Amit Alexander

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.

Prospects of pharmaceuticals and biopharmaceuticals loaded microparticles prepared by double emulsion technique for controlled delivery

Several methods and techniques are potentially useful for the preparation of microparticles in the field of controlled drug delivery. The type and the size of the microparticles, the entrapment, release characteristics and stability of drug in microparticles in the formulations are dependent on the method used. One of the most common methods of preparing microparticles is the single emulsion technique. Poorly soluble, lipophilic drugs are successfully retained within the microparticles prepared by this method. However, the encapsulation of highly water soluble compounds including protein and peptides presents formidable challenges to the researchers. The successful encapsulation of such compounds requires high drug loading in the microparticles, prevention of protein and peptide degradation by the encapsulation method involved and predictable release, both rate and extent, of the drug compound from the microparticles. The above mentioned problems can be overcome by using the double emulsion technique, alternatively called as multiple emulsion technique. Aiming to achieve this various techniques have been examined to prepare stable formulations utilizing w/o/w, s/o/w, w/o/o, and s/o/o type double emulsion methods. This article reviews the current state of the art in double emulsion based technologies for the preparation of microparticles including the investigation of various classes of substances that are pharmaceutically and biopharmaceutically active.

Alginate based hydrogel as a potential biopolymeric carrier for drug delivery and cell delivery systems: present status and applications.

Alginate is a non-toxic, biocompatible and biodegradable natural polymer with a number of peculiar physicochemical properties for which it has wide applications in drug delivery and cell delivery systems. Hydrogel formation can be obtained by interactions of anionic alginates with multivalent inorganic cations by simple ionotropic gelation method. Hydrophilic polymeric network of three dimensional cross linked structures of hydrogels absorb substantial amount of water or biological fluids. Among the numerous biomaterials used for hydrogel formation alginate has been and will continue to be one of the most important biomaterial. Therefore, in view of the vast literature support, we focus in this review on alginate - based hydrogel as drug delivery and cell delivery carriers for biomedical applications. Various properties of alginates, their hydrogels and also various techniques used for preparing alginate hydrogels have been reviewed.

Recent expansions in an emergent novel drug delivery technology: Emulgel.

Emulgel is an emerging topical drug delivery system to which if more effort is paid towards its formulation & development with more number of topically effective drugs it will prove a boon for derma care & cosmetology. Emulgels are either emulsion of oil in water or water in oil type, which is gelled by mixing it with gelling agent. Incorporation of emulsion into gel increases its stability & makes it a dual control release system. Due to lack of excess oily bases & insoluble excipients, it shows better drug release as compared to other topical drug delivery system. Presence of gel phase makes it a non greasy & favors good patient compliance. These reviews give knowledge about Emulgel including its properties, advantages, formulation considerations, and its recent advances in research field. All factors such as selection of gelling agent, oil agent, emulsifiers influencing the stability and efficacy of Emulgel are discussed. All justifications are described in accordance with the research work carried out by various scientists. These brief reviews on formulation method have been included. Current research works that carried out on Emulgel are also discussed and highlighted the wide utility of Emulgel in topical drug delivery system. After the vast study, it can be concluded that the Emulgels appear better & effective drug delivery system as compared to other topical drug delivery system. The comprehensive analysis of rheological and release properties will provide an insight into the potential usage of Emulgel formulation as drug delivery system.

Polyethylene glycol (PEG)-Poly(N-isopropylacrylamide) (PNIPAAm) based thermosensitive injectable hydrogels for biomedical applications.

Protein and peptide delivery by the use of stimuli triggered polymers remains to be the area of interest among the scientist and innovators. In-situ forming gel for the parenteral route in the form of hydrogel and implants are being utilized for various biomedical applications. The formulation of gel depends upon factors such as temperature modulation, pH changes, the presence of ions and ultra-violet irradiation, from which drug is released in a sustained and controlled manner. Among various stimuli triggered factors, thermoresponsive is the most potential one for the delivery of protein and peptides. Poly(ethylene glycol) (PEG) based copolymers play a crucial role as a biomedical material for biomedical applications, because of its biocompatibility, biodegradability, thermosensitivity and easy controlled characters. This review, stresses on the physicochemical property, stability and compositions prospects of smart thermoresponsive polymer specifically, PEG/Poly(N-isopropylacrylamide) (PNIPAAm) based thermoresponsive injectable hydrogels, recently utilized for biomedical applications. PEG-PNIPAAm based hydrogel exhibits good gelling mechanical strength and minimizes the initial burst effect of the drug. In addition, upon changing the composition and proportion of the copolymer molecular weight and ratio, the gelling time can be reduced to a great extent providing better sol-gel transition. The hydrogel formed by the same is able to release the drug over a long duration of time, meanwhile is also biocompatible and biodegradable. Manuscript will give the new researchers an idea about the potential and benefits of PNIPAAm based thermoresponsive hydrogels for the biomedical application.

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.

Synthesis, characterization and in vitro studies of pegylated melphalan conjugates.

Melphalan, a drug used for the treatment of breast, ovaries and a certain type of cancer in the bone marrow, was conjugated to linear methoxy poly (ethylene glycol) (M-PEG) of 2000 and 5000, Da. An ester linkage between polymer and drug was used in the coupling to yield a polymeric prodrug. Purified esters were characterized by Maldi-Tof and IR spectroscopy methods. The modification allowed overcoming the known melphalan aqueous solubility problem (0.1 µg/ml) leading us to obtain a polymer-drug bioconjugate more suitable for oral and parental administration. It was found that molecular weight of M-PEG is critical for the conjugates stability, aqueous solubility (80 times and 123 times higher aqueous solubility for M-PEG 2000 and M-PEG 5000, respectively), and hemolytic activity. The melphalan caused 100% hemolysis above the concentration 3.5 µg/ml in 1 h. whereas conjugate of M-PEG 2000 and M-PEG 5000 shows 81.3 ± 0.5% and 48.8 ± 1.5% hemolysis, respectively at 32 µg/ml after1 h. Further In vitro anticancer activity of melphalan and its conjugates was performed with breast cancer MCF-7 cell lines. It shows that LD50 concentration was higher 1.14 and 2 µm for M-PEG 2000 and M-PEG 5000, respectively in comparison to pure melphalan (0.74 µm). Above studies revealed improved pharmacokinetics properties upon conjugation.