Manisha Pandey

Recent advances in TPGS-based nanoparticles of docetaxel for improved chemotherapy

Docetaxel (DTX) is one of the important antitumor drugs, being used in several common chemotherapies to control leading cancer types. Severe toxicities of the DTX are prominent due to sudden parenteral exposure of desired loading dose to maintain the therapeutic concentration. Field of nanotechnology is leading to resist sudden systemic exposure of DTX with more specific delivery to the site of cancer. Further nanometric size range of the formulation aid for prolonged circulation, thereby extensive exposure results better efficacy. In this article, we extensively reviewed the therapeutic benefit of incorporating d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS, or simply TPGS) in the nanoparticle (NP) formulation of DTX for improved delivery, tumor control and tolerability. TPGS is well accepted nonionic-ampiphilic polymer which has been identified in the role of emulsifier, stabilizer, penetration enhancer, solubilizer and in protection in micelle. Simultaneously, P-glycoprotein inhibitory activity of TPGS in the multidrug resistant (MDR) cancer cells along with its apoptotic potential are the added advantage of TPGS to be incorporated in nano-chemotherapeutics. Thus, it could be concluded that TPGS based nanoparticulate application is an advanced approach to improve therapeutic efficacy of chemotherapeutic agents by better internalization and sustained retention of the NPs.

Recent Update on Nanoemulgel as Topical Drug Delivery System

Being an emerging transdermal delivery tool, nanoemulgel, has proved to show surprising upshots for the lipophilic drugs over other formulations. This lipophilic nature of majority of the newer drugs developed in this modern era resulting in poor oral bioavailability, erratic absorption, and pharmacokinetic variations. Therefore, this novel transdermal delivery system has been proved to be advantageous over other oral and topical drug delivery to avoid such disturbances. These nanoemulgels are basically oil-in-water nanoemulsions gelled with the use of some gelling agent in it. This gel phase in the formulation is nongreasy, which favors user compliance and stabilizes the formulation through reduction in surface as well as interfacial tension. Simultaneously, it can be targeted more specifically to the site of action and can avoid first-pass metabolism and relieve the user from gastric/systemic incompatibilities. This brief review is focused on nanoemulgel as a better topical drug delivery system including its components screening, formulation method, and recent pharmacokinetic and pharmacodynamic advancement in research studies carried out by the scientists all over the world. Therefore, at the end of this survey it could be inferred that nanoemulgel can be a better and effective drug delivery tool for the topical system.

Hyaluronic acid-modified betamethasone encapsulated polymeric nanoparticles: fabrication, characterisation, in vitro release kinetics, and dermal targeting

Atopic dermatitis (AD) is a chronically relapsing eczematous skin disease characterised by frequent episodes of rashes, severe flares, and inflammation. Till date, there is no absolute therapy for the treatment of AD; however, topical corticosteroids (TCs) are the majorly prescribed class of drugs for the management of AD in both adults and children. Though, topical route is most preferable; however, limited penetration of therapeutics across the startum cornum (SC) is one of the major challenges for scientists. Therefore, the present study was attempted to fabricate a moderate-potency TC, betamethasone valerate (BMV), in the form of chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. To further improve the targeting efficiency of BMV and to potentiate its therapeutic efficacy, the fabricated BMV-CS-NPs were coated with hyaluronic acid (HA). The prepared NPs were characterised for particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, loading capacity, crystallinity, thermal behaviour, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimised HA-BMV-CS-NPs exhibited optimum physicochemical characteristics including finest particle size (<u2009300u2009±u200928xa0nm), higher zeta potential (+u200958u2009±u20098xa0mV), and high entrapment efficiency (86u2009±u20095.6%) and loading capacity (34u2009±u20097.2%). The in vitro release study revealed that HA-BMV-CS-NPs displayed Fickian diffusion-type mechanism of release in simulated skin surface (pH 5.5). Drug permeation efficiency of BMV was comparatively higher in case of BMV-CS-NPs; however, the amount of drug retained into the epidermis and the dermis was comparatively higher in case of HA-BMV-CS-NPs, compared to BMV-CS-NPs. Conclusively, we anticipate that HA-BMV-CS-NPs could be a promising nanodelivery system for efficient dermal targeting of BMV and improved anti-AD efficacy.

Nanotechnology based approaches for anti-diabetic drugs delivery

Nanotechnology science has been diverged its application in several fields with the advantages to operate with nanometric range of objects. Emerging field of nanotechnology has been also being approached and applied in medical biology for improved efficacy and safety. Increased success in therapeutic field has focused several approaches in the treatment of the common metabolic disorder, diabetes. The development of nanocarriers for improved delivery of different oral hypoglycemic agents compared to conventional therapies includes nanoparticles (NPs), liposomes, dendrimer, niosomes and micelles, which produces great control over the increased blood glucose level and thus becoming an eye catching and most promising technology now-a-days. Besides, embellishment of nanocarriers with several ligands makes it more targeted delivery with the protection of entrapped hypoglycaemic agents against degradation, thereby optimizing prolonged blood glucose lowering effect. Thus, nanocarriers of hypoglycemic agents provide the aim towards improved diabetes management with minimized risk of acute and chronic complications. In this review, we provide an overview on distinctive features of each nano-based drug delivery system for diabetic treatment and current NPs applications in diabetes management.

Safety against nephrotoxicity in paclitaxel treatment: Oral nanocarrier as an effective tool in preclinical evaluation with marked in vivo antitumor activity

ABSTRACT Oral paclitaxel (PTXL) formulations freed from cremophor® EL (CrEL) is always in utmost demand by the cancerous patients due to toxicities associated with the currently marketed formulation. In our previous investigation [Int. J. Pharm. 2014; 460:131], we have developed an oral oil based nanocarrier for the lipophilic drug, PTXL to target bioavailability issue and patient compliance. Here, we report in vivo antitumor activity and 28‐day sub‐chronic toxicity of the developed PTXL nanoemulsion. It was observed that the apoptotic potential of oral PTXL nanoemulsion significantly inhibited the growth of solid tumor (59.2 ± 7.17%; p < 0.001) without causing any explicit toxicity. The 6.5 mg/kg and 3 mg/kg oral PTXL nanoemulsion dose did not cause any notable alteration in haematological, biochemical/structural characteristics during 28‐day sub‐chronic toxicity studies in the experimental mice. Whereas, the toxicity of 12.8 mg/kg body weight dose showed decrease in RBC, haemoglobin and neutrophil counts. In contrast, marketed PTXL (Taxol®) was found to be comparatively more toxic to the experimental animals. Taxol® treatment resulted glomerulonephritis in histopathological examination, which could be correlated with increased level of creatinine and associated nephrotoxicity. This investigations conclude that the developed oral nanoemulsion presents a viable therapeutics bio‐system to step towards clinical application as well as substitute CrEL based PTXL formulations. Graphical abstract Figure. No Caption available. HighlightsPronounced in vivo antitumor efficacy of oral paclitaxel nanoemulsion in solid tumor bearing model.The 28‐day toxicity study of the nanoemulsion proved to be a viable media to deliver paclitaxel.Overall, devoid of Cremophor® EL in paclitaxel formulation has proved its safety against nephrotoxicity.The developed nanosystem pose higher potential to step towards its clinical application.

An update on natural compounds in the remedy of diabetes mellitus: A systematic review

Herbal medicine, phytomedicine or botanical medicine are synonymous, utilizes plants intended for medicinal purposes. Medicinal use of herbal medicine in the treatment and prevention of diseases including diabetes has a long history compared to conventional medicine. Diabetes is one of the major public health concerns over the world. Diabetes or hyperglycemia is considered to be one of the common public health hazard; optimal control of which is still not possible. Persistent hyperglycemia or uncontrolled diabetes has the potential to cause serious complications such as kidney disease, vision loss, cardiovascular disease, and lower-limb amputations which contributed towards morbidity and mortality in diabetes. There are various approaches to treat and prevent diabetes as well as its secondary complications, one of it is herbal medicines. However, the selection of herbs might depends on several factors, which include the stage of progression of diabetes, types of comorbidities that the patients are having, availability, affordability as well as the safety profile of the herbs. This review focuses on the herbal and natural remedies that play the role in the treatment or prevention of this morbid disorder – diabetes, including their underlying mechanisms for the blood glucose-lowering property and the herbal products already been marketed for the remedial action of diabetes.

Nanomedicines as emerging platform for simultaneous delivery of cancer therapeutics: new developments in overcoming drug resistance and optimizing anticancer efficacy

Abstract Development and formulation of an efficient and safe therapeutic regimen for cancer theranostics are dynamically challenging. The use of mono-therapeutic cancer regimen is generally restricted to optimal clinical applications, on account of drug resistance and cancer heterogeneity. Combinatorial treatments can employ multi-therapeutics for synergistic anticancer efficacy whilst reducing the potency of individual moieties and diminishing the incidence of associated adverse effects. The combo-delivery of nanotherapeutics can optimize anti-tumor efficacy while reversing the incidence of drug resistance, aiming to homogenize pharmacological profile of drugs, enhance circulatory time, permit targeted drug accumulation, achieve multi-target dynamic approach, optimize target-specific drug binding and ensure sustained drug release at the target site. Numerous nanomedicines/nanotherapeutics have been developed by having dynamic physicochemical, pharmaceutical and pharmacological implications. These innovative delivery approaches have displayed specialized treatment effects, alone or in combination with conventional anticancer approaches (photodynamic therapy, radiotherapy and gene therapy), while reversing drug resistance and potential off-target effects. The current review presents a comprehensive overview of nanocarrier aided multi-drug therapies alongside recent advancements, future prospects, and the pivotal requirements for interdisciplinary research.

An overview of application of silver nanoparticles for biomaterials in dentistry

Oral cavity is a gateway to the entire body and protection of this gateway is a major goal in dentistry. Plaque biofilm is a major cause of majority of dental diseases and although various biomaterials have been applied for their cure, limitations pertaining to the material properties prevent achievement of desired outcomes. Nanoparticle applications have become useful tools for various dental applications in endodontics, periodontics, restorative dentistry, orthodontics and oral cancers. Off these, silver nanoparticles (AgNPs) have been used in medicine and dentistry due to its antimicrobial properties. AgNPs have been incorporated into biomaterials in order to prevent or reduce biofilm formation. Due to greater surface to volume ratio and small particle size, they possess excellent antimicrobial action without affecting the mechanical properties of the material. This unique property of AgNPs makes these materials as fillers of choice in different biomaterials whereby they play a vital role in improving the properties. This review aims to discuss the influence of addition of AgNPs to various biomaterials used in different dental applications.

Transferrin receptors-targeting nanocarriers for efficient targeted delivery and transcytosis of drugs into the brain tumors: a review of recent advancements and emerging trends

Treatment of glioblastoma multiforme (GBM) is a predominant challenge in chemotherapy due to the existence of blood–brain barrier (BBB) which restricts delivery of chemotherapeutic agents to the brain together with the problem of drug penetration through hard parenchyma of the GBM. With the structural and mechanistic elucidation of the BBB under both physiological and pathological conditions, it is now viable to target central nervous system (CNS) disorders utilizing the presence of transferrin (Tf) receptors (TfRs). However, overexpression of these TfRs on the GBM cell surface can also help to avoid restrictions of GBM cells to deliver chemotherapeutic agents within the tumor. Therefore, targeting of TfR-mediated delivery could counteract drug delivery issues in GBM and create a delivery system that could cross the BBB effectively to utilize ligand-conjugated drug complexes through receptor-mediated transcytosis. Hence, approach towards successful delivery of antitumor agents to the gliomas has been making possible through targeting these overexpressed TfRs within the CNS and glioma cells. This review article presents a thorough analysis of current understanding on Tf-conjugated nanocarriers as efficient drug delivery system.

Carbon nanotube scaffolds as emerging nanoplatform for myocardial tissue regeneration: A review of recent developments and therapeutic implications

Myocardial infarction (cardiac tissue death) is among the most prevalent causes of death among the cardiac patients due to the inability of self-repair in cardiac tissues. Myocardial tissue engineering is regarded as one of the most realistic strategies for repairing damaged cardiac tissue. However, hindrance in transduction of electric signals across the cardiomyocytes due to insulating properties of polymeric materials worsens the clinical viability of myocardial tissue engineering. Aligned and conductive scaffolds based on Carbon nanotubes (CNT) have gained remarkable recognition due to their exceptional attributes which provide synthetic but viable microenvironment for regeneration of engineered cardiomyocytes. This review presents an overview and critical analysis of pharmaceutical implications and therapeutic feasibility of CNT based scaffolds in improving the cardiac tissue regeneration and functionality. The expository analysis of the available evidence revealed that inclusion of single- or multi-walled CNT into fibrous, polymeric, and elastomeric scaffolds results in significant improvement in electrical stimulation and signal transduction through cardiomyocytes. Moreover, incorporation of CNT in engineering scaffolds showed a greater potential of augmenting cardiomyocyte proliferation, differentiation, and maturation and has improved synchronous beating of cardiomyocytes. Despite promising ability of CNT in promoting functionality of cardiomyocytes, their presence in scaffolds resulted in substantial improvement in mechanical properties and structural integrity. Conclusively, this review provides new insight into the remarkable potential of CNT aligned scaffolds in improving the functionality of engineered cardiac tissue and signifies their feasibility in cardiac tissue regenerative medicines and stem cell therapy.