeted US chemotherapeutic approach to inhibit breast cancer growth.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. Use of anodized titanium alloy as drug carrier: Ibuprofen as model of drug releasing.

    PubMed

    Doadrio, Antonio L; Conde, A; Arenas, M A; Hernández-López, J M; de Damborenea, J J; Pérez-Jorge, Concepción; Esteban, Jaime; Vallet-Regí, Maria

    2015-08-15

    The use of osteoarticular implants has improved the quality of life of millions of patients. In this work nanotubular structures tailored made on Ti6Al4V substrates was used as drug delivery system of ibuprofen as a proof of concept. Three different nanotubular films with different sizes and forms (NT, NT+ and NTb) were analysed. Samples were soaked in a solution of 660 mg ibuprofen/20 mL n-pentane. The ibuprofen release in aqueous medium was evaluated by liquid chromatography reversed-phase (RP-HPLC). To calculate the observed constant k, the amount of ibuprofen released was plotted versus the time using linear regression according to the zero-order, first-order, second-order and Higuchi model. The release of ibuprofen was constant and independent of the concentration. The kinetic constant obtained was 0.021 (NT), 0.022 (NT+) and 0.013 (NTb) being the correlation factor of 0.98 (zero-order) where the maximum correlation factor was reached. These results indicate that the delivery process from NT and NT+ is similar and slower that NTb. In all the cases was inside the therapeutically range. These results showed the potential of these modifications in order to develop implants that can carry different molecules of medical importance.

  3. Understanding interactions between Chinese medicines and pharmaceutical drugs in integrative healthcare.

    PubMed

    Chan, Kelvin

    2015-02-01

    In the 21st century, the public are more informed, mainly via the Internet, about health and medical products and have become more knowledgeable about matters relating to their health conditions and well-being in curing and preventing illnesses. They often self-medicate themselves with various health products and over-the-counter (OTC) medicines apart from prescribed pharmaceutical drugs (PD). Some of those non-prescribed products may have doubtful quality control and contain harmful additives or unchecked ingredients; thus their usefulness is in doubt. The increasing popularity world-wide of using Chinese medicines (CM) and related OTC functional products has raised concerns over their concomitant use with PD and the consequential adverse effects. In most cases the alleged causes of adverse effects are linked with herbal sources, although the authorised information on the interactions between CM-PD is not plentiful in the literature. There is an urgent need for such a data base. The future professionals in health and medical care should be knowledgeable or aware of what their patients have been taking or given. In actual practice the patients may receive both treatments intentionally or unintentionally, with or without the awareness of the practitioner. In these situations a reliable database for interactions between CM-PD will be extremely useful for consultation when treatment problems appear or during emergency situations. Their combining of medications may be involved with possible outcomes of adverse reactions or beneficial effects. Such a database will be welcomed by both practitioners of herbal medicines and orthodox medicine practitioners in the emerging trend of integrative medicine. The author has been involved in various research projects of basic and clinical aspects in mainly CM among other herbal and PD. Examples will be given largely on those related to these disciplines as illustrations in this overview.

  4. Comparison of solid self-microemulsifying drug delivery system (solid SMEDDS) prepared with hydrophilic and hydrophobic solid carrier.

    PubMed

    Oh, Dong Hoon; Kang, Jun Hyeok; Kim, Dong Wuk; Lee, Beom-Jin; Kim, Jong Oh; Yong, Chul Soon; Choi, Han-Gon

    2011-11-28

    In order to compare the effects of hydrophilic and hydrophobic solid carrier on the formation of solid self-microemulsifying drug delivery system (SMEDDS), two solid SMEDDS formulations were prepared by spray-drying the solutions containing liquid SMEDDS and solid carriers. Colloidal silica and dextran were used as a hydrophobic and a hydrophilic carrier, respectively. The liquid SMEDDS, composed of Labrafil M 1944 CS/Labrasol/Trasncutol HP (12.5/80/7.5%) with 2% w/v flurbiprofen, gave a z-average diameter of about 100 nm. Colloidal silica produced an excellent conventional solid SMEDDS in which the liquid SMEDDS was absorbed onto its surfaces. It gave a microemulsion droplet size similar to that of the liquid SMEDDS (about 100 nm) which was smaller than the other solid SMEDDS formulation. In the solid SMEDDS prepared with dextran, liquid SMEDDS was not absorbed onto the surfaces of carrier but formed a kind of nano-sized microcapsule with carrier. However, the drug was in an amorphous state in two solid SMEDDS formulations. Similarly, they greatly improved the dissolution rate and oral bioavailability of flurbiprofen in rats due to the fast spontaneous emulsion formation and the decreased droplet size. Thus, except appearance, hydrophilic carrier (dextran) and hydrophobic carrier (colloidal silica) hardly affected the formation of solid SMEDDS such as crystalline properties, dissolution and oral bioavailability.

  5. 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

  6. Presence of the pharmaceutical drug carbamazepine in coastal systems: effects on bivalves.

    PubMed

    Almeida, Angela; Calisto, Vânia; Esteves, Valdemar I; Schneider, Rudolf J; Soares, Amadeu M V M; Figueira, Etelvina; Freitas, Rosa

    2014-11-01

    Carbamazepine (CBZ), an antiepileptic drug, is one of the most commonly detected pharmaceutical drugs in aquatic ecosystems, and is used as a marker of urban pollution. Since CBZ is designed to exert a biological effect, when it reaches aquatic environment high probability exist for toxic effects on non-target organisms. The present study evaluated the acute toxicity of environmentally relevant concentrations of CBZ (0.00, 0.03, 0.30, 3.00, 9.00μg/L) in the edible clams Venerupis decussata (a native species) and Venerupis philippinarum (an invasive species) collected from the Ria de Aveiro. The effects on both species were assessed through the use of a battery of biomarkers mainly related with health status and oxidative stress. Furthermore, in this work an alternative and promising tool, the direct competitive immunoassay ELISA, for the direct CBZ quantification in clam's tissues, was applied. The results of the present work showed that CBZ in clam's tissues increased with the exposure concentration and V. decussata gave slightly higher values than V. philippinarum. Although the clams accumulated lower levels of CBZ than the concentration of exposure, these concentrations were enough to impair the health status and induce oxidative stress. However, a different response to CBZ was observed in the two species. While in V. philippinarum the lipid peroxidation levels increased at the highest CBZ concentration (9.00μg/L), in V. decussata a significant decrease was seen. Moreover, glutathionse S-transferase activity was stimulated in V. decussata and decreased in V. philippinarum. Nevertheless, an induction of glutathione reductase, superoxide dismutase and cytochrome P450 3A4 activities was found in both species as a result of the exposure. The results indicate that, probably, V. philippinarum have a less efficient antioxidant system than V. decussata, and are therefore less capable to neutralize oxidative stress and consequently more sensitive to CBZ. The risk

  7. Synthesis of amphiphilic copolymers containing zwitterionic sulfobetaine as pH and redox responsive drug carriers.

    PubMed

    Cai, Mengtan; Leng, Mengtian; Lu, Aijing; He, Liu; Xie, Xiaoxiong; Huang, Lei; Ma, Yuhao; Cao, Jun; Chen, Yuanwei; Luo, Xianglin

    2015-02-01

    Amphiphilic poly(ɛ-caprolactone)-SS-poly(N,N-diethylaminoethyl methacrylate)-r-poly(N-(3-sulfopropyl)-N-methacrylate-N,N-diethylammonium-betaine) (PCL-SS-PDEASB) was designed and synthesized successfully. pH and redox dually responsive micelles were prepared based on the obtained copolymers, with zwitterionic sulfobetaines as hydrophilic shell, DEA as pH sensitive content and disulfide as redox responsive linkage. The micelle diameters were all less than 200 nm and the micelle diameter distributions were narrow. These micelles could be triggered by pH and redox condition. The drug release from the drug-loaded micelles displayed fastest under simultaneously acidic and reductive conditions. Results of in vitro cell toxicity evaluation showed that introduction of sulfobetaines could greatly decrease the toxicity of poly(ɛ-caprolactone)-SS-poly(N,N-diethylaminoethyl methacrylate) (PCL-SS-PDEA) micelles. DOX-loaded PCL-SS-PDEASB micelles showed higher efficiency to kill HeLa cells than DOX-loaded PCL-PDEASB micelles. Half inhibitory concentration (IC50) of DOX-loaded PCL-SS-PDEASB micelles decreased with the content of sulfobetaines increasing and was even closer to that of DOX·HCl. Thus, the pH and redox dually responsive biodegradable micelles generated by PCL-SS-PDEASB may be potential smart drug carriers for tumor targeted delivery. PMID:25531063

  8. Biodegradable double nanocapsule as a novel multifunctional carrier for drug delivery and cell imaging.

    PubMed

    Qian, Kun; Wu, Jing; Zhang, Enqi; Zhang, Yingge; Fu, Ailing

    2015-01-01

    Highly-efficient delivery of macromolecules into cells for both imaging and therapy (theranostics) remains a challenge for the design of a delivery system. Here, we suggested a novel hybrid protein-lipid polymer nanocapsule as an effective and nontoxic drug delivery and imaging carrier. The biodegradable nanocapsules showed the typical double emulsion features, including fluorescently labeled bovine serum albumin shell, oil phase containing poly(lactic-co-glycolic acid) and linoleic acid, and inner aqueous phase. The nanocapsules were spherical in shape, with an average size of about 180 nm. Proteins packed into the inner aqueous phase of the nanocapsules could be delivered into cells with high efficiency, and the fluorescence of the fluorescently labeled bovine serum albumin could be used for tracing the protein migration and cellular location. Further studies suggested that the co-delivery of transcription factor p53 and lipophilic drug paclitaxel with the nanocapsules acted synergistically to induce Hela cell apoptosis, and the fluorescence of apoptotic cells was clearly observed under a fluorescence microscope. Such multifunctional delivery system would have great potential applications in drug delivery and theranostic fields.

  9. 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.

  10. 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.

  11. Asymmetrical flow field-flow fractionation and multiangle light scattering for analysis of gelatin nanoparticle drug carrier systems.

    PubMed

    Fraunhofer, Wolfgang; Winter, Gerhard; Coester, Conrad

    2004-04-01

    The physicochemical properties of nanosized colloidal drug carrier systems are of great influence on drug efficacy. Consequently, a broad spectrum of analytical techniques is applied for comprehensive drug carrier characterization. It is the primary objective of this paper to present asymmetrical flow field-flow fractionation (AF4), coupled online with multiangle light scattering detection, for the characterization of gelatin nanoparticles. Size and size distribution of drug-loaded and unloaded nanoparticles were determined, and data were correlated with results of state-of-the-art methods, such as scanning electron microscopy and photon correlation spectroscopy. Moreover, the AF4 fractionation of gelatin nanoparticulate carriers from a protein model drug is demonstrated for the first time, proposing a feasible way to assess the amount of loaded drug in situ without sample preparation. This hypothesis was set into practice by monitoring the drug loading of nanoparticles with oligonucleotide payloads. In this realm, various fractions of gelatin bulk material were analyzed via AF4 and size-exclusion high-pressure liquid chromatography. Mass distributions and high-molecular-weight fraction ratios of the gelatin samples varied, depending on the separation method applied. In general, the AF4 method demonstrated the ability to comprehensively characterize polymeric gelatin bulk material as well as drug-loaded and unloaded nanoparticles in terms of size, size distribution, molecular weight, and loading efficiency.

  12. 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

  13. 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.

  14. Nanostructured lipid carriers (NLC) for parenteral delivery of an anticancer drug.

    PubMed

    Chinsriwongkul, Akhayacatra; Chareanputtakhun, Ponwanit; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Sila-on, Warisada; Ruktanonchai, Uracha; Opanasopit, Praneet

    2012-03-01

    The purpose of this research was to formulate nanostructured lipid carriers (NLC) for the parenteral delivery of an anticancer drug, all-trans retinoic acid (ATRA). The ATRA was incorporated into NLC by the de novo emulsification method. The effect of the formulation factor, i.e., type and oil ratio, initial ATRA concentration on physicochemical properties was determined. The anticancer efficacy of ATRA-loaded NLC on HL-60 and HepG2 cells was also studied. NLC was formulated using a blend of solid lipids (cetyl palmitate) and liquid lipids (soybean oil (S), medium-chain triglyceride (M), S/oleic acid (O; 3:1) and M/O (3:1)) at a weight ratio of 1:1. ATRA-loaded NLC had an average size of less than 200 nm (141.80 to 172.95 nm) with a narrow PDI and negative zeta potential that was within an acceptable range for intravenous injection. The results indicated that oleic acid enhanced the ATRA-loading capacity of NLC. In vitro ATRA release was only approximately 4.06% to 4.34% for 48 h, and no significant difference in ATRA release rate from all NLC formulations in accordance with the composition of the oil phase. Moreover, no burst release of the drug was observed, indicating that NLC could prolong the release of ATRA. The initial drug concentration affected the photodegradation rate but did not affect the release rate. All ATRA-loaded NLC formulations exhibited the photoprotective property. The cytotoxicity results showed that all ATRA-loaded NLC had higher cytotoxicity than the free drug and HL-60 cells were more sensitive to ATRA than HepG2 cells. PMID:22167418

  15. 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

  16. Public perceptions of the pharmaceutical industry and drug safety: implications for the pharmacovigilance professional and the culture of safety.

    PubMed

    Olsen, Axel K; Whalen, Matthew D

    2009-01-01

    A survey of the US public titled 'Consumer Perceptions on Drug Safety' was conducted in October 2006. The survey was undertaken at that time because of the heightened public awareness of drug safety concerns over rofecoxib (Vioxx(R)) and pediatric antidepressant use. The survey was designed with questions related to public perception of the pharmaceutical industry, the US FDA, Congress and whether the US public perceived there to be a safety crisis. The survey consisted of 1726 US men and women aged 18 years and over. The survey results showed that the FDA, Congress and US pharmaceutical companies are perceived as having a notable amount of responsibility to ensure safety (by 75%, 41% and 70% of respondents, respectively). Additionally, 96% of the survey respondents indicated that they had some level of concern about adverse reactions to prescription drugs that are taken as directed. Seventy-six percent of the respondents were 'fairly' to 'extremely' concerned about adverse reactions, while approximately 42% of the survey respondents' opinions ranged from 'somewhat distrusting' to 'strongly distrusting' of the pharmaceutical companies that develop drugs. These findings are comparable to those in surveys conducted by the Kaiser Family Foundation in 2005 and PriceWaterhouseCoopers in 2007. These surveys suggest that about half the respondents believe there is both the need and desire for reform in drug safety by the pharmaceutical industry and the FDA. In reports from 2006 and 2007, the Institute of Medicine challenges the healthcare system and the FDA to adopt the principles of the culture of safety. While there have been steps taken to address the recommendations of the reports, as exemplified by the FDA Amendment Act of 2007 and the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European Consortium, true reform across the life sciences sector will only come through broad adoption of these principles. Thus, it is particularly important for

  17. A rapid HPLC procedure for analysis of analgesic pharmaceutical mixtures for quality assurance and drug diversion testing.

    PubMed

    Wolf, Carl E; Poklis, Alphonse

    2005-10-01

    A simple high-performance liquid chromatographic (HPLC) method that allows for the rapid identification and quantification of analgesic and anesthetic solutions typically used in surgical procedures or patient controlled analgesia is presented. The separation of bupivacaine, clonidine, fentanyl, hydromorphone, midazolam, and morphine is complete in less than 20 min. The method allows test solutions to be either directly injected or diluted prior to injection into the HPLC system. The method is useful from the standpoint that pharmaceutical preparations are usually submitted with the known drug of interest and expected concentration. The method is also useful for initial screening of solutions submitted that are either unknown or of questionable identity. The method has been successfully applied as part of hospital-based quality control and quality assurance programs to detect not only errors in the preparation of solutions of scheduled drugs, but also to uncover illegal diversion of drugs of abuse by medical personnel.

  18. Fabrication of new drug imprinting polymer beads for selective extraction of naproxen in human urine and pharmaceutical samples.

    PubMed

    Panahi, Homayon Ahmad; Feizbakhsh, Alireza; Khaledi, Sardar; Moniri, Elham

    2013-01-30

    A drug imprinting polymer based on suspension polymerization was prepared with N,N-dimethylacrylamide and 1-(N,N-bis-carboxymethyl) amino-3-allylglycerol as functional monomers, N,N methylene diacrylamid as the cross-linker, naproxen as the template and 2,2'-azobis (2-methylbutyronitrile) as the initiator. The drug imprinted polymer was characterized by Fourier transform infrared spectroscopy, elemental analysis, thermogravimetric analysis and transmission electron microscopy. The imprinted polymer of agglomerated micro-particles with multi-pores was used for solid phase extraction. The drug imprinted polymer sorbent was selective for naproxen. The profile of the naproxen uptake by the sorbent reflects good accessibility of the active sites in the imprinted polymer sorbent. In addition, the equilibrium adsorption data of naproxen by imprinted polymer were analyzed by Langmuir isotherm models. The developed method was utilized for determination of naproxen in pharmaceutical and human urine samples by high performance liquid chromatography with satisfactory results.

  19. 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

  20. Eudragit E100 as a drug carrier: the remarkable affinity of phosphate ester for dimethylamine.

    PubMed

    Guzmán, M L; Manzo, R H; Olivera, M E

    2012-09-01

    Therapeutic agents containing phosphate groups in their molecules have increasing therapeutic impact. The object of this study was to characterize the cationic polyelectrolyte Eudragit E100 (EuE100) as a carrier for drugs containing phosphate groups, using dexamethasone phosphate (DP) as a model. A series of EuE100-DP complexes was obtained by acid-base reaction in which DP neutralized 12.5-75% of the basic groups of EuE100. The solids obtained after solvent evaporation revealed by spectroscopic characterization the complete reaction between the components through the ionic interaction between the amine groups of EuE100 and the phosphate groups of DP. The reversibility of the counterion condensation, evaluated through the proton-withdrawing effect produced by the ionic exchange generated by titration with NaCl, showed a remarkable high affinity between EuE100 and DP. In line, drug delivery in bicompartimental Franz cells toward water as receptor medium was very slow (2% in 6 h). However, it was increased as water was replaced by NaCl solution, which upon diffusion generates ionic exchange. A sustained release of DP with noticeable zero order kinetics accounted for a remarkable high affinity, mainly due to the electrostatic attraction. The release rate remains constant regardless of the saline concentration of the media. Besides, the delivery control is maintained even in gastric simulated fluid, a property not informed previously for EuE100 complexes. PMID:22808998

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Room-temperature phosphorimetric method for the determination of the drug naphazoline in pharmaceutical preparations.

    PubMed

    Segura Carretero, A; Cruces Blanco, C; Cañabate Díaz, B; Fernández Gutiérrez, A

    1998-05-01

    A selective and sensitive micelle-stabilized room-temperature phosphorimetric (MS-RTP) method for the determination of naphazoline in pharmaceutical preparations is described. The method is based on obtaining a phosphorescence signal from naphazoline using a micellar agent (sodium dodecyl sulfate), a heavy atom salt (TINO3) and a deoxygenation agent (Na2SO3). Optimization of the various conditions permitted the establishment of an MS-RTP method for naphazoline determination with a detection limit of 64.2 ng ml-1 and a relative standard deviation of 3.74% at the 500 ng ml-1 level. The method was applied to the analysis of pharmaceutical preparations.

  9. 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

  10. 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.

  11. Comparison between micellar liquid chromatography and capillary zone electrophoresis for the determination of hydrophobic basic drugs in pharmaceutical preparations.

    PubMed

    Torres-Cartas, S; Martín-Biosca, Y; Sagrado, S; Villanueva-Camañas, R M; Medina-Hernández, M J

    2007-01-01

    The determination of highly hydrophobic basic compounds by means of conventional reversed-phase liquid chromatographic methods has several drawbacks. Owing to the characteristics of micellar liquid chromatography (MLC) and capillary electrophoresis (CE), these techniques could be advantageous alternatives to reversed-phase chromatographic methods for the determination of these kinds of compounds. The objective of this study was to develop and compare MLC and CE methods for the determination of antipsychotic basic drugs (amitryptiline, haloperidol, perphenazine and thioridazine) in pharmaceutical preparations. The chromatographic determination of the analytes was performed on a Kromasil C(18) analytical column; the mobile phase was 0.04 m cetyltrimethylammonium bromide (CTAB), at pH 3, containing 5% 1-butanol, at a flow rate of 1 mL/min. The CE separation was performed in a fused-silica capillary with a 50 mm tris-(hydroxymethyl)-aminomethane buffer, pH 7, at an applied voltage of 20 kV, using barbital as internal stardard. The proposed methods are suitable for a reliable quantitation of these compounds in the commercial tablets and drops in terms of accuracy and precision and require a very simple pre-treatment of the samples. By comparing the performance characteristics and experimental details of the MLC and CE methods we conclude that CE seems to be slightly better than MLC in the determination of highly hydrophobic compounds in pharmaceuticals in terms of resolution and economy, taking into account that the limits of detection are not a handicap in pharmaceutical samples.

  12. Comparison of pharmaceutical properties of topical non-steroidal anti-inflammatory drug preparations on quality of life.

    PubMed

    Shibata, Yuuka; Ikeda, Hiroaki; Kondou, Yoshihiro; Kihira, Kenji

    2005-05-01

    To compare the effects of different pharmaceutical properties of commercially available topical nonsteroidal antiinflammatory drugs (NSAIDs) on the quality of life, we administered a questionnaire to 65 healthy volunteers. We investigated five creams, five gels, and four solutions of topical NSAID preparations in this study. The survey was conducted to clarify the relationship of their answers and pharmaceutical properties of the topical NSAID preparations. Questions addressed spreadability, smell, viscosity, and comfort level of the topical NSAID preparations. Among the five creams, Napageln had lower spreadability, less smell, and greater viscosity than the other preparations. Because of its easy spreadability, weak smell, and low viscosity, the volunteers favored Sector cream among the cream preparations. Among the five gel preparations, Inteban had less spreadability, stronger smell, and higher viscosity than the other preparations. The volunteers favored Epatec over the other gel preparations. All four solutions had the odor of menthol and other artificial ingredients, except for Napageln. These findings indicate that information on the pharmaceutical properties of commercially available topical NSAID preparations will be helpful to physicians and pharmacists in conducting medical treatment and prescribing.

  13. 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

  14. 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

  15. 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.

  16. In-line NIR spectroscopy for the understanding of polymer-drug interaction during pharmaceutical hot-melt extrusion.

    PubMed

    Saerens, Lien; Dierickx, Lien; Quinten, Thomas; Adriaensens, Peter; Carleer, Robert; Vervaet, Chris; Remon, Jean Paul; De Beer, Thomas

    2012-05-01

    The aim was to evaluate near-infrared spectroscopy for the in-line determination of the drug concentration, the polymer-drug solid-state behaviour and molecular interactions during hot-melt extrusion. Kollidon® SR was extruded with varying metoprolol tartrate (MPT) concentrations (20%, 30% and 40%) and monitored using NIR spectroscopy. A PLS model allowed drug concentration determination. The correlation between predicted and real MPT concentrations was good (R(2)=0.97). The predictive performance of the model was evaluated by the root mean square error of prediction, which was 1.54%. Kollidon® SR with 40% MPT was extruded at 105°C and 135°C to evaluate NIR spectroscopy for in-line polymer-drug solid-state characterisation. NIR spectra indicated the presence of amorphous MPT and hydrogen bonds between drug and polymer in the extrudates. More amorphous MPT and interactions could be found in the extrudates produced at 135°C than at 105°C. Raman spectroscopy, DSC and ATR FT-IR were used to confirm the NIR observations. Due to the instability of the formulation, only in-line Raman spectroscopy was an adequate confirmation tool. NIR spectroscopy is a potential PAT-tool for the in-line determination of API concentration and for the polymer-drug solid-state behaviour monitoring during pharmaceutical hot-melt extrusion.

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... dispensed at the point of sale or, in the case of dispensing by mail order, at the time of delivery of the... 42 Public Health 3 2011-10-01 2011-10-01 false Public disclosure of pharmaceutical prices for... OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION...

  18. 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

  19. Investigation of vesicle electrokinetic chromatography as an in vitro assay for the estimation of intestinal permeability of pharmaceutical drug candidates.

    PubMed

    Pascoe, Robert J; Masucci, John A; Foley, Joe P

    2006-02-01

    As the pharmaceutical industry continues the daunting search for novel drug candidates, there remains a need for rapid screening methods not only for biological activity, but for physiochemical properties as well. It is invaluable that adequate model systems for absorption and/or bioavailability be developed early in the drug evaluation process to avoid the loss of promising compounds late in development. The focus of this paper is the use of vesicle EKC (VEKC) as a high-throughput, easy, cost-effective, and predictive model for the passive transcellular diffusion of drug candidates in the intestinal epithelium. Vesicles are large aggregates of molecules containing a spherical bilayer structure encapsulating an internal cavity of solvent. It is this bilayer structure that makes vesicles attractive as model membranes. In this study, vesicles were synthesized from both phospholipids and surfactant aggregates, and then employed as pseudostationary phases in EKC (VEKC). The interaction of drug molecules with vesicles in EKC was then used as the basis for an in vitro assay to evaluate passive diffusion. The VEKC technique showed a statistical correlation between the retention of drug candidates using surfactant and phospholipid vesicles and passive diffusion data (log Pow and colon adenocarcinoma). VEKC analysis offers high-throughput capabilities due to the short run times, low sample, and solvent volumes necessary, as well as instrument automation. However, due to the complexity of drug absorption in the intestine, difficulty arises when a single in vitro model is used to predict in vivo absorption characteristics. Therefore, the retention of drug candidates using VEKC in conjunction with other permeability prediction methods can provide a primary screen for a large number of drug candidates early in the drug discovery process with minimal resources.

  20. Crosslinked hydrogels—a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

    PubMed Central

    Sun, Dajun D.; Lee, Ping I.

    2014-01-01

    Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs. PMID:26579361

  1. Stable polymer micelle systems as anti-cancer drug delivery carriers

    NASA Astrophysics Data System (ADS)

    Zeng, Yi

    2005-07-01

    Several temporarily stable polymer micelle systems that might be used as ultrasonic-activated drug delivery carriers were synthesized and investigated. These polymeric micelle systems were PlurogelRTM, Tetronic RTM, poly(ethylene oxide)-b-poly(N-isopropylacrylamide) and poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-lactate n). In previous work in our lab, Pruitt et al. developed a stabilized drug carrier named PlurogelRTM [5, 6]. Unfortunately, the rate of the successful PlurogelRTM synthesis was only about 30% by simply following Pruitt's process. In this work, this rate was improved to 60% by combining the process of adding 0.15 M NaCl and/or 10 mul/ml n-butanol and by preheating the solution before polymerization. TetronicsRTM were proved not to be good candidates to form temporarily stable polymeric micelle system by polymerizing interpenetrating networks inside their micelle cores. Tetronic micelle systems treated by this process still were not stable at concentrations below their critical micelle concentration (CMC). Poly(ethylene oxide)-b-poly(N-isopropylacrylamide)-N,N-bis(acryloyl)cystamine micelle-like nanoparticles were developed and characterized. When the N,N-bis(acryloyl)cystamine (BAC) was from 0.2 wt% to 0.75 wt% of the mass of poly(N-isopropylacrylamide), diameters of the nanoparticles at 40°C were less than 150 nm. The cores of the nanoparticles were hydrophobic enough to sequester 1,6-diphenylhexatriene (DPH) and the anti-cancer drug doxorubicin (DOX). Nanoparticles with 0.5 wt% BAC stored at room temperature in 0.002 mg/ml solutions were stable for up to two weeks. Poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-lactate n) micelle systems were synthesized and characterized. The degree of polymerization of lactate side group, n, was 3 or 5. The copolymers with N-isopropylacrylamide:2-hydroxyethyl methacrylate-lactate3: poly(ethylene oxide) (NIPAAm:HEMA-lactate 3:PEO) ratios of

  2. Biodegradable tocopherol acetate as a drug carrier to prevent ureteral stent-associated infection.

    PubMed

    Elayarajah; Rajendran, R; Venkatrajah; Sreekumar, Sweda; Sudhakar, Asa; Janiga; Sreekumar, Soumya

    2011-03-01

    Biomaterial-centred bacterial infections present common and challenging complications with medical implants like ureteral stent which provide substratum for the biofilm formation. Hence the purpose of this study is to make antibacterial stent surface with biodegradable polymer (tocopherol acetate) and anti-infective agents (norfloxacin and metronidazole) using a modified dip-coating procedure. This is done by impregnating the stent pieces in the anti-infective solution (a mixture of norfloxacin-metronidazole and polymer) for uniform surface coating (drug-carrier-coated stents). After coating, agar diffusion test was performed as qualitative test to find out the sensitivity of coated stents against the clinical isolates, Staphylococcus epidermidis and Escherichia coli. Quantitative test was measured by calculating the numbers of adhered bacteria on coated and uncoated stents by incubating the stent pieces in artificial urine. Difference in the number of viable bacteria adhered on the surface of coated and uncoated stents were statistically calculated using chi square test with p < 0.05 considered significant. The stent colonising ability of Staphylococcus epidermidis and Escherichia coli in a controlled environment chamber was determined using two-challenge dose of the isolates by in vitro challenge test. In qualitative test, the zone of inhibition around the coated stents showed sensitivity against the clinical isolates. In quantitative test, the number of adhered bacteria on the surface of coated stents was reduced to a significant level (p < 0.05). The polymer, tocopherol acetate is highly biodegradable in nature. Due to its degrading ability in body tissues, it releases the anti-infective drugs at a constant and sustained rate.

  3. Simultaneous Determination of Eight Hypotensive Drugs of Various Chemical Groups in Pharmaceutical Preparations by HPLC-DAD.

    PubMed

    Stolarczyk, Mariusz; Hubicka, Urszula; Żuromska-Witek, Barbara; Krzek, Jan

    2015-01-01

    A new sensitive, simple, rapid, and precise HPLC method with diode array detection has been developed for separation and simultaneous determination of hydrochlorothiazide, furosemide, torasemide, losartane, quinapril, valsartan, spironolactone, and canrenone in combined pharmaceutical dosage forms. The chromatographic analysis of the tested drugs was performed on an ACE C18, 100 Å, 250×4.6 mm, 5 μm particle size column with 0.0.05 M phosphate buffer (pH=3.00)-acetonitrile-methanol (30+20+50 v/v/v) mobile phase at a flow rate of 1.0 mL/min. The column was thermostatted at 25°C. UV detection was performed at 230 nm. Analysis time was 10 min. The elaborated method meets the acceptance criteria for specificity, linearity, sensitivity, accuracy, and precision. The proposed method was successfully applied for the determination of the studied drugs in the selected combined dosage forms. PMID:26651566

  4. An improved approach to measuring drug innovation finds steady rates of first-in-class pharmaceuticals, 1987-2011.

    PubMed

    Lanthier, Michael; Miller, Kathleen L; Nardinelli, Clark; Woodcock, Janet

    2013-08-01

    For more than a decade, industry analysts and policy makers have raised concerns about declining pharmaceutical innovation, citing declining numbers of new molecular entities (NMEs) approved in the United States each year. Yet there is little consensus on whether this is the best measure of "innovation." We examined NME approvals during 1987-2011 and propose the three distinct subcategories of NMEs--first-in-class, advance-in-class, and addition-to-class--to provide more nuanced and informative insights into underlying trends. We found that trends in NME approvals were largely driven by addition-to-class, or "me too," drug approvals, while first-in-class approvals remained fairly steady over the study period. Moreover, the higher proportion of first-in-class drug approvals over the most recent decade is an encouraging sign of the health of the industry as a whole.

  5. Simultaneous Determination of Eight Hypotensive Drugs of Various Chemical Groups in Pharmaceutical Preparations by HPLC-DAD.

    PubMed

    Stolarczyk, Mariusz; Hubicka, Urszula; Żuromska-Witek, Barbara; Krzek, Jan

    2015-01-01

    A new sensitive, simple, rapid, and precise HPLC method with diode array detection has been developed for separation and simultaneous determination of hydrochlorothiazide, furosemide, torasemide, losartane, quinapril, valsartan, spironolactone, and canrenone in combined pharmaceutical dosage forms. The chromatographic analysis of the tested drugs was performed on an ACE C18, 100 Å, 250×4.6 mm, 5 μm particle size column with 0.0.05 M phosphate buffer (pH=3.00)-acetonitrile-methanol (30+20+50 v/v/v) mobile phase at a flow rate of 1.0 mL/min. The column was thermostatted at 25°C. UV detection was performed at 230 nm. Analysis time was 10 min. The elaborated method meets the acceptance criteria for specificity, linearity, sensitivity, accuracy, and precision. The proposed method was successfully applied for the determination of the studied drugs in the selected combined dosage forms.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

    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

    2014-11-01

    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.

  13. Early pharmaceutical profiling to predict oral drug absorption: current status and unmet needs.

    PubMed

    Bergström, Christel A S; Holm, René; Jørgensen, Søren Astrup; Andersson, Sara B E; Artursson, Per; Beato, Stefania; Borde, Anders; Box, Karl; Brewster, Marcus; Dressman, Jennifer; Feng, Kung-I; Halbert, Gavin; Kostewicz, Edmund; McAllister, Mark; Muenster, Uwe; Thinnes, Julian; Taylor, Robert; Mullertz, Anette

    2014-06-16

    Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silico and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered.

  14. 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)...

  15. 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.

  16. Fast enantiomeric separation of basis drugs by electrokinetic chromatography. Application to the quantitation of terbutaline in a pharmaceutical preparation.

    PubMed

    García-Ruiz, C; Marina, M L

    2001-09-01

    Electrokinetic chromatography (EKC) using micelles of bile salts alone or mixed with sodium dodecyl sulfate (SDS) and neutral, anionic, or cationic cyclodextrins (CDs) in the separation buffer has been employed in order to achieve fast enantiomeric separation of basic drugs. A study of the enantiomeric separation ability of these chiral selectors concerning four basic drugs (epinephrine, terbutaline, clenbuterol, and salbutamol) has been carried out under different experimental conditions. The best chiral selectors to perform the enantiomeric separation of these drugs were neutral beta-CD derivatives, specifically permethylated beta-CD PM-beta-CD. The effect of the PM-beta-CD concentration, temperature, and applied voltage on the enantiomeric resolution of the basic drugs was investigated. The use of a 25 mM ammonium acetate buffer (pH 5.0), 30 mM in PM-beta-CD together with an applied voltage of 20 kV and a temperature of 15 degrees C enabled the individual and fast enantiomeric separation of epinephrine, norepinephrine, terbutaline, clenbuterol, and salbutamol each one into its two enantiomers in less than 3 min. The EKC method was validated (precision and accuracy) to quantitate terbutaline in a pharmaceutical preparation, obtaining a limit of detection of 4 microg/mL.

  17. 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.

  18. Preliminary thermoluminescence and optically stimulated luminescence investigation of commercial pharmaceutical preparations towards the drug sterilization dosimetry.

    PubMed

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

    2014-09-01

    Drug sterilization with ionizing radiation is a well-established technology and is gaining ground the last decades due to its numerous advantages. Identification of irradiated drugs would be interesting and, in this respect, the present work aims, for the first time to the authors' best knowledge, to explore whether OSL and TL can be employed as methods for post-sterilization dosimetry on commercial drugs, i.e., as tools for the detection of irradiated drugs. Five widely used drugs, i.e., Daktarin(®), Aspirin(®), Panadol(®), Brufen(®) and Procef(®), are used for this purpose. Preliminary findings are very promising towards the post-sterilization dosimetry and the use of commercial drugs for normal and/or accidental dosimetry. PMID:24922552

  19. Preliminary thermoluminescence and optically stimulated luminescence investigation of commercial pharmaceutical preparations towards the drug sterilization dosimetry.

    PubMed

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

    2014-09-01

    Drug sterilization with ionizing radiation is a well-established technology and is gaining ground the last decades due to its numerous advantages. Identification of irradiated drugs would be interesting and, in this respect, the present work aims, for the first time to the authors' best knowledge, to explore whether OSL and TL can be employed as methods for post-sterilization dosimetry on commercial drugs, i.e., as tools for the detection of irradiated drugs. Five widely used drugs, i.e., Daktarin(®), Aspirin(®), Panadol(®), Brufen(®) and Procef(®), are used for this purpose. Preliminary findings are very promising towards the post-sterilization dosimetry and the use of commercial drugs for normal and/or accidental dosimetry.

  20. 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

  1. 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.

  2. 78 FR 26375 - Food and Drug Administration/International Society for Pharmaceutical Engineering Co-Sponsorship...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-06

    ... Manufacturing Practices): Creating, Implementing, and Sustaining a Culture of Quality AGENCY: Food and Drug... entitled ``Redefining the `C' in CGMP: Creating, Implementing and Sustaining a Culture of...

  3. 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.

  4. 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.

  5. 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.

  6. Structural and haemostatic features of pharmaceutical heparins from different animal sources: challenges to define thresholds separating distinct drugs

    PubMed Central

    Tovar, Ana M. F.; Santos, Gustavo R. C.; Capillé, Nina V.; Piquet, Adriana A.; Glauser, Bianca F.; Pereira, Mariana S.; Vilanova, Eduardo; Mourão, Paulo A. S.

    2016-01-01

    Heparins extracted from different animal sources have been conventionally considered effective anticoagulant and antithrombotic agents despite of their pharmacological dissimilarities. We performed herein a systematic analysis on the physicochemical properties, disaccharide composition, in vitro anticoagulant potency and in vivo antithrombotic and bleeding effects of several batches of pharmaceutical grade heparins obtained from porcine intestine, bovine intestine and bovine lung. Each of these three heparin types unambiguously presented differences in their chemical structures, physicochemical properties and/or haemostatic effects. We also prepared derivatives of these heparins with similar molecular weight differing exclusively in their disaccharide composition. The derivatives from porcine intestinal and bovine lung heparins were structurally more similar with each other and hence presented close anticoagulant activities whereas the derivative from bovine intestinal heparin had a higher proportion of 6-desulfated α-glucosamine units and about half anticoagulant activity. Our findings reasonably indicate that pharmaceutical preparations of heparin from different animal sources constitute distinct drugs, thus requiring specific regulatory rules and therapeutic evaluations. PMID:27752111

  7. Development, optimization and validation of a rapid colorimetric microplate bioassay for neomycin sulfate in pharmaceutical drug products.

    PubMed

    Francisco, Fabiane Lacerda; Saviano, Alessandro Morais; Pinto, Terezinha de Jesus Andreoli; Lourenço, Felipe Rebello

    2014-08-01

    Microbiological assays have been used to evaluate antimicrobial activity since the discovery of the first antibiotics. Despite their limitations, microbiological assays are widely employed to determine antibiotic potency of pharmaceutical dosage forms, since they provide a measure of biological activity. The aim of this work is to develop, optimize and validate a rapid colorimetric microplate bioassay for the potency of neomycin in pharmaceutical drug products. Factorial and response surface methodologies were used in the development and optimization of the choice of microorganism, culture medium composition, amount of inoculum, triphenyltetrazolium chloride (TTC) concentration and neomycin concentration. The optimized bioassay method was validated by the assessment of linearity (range 3.0 to 5.0μg/mL, r=0.998 and 0.994 for standard and sample curves, respectively), precision (relative standard deviation (RSD) of 2.8% and 4.0 for repeatability and intermediate precision, respectively), accuracy (mean recovery=100.2%) and robustness. Statistical analysis showed equivalency between agar diffusion microbiological assay and rapid colorimetric microplate bioassay. In addition, microplate bioassay had advantages concerning the sensitivity of response, time of incubation, and amount of culture medium and solutions required.

  8. 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.

  9. 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

  10. 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.

  11. The application of in silico drug-likeness predictions in pharmaceutical research.

    PubMed

    Tian, Sheng; Wang, Junmei; Li, Youyong; Li, Dan; Xu, Lei; Hou, Tingjun

    2015-06-23

    The concept of drug-likeness, established from the analyses of the physiochemical properties or/and structural features of existing small organic drugs or/and drug candidates, has been widely used to filter out compounds with undesirable properties, especially poor ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles. Here, we summarize various approaches for drug-likeness evaluations, including simple rules/filters based on molecular properties/structures and quantitative prediction models based on sophisticated machine learning methods, and provide a comprehensive review of recent advances in this field. Moreover, the strengths and weaknesses of these approaches are briefly outlined. Finally, the drug-likeness analyses of natural products and traditional Chinese medicines (TCM) are discussed.

  12. 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

  13. Hydrocortisone and dexamethasone in very deformable drug carriers have increased biological potency, prolonged effect, and reduced therapeutic dosage.

    PubMed

    Cevc, Gregor; Blume, Gabriele

    2004-05-27

    We characterised biological properties of novel formulations of two low-potency glucocorticosteroids, dexamethasone and hydrocortisone, which have an equivalent dose ratio of 1:50 in vasoconstriction tests. The rate of such carrier-mediated, mainly non-diffusive glucocorticosteroids transport with very deformable lipid vesicles (Transfersomes) through the skin, and the corresponding cutaneous drug biodistribution data, were complemented with the drug bio-efficacy studies. The minimum effective drug dose that reduces arachidonic acid-induced murine ear oedema by 50% was used as one bioactivity indicator. The minimum drug amount ensuring such an effect in mouse skin decreases appreciably when a corticosteroid is applied epicutaneously with very deformable vesicles rather than a lotion or a crème. Specifically, the minimum effective dose for hydrocortisone in very deformable carriers is 2-3 microg cm(-2) whereas for the crème- or lotion-like preparations at least 10 microg cm(-2) is required. Such three- to fivefold relative increase of hydrocortisone potency is accompanied by at least 13%, and more often >20%, absolute drug potency enhancement. The delivery of hydrocortisone with very deformable carriers moreover prolongs the suppression of the drug-induced oedema nearly 2-fold (to approximately 24 h per application). The effective dose of dexamethasone delivered with very deformable vesicles into murine skin is reduced >10 times compared with the crème- or lotion-based products. Specifically, less than 0.1 microg cm(-2) dexamethasone in very deformable vesicles suppresses the arachidonic acid-induced murine ear oedema >50%, on the average. Dexamethasone use on the skin in such vesicles extends the duration of drug action fourfold, compared with a commercial crème, i.e. to >48 h per application. Epicutaneous use of glucocorticosteroids in very deformable vesicles also diminishes such drug's abrasion sensitivity and may increase the general robustness of drug

  14. 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.

  15. Effect of mergers and acquisitions on drug discovery: perspective from a case study of a Japanese pharmaceutical company.

    PubMed

    Shibayama, Sotaro; Tanikawa, Kunihiro; Fujimoto, Ryuhei; Kimura, Hiromichi

    2008-01-01

    The pharmaceutical industry has experienced intermittent waves of mergers and acquisitions (M&As) since the 1980s and recently appeared to be in yet another wave. Previous studies indicated rather negative impacts of consolidation on research and development, suggesting that they do not necessarily lead to long-term reinforcement of research capabilities, although they may enrich the drug pipeline in the short term. However, recent studies have implied a positive side in terms of knowledge-base transfer. Further micro-organizational studies suggested that scientists learned new knowledge and approaches from partner scientists and improved their performance and innovation. These findings imply that measures for the scientist-level integration after M&As would reinforce fundamental research capabilities in the long term. PMID:18190869

  16. Effect of mergers and acquisitions on drug discovery: perspective from a case study of a Japanese pharmaceutical company.

    PubMed

    Shibayama, Sotaro; Tanikawa, Kunihiro; Fujimoto, Ryuhei; Kimura, Hiromichi

    2008-01-01

    The pharmaceutical industry has experienced intermittent waves of mergers and acquisitions (M&As) since the 1980s and recently appeared to be in yet another wave. Previous studies indicated rather negative impacts of consolidation on research and development, suggesting that they do not necessarily lead to long-term reinforcement of research capabilities, although they may enrich the drug pipeline in the short term. However, recent studies have implied a positive side in terms of knowledge-base transfer. Further micro-organizational studies suggested that scientists learned new knowledge and approaches from partner scientists and improved their performance and innovation. These findings imply that measures for the scientist-level integration after M&As would reinforce fundamental research capabilities in the long term.

  17. 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

  18. 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

  19. 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

  20. [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.

  1. The NCGC pharmaceutical collection: a comprehensive resource of clinically approved drugs enabling repurposing and chemical genomics.

    PubMed

    Huang, Ruili; Southall, Noel; Wang, Yuhong; Yasgar, Adam; Shinn, Paul; Jadhav, Ajit; Nguyen, Dac-Trung; Austin, Christopher P

    2011-04-27

    Small-molecule compounds approved for use as drugs may be "repurposed" for new indications and studied to determine the mechanisms of their beneficial and adverse effects. A comprehensive collection of all small-molecule drugs approved for human use would be invaluable for systematic repurposing across human diseases, particularly for rare and neglected diseases, for which the cost and time required for development of a new chemical entity are often prohibitive. Previous efforts to build such a comprehensive collection have been limited by the complexities, redundancies, and semantic inconsistencies of drug naming within and among regulatory agencies worldwide; a lack of clear conceptualization of what constitutes a drug; and a lack of access to physical samples. We report here the creation of a definitive, complete, and nonredundant list of all approved molecular entities as a freely available electronic resource and a physical collection of small molecules amenable to high-throughput screening.

  2. 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

  3. 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).

  4. 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

  5. A carrier-mediated prodrug approach to improve the oral absorption of antileukemic drug decitabine.

    PubMed

    Zhang, Youxi; Sun, Jin; Gao, Yikun; Jin, Ling; Xu, Youjun; Lian, He; Sun, Yongbing; Sun, Yinghua; Liu, Jianyu; Fan, Rui; Zhang, Tianhong; He, Zhonggui

    2013-08-01

    Decitabine (5-aza-2'-deoxycytidine, DAC) is a novel DNA methyltransferase (DNMT) inhibitor for the treatment of myelodysplastic syndrome, acute and chronic myeloid leukemia. However, it exhibits a low oral bioavailability (only 9% in mice), because of low permeability across the intestine membrane and rapid metabolism to inactive metabolite. To utilize the carrier-mediated prodrug approach for improved absorption of decitabine, a series of amino acid-decitabine conjugates were synthesized to target the intestinal membrane transporter, hPepT1. The Caco-2 permeability of the prodrugs was screened, and two l-val (aliphatic, compound 4a) and l-phe (aromatic, compound 4c) prodrugs with higher permeability were selected for further studies. The uptake of Gly-Sar by Caco-2 cells could be competitively inhibited by compounds 4a and 4c, with IC50 being 2.20 ± 0.28 mM and 3.46 ± 0.16 mM, respectively. The uptake of compounds 4a and 4c was markedly increased in the leptin-treated Caco-2 cells compared with the control Caco-2 cells, suggesting that hPepT1-mediated transport contributes to oral absorption of compounds 4a and 4c. The prodrugs were evaluated for their stability in various phosphate buffers, rat plasma, tissue homogenates, and gastrointestinal fluids. Compounds 4a and 4c were stable in gastrointestinal tract at pH 6.0 but could be quickly converted into DAC in plasma and tissue homogenates after absorption. The oral absolute bioavailability of DAC was 46.7%, 50.9%, and 26.9% after compounds 4a, 4c, and DAC were orally administered to rats at a dose of 15 mg/kg, respectively. The bioavailability of compounds 4a and 4c in rats was both reduced to about 32% when orally coadministrated with typical hPepT1 substrate Gly-Sar (150 mg/kg). Overall, compounds 4a and 4c can significantly enhance the intestinal membrane permeability of DAC, followed by rapid and mostly bioactivation to parent drug in intestinal and hepatic tissues before entry into systemic circulation

  6. 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

  7. 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.

  8. Civil responsibility for driving under the influence of pharmaceutical drugs in Germany.

    PubMed

    Fuellmich, R

    1995-01-01

    The dangers of medication for traffic safety have been vastly underestimated in modern society. The widespread and ever-growing use of medical drugs - in particular psychopharmaca - without a thought given to how these drugs may affect the ability to drive a car, gives a clear indication that it is time to take a close look at the problem. This article focuses on the civil liability under German law for traffic accidents resulting from the use of medication. Basically, three potential defendants come to mind when one searches for addresses of claims for damages. Apart from the driver himself or herself, these are the doctor who prescribed the drug and the manufacturer who manufactured the drug. This article argues that - at least from a German law perspective - in many cases it will ultimately make more sense to include the doctor (on a negligence liability theory) and the drug manufacturer (on a strict liability theory) as defendants in an action for damages than merely to go after the obvious perpetrator, namely the driver.

  9. Drug resistance, patent resistance: Indian pharmaceuticals and the impact of a new patent regime.

    PubMed

    Halliburton, M

    2009-01-01

    This article highlights potential public health effects of India's Patents Act of 2005, which was implemented to conform to the requirements of the World Trade Organisation's Trade-Related Aspects of Intellectual Property Agreement (TRIPS), a new legal regime that will likely have a significant impact on access to HIV/AIDS medications in much of the world. This new patent law may play a role in keeping new antiretroviral (ARV) medications, including improved first-line medications and second-line drugs that are being developed for first-line drug resistant HIV, financially out of reach for many people living with HIV/AIDS in poor countries. India's drug industry, which had thrived under earlier patent laws that protected processes but not products in the case of medications, had brought down the price of ARV drugs in South Asia and Africa by more than 90%. While most existing drugs are grandfathered under the new patent laws, newer ARV medications may be barred from manufacture by Indian companies. This article analyses the effects of the coming together of this new legal regime, the global political economy and emerging resistance to HIV/AIDS medications, and evaluates efforts to mitigate the negative public health effects of the new patent laws.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Electroanalysis of antitubercular drugs in pharmaceutical dosage forms and biological fluids: a review.

    PubMed

    Thapliyal, Neeta; Karpoormath, Rajshekhar V; Goyal, Rajendra N

    2015-01-01

    Tuberculosis remains a major global public health problem. Given the need for extensive analysis of antitubercular drugs, the development of sensitive, reliable and facile analytical methods to determine these compounds becomes necessary. Electrochemical techniques have inherent advantages over other well-established analytical methods, this review aiming to provide an updated overview of the latest trends (from 2006 till date) in the voltammetric determination of antitubercular drugs. Furthermore, the advantages and limitations of these methods are critically discussed. The review reveals that in spite of using a variety of chemically modified electrodes to determine antitubercular drugs, there is still a dearth of applicability of the voltammetric methods to quantify these compounds in human body fluids, especially in blood plasma.

  15. Toxins and derivatives in molecular pharmaceutics: Drug delivery and targeted therapy.

    PubMed

    Zhan, Changyou; Li, Chong; Wei, Xiaoli; Lu, Wuyuan; Lu, Weiyue

    2015-08-01

    Protein and peptide toxins offer an invaluable source for the development of actively targeted drug delivery systems. They avidly bind to a variety of cognate receptors, some of which are expressed or even up-regulated in diseased tissues and biological barriers. Protein and peptide toxins or their derivatives can act as ligands to facilitate tissue- or organ-specific accumulation of therapeutics. Some toxins have evolved from a relatively small number of structural frameworks that are particularly suitable for addressing the crucial issues of potency and stability, making them an instrumental source of leads and templates for targeted therapy. The focus of this review is on protein and peptide toxins for the development of targeted drug delivery systems and molecular therapies. We summarize disease- and biological barrier-related toxin receptors, as well as targeted drug delivery strategies inspired by those receptors. The design of new therapeutics based on protein and peptide toxins is also discussed.

  16. 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

  17. The cost of multiple sclerosis drugs in the US and the pharmaceutical industry

    PubMed Central

    Bourdette, Dennis N.; Ahmed, Sharia M.; Whitham, Ruth H.

    2015-01-01

    Objective: To examine the pricing trajectories in the United States of disease-modifying therapies (DMT) for multiple sclerosis (MS) over the last 20 years and assess the influences on rising prices. Methods: We estimated the trend in annual drug costs for 9 DMTs using published drug pricing data from 1993 to 2013. We compared changes in DMT costs to general and prescription drug inflation during the same period. We also compared the cost trajectories for first-generation MS DMTs interferon (IFN)–β-1b, IFN-β-1a IM, and glatiramer acetate with contemporaneously approved biologic tumor necrosis factor (TNF) inhibitors. Results: First-generation DMTs, originally costing $8,000 to $11,000, now cost about $60,000 per year. Costs for these agents have increased annually at rates 5 to 7 times higher than prescription drug inflation. Newer DMTs commonly entered the market with a cost 25%–60% higher than existing DMTs. Significant increases in the cost trajectory of the first-generation DMTs occurred following the Food and Drug Administration approvals of IFN-β-1a SC (2002) and natalizumab (reintroduced 2006) and remained high following introduction of fingolimod (2010). Similar changes did not occur with TNF inhibitor biologics during these time intervals. DMT costs in the United States currently are 2 to 3 times higher than in other comparable countries. Conclusions: MS DMT costs have accelerated at rates well beyond inflation and substantially above rates observed for drugs in a similar biologic class. There is an urgent need for clinicians, payers, and manufacturers in the United States to confront the soaring costs of DMTs. PMID:25911108

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 77 FR 26768 - Food and Drug Administration/International Society for Pharmaceutical Engineering Cosponsorship...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ..., and Sustaining a Culture of Compliance AGENCY: Food and Drug Administration, HHS. ] ACTION: Notice of... Culture of Compliance.'' DATES: Date and Time: The public workshop will be held on June 4, 2012, 9 a.m. to.... Topics for discussion include the following: (1) The Business Case For Change; (2) Quality...

  4. 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.

  5. Mechanistic modeling identifies drug-uptake history as predictor of tumor drug resistance and nano-carrier-mediated response.

    PubMed

    Pascal, Jennifer; Ashley, Carlee E; Wang, Zhihui; Brocato, Terisse A; Butner, Joseph D; Carnes, Eric C; Koay, Eugene J; Brinker, C Jeffrey; Cristini, Vittorio

    2013-12-23

    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 diseases 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 the 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 the 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;" that is, 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. A pharmaceutical company user's perspective on the potential of high content screening in drug discovery.

    PubMed

    Hoffman, Ann F; Garippa, Ralph J

    2007-01-01

    It is early to fully reflect on the state of the art in high content screening (HCS), because it is still a relatively new approach in drug discovery. Although the development of the first microscopes are a century old and the first confocal microscope is only 20 yr old, the fluorescent probes used within HCS along with the combination of robotic automation and integrated software technologies are quite new. HCS will require a few more years to fully demonstrate its potential power in drug discovery. Within the last year, however, one has seen this ever-expanding field lure participants in from all areas of science, introducing newer versions of instruments and reagents such that the combined efforts result in platforms and tools that meet many organizational goals in multiple ways. The potential of HCS today lies in its versatility. HCS can be used for primary screening, basic research, target identification, biomarkers, cytotoxicity, and helping to predict clinical outcomes. HCS is being applied to stem cells, patient cells, primary hepatocytes, and immortalized cultured cells. We have noted for individual specialized assays, there are multiple solutions just as there are for those standardized universally accepted assays. Whether we have needed to query cellular processes under live conditions or wanted to follow kinetically the course of a compound's effects on particular cellular reactions, we have been hampered by only a few limitations. This chapter offers a glimpse inside the use of HCS in our drug discovery environment.

  14. Chitins and chitosans as immunoadjuvants and non-allergenic drug carriers.

    PubMed

    Muzzarelli, Riccardo A A

    2010-02-21

    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.

  15. 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.

  16. 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.

  17. 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

  18. Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases

    PubMed Central

    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

  19. Novel biodegradable polyesters. Synthesis and application as drug carriers for the preparation of raloxifene HCl loaded nanoparticles.

    PubMed

    Bikiaris, Dimitrios; Karavelidis, Vassilios; Karavas, Evangelos

    2009-01-01

    Raloxifene HCl is a drug with poor bioavailability and poor water solubility. Furthermore nomicron pharmaceutically acceptable organic solvent has been reported before to dilute the drug. It was observed that Raloxifene HCl can be diluted in a solvent mixture of acetone/water or ethanol/water. The aim of this study was to use biodegradable polymers in order to prepare Raloxifene HCl nanoparticles. For this purpose a series of novel biodegradable poly(ethylene succinate-co-propylene adipate) P(ESu-co-PAd) polyesters were synthesized following the polycondensation method and further, poly(ethylene succinate) (PESu) and poly(propylene adipate) (PPAd) were used. The prepared polyesters were characterized by intrinsic viscosity measurements, end group analysis, enzymatic hydrolysis, Nuclear Magnetic Resonance Spectroscopy ((1H)-NMR and (13)C-NMR) and Wide-angle X-ray Diffractometry (WAXD). The drug nanoparticles have been prepared by a variation of the co-precipitation method and were studied by Wide-angle X-ray Diffractometry (WAXD), FTIR spectrometry, light scattering size distribution, Scanning Electron Microscopy (SEM) and release behavior measurements. The interactions between the polymers and the drug seem to be limited, so the drug occurs in crystalline form in all nanoparticles. The size of the nanoparticles seems to be in the range of 150-350 nm, depending on the polymer that was used. The drug release depends on the melting point and degree of crystallinity of the polyesters used. An initial high release rate was recorded followed by very slow rates of controlled release. PMID:19633613

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. Self assembly of amphiphilic (PEG)(3)-PLA copolymer as polymersomes: preparation, characterization, and their evaluation as drug carrier.

    PubMed

    Jain, Jay Prakash; Kumar, Neeraj

    2010-04-12

    (PEG)(3)-PLA copolymer has been explored for the formation of polymersomes. For this, three chains of methoxy-PEG(1100) were directly attached to citric acid by esterification. (Methoxy-PEG(1100))(3)-citrate was then reacted at its hydroxyl terminal with different moles of d,l-lactide by ring-opening polymerization to obtain polymers with five different PEG-to-PLA ratios ranging from 10:90 to 90:10. Polymers were characterized by GPC, FTIR, (1)H NMR, and DSC, films were characterized for hydrophilicity by contact angle, and surface topography was observed by SEM and AFM. All five polymers were evaluated for the formation of polymersomes. Among these, polymers with PEG content of 10-30% were able to self-assemble into polymersomes. To affirm their self-arrangement and drug carrier properties, hydrophilic and hydrophobic dyes were simultaneously encapsulated in these structures. SEM and TEM analysis of the blank polymersomes confirmed the vesicular nature of the polymersomes, whereas CLSM analysis of dye-loaded polymersomes demonstrated the presence of two separate regions viz. hydrophilic core and hydrophobic wall. Hydrophobic dye, fluorescein was released relatively faster from the wall of polymersomes, whereas hydrophilic dye, propidium iodide, was released in controlled fashion up to 18 days. It is expected that these systems may serve as a suitable carrier for simultaneous or separate delivery of drug molecules with varying physicochemical properties.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. Study of a microwave assisted vacuum drying process applied to the granulated pharmaceutical drug hydrochlorthiazide.

    PubMed

    Berteli, Michele N; Marsaioli, Antonio Júnior; Rodier, Elisabeth

    2007-01-01

    Drying processes have evolved considerably over the years, aiming at the best conditions to shorten the processing time, but maintaining the highest final product quality. The application of vacuums to the microwave drying process might be interesting, especially for thermally sensitive products because the reduced boiling point of the solvent allows a lower temperature processing. The objective of the present work is to study and evaluate the process of drying a granulated product that is the basis of the drug hydrochlorthiazide, with an initial moisture content of 21% in dry basis. This study monitored the drying kinetics, product temperature and power absorbed by the sample using a bench scale vacuum microwave dryer. The equipment consisted of a cylindrical pressure vessel crossed by a wave guide, setting up a system whereby the vacuum pressure, the sample weight and the incident, reflected and residual microwave powers could be measured and evaluated, throughout the entire process. The experimental runs were established with an approximate incident microwave power at 20 W for absolute pressure levels of 50 and 75 mbar, working with samples of about 1.4 g. It was observed that the vacuum microwave process kinetics at both pressure levels showed little difference. The processes were carried out almost entirely in a regime of water evaporation, the product's temperature remaining below the solvent boiling temperature. The drying times were similar for both processes, whereas the absorbed power was slightly higher at the pressure of 75 mbar.

  19. Effects of pharmaceuticals on aquatic invertebrates. Part I. The antiepileptic drug carbamazepine.

    PubMed

    Oetken, M; Nentwig, G; Löffler, D; Ternes, T; Oehlmann, J

    2005-10-01

    The effects of the antiepileptic drug carbamazepine (CBZ) were studied in three freshwater invertebrate species representing different taxonomic groups, life histories, and habitats in aquatic ecosystems. The oligochaete Lumbriculus variegatus was exposed by way of CBZ-spiked sediments at nominal concentrations between 0.625 and 10 mg/kg dry weight (dw) for 28 days. At the end of the test, reproduction and biomass were monitored as end points. The non-biting midge Chironomus riparius was exposed to CBZ in a series of tests at nominal CBZ concentrations in sediment ranging from 0.16 to 100 mg/kg dw at 20 degrees C and 23 degrees C. Emergence and gender ratio were monitored at the end of the test. The freshwater snail Potamopyrgus antipodarum as the third test species was used in a chronic reproduction test for 28 days at aqueous CBZ concentrations from 0.4 to 250 mg/L. Whereas for the oligochaete and the snail no effects were observed, C. riparius exhibited a significant and concentration-dependent decrease of emergence in all test series. No observed effect concentrations and 10% effect concentrations were in the range of 33 to 140 and 70 to 210 microg/kg dw, respectively, based on measured CBZ concentrations in sediments. These low values indicate that CBZ may pose a potential threat for the survival of C. riparius and probably also for other aquatic insect populations in the field.

  20. Pharmaceutical virtue.

    PubMed

    Martin, Emily

    2006-06-01

    In the early history of psychopharmacology, the prospect of developing technologically sophisticated drugs to alleviate human ills was surrounded with a fervor that could be described as religious. This paper explores the subsequent history of the development of psychopharmacological agents, focusing on the ambivalent position of both the industry and its employees. Based on interviews with retired pharmaceutical employees who were active in the industry in the 1950s and 1960s when the major breakthroughs were made in the development of MAOIs and SSRIs, the paper explores the initial development of educational materials for use in sales campaigns. In addition, based on interviews with current employees in pharmaceutical sales and marketing, the paper describes the complex perspective of contemporary pharmaceutical employees who must live surrounded by the growing public vilification of the industry as rapacious and profit hungry and yet find ways to make their jobs meaningful and dignified. The paper will contribute to the understudied problem of how individuals function in positions that require them to be part of processes that on one description constitute a social evil, but on another, constitute a social good.

  1. Polymeric drugs: Advances in the development of pharmacologically active polymers.

    PubMed

    Li, Jing; Yu, Fei; Chen, Yi; Oupický, David

    2015-12-10

    Synthetic polymers play a critical role in pharmaceutical discovery and development. Current research and applications of pharmaceutical polymers are mainly focused on their functions as excipients and inert carriers of other pharmacologically active agents. This review article surveys recent advances in alternative pharmaceutical use of polymers as pharmacologically active agents known as polymeric drugs. Emphasis is placed on the benefits of polymeric drugs that are associated with their macromolecular character and their ability to explore biologically relevant multivalency processes. We discuss the main therapeutic uses of polymeric drugs as sequestrants, antimicrobials, antivirals, and anticancer and anti-inflammatory agents.

  2. [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

  3. 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

  4. The compatibility of Tacrine molecule with poly(n-butylcyanoacrylate) and Chitosan as efficient carriers for drug delivery: A molecular dynamics study.

    PubMed

    Eslami, Mahboobeh; Nikkhah, Sousa Javan; Hashemianzadeh, Seyed Majid; Sajadi, Seyed Abolfazl Seyed

    2016-01-20

    According to the critical role of drug delivery in the treatment of diseases of the central nervous system (CNS), the selection of a suitable carrier plays an important role in the greater effectiveness of drugs. Due to good biocompatibility, biodegradability and low toxicity of polymeric nanoparticles, especially poly(n-butylcyanoacrylate) (PBCA) and Chitosan, these nanoparticles are considered as efficient carriers in drug delivery to the brain. In order to investigate the compatibility of these two polymers with different degrees of polymerization versus a Tacrine unit as the most well known drug for the treatment of Alzheimer's disease, molecular dynamics simulation (MD) is used as a principal tool for studying molecular systems. Interaction energy of the polymer/Tacrine systems, the radius of gyration of the Chitosan and PBCA during the simulation time, solubility and Flory-Huggins interaction parameters has been calculated. According to the results, the Tacrine molecule exhibited higher compatibility with PBCA than Chitosan. Moreover, the interaction between the Tacrine molecules and PBCA nanoparticles became stronger by increasing the length of polymer chain while it was not observed as a regular trend for Chitosan/Tacrine systems. By using these MD simulations, it is possible to find the most appropriate polymer as an efficient drug carrier. We note that the methodology applied here for modeling the polymer/Tacrine system is not restricted to the specific formulations of Tacrine and Chitosan (or PBCA) in the current work and can be extended to various other traditional or new drugs and different polymer drug carriers.

  5. Comparative studies on drug binding to the purified and pharmaceutical-grade human serum albumins: Bridging between basic research and clinical applications of albumin.

    PubMed

    Ashrafi-Kooshk, Mohammad Reza; Ebrahimi, Farangis; Ranjbar, Samira; Ghobadi, Sirous; Moradi, Nastaran; Khodarahmi, Reza

    2015-09-01

    Human serum albumin (HSA), the most abundant protein in blood plasma, is a monomeric multidomain protein that possesses an extraordinary capacity for binding, so that serves as a circulating depot for endogenous and exogenous compounds. During the heat sterilization process, the structure of pharmaceutical-grade HSA may change and some of its activities may be lost. In this study, to provide deeper insight on this issue, we investigated drug-binding and some physicochemical properties of purified albumin (PA) and pharmaceutical-grade albumin (PGA) using two known drugs (indomethacin and ibuprofen). PGA displayed significantly lower drug binding capacity compared to PA. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between the drugs and the proteins are different from each other. Surface hydrophobicity as well as the stability of PGA decreased compared to PA, also surface hydrophobicity of PA and PGA increased upon drugs binding. Also, kinetic analysis of pseudo-esterase activities indicated that Km and Vmax parameters for PGA enzymatic activity are more and less than those of PA, respectively. This in vitro study demonstrates that the specific drug binding of PGA is significantly reduced. Such studies can act as connecting bridge between basic research discoveries and clinical applications.

  6. 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.

  7. Transdermal immunization with large proteins by means of ultradeformable drug carriers.

    PubMed

    Paul, A; Cevc, G; Bachhawat, B K

    1995-12-01

    By means of novel, ultradeformable and self-optimizing agent carriers called transfersomes, large molecules can be brought into the body through intact permeability barriers. This permits non-invasive immunization through normal skin and gives rise to a similar or even slightly higher antibody titer than subcutaneous injections of the same immunogen formulation. The former type of immunization also results in a higher IgA/IgG ratio in the blood than the repeated immunogen injections, as shown here for a soluble protein, human serum albumin, as well as for an integral membrane protein, gap junction protein, in mice.

  8. Topical delivery of dexamethasone acetate from hydrogel containing nanostructured liquid carriers and the drug.

    PubMed

    Tung, Nguyen-Thach; Huyen, Vu-Thu; Chi, Sang-Cheol

    2015-11-01

    The potential of hydrogel containing nanostructured lipid carriers (NLC) to enhance the skin permeation rate and skin deposition of dexamethasone acetate (DEA) was investigated. The particle size of obtained NLCs was around 224.4 nm. NLCs had core-shell structure and DEA existed in amorphous state in NLCs. The permeation rate of DEA through excised mouse skins from hydrogel containing DEA-NLC (DEA-NLC-hydrogel) was 7.3 times higher than DEA-ointment. The skin deposition of DEA from DEA-NLC-hydrogel increased 3.8 folds compared to that from solution of DEA in hydrogel (DEA-hydrogel).

  9. The Impact of Variables on Particle Size of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers; A Comparative Literature Review.

    PubMed

    Azhar Shekoufeh Bahari, Leila; Hamishehkar, Hamed

    2016-06-01

    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

  10. 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

  11. A study of the formulation design of acoustically active lipospheres as carriers for drug delivery.

    PubMed

    Fang, Jia-You; Hung, Chi-Feng; Liao, Mei-Hui; Chien, Chih-Chen

    2007-08-01

    Acoustically active lipospheres (AALs) were prepared using perfluorocarbons and coconut oil as the cores of inner phase. These AALs were stabilized using coconut oil and phospholipid coatings. A lipophilic antioxidant, resveratrol, was the model drug loaded into the AALs. AALs with various percentages of perfluorocarbons and oil were prepared to examine their physicochemical and drug release properties. Co-emulsifiers such as Brij 98 and Pluronic F68 (PF68) were also incorporated into AALs for evaluation. AALs with high resveratrol encapsulation rates ( approximately 90%) were prepared, with a mean droplet size of 250-350nm. The AALs produced with perfluorohexane as the core material had larger particle sizes than those with perfluoropentane. Resveratrol in these systems exhibited retarded drug release in both the presence and absence of plasma in vitro; the formulations with high oil and perfluorocarbon percentages showed the lowest drug release rates. The addition of PF68 slightly but significantly reduced resveratrol delivery from the AALs. Ultrasound treatment of 1MHz produced an increase in the drug release from the systems, illustrating the drug-targeting effect of the combination of AALs and ultrasound.

  12. 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

  13. Europium-doped amorphous calcium phosphate porous nanospheres: preparation and application as luminescent drug carriers

    NASA Astrophysics Data System (ADS)

    Chen, Feng; Zhu, Ying-Jie; Zhang, Kui-Hua; Wu, Jin; Wang, Ke-Wei; Tang, Qi-Li; Mo, Xiu-Mei

    2011-12-01

    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.

  14. The effect of a PEG versus a chitosan coating on the interaction of drug colloidal carriers with the ocular mucosa.

    PubMed

    De Campos, Angela M; Sánchez, Alejandro; Gref, Ruxandra; Calvo, Pilar; Alonso, María J

    2003-09-01

    The influence of the surface characteristics of colloidal drug carriers in their interaction with different biological surfaces is becoming increasingly evident. In order to investigate the importance of these characteristics in their interaction with the ocular mucosa, we developed three types of nanocapsules that differ in their surface properties: poly- epsilon -caprolactone (PECL) nanocapsules, chitosan (CS)-coated PECL nanocapsules and poly(ethylene glycol) (PEG)-coated PECL nanocapsules. Two different approaches were used to form these polymer coated nanocapsules: (i) the electrostatic anchorage of the coating onto the PECL nanocapsules-in the case of CS-and (ii) the use of the previously synthesized copolymer PECL-PEG for the formation of the nanocapsules. In both cases, the systems, prepared by the interfacial deposition technique, were loaded with a fluorescent dye (rhodamine) in order to quantify and visualize their interaction with the ocular surface ex vivo and in vivo. An important conclusion from the ex vivo studies is that the developed systems, and specially the CS-coated ones, enhanced the penetration of the encapsulated dye through the cornea. This effect was not simple due to the physical presence of the nanocapsules but to their ability to carry the encapsulated compound. The second conclusion from the confocal laser scanning microscopy (CLSM) studies is that the systems were able to enter the corneal epithelium by a transcellular pathway and that the penetration rate was dependent on the coating composition. The images suggest that the PEG coating accelerates the transport of the nanocapsules across the whole epithelium, whereas the CS coating favours the retention of the nanocapsules in the superficial layers of the epithelium. The specific behaviour of CS-coated systems was also corroborated in vivo. These results indicate that the surface composition of colloidal drug carriers affects their biodistribution in the eye. Therefore, this surface

  15. Liquid crystalline phase as a probe for crystal engineering of lactose: carrier for pulmonary drug delivery.

    PubMed

    Patil, Sharvil S; Mahadik, Kakasaheb R; Paradkar, Anant R

    2015-02-20

    The current work was undertaken to assess suitability of liquid crystalline phase for engineering of lactose crystals and their utility as a carrier in dry powder inhalation formulations. Saturated lactose solution was poured in molten glyceryl monooleate which subsequently transformed into gel. The gel microstructure was analyzed by PPL microscopy and SAXS. Lactose particles recovered from gels after 48 h were analyzed for polymorphism using techniques such as FTIR, XRD, DSC and TGA. Particle size, morphology and aerosolisation properties of prepared lactose were analyzed using Anderson cascade impactor. In situ seeding followed by growth of lactose crystals took place in gels with cubic microstructure as revealed by PPL microscopy and SAXS. Elongated (size ∼ 71 μm) lactose particles with smooth surface containing mixture of α and β-lactose was recovered from gel, however percentage of α-lactose was more as compared to β-lactose. The aerosolisation parameters such as RD, ED, %FPF and % recovery of lactose recovered from gel (LPL) were found to be comparable to Respitose® ML001. Thus LC phase (cubic) can be used for engineering of lactose crystals so as to obtain particles with smooth surface, high elongation ratio and further they can be used as carrier in DPI formulations.

  16. 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

  17. 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.

  18. Fabrication of drug-loaded edible carrier substrates from nanosuspensions by flexographic printing.

    PubMed

    Palo, Mirja; Kolakovic, Ruzica; Laaksonen, Timo; Määttänen, Anni; Genina, Natalja; Salonen, Jarno; Peltonen, Jouko; Sandler, Niklas

    2015-10-30

    The main goal of the current work was to investigate the possible use of flexographic printing for the conversion of nanosuspensions into solid dosage forms. Aqueous nanosuspensions of indomethacin (IND) and itraconazole (ITR) with Poloxamer 407 as the stabilizer agent were prepared by wet ball-milling. The nanosuspensions were flexographically printed on three different substrates, including two commercially available edible substrates. The printed formulations were characterized with X-ray diffractometry (XRD) and scanning electron microscopy (SEM). In addition, dissolution studies for the printed IND and ITR formulations were conducted. The mean particle size of milled nanosuspensions of IND and ITR was 422.6 ± 7.7 nm and 698.1 ± 14.0 nm, respectively. The SEM imaging showed even distribution of nanosuspensions on the substrates after printing without any evident agglomeration. The printed formulations contained drug at least partially in crystalline form. The drug dissolution rate from the prepared formulations was improved compared to the pure drug. The drug release from the preparations on edible substrates was slightly slower due to the incorporation of the drug particles into the substrate matrix. In conclusion, the results indicated that flexographic printing can be considered as a promising fabrication method of solid nanoparticulate systems with enhanced dissolution behavior.

  19. Self-degrading niosomes for encapsulation of hydrophilic and hydrophobic drugs: An efficient carrier for cancer multi-drug delivery.

    PubMed

    Sharma, Varsha; Anandhakumar, Sundaramurthy; Sasidharan, Manickam

    2015-11-01

    In this study, we have examined the encapsulation and release of hydrophilic and hydrophobic drugs in self-degrading niosomes as a unique method for anticancer therapy. Niosomes were prepared by amphiphilic self-assembly of Tween 80 and cholesterol through film hydration method. Encapsulation studies with two active molecules curcumin and doxorubicin hydrochloride (Dox) showed that curcumin is supposed to accumulate in the shell whereas Dox accumulates in the inner aqueous core of the niosome. Confocal studies indicated that nile red adsorbs preferentially to the head group of the Tween 80 and forms two separate layers in the shell. It was also seen that the niosomes undergo self-degradation in PBS through a sequential process, forming interconnected pores followed by complete collapse after 1week. The release profile shows two phases: i) initial Dox release in the first two days, followed by ii) curcumin release over 7days. Enhanced (synergistic) cytotoxicity was observed for dual-drug loaded niosomes against HeLa cell lines. Thus these niosomes are shown to offer a promising delivery system for hydrophobic and hydrophilic drugs collectively.

  20. 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

  1. 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

  2. Rational Design of Targeted Next-Generation Carriers for Drug and Vaccine Delivery.

    PubMed

    Narasimhan, Balaji; Goodman, Jonathan T; Vela Ramirez, Julia E

    2016-07-11

    Pattern recognition receptors on innate immune cells play an important role in guiding how cells interact with the rest of the organism and in determining the direction of the downstream immune response. Recent advances have elucidated the structure and function of these receptors, providing new opportunities for developing targeted drugs and vaccines to treat infections, cancers, and neurological disorders. C-type lectin receptors, Toll-like receptors, and folate receptors have attracted interest for their ability to endocytose their ligands or initiate signaling pathways that influence the immune response. Several novel technologies are being developed to engage these receptors, including recombinant antibodies, adoptive immunotherapy, and chemically modified antigens and drug delivery vehicles. These active targeting technologies will help address current challenges facing drug and vaccine delivery and lead to new tools to treat human diseases.

  3. 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.

  4. Liposomes as carriers of hydrophilic small molecule drugs: strategies to enhance encapsulation and delivery.

    PubMed

    Eloy, Josimar Oliveira; Claro de Souza, Marina; Petrilli, Raquel; Barcellos, Juliana Palma Abriata; Lee, Robert J; Marchetti, Juliana Maldonado

    2014-11-01

    Although hydrophilic small molecule drugs are widely used in the clinic, their rapid clearance, suboptimal biodistribution, low intracellular absorption and toxicity can limit their therapeutic efficacy. These drawbacks can potentially be overcome by loading the drug into delivery systems, particularly liposomes; however, low encapsulation efficiency usually results. Many strategies are available to improve both the drug encapsulation efficiency and delivery to the target site to reduce side effects. For encapsulation, passive and active strategies are available. Passive strategies encompass the proper selection of the composition of the formulation, zeta potential, particle size and preparation method. Moreover, many weak acids and bases, such as doxorubicin, can be actively loaded with high efficiency. It is highly desirable that once the drug is encapsulated, it should be released preferentially at the target site, resulting in an optimal therapeutic effect devoid of side effects. For this purpose, targeted and triggered delivery approaches are available. The rapidly increasing knowledge of the many overexpressed biochemical makers in pathological sites, reviewed herein, has enabled the development of liposomes decorated with ligands for cell-surface receptors and active delivery. Furthermore, many liposomal formulations have been designed to actively release their content in response to specific stimuli, such as a pH decrease, heat, external alternating magnetic field, ultrasound or light. More than half a century after the discovery of liposomes, some hydrophilic small molecule drugs loaded in liposomes with high encapsulation efficiency are available on the market. However, targeted liposomes or formulations able to deliver the drug after a stimulus are not yet a reality in the clinic and are still awaited.

  5. A highly tumor-specific light-triggerable drug carrier responds to hypoxic tumor conditions for effective tumor treatment.

    PubMed

    Park, Wooram; Bae, Byoung-chan; Na, Kun

    2016-01-01

    Light-triggered drug delivery is among the most investigated stimulus-response strategies and has been widely explored in cancer treatment. However, the limited specificity of light-triggered drug delivery reduces the therapeutic efficacy and causes considerable undesirable side effects. In this work, we demonstrate a highly tumor-specific light-triggerable drug carrier (H-LTDC) induced by a combination of internal (i.e., tumor hypoxia) and external stimuli (i.e., light). The doxorubicin (DOX)-loaded H-LTDC was self-assembled from type-1-reactive oxygen species (ROStype1)-mediated degradable chondroitin sulfate (CS) conjugated with a photosensitizer (PS), Pheophorbide-a, which has a spherical shape and a uniform size distribution. Under hypoxic conditions, ROSType1 was mainly generated due to the electron-rich sulfate groups in the polysaccharide backbone. The ROStype1 generated by H-LTDC allowed laser-triggered drug release at low oxygen concentrations. From the in vitro cytotoxicity tests with colon cancer cells (HCT-116), under laser irradiation, DOX-loaded H-LTDCs showed higher toxicity under hypoxic conditions than that under normoxic conditions. In vivo and ex vivo biodistribution studies demonstrated that H-LTDCs selectively accumulated in the tumor tissues. As a result, drug-loaded H-LTDCs exhibited high anti-tumor activity in vivo. Overall, we believe that this approach could represent a promising platform for the treatment of tumor and hypoxia-associated diseases without undesirable side effects.

  6. 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.

  7. Electroanalytical characteristics of antipsychotic drug ziprasidone and its determination in pharmaceuticals and serum samples on solid electrodes.

    PubMed

    Kul, Dilek; Gumustas, Mehmet; Uslu, Bengi; Ozkan, Sibel A

    2010-06-30

    Ziprasidone is a psychotropic agent used for the treatment of schizophrenia. Its oxidation was investigated electrochemically at boron-doped diamond and glassy carbon electrodes using cyclic, differential pulse, and square wave voltammetry. The dependence of the peak current and peak potentials on pH, concentration, nature of the buffer, and scan rate were examined. The process was diffusion and adsorption controlled for boron-doped diamond and glassy carbon electrodes, respectively. The possible mechanism of oxidation was discussed with some model compounds that have indole and piperazine oxidations. A linear response was obtained between 8 x 10(-7) and 8 x 10(-5) M for the first peak in acetate buffer (pH 5.5) and between 2 x 10(-6) and 2 x 10(-4) M for the second peak in 0.1 M H(2)SO(4) with boron-doped diamond electrode for differential pulse and square wave voltammetric techniques. The reproducibility and accuracy of the proposed methods were found between 0.31 and 1.20, 99.27 and 100.22, respectively. The recovery studies were also achieved to check selectivity and accuracy of the methods. The proposed methods were applied for the determination of ziprasidone from pharmaceutical dosage forms and human serum samples without any time-consuming extraction, separation, evaporation or adsorption steps prior to drug assay except precipitation of the proteins using acetonitrile. The results were statistically compared with those obtained through an established LC-UV technique, no significant differences were been found between the voltammetric and LC methods.

  8. 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

  9. 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

  10. Synthesis and Evaluation of Thermo-Sensitive