Junaid Khan

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.

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.

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.

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.

Preparation and evaluation of luteolin–phospholipid complex as an effective drug delivery tool against GalN/LPS induced liver damage

Abstract Context: The phyto-phospholipid complexation technique is a promising approach to improve the bioavailability and efficacy of flavonoids. Objective: The objective of this study was to improve the bioavailability and efficacy of luteolin by phospholipid complexation against inflammatory liver damage. Materials and methods: The phospholipid complex of luteolin (LPC) was prepared by solvent evaporation accompanied by freeze drying. The physicochemical properties of LPC were investigated by means of spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Pharmacokinetic parameters in rats were determined and the hepatoprotective potential was assessed against d-galctosamine and lipopolysaccharide (GalN/LPS) induced hepatic damage. Results: LPC showed drug loading of 74.14% and average particle size 147.4 nm. The results of FTIR, thermal and diffraction studies confirmed the formation of complex. The aqueous/n-octanol solubility showed improvements. LPC showed an increase in relative in vivo bioavailability to 535.31% of pure luteolin. The histological and biochemical changes induced by GalN/LPS were significantly ameliorated by LPC. Discussion: Hepatoprotective effect of LPC was more profound than luteolin with a particle size suitable for passive targeting of inflammatory sites. Conclusion: LPC was successfully formulated under optimized conditions and is an efficient drug delivery system for oral administration of luteolin with enhanced bioavailability and hepatoprotective potential.

Exploring the role of polymeric conjugates toward anti-cancer drug delivery: Current trends and future projections

ABSTRACT Utilizing the diverse features of biocompatible polymers to target drugs into the tumor/s has been a research hotspot since last decade. Such polymeric conjugates of anti‐cancer drugs have proven their potential in providing sustained release of drugs with reduced systemic toxicity and improved tumor retention. Polymers like polyethylene glycol (PEG), N‐(2‐Hydroxypropyl) methacrylamide (HPMA), Polylactic‐co‐glycolic acid (PLGA), Polyamidoamine (PAMAM), and others remain exploited for their specific as well as shared characteristics in the rational delivery of anti‐cancer agents. Variable nano size, attachment with tumor‐specific proteins, responsiveness to stimuli and ability to deliver a wide range of molecules like drugs, antibodies and peptides are some of the achievements of polymeric nano‐conjugates so far. Many such conjugates have shown potential clinically which has attracted the researchers and promoted further advancements of the technique. Apart from achievements the polymeric conjugates suffer from shortcomings like poor drug loading and chances of potential chronic‐systemic toxicities. The review highlights key findings of research in recent time and advancements taking place in the field of polymeric conjugates of anti‐cancer drugs along with the limitations. We have also emphasized on newer and relatively less explored applications of tumor‐targeted polymeric conjugates which can add new dimensions to this technique.