Shailendra Saraf

Approaches for breaking the barriers of drug permeation through transdermal drug delivery

Transdermal drug delivery system (TDDS) utilizes the skin as executable route for drug administration but the foremost barrier against drug permeability is the stratum corneum and therefore, it limits therapeutic bioavailability of the bioactive. This review focuses on the recent advancements in the TDDS which include iontophoresis, sonophoresis, electroporation, microneedles, magnetophoresis, photomechanical waves and electron beam irradiation. These advancements are exhaustively discussed with techniques involved with their beneficial claims for different categories of bioactive. However, a lot of research has been carried out in TDDS, still the system has many pros and cons such as inconsistent drug release, prevention of burst release formulation and problems related to toxicity. In addition to that, to exploit the TDDS more efficiently scientists have worked on some combinational approaches for manufacturing TDDS viz., chemical-iontophoresis, chemical-electroporation, chemical-ultrasound, iontophoresis-ultrasound, electroporation-iontophoresis electroporation-ultrasound and pressure waves-chemicals and reported the synergistic effect of the same for safe, effective and practical use of TDDS. The present article covers all the above-mentioned aspects in detail and hence the article will assuredly serve as an enlightening tool for the visionaries working in the concerned area.

Recent advances and future prospects of phyto-phospholipid complexation technique for improving pharmacokinetic profile of plant actives

The phyto-phospholipid complexation technique has emerged as one of the leading methods of improving bioavailability of phytopharmaceuticals having poor competency of solubilizing and crossing the biological membranes. Several plant actives in spite having potent in vitro pharmacological activities have failed to demonstrate similar in vivo response. Such plant actives have been made more effective systemically by incorporating them with dietary phospholipids forming new cellular structures which are amphipathic in nature. In the last few years phospholipids have been extensively explored for improved bioavailability and efficacy of plant drugs. Further, it is also much relevant to mention that phospholipids show unique compatibility with biological membranes and have inherent hepatoprotective activity. Different methods have been adopted to formulate phospholipid complexes of plant extractives utilizing varying solvent systems, molar ratios of drug/phospholipids and different drying techniques. Some methods of formulating such drug-phospholipid complexes have been patented as well. However, the stability of phyto-phospholipid complexes is still a matter of concern which needs attention. But still a number of products exploiting this technique are under clinical trials and some of them are now in market. The current review highlights key findings of recent years with our own viewpoints which can give the new directions to this strategy and also includes advancements in the technical aspects of phyto-phospholipid formulations which have been done in the recent past with future challenges.

Poly(ethylene glycol)–poly(lactic-co-glycolic acid) based thermosensitive injectable hydrogels for biomedical applications

Stimuli triggered polymers provide a variety of applications related with the biomedical fields. Among various stimuli triggered mechanisms, thermoresponsive mechanisms have been extensively investigated, as they are relatively more convenient and effective stimuli for biomedical applications. In a contemporary approach for achieving the sustained action of proteins, peptides and bioactives, injectable depots and implants have always remained the thrust areas of research. In the same series, Poloxamer based thermogelling copolymers have their own limitations regarding biodegradability. Thus, there is a need to have an alternative biomaterial for the formulation of injectable hydrogel, which must remain biocompatible along with safety and efficacy. In the same context, poly(ethylene glycol) (PEG) based copolymers play a crucial role as a biomedical material for biomedical applications, because of their biocompatibility, biodegradability, thermosensitivity and easy controlled characters. This review stresses on the physicochemical property, stability and composition prospects of smart PEG/poly(lactic-co-glycolic acid) (PLGA) based thermoresponsive injectable hydrogels, recently utilized for biomedical applications. The manuscript also highlights the synthesis scheme and stability characteristics of these copolymers, which will surely help the researchers working in the same area. We have also emphasized the applied use of these smart copolymers along with their formulation problems, which could help in understanding the possible modifications related with these, to overcome their inherent associated limitations.

Influence of selected formulation variables on the preparation of enzyme-entrapped eudragit S100 microspheres

The aim of this work is to study the influence of formulation parameters in the preparation of sustained release enzyme-loaded Eudragit S100 microspheres by emulsion solvent diffusion technique. A 32 full factorial experiment was designed to study the effects of the amount of solvent (dichloromethane) and stabilizers (Tween 20, 40, or 80) on the drug content and microsphere size. The results of analysis of variance test for both effects indicated that the test is significant. The effect of amount of stabilizer was found to be higher on both responses (SSY1=45.60; SSY2=737.93), whereas solvent concentration comparatively produced significant effect on the size of microspheres (SSY1=0.81; SSY2=358.83). Scanning electron microscopy of microspheres with maximum drug content (2.5 mL dichloromethane and 0.1 mL Tween 80) demonstrated smooth surface spherical particles with mean diameter of 56.83±2.88 µm. The effect of formulation variables on the integrity of enzyme was confirmed by in vitro proteolytic activity. The enteric nature of microspheres was evaluated and results demonstrated ∼6% to 7% release of enzyme in acidic medium. The release of enzyme from microspheres followed Higuchi kinetics. In phosphate buffer, microspheres showed an initial burst release of 20.34%±2.35% in 1 hour with additional 58.79%±4.32% release in the next 5 hours. Three dimensional response graphs were presented to visualize the effect of independent variables on the chosen response. Thus, Eudragit S100 microspheres can be successfully prepared for oral delivery of enzymes with desirable characters in terms of maximum loading and diffusion release pattern.

Role of herbal bioactives as a potential bioavailability enhancer for Active Pharmaceutical Ingredients

The current review emphasizes on the herbal bioenhancers which themselves do not possess inherent pharmacological activity of their own but when co-administered with Active Pharmaceutical Ingredients (API), enhances their bioavailability and efficacy. Herbal bioenhancers play a crucial role in enhancing the bioavailability and bioefficacy of different classes of drugs, such as antihypertensives, anticancer, antiviral, antitubercular and antifungal drugs at low doses. This paper highlights various natural compounds that can be utilized as an efficient bioenhancer. Several herbal compounds including piperine, quercetin, genistein, naringin, sinomenine, curcumin, and glycyrrhizin have demonstrated capability to improve the pharmacokinetic parameters of several potent API. This article also focuses on various United States patents on herbal bioenhancers, which has proved to be beneficial in improving oral absorption of nutraceuticals like vitamins, minerals, amino acids and certain herbal compounds. The present paper also describes proposed mechanism of action, which mainly includes absorption process, drug metabolism, and action on drug target. The herbal bioenhancers are easily available, safe, free from side effects, minimizes drug toxicity, shortens the duration of treatment, lowers the drug resistance problems and minimizes the cost of treatment. Inspite of the fact that herbal bioenhancers provide an innovative concept for enhancing the bioavailability of several potent drugs, there are numerous bioenhancers of herbal origin that are yet to be explored in several vital areas. These bioenhancers must also be implied to enhance the bioavailability and bioefficacy through routes other than the oral route of drug delivery. There is a vast array of unexploited plants which can be investigated for their drug bioenhancing potency. The toxicity profiles of these herbal bioenhancers must not be overlooked. Researches must be carried out to solve these issues and to deliver a safe and effective dose of drugs to attain desired pharmacological response.

Advancement in stimuli triggered in situ gelling delivery for local and systemic route

Introduction: Current research efforts focused on the design and evaluation of drug delivery systems that are easy to administer require decreased administration frequency, and provide sustained drug release in order to increase clinical efficacy and compliance of the patients. The gel forming smart polymeric formulations offer numerous applications resemble sustained and prolonged action in contrast to conventional drug delivery systems. Areas covered: Article summarizes type of bioactive, sol–gel triggering factors, dose, rationales, and polymers involved in gelation with respect to their route of administration. A lot of work has been done with smart polymeric gelling system taking the advantage of stimuli (temperature and pH) triggered sol–gel phase-transition in the administered area that have great prospective in biomedical and pharmaceutical applications, particularly in target-specific controlled drug delivery systems. Expert opinion: Although the principle of gelation is so attractive, key issues remain to be solved which include (i) variability of the drug release, (ii) avoidance of burst release in case of depot formulation, and (iii) issues related to toxicity. Unfortunately, till now area concerning the detailed processes of the gelling formation is still not much explored. Despite this proclamation, many efforts are made in industry and institutions to improve concerned approaches. New materials and approaches enter the preclinical and clinical phases and one can be sure that this strategy will gain further clinical importance within the next years. Thus, this review article will assuredly serve as an informative tool for the innovators working in the concern area.

Recent expansion of pharmaceutical nanotechnologies and targeting strategies in the field of phytopharmaceuticals for the delivery of herbal extracts and bioactives

Application of pharmaceutical nanotechnology (nanomedicines) for plant actives and extracts, is gaining a tremendous growth and interest among the scientists. This emerging herbal revolution has headed towards the development of another approaches for the delivery of poorly soluble herbal bioactives and plant extracts for enhancing their bioavailability and efficacy. In the same context, a majority of pharmaceutical nanotechnologies and targeting strategies including phytosomes, nanoparticles, hydrogels, microspheres, transferosomes and ethosomes, self nano emulsifying drug delivery systems (SNEDDS), self micro emulsifying drug delivery systems (SMEDDS) has been applied for the delivery of bioactives and plant extracts and were identified and explored. These pharmaceutical nanotechnologies have been proven to be the most efficient and reliable delivery systems, as these enhance the solubility, absorption, pharmacokinetics, bioavailability and provide protection from toxicity. Considering these aspects, the present review highlights the present scenario related to the expansion of novel herbal formulations utilizing the nanotechnologies and compilation of their delivery types and mechanism, methodology, loaded drug, drug size, entrapment efficiency of drug, in vivo activity and its application. Moreover, this review article provides an understanding of therapeutic efficacy of the herbal medicines to be loaded into the novel drug delivery system for various biomedical applications.

Recent approaches for reducing hemolytic activity of chemotherapeutic agents.

Drug induced hemolysis is a frequent complication associated with chemotherapy. It results from interaction of drug with erythrocyte membrane and leads to cell lysis. In recent past, various approaches were made to reduce drug-induced hemolysis, which includes drug polymer conjugation, drug delivery via colloidal carriers and hydrogels, co-administration of botanical agents and modification in molecular chemistry of drug molecules. The basic concept behind these strategies is to protect the red blood cells from membrane damaging effects of drugs. There are several examples of drug polymer conjugate that either are approved by Food and Drug Administration or are under clinical trial for delivering drugs with reduced toxicities. Likewise, colloidal carriers are also used successfully nowadays for the delivery of various chemotherapeutic agents like gemcitabine and amphotericin B with remarkable decrease in their hemolytic activity. Similarly, co-administration of botanical agents with drugs works as secondary system proving protection and strength to erythrocyte membranes. In addition to the above statement, interaction hindrance between RBC and drug molecule by molecular modification plays an important role in reducing hemolysis. This review predominantly describes the above recent approaches explored to achieve the reduced hemolytic activity of drugs especially chemotherapeutic agents.

Luteolin-phospholipid complex: preparation, characterization and biological evaluation.

This study aims to develop novel carrier system incorporating luteolin, a poorly soluble biologically active plant active.

Formulation and evaluation of chitosan‐based long‐acting injectable hydrogel for PEGylated melphalan conjugate

In this study, we have used melphalan (ML) as a model drug, used extensively for the treatment of breast cancer. Due to its remarkable haemolytic activity, clinical application of this drug is limited.