Showing papers in "Critical Reviews in Therapeutic Drug Carrier Systems in 2009"

Lipid-based Nanoparticles as Pharmaceutical Drug Carriers: From Concepts to Clinic

Abstract: 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 conclude with a few examples of clinically successful formulations of currently available lipid-based nanoparticles.

Self-emulsifying drug delivery systems (SEDDS): formulation development, characterization, and applications.

Abstract: Self-emulsifying drug delivery systems (SEDDS) possess unparalleled potential in improving oral bioavailability of poorly water-soluble drugs. Following their oral administration, these systems rapidly disperse in gastrointestinal fluids, yielding micro- or nanoemulsions containing the solubilized drug. Owing to its miniscule globule size, the micro/nanoemulsifed drug can easily be absorbed through lymphatic pathways, bypassing the hepatic first-pass effect. We present an exhaustive and updated account of numerous literature reports and patents on diverse types of self-emulsifying drug formulations, with emphasis on their formulation, characterization, and systematic optimization strategies. Recent advancements in various methodologies employed to characterize their globule size and shape, ability to encapsulate the drug, gastrointestinal and thermodynamic stability, rheological characteristics, and so forth, are discussed comprehensively to guide the formula-tor in preparing an effective and robust SEDDS formulation. Also, this exhaustive review offers an explicit discussion on vital applications of the SEDDS in bioavailability enhancement of various drugs, outlining an overview on myriad in vitro, in situ, and ex vivo techniques to assess the absorption and/ or permeation potential of drugs incorporated in the SEDDS in animal and cell line models, and the subsequent absorption pathways followed by them. In short, the current article furnishes an updated compilation of wide-ranging information on all the requisite vistas of the self-emulsifying formulations, thus paving the way for accelerated progress into the SEDDS application in pharmaceutical research.

Paclitaxel in cancer treatment: perspectives and prospects of its delivery challenges.

Abstract: Paclitaxel (PTX) is a potent anticancer agent whose clinical usefulness is marred by a delivery problem that is caused by its unfavorable pharmacokinetic and physical properties. Paclitaxel is currently formulated in a mixture of Cremophor EL and ethanol, which is diluted 5-20 times with normal saline or 5% dextrose prior to administration via slow infusion to avoid precipitation in plasma. Many adverse reactions to the PTX formulation have been reported because of the presence of Cremophor EL, including hypersensitivity reactions, nephrotoxicity, and neurotoxicity. Cremophor EL also causes vasodilation, labored breathing, lethargy, hypotension, and leaching of plasticizers, such as diethylhexylpthalate, from the polyvinylchloride infusion bags/sets. Significant research efforts have been conducted to develop an alternative formulation approach to increase the aqueous solubility of PTX without using Cremophor, thereby decreasing its toxicity. This article reviews the various investigated formulation approaches including pastes; liposomes; conjugates with antibodies, peptides, and fatty acids; nanospheres and microspheres; cyclodextrin complexes; emulsions; mucoadhesive gel; prodrugs; and nanoparticulate systems. The pros and cons of each approach are also discussed. Finally, this review concludes with a discussion of nanoparticulate delivery, which is the most promising PTX delivery system of the future because it incorporates the benefits of other approaches such as conjugation, complexation, and prodrugs.

Role of block copolymer nanoconstructs in cancer therapy.

Abstract: Drug, gene, and protein delivery is a very challenging and exciting area in nanobiotechnology where block copolymers are increasingly considered especially as carriers for pharmacotherapy of various cancers. Cancer chemotherapy is particularly challenging because of nonselective distribution of drugs, associated severe toxicity, multidrug resistance, and chronic treatments influencing the quality-adjusted life of patients. These limitations lead to incomplete cure and render many drugs ineffective in treating cancers. Liposomes are currently more advanced in clinical trials and industrial developments but they lack stability and pose difficulties in functionalizing liposomes. More recently, various types of polymer-based nanoconstructs have been designed and synthesized, and are being investigated for the cancer chemotherapy applications. This review discusses the most significant and recent developments on specific self-assembled block copolymers as a carrier system such as micelles and vesicles, which can be successfully used to enhance the solubility of hydrophobic drugs, helpful in targeting selective sites in the body, delivering active molecules in a control manner, and reducing the side effects in the treatment of cancer.

In situ gelling polymers in ocular drug delivery systems: a review.

Abstract: The review article aims to highlight the recent developments in various in situ gel-forming polymeric systems that are used to achieve prolonged contact time of drugs with the cornea and increase their ocular bioavailability. These phase-change polymers, which trigger the drug release in response to external stimuli, are the most investigated in controlled drug delivery. The present review summarizes in detail these various polymers, which undergo sol-gel transition due to physical (temperature) or chemical (pH, ions) stimuli when instilled in the eye. As a whole, this article provides valuable insight into current trends in the field of in situ gel-forming ocular drug delivery systems.

Recent developments of biodegradable and biocompatible materials based micro/nanoparticles for delivering macromolecular therapeutics.

Abstract: Developments in biotechnology have seen the growing use of macromolecules containing proteins, peptides, vaccines, antigens, genes, and growth factors as therapeutic agents. Because these macromolecules are easily denatured and metabolized rapidly in vivo, their protection and controlled release are required. Biodegradable and biocompatible materials based micro/nanoparticles (MPs/NPs) show great potential for delivering macromolecular therapeutics. One of the greatest challenges in the delivery of macromolecules from biodegradable and biocompatible MPs/NPs is the controlled and complete release of the drugs in their native forms. Unfortunately, the present drug delivery systems cannot satisfy the requirement; thus, more research is expected. This article discusses the recent developments in the field of macromolecular delivery.

Dry powder nasal vaccines as an alternative to needle-based delivery.

Abstract: Drug delivery to the nasal cavity has been achieved using a variety of systems. Dry powder vaccines offer the advantages of chemical and physical stability in comparison to liquid formulations. An intranasal vaccine can elicit both a local and systemic immune response. Mucoadhesive compounds can extend the residence time for powder formulations on the nasal mucosa, potentially increasing the immune response. Manufacture and characterization of a formulation containing particles of a dry powder vaccine are discussed.

Extrusion-spheronization: process variables and characterization.

Abstract: Multiparticulate systems have undergone great development in the past decade fueled by the better understanding of their multiple roles as a suitable delivery system With the passage of time, significant advances have been made in the process of pelletization due to the incorporation of specialized techniques for their development Extrusion-spheronization seems to be the most promising process for the optimum delivery of many potent drugs having high systemic toxicity It also offers immense pharmaceutical applicability due to the benefits of high loading capacity of active ingredient(s), narrow size distribution, and cost-effectiveness On application of a specific coat, these systems can also aid in site-specific delivery, thereby enhancing the bioavailability of many drugs The current review focuses on the process of extrusion-spheronization and the operational (extruder types, screen pressure, screw speed, temperature, moisture content, spheronization load, speed and time) and formulation (excipients and drugs) variables, which may affect the quality of the final pellets Various methods for the evaluation of the quality of the pellets with regard to the size distribution, shape, friability, granule strength, density, porosity, flow properties, and surface texture are discussed

Pharmacoscintigraphy: A Blazing Trail for the Evaluation of New Drugs and Delivery Systems

Abstract: The drug development process is becoming increasingly sophisticated; as a result, the need for rapid and accurate means of predicting the in vivo behavior of drug products continues to grow. Preclinical in vivo evaluations involve the sacrifice of many animals and hence raise ethical issues. Therefore, noninvasive methods for assessing the in vivo behavior of drug products in animals have become an attractive alternative. Gamma scintigraphy is an established radiological-imaging technique that has been used in medical practice for the past several decades. Gamma scintigraphy is also used during clinical evaluations to map the formulation as it traverses the human body in real time. Combining this information with the pharmacokinetic data gives valuable information about the release and absorption mechanisms of drugs from their products. This technique also provides a handy tool for evaluating formulations at the preclinical and clinical stages of development for researchers who work in targeted drug delivery using novel drug carrier systems. The current review explores the use of pharmacoscintigraphy, a science that integrates gamma scintigraphy and conventional pharmacokinetics in the process of drug development.

Bioconjugates: harnessing potential for effective therapeutics.

Abstract: The accomplishment of selective delivery can be brought through efficient drug targeting in which the attack of drug moiety is visualized only by the diseased organ and not by the organs of the whole body. This, in turn, consequently minimizes the unwanted effects or side effects caused by the drug action on the other organs. Bioconjugation is a fascinating technique that explores new vistas of drug delivery, and at the same time opens new possibilities for safe and effective therapy. This review is dedicated to and describes the science of bioconjugation and its potential in the drug delivery field, including different bioconjugates and their use in various therapeutic strategies. These have been classified as polymer based, macromolecule based, carrier based, and novel bioconjugates. This review describes the utility of bioconjugates in major diseases like cancer and others, and discusses experiments and research on the same. Bioconjugates have immense potential and extend a promising future in the drug delivery field. The review can act as a quick reference for those actively engaged in drug delivery and drug research to help overcome the hurdles of therapeutics.

Enhancement of transdermal delivery of heparin by various physical and chemical enhancement techniques.

Abstract: Conventional anticoagulants such as unfractionated heparin and warfarin have numerous limitations compared with low-molecular-weight heparin (LMWH). However, the need for repetitive parenteral administration is still a major disadvantage of LMWH, and the absorption of macromolecules such as LMWH across the gastrointestinal tract is very poor. Due to these problems with oral delivery of LMWH, transdermal delivery can be considered as an alternate route of administration. However, overcoming the skin barrier is necessary for the transport of larger molecules across the stratum corneum. This review focuses on the transdermal delivery of LMWH, providing a brief overview of heparin delivery via invasive and oral routes and discusses the advantages of using LMWH rather than heparin for transdermal delivery, and the primary reasons for poor permeability of LMWH. Various strategies employed for transdermal delivery of heparin are summarized, and chemical and physical enhancement techniques or suitable formulations that can be used to improve transcutaneous penetration and various chemical enhancers that act on the skin by different modes of action are discussed. We also consider physical approaches such as iontophoresis, electroporation, and ultrasound, as well as combination strategies to deliver heparin. The developments in physical and chemical enhancement strategies over the past decade are summarized. In addition, recent novel approaches such as microneedles employed for the transdermal delivery of LMWH are also discussed.

Steroid Receptors as Molecular Targets for Cancer Diagnosis and Therapy

Abstract: The targeted delivery of chemotherapeutics is essential to minimizing the side effects by sparing the normal tissues by exposure to cytotoxic agents. The various receptors are overexpressed on the surface of the tumor tissues as compared to the normal tissues because their requirement for various essential components is high for the growth and development of tumor tissues. These overexpressed receptors on the tumor surface have been investigated for selective delivery of imaging, cytotoxic, or other therapeutic agents. Hormonal receptors viz. peptide and steroid receptors (SRs), which are present over the tumor surface, are also used for tumor targeting of various molecules for therapeutic use or imaging purpose. The key role of SRs is in the transactivation step of protein synthesis and to maintain the homeostasis in normal and diseased states. These receptors are overactivated in different diseases, including tumorigenesis. Hence, these SRs may act as a potential target for selective delivery of different therapeutic or cytotoxic agents. The selective delivery of these agents may be a better treatment strategy for endocrine cancer because it results in cytosolic and nuclear delivery of cytotoxic agents as well. The objective of the present review is to explore the importance of sex SRs as a vital target in endocrine cancer therapy. Potential strategies investigated for the delivery of imaging agents, chemotherapeutics, and toxins via steroidal ligands have been discussed. The importance of gene therapy in different diseases, including endocrine cancer, is well defined; thus, some effective gene delivery approaches investigated in endocrine cancer via steroidal ligands have also been discussed.