Microsponges: a futuristic approach for oral drug delivery

INTRODUCTION: Microparticulate drug delivery systems have, due to their advantages, guided researchers across the globe to explore them as drug carriers. This has, sequentially, led to the development of microsponges in 1988. These porous microspheres were exclusively designed for chronotherapeutic topical drug delivery but attempts to utilize them for oral, pulmonary and parenteral drug delivery were also made. Researchers have extensively studied their properties and characteristics affecting the drug release and loading. Various advances were made with this carrier particle resulting in the development of various novel development techniques and carrier particles. AREAS COVERED: This review deals with the considerations of the drug material to be entrapped in microsponges, pharmaceutical considerations for fabrication of microsponges, their potential for oral drug delivery, clinical perspectives and also provides an insight on the recent advances made in this field and future prospect. EXPERT OPINION: Clinical studies show that these carriers can increase drug efficacy. Due to their potential advantages over other carrier particles, microsponges form a prospective platform for the oral delivery of pharmaceuticals and biopharmaceuticals. Although these carriers have several advantages, they too possess some drawbacks which limit their commercialization for oral application.     

Polymeric nanoparticles for the drug delivery to the central nervous system

BACKGROUND: Nanoparticulate polymeric systems (nanoparticles [Np]) have been widely studied for the delivery of drugs to a specific target site. This approach has been recently considered for the therapy of brain diseases. The major problem in accessing the CNS is linked to the presence of the blood-brain barrier. OBJECTIVE: The present review deals with the different strategies that have been developed in order to allow Np drug carriers entry into the CNS parenchyma. Among these, the use of magnetic Np, Np conjugation with ligands for blood-brain barrier receptors, with antibodies, and the use of surfactants have been considered. METHODS: All the literature available is reviewed in order to highlight the potential of this drug delivery system to be used as a drug carrier for the treatment of CNS pathologies. CONCLUSIONS: Polymeric Np have been shown to be promising carriers for CNS drug delivery due to their potential both in encapsulating drugs, hence protecting them from excretion and metabolism, and in delivering active agents across the blood-brain barrier without inflicting any damage to the barrier. Different polymers have been used and different strategies have been applied; among these, the use of specific ligands to enhance the specificity of drugs delivered to the CNS has recently been considered. At present, clinical trials are being conducted appeared for the use of these drug carriers but none related to the treatment of CNS diseases.     

Microsponges: a futuristic approach for oral drug delivery

Introduction: Microparticulate drug delivery systems have, due to their advantages, guided researchers across the globe to explore them as drug carriers. This has, sequentially, led to the development of microsponges in 1988. These porous microspheres were exclusively designed for chronotherapeutic topical drug delivery but attempts to utilize them for oral, pulmonary and parenteral drug delivery were also made. Researchers have extensively studied their properties and characteristics affecting the drug release and loading. Various advances were made with this carrier particle resulting in the development of various novel development techniques and carrier particles.

Areas covered: This review deals with the considerations of the drug material to be entrapped in microsponges, pharmaceutical considerations for fabrication of microsponges, their potential for oral drug delivery, clinical perspectives and also provides an insight on the recent advances made in this field and future prospect.

Expert opinion: Clinical studies show that these carriers can increase drug efficacy. Due to their potential advantages over other carrier particles, microsponges form a prospective platform for the oral delivery of pharmaceuticals and biopharmaceuticals. Although these carriers have several advantages, they too possess some drawbacks which limit their commercialization for oral application.     

Liposomal drug delivery systems--clinical applications

Liposomes have been widely investigated since 1970 as drug carriers for improving the delivery of therapeutic agents to specific sites in the body. As a result, numerous improvements have been made, thus making this technology potentially useful for the treatment of certain diseases in the clinics. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. The current pharmaceutical preparations of liposome-based therapeutic systems mainly result from our understanding of lipid-drug interactions and liposome disposition mechanisms. The insight gained from clinical use of liposome drug delivery systems can now be integrated to design liposomes that can be targeted on tissues, cells or intracellular compartments with or without expression of target recognition molecules on liposome membranes. This review is mainly focused on the diseases that have attracted most attention with respect to liposomal drug delivery and have therefore yielded most progress, namely cancer, antibacterial and antifungal disorders. In addition, increased gene transfer efficiencies could be obtained by appropriate selection of the gene transfer vector and mode of delivery.     

Design strategies to improve soluble macromolecular delivery constructs

Macromolecular therapeutics provide numerous benefits for the delivery of cytotoxic or poorly soluble drugs in vivo. However, these constructs often encounter barriers for drug delivery on both the systemic and subcellular level. Many soluble polymer carriers have been designed to surmount specific physiological barriers individually, but less work has been dedicated to designing an all-encompassing construct that addresses multiple therapeutic barriers at once. Incorporation of multiple agents already individually known to increase effectiveness into one carrier could further improve current drug delivery technology. Recent developments in subcellular delivery of therapeutic agents in soluble macromolecular carriers are discussed in the context of the future possibility for the design of an all-encompassing soluble multi-functional drug delivery vehicle.     

Drug delivery systems. 1. site-specific drug delivery using liposomes as carriers

Drug delivery systems, offering controlled delivery of biologically active agents, are rapidly gaining importance in pharmaceutical research and development. To achieve controlled drug delivery, i.e., the administration of drugs so that optimal amount reaches the target site to cure or control the disease state, increasingly sophisticated systems containing different carriers have been developed. Macromolecules represent one of the carriers involved, and they have taken on a significantly prominent role in various modes of administration of therapeutic agents. Among macromolecules, for example, synthetic copolymers, polysaccharides, liposomes, polyanions and antibodies, as drug carriers, liposomes have proved most effective for diseases affecting the reticuloendothelial system and blood cells in particular. Liposomes, which are vesicles consisting of one or more concentrically ordered assemblies of phospholipids bilayers, range in size from a nanometer to several micrometers. Phospholipids such as egg phosphatidylcholine, phosphatidylserine, synthetic dipalmitoyl-DL-alpha-phosphatidylcholine or phosphatidylinositol, have been used in conjunction with cholesterol and positively or negatively charged amphiphiles such as stearylamine or phosphatidic acid. Alteration of surface charge has been shown to enhance drug incorporation and also influence drug release. Because of the multifold characteristics as drug carriers, liposomes have been investigated extensively as carriers of anticancer agents for the past several years. Liposomal entrapments include a variety of pharmacologically active compounds such as antimalarial, antiviral, anti-inflammatory and anti-fungal agents as well as antibiotics, prostaglandins, steroids and bronchodilators to name a few. The liposomal entrapment has been shown to have considerable effect on the pharmacokinetics and tissue distribution of administered drugs. Despite the potential value of liposomes as unique carriers, the major obstacles are the first order targeting of a systemically given liposomes, physical stability and manufacture of the liposomal products and these problems still remain to be overcome. Drug delivery systems evolving in the 1980s have become increasingly dependent on fundamental cell-biology and receptor-mediated endocytotic mechanisms. Drug delivery systems during the 1990s may take advantage of the specificity of receptor-mediated uptake mechanisms as well as polymer chemistry and cell-biology in order to introduce more precise and efficient target-specific delivery systems that are based especially on the liposome technology.     

Targeting intracellular targets

Many therapeutic agents have intracellular compartments as their site of action. Targeted delivery of these agents to their specific intracellular targets could result in enhanced therapeutic efficacy and reduced toxicity. Various carriers have been shown useful in targeted delivery of different classes of therapeutic agents. Among these carriers, biodegradable nanoparticles formulated from biocompatible polymers poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA) have shown the potential for sustained intracellular delivery of different therapeutic agents. In this review, we discuss different intracellular targets, barriers to intracellular delivery, mechanism and pathways of intracellular delivery, and various carriers and approaches that have been investigated for intracellular drug delivery.     

Cell-based drug delivery

Drug delivery has been greatly improved over the years by means of chemical and physical agents that increase bioavailability, improve pharmacokinetic and reduce toxicities. At the same time, cell based delivery systems have also been developed. These possesses a number of advantages including prolonged delivery times, targeting of drugs to specialized cell compartments and biocompatibility. Here we'll focus on erythrocyte-based drug delivery. These systems are especially efficient in releasing drugs in circulations for weeks, have a large capacity, can be easily processed and could accommodate traditional and biologic drugs. These carriers have also been used for delivering antigens and/or contrasting agents. Carrier erythrocytes have been evaluated in thousands of drug administration in humans proving safety and efficacy of the treatments. Erythrocyte-based delivery of new and conventional drugs is thus experiencing increasing interests in drug delivery and in managing complex pathologies especially when side effects could become serious issues.     

Emulsion forming drug delivery system for lipophilic drugs

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

Human peptide transporters: therapeutic applications

Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2, which possess transport activity, have been identified. The transporters are not drug targets per se, but due to uniquely broad substrate specificity they have proven to be relevant in drug therapy at the level of drug transport. Therapeutic agents such as orally active β-lactam antibiotics, bestatin, prodrugs of acyclovir and gancyclovir have oral bioavailabilities, which are largely a result of their interaction with PepT1. The transporters have therefore received considerable attention in relation to drug delivery. The aim of the present review is to highlight structural requirements for binding to peptide transporters, as well as their role in drug delivery and in potential future drug design and targeted tissue delivery of peptides and peptidomimetics.     

Bioadhesive microspheres as a controlled drug delivery system

The concept of controlled drug delivery has been traditionally used to obtain specific release rates or spatial targeting of active ingredients. The phenomenon of bioadhesion, introduced by Park and Robinson [Park, K., Robinson, J.R., 1984. Bioadhesive polymers as platforms for oral controlled drug delivery: method to study bioadhesion. Int. J. Pharm. 198, 107-127], has been studied extensively in the last decade and applied to improve the performance of these drug delivery systems. Recent advances in polymer science and drug carrier technologies have promulgated the development of novel drug carriers such as bioadhesive microspheres that have boosted the use of "bioadhesion" in drug delivery. This article presents the spectrum of potential applications of bioadhesive microspheres in controlled drug delivery ranging from the small molecules, to peptides, and to the macromolecular drugs such as proteins, oligonucleotides and even DNA. The development of mucus or cell-specific bioadhesive polymers and the concepts of cytoadhesion and bioinvasion provide unprecedented opportunities for targeting drugs to specific cells or intracellular compartments. Developments in the techniques for in vitro and in vivo evaluation of bioadhesive microspheres have also been discussed.     

Lipid-based drug delivery systems for cancer treatment

It is a fact that chemotherapy agents have little specificity for cancer cells, this leading to low concentrations into the tumor interstititum and severe side effects on healthy tissues. The formulation of lipid-based nanomedicines against cancer has been hypothesized to improve drug localization into the tumor tissue and to increase the anticancer efficacy of concentional drugs, while minimizing their systemic adverse effects. In this review, special attention is devoted to the analysis of the state-of-the-art in the development of lipid-based drug carriers against cancer. Specifically, the most significant in vitro and in vivo results on the use of niosomes, liposomes, and solid lipid nanoparticles are revised. It is concluded that biodistribution profiles of chemotherapy agents can be controlled by their loading to such nanoplatforms. Lipid-based nanomedicines offer an interesting approach to the delivery of anticancer drugs to brain tumors, and to reverse multi-drug resistance of cancer cells. Finally, a deep evaluation of the applicability of drug delivery strategies in the formulation of lipid-based nanoplatforms is carried out. They involve active drug targeting (including ligand-mediated delivery, and stimuli-sensitive carriers), and passive drug targeting (through the enhanced permeability and retention effect) to tumors.     

Albumin corona on nanoparticles – a strategic approach in drug delivery

Nanomaterials have been used widely for delivery of therapeutic agents. Protein–nanoparticle (NP) complexes have gained importance as vehicles for targeted drug delivery due to increased ease of administration, stability and half-life of drug, and reduced toxic side effects. Designing of phospholipid–bovine serum albumin (BSA) complexes and stealth NPs with BSA has paved the way for drug delivery carriers with prolonged blood circulation times. Preformed albumin corona has shown to decrease non-specific association and thereby reduce the clearance rate. Albumin corona has enabled the localization of drug carriers in specific tissues such as liver and heart, thus regulating biodistribution. Tailored albumin–NP conjugates have also enabled controlled degradation of NP and drug release. However, the binding of albumin with NP is associated with conformational and functional modulations in protein as observed with silver, gold and superparamagnetic iron oxide NPs. In this review, we highlight the various potential albumin–NP hybrids as nano drug carriers.     

New drug formulations for cancer therapy

Despite recent emergence of novel therapeutic agents the major progress achieved in cancer treatments results from conventional drugs used for cytotoxic or hormone therapy. Over the past 20 years, a more rational and more pharmacological-based approach to chemotherapy has led to major successes. One of the most promising avenues of research is to improve the pharmacokinetic properties of well-known anticancer drugs (bioavailability, distribution, targeting, drug carriers) by modifications of their formulations (new drug delivery systems). As an example, new pharmaceutical forms of analogs of LH-RH, (microparticles or implants) permitting sustained release of the drug for months, are now largely used in the routine chemotherapy for prostate cancers. Improvement of the oral bioavailabilty of drugs previously administered only by the parenteral route is simplifying treatment protocols. Parenteral delivery of doxorubicine entrapped in liposomes (pegylated liposomes) decreases the cardiotoxicity and increases the half-live of this drug widely used in the treatment of breast carcinomas. Molecular targeting using immunocarriers such as immunoliposomes is also a very strong field of research.     

Classification of stimuli–responsive polymers as anticancer drug delivery systems

Abstract

Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli–responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli–responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed.     

Polymeric nanoparticles for oral delivery of drugs and vaccines: a critical evaluation of in vivo studies

Oral drug delivery is the preferred route of administration of drugs. Because of their versatility, nanoparticles often have been investigated for the delivery of a wide number of drugs by this route. This article first examines the physicochemical, pharmaceutical and technological aspects that make nanoparticles a potential oral delivery system for drugs and active biomolecules. Next, upon consideration of in vivo studies, the pharmacokinetic, pharmacological and therapeutic aspects of orally administered nanoparticles are described. Special emphasis is placed on improvement of oral bioavailability of drugs incorporated into nanoparticles. Two main mechanisms involved in enhancing drug absorption are discussed: the protection of drug by nanoparticles against harsh conditions in the gut and the prolongation of gastrointestinal transit of nanoparticles by using bioadhesive polymers. Furthermore, nanoparticle uptake by intestinal cells and oral vaccination by these colloidal carriers are also covered. In this context, the immune responses elicited as well as the protection against pathogens induced by antigen-loaded nanoparticles administered by the oral route are presented. Finally, the main limitations and perspectives of these colloidal carriers as oral drug delivery systems are discussed.     

Tuberculosis: from molecular pathogenesis to effective drug carrier design

In the past two decades, tuberculosis has gone from being a forgotten disease to a modern and recrudescent pathology. Tuberculosis is a curable infection and most of the negative therapeutic outcomes are related to poor patient compliance, which could be solved by new drug delivery approaches. By using such approaches the technological drawbacks of the currently used therapeutic agents could be addressed. In addition, optimum effectiveness of the drug by targeting the infection reservoirs could be achieved. In this article we compile the general physiological aspects of the infection along with new research updates especially on novel carriers used in the prevention of tuberculosis which might enhance therapeutic efficacy and patient compliance.