Showing papers in "Critical Reviews in Therapeutic Drug Carrier Systems in 2013"

Poly(lactic-co-glycolic) acid-controlled-release systems: experimental and modeling insights.

Abstract: Poly(lactic-co-glycolic acid) (PLGA) has been the most successful polymeric biomaterial used in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in the formulation of drug release devices. Mathematical modeling is a useful tool for identifying, characterizing, and predicting mechanisms of controlled release. The advantages and limitations of poly(lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled-release technology that utilize PLGA. Mathematical modeling applied toward controlled-release rates from PLGA-based devices also will be discussed to provide a complete picture of a state-of-the-art understanding of the control that can be achieved with this polymeric system, as well as the limitations.

Nanocurcumin: a promising therapeutic advancement over native curcumin.

Abstract: Curcumin, a naturally occurring polyphenolic compound, is known to have a wide range of therapeutic and pharmacological properties. Although it is a considerably promising compound, its poor water solubility and fast degradation profile make it compromise over its bioavailability way below the threshold level on administration. Over a period of time, a lot of emphasis has been given to improve the biodistribution of native curcumin, but it is only recently that the application of the field of nanotherapeutics has significantly improved its therapeutic efficacy. This is through the development of nanorange formulations of curcumin, popularly known as the "nanocurcumin." These attempts have given a strong platform to reap all the biological benefits from this phytodrug, which was not significantly plausible earlier. This review gives an insight into the reasons that make nanocurcumin a more therapeutically advanced drug than its native counterpart. It also discusses various nanometric formulations of curcumin that have been reported for its controlled and targeted delivery along with a critical comparison of its therapeutic efficacy with free curcumin. We also summarize the biological applications, patented technologies, and current status of the ongoing clinical trials related to nanocurcumin.

Stimuli-sensitive hydrogels: an excellent carrier for drug and cell delivery.

Abstract: The stimuli-sensitive hydrogel is an injectable formulation that is used to deliver drugs, cells, and genes into the body. Hydrogels are available in various physical forms such as solid molded, pressed powder matrix, microparticle, coating, or membrane forms. The network structure of hydrogels can be macroporous, microporous, or nonporous. Different categories of biomaterials, such as natural, synthetic, and combinations (e.g., semisynthetic such as natural-natural, natural-synthetic, and synthetic-synthetic polymers), are commonly used in hydrogel preparation. Classification of hydrogels mainly depends upon physical stimuli (temperature, electric fields, solvent composition, light, pressure, sound, and magnetic fields) and chemical or biochemical stimuli (pH, ions, and specific molecular recognition events). Several approaches for the synthesis of hydrogels have been reported, including emulsification, micromolding, photolithography, isostatic ultra high pressure, and microfluidic techniques. Hydrogels provide structural integrity and cellular organization, serve as tissue barriers, act as bioadhesive and drug depots, deliver bioactive agents and cells, and possess unique swelling properties and structures. This review provides a detailed account of the need for development of hydrogels, along with the materials used and techniques adopted to manufacture scaffolds for tissue engineering and for prolonged drug, cell, and gene delivery.

Peptide and protein delivery using new drug delivery systems.

Abstract: Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.

A new horizon in modifications of chitosan: syntheses and applications.

Abstract: Chitosan is a naturally occurring biopolymer having diversified applications not only in the pharmaceutical field, but also in the biomedical profession. The presence of functional groups, i.e., hydroxyl, acetamido, and amine in the chitosan parent backbone, makes it a suitable candidate for chemical modification, and introduces desired physicochemical and biochemical properties, without any changes in its fundamental skeleton. The various modifications, i.e., alkylation, acylation, quaternization, hydroxyalkylation, carboxyalkylation, thiolation, sulfation, phosphorylation, enzymatic modifications, oligomerization, and graft copolymerization with assorted modifications, and their pharmaceutical and biomedical applications, are discussed in this article. Additionally, it is also limelighted how the chemically engineered chitosan has established a better place with regard to the vista of applications in the arena of sciences such as pharmaceutical, biomedical, biotechnological, tissue engineering, the textile industry, chemistry, the food industry, and many more. This review, hopefully, could enrich knowledge and bring forth new thoughts in line with progress in chitosan polymer science.

A pharmacokinetic overview of nanotechnology-based drug delivery systems: an ADME-oriented approach.

Abstract: With the extensive progress in nanotechnology-based drug delivery systems, pharmacokinetic evaluations have gained much attention from researchers as a central part of the study of these systems. Because the fulfillment of any therapeutic goal(s) by a novel drug delivery system requires that the absorption, distribution, metabolism, and excretion (ADME) be considered from the early stages of the system design to the final clinical evaluations, extensive knowledge of the pharmacokinetic aspects related to ADME is a crucial part of research in this field. The main objectives of the nanotechnology-based drug delivery systems from a pharmacokinetic viewpoint are (1) an improved drug-release profile in vivo, (2) enhanced drug absorption, (3) site-directed drug distribution, (4) a modified drug metabolism pattern, (5) prolonged drug residence time in body (e.g., in blood circulation), and (6) delayed and/or decreased renal excretion of the drug. Accordingly, the purpose of the current review is to present an insightful summary of pharmacokinetic analyses of nanotechnology-based drug delivery systems along with a critical review of recent findings.

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

Abstract: 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.

Psoriasis clinical implications and treatment: a review.

Abstract: Psoriasis is a common skin disorder affecting the population worldwide. It is a T-cell mediated autoimmune disorder leading to keratinocyte hyperproliferation. Psoriasis has genetic predisposition that is further aggravated by certain stimulating factors. In spite of significant advances in understanding the pathogenesis of psoriasis, the exact etiology of the disease remains unknown. The clinical manifestations of this disease include various forms that affect different parts of the body. Treatment options vary according to the mode of application or severity of the disease. Earlier treatments have included application of emollients or keratolytic agents to hydrate the skin or shed off the skin. But later treatments have been modified to treat the underlying T-cell proliferation. Hence, topical treatments like coal tar, vitamin D, retinoids, topical calcineurin inhibitors for treating mild psoriasis, systemic treatments including methotrexate, cyclosporine, acitretin, hydroxyurea, as well as light therapy for severe psoriasis have become more prominent. Current treatment modalities are associated with the risk of serious side effects from prolonged treatment. Combinations of these therapies have provided effective and rapid modalities to suppress the disease and reduce the side effects of treatment. In addition, newer carrier systems for conventional drugs are being developed to improve the effectiveness of treatment and reduce the side effects. Development of biologics and gene therapy have revolutionized the treatment of this skin disease. Although an array of therapies to suppress the psoriatic condition exists, none are curative.

Nanomedicines for treatment of viral diseases.

Abstract: Viral diseases affect millions of people worldwide, with a high impact on human health and socioeconomic development. More than 40 million people are affected with human immunodeficiency virus (HIV) alone. This review discusses the various nanocarriers (e.g., liposomes, solid lipid nanoparticles, polymeric nanoparticles, inorganic nanoparticles, etc.) based on approaches that have been applied in the literature and in the clinic to combat the different challenges faced by the antiviral therapy. The recent developments in smart delivery technologies (e.g., immunoliposomes) targeting delivery to the lectin receptors and cell-penetrating peptides for site-specific delivery of antiviral agents at the viral reservoirs are also been discussed.

Nano-aggregates: emerging delivery tools for tumor therapy.

Abstract: A plethora of formulation techniques have been reported in the literature for site-specific targeting of water-soluble and -insoluble anticancer drugs. Along with other vesicular and particulate carrier systems, nano-aggregates have recently emerged as a novel supramolecular colloidal carrier with promise for using poorly water-soluble drugs in molecular targeted therapies. Nano-aggregates possess some inherent properties such as size in the nanometers, high loading efficiency, and in vivo stability. Nano-aggregates can provide site-specific drug delivery via either a passive or active targeting mechanism. Nano-aggregates are formed from a polymer-drug conjugated amphiphilic block copolymer. They are suitable for encapsulation of poorly water-soluble drugs by covalent conjugation as well as physical encapsulation. Because of physical encapsulation, a maximum amount of drug can be loaded in nano-aggregates, which helps to achieve a sufficiently high drug concentration at the target site. Active transport can be achieved by conjugating a drug with vectors or ligands that bind specifically to receptors being overexpressed in the tumor cells. In this review, we explore synthesis and tumor targeting potential of nano-aggregates with active and passive mechanisms, and we discuss various characterization parameters, ex vivo studies, biodistribution studies, clinical trials, and patents.

In situ gel-forming system: an attractive alternative for nasal drug delivery.

Abstract: Intranasal delivery is one of the most interesting and challenging endeavors facing pharmaceutical scientists. The conventional nasal drug delivery systems including solutions, suspensions, and ointments show drawbacks such as short residence in the nasal cavity, highly variable efficiency, low permeability, and inconvenient administration. In situ gel-forming systems are an interesting polymeric system that exists as flowing aqueous solution before administration and undergoes phase transition to form a viscoelastic gel in a physiologic environment. Benefiting from the merits of both a solution and a gel, an impressive number of in situ gel-forming systems induced by temperature, pH, and ions have been prepared for use in nasal drug delivery in the past few years. In situ gel-forming systems increase the retention of drugs in the nasal cavity, and some of them also show permeation-enhancing capabilities. This article reviews the in situ gel-forming systems used for nasal drug delivery and introduces their gelling mechanisms and other favorable features for intranasal delivery. It also describes the release patterns and drug stability of in situ gels as well as their in vivo performances and local safety following nasal administration.

Options and opportunities for clinical management and treatment of psoriasis.

Abstract: Psoriasis is a complex, multifactorial disease that appears to be influenced by immune-mediated components. For many years the pathogenesis of psoriasis has been discordant; the clinical picture suggested that the psoriasis was secondary to abnormal keratinocyte proliferation and differentiation, but later the role of the T cell was revealed. A variety of treatment options range from topical agents (e.g., coal tar, dithranol, and emollients for milder forms) to systemic agents (i.e., methotrexate or cyclosporin), and phototherapy. Recently, biologics have been added to this list that target particular steps in the immune or inflammatory pathways. Various nanocarriers (e.g., liposomes, niosomes, and microemulsions) have been successfully exploited for the delivery of several antipsoriatic drugs. This review provides insight into various psoriasis treatment strategies-from conventional to novel-currently in use or in development as well as the novel targets that have been explored and/or investigated for anti-psoriatic therapy. The pathogenesis of psoriasis and some of the topical, systemic biological, and novel approaches currently in use or in development are reviewed here. The pros and cons of each treatment strategy are presented, as are some of the animal models used to study features reminiscent of psoriasis. This information can be used to better the understanding of treatment options for this disease.

Dissolution criticality in developing solid oral formulations: from inception to perception.

Abstract: Currently, dissolution testing has become a vital tool for accessing product performance, especially in the hierarchy of solid oral dosage forms. With advances in complicated, expensive, and sophisticated analytical instruments, characterization of formulations has become easier, but simple dissolution assembly is gradually gaining momentum from industrial environs as well as regulatory agencies. As such, simple dissolution testing involves many complexities which must be properly understood to reach correct conclusions. The appropriate selection of multiple parameters (e.g., apparatus, medium, agitation, etc.) involved in dissolution testing and understanding their impact on analysis require thorough subject knowledge. In the words of regulatory provisions, in vitro dissolution testing can become a surrogate for expensive and tedious bioequivalence studies in special cases (i.e., when a biowaiver is recommended). As a consequence, reduced human testing as well as lower product development cost ultimately benefit patients and society. Therefore, the dissolution science has recently become one of the keys for success for formulation scientists, especially generic manufacturers. While designing dissolution methodologies, generic manufacturers need to follow the respective regulatory guidelines at the product development stage; concomitant data are required for the approval process. This comprehensive review is an earnest attempt to acquaint readers with the history, contemporary practices, and relevant issues regarding dissolution which may become a guiding tool for overcoming challenges and opening better prospects in product development.

Particulate pulmonary delivery systems containing anti-tuberculosis agents.

Abstract: There is renewed interest in delivering anti-tuberculosis (TB) drugs to the lungs by inhalation. Several groups have investigated particulate pulmonary drug delivery formulations containing anti-TB agents, prepared using a variety of design approaches and processes. This review summarizes trends that indicate feasibility and translation of research efforts aimed at developing inhaled therapies for TB. Whereas formulations intended for reconstitution as solutions prior to nebulization can be produced with relative ease, particle engineering for powder formulations is more specialized. Spray drying and emulsion methods used to prepare particulate pulmonary delivery systems of anti-TB agents are compared. Pharmaceutical characterization is outlined. Administration of repeated inhalations to laboratory animals, especially under Animal Biosafety Level-3 (ABSL-3) containment as required for TB research, is another major challenge. Techniques employed by different groups are reviewed in the context of suitability for drug delivery and amenability towards use in ABSL-3 settings. It is concluded that spray drying is suitable for production of inhalable particles, rigorous physicochemical characterization is necessary for developing inhaled therapies as drug products, and pulmonary delivery of formulations containing anti-TB drugs to animals infected with Mycobacterium tuberculosis can best be carried out using handheld devices.

Nanoformulations for delivery of biomolecules: focus on liposomal variants for siRNA delivery.

Abstract: The potency of biomolecules assures therapy for as well as prevention of many disorders. However, their stability and delivery to the site of action remain a major challenge for successful therapeutic application. With advantages of nanoformulations, such as systemic environmental protection, controlled and site specific release, many of these bio-molecules have found their place in preventive, curative, or immunization-based therapies. Nanoformulations have indeed become a boon for the delivery of biomolecules with such challenges. Among biomolecules, small interfering RNA (siRNA)-based therapeutics has broad range of applications for disorders that may be pathological, metabolic, or physiological. However, certain challenges with respect to biological and delivery constraints need a priori consideration. From this perspective, liposomal delivery has made substantial progress to meet most of the delivery-related (pharmacokinetic) problems associated with siRNA. Furthermore, need-based development has led to the evolution of variants of liposomes. In this review we focus on the scope of siRNA and the trend of rationalized development of liposomal variants to explore its potential therapeutic implication.