Current Nanomedicine - Volume 7, Issue 3, 2017

Background: Cancer nanotherapy integrate efficacious molecules that otherwise could not be used because of their high toxicity and exploit multiple mechanisms of actions (e.g. multifunctional gels, functional polymers, hybrid nanoparticles). The aim of this review is to contemplate the designed and developed nanoparticulate systems that exhibit a benefit in cancer nanotherapy strongly related with the properties of the nanoplatforms formulation. Method: Systemic search and review of papers regarding cancer nanotherapy took place via MedLine and abstract presentations of international conferences. Results: The recent advances in the development of self-assembled structures of lipids- (i.e. liposomes, niosomes, etc.) and of polymers- (micelles, polymersomes, dendrimers, polymeric nanoparticles, hydrogels, etc.) as well as clinical perspectives will be discussed on the basis of pharmaceutical nanotechnology considerations, and on their in vitro and in vivo evaluation. Chimeric/Mixed nanoplatforms that are composed at least of two different in nature biomaterials (i.e. phospholipids and polymers) can be considered as new technological outcomes in cancer nanotherapy that could be able to deliver anticancer drugs to specific tissues. Conclusion: They can improve the pharmacokinetics/pharmacodynamics behavior of antitumor molecules, affect their total bioavailability and provide innovative delivery behavior due to their nanotechnological profile.

Background: Quality by Design (QbD) is a common word these days, where the concepts possess multidimensional applications in pharmaceutical product development. QbD as an approach has excellent prospective in nanomedicines scale-up. Method: Being instituted by ICH and USFDA, QbD primarily emphasizes on product and process understanding for producing finished products meeting the customer satisfaction. It works on the principle of envisioning product quality at very first stage for avoiding quality crisis. QbD has multiple advantages including development of high quality drug products and robust processes, reduces failures, and ultimately improves customer satisfaction for meeting the regulatory demands. As far as the USFDA is concerned, the agency is expecting implementation of QbD in the applications filed for approval of new drug products and generic products. Owing to the high degree of fruition and increasing demand of the concept, the application of QbD has percolated to almost all types of pharmaceutical formulations including the complex nanotechnology-based products and devices. The agency is an encouraging industry to focus more on adopting QbD-oriented development of nanomedicine for ease of monitoring their quality, safety and efficacy. Results: Looking into the current need and demand of the concept, the present article provides a holistic account on the fundamentals principles and vital elements of QbD, followed by special emphasis with respect to the development of nanotechnology products. Conclusion: Concisely, this present article is a help to the formulation and biomedical scientists working on the development of nanomedicines using the QbD principles.

Objective: The purpose of the study was to formulate and evaluate thiolated chitosan based nanoparticulate mucoadhesive ophthalmic in situ gelling system of prulifloxacin for bacterial keratoconjunctivitis. Method: Low molecular weight chitosan was modified to thiolated chitosan in the laboratory and confirmed with FTIR and DSC studies. Thiolated chitosan nanoparticles were prepared and incorporated in a polymeric sol-gel system containing prulifloxacin for the ophthalmic drug delivery. The prepared formulation was characterized for the various physicochemical properties i.e., particle size, zeta potential, gelation time, mucoadhesion strength study and the optimized formulation was characterized for in vitro drug release study, ocular irritation study, antimicrobial efficacy study and stability study etc. Results: Gelation pH was found to be 7.2±0.2. The acquired SEM images of the optimized NPs showed good mean particle size below 16 nm. Drug entrapment efficiency was found to be more than 80%. PFL-TCS loaded NPs sol-gel system showed sustain release for a period of 12 hours. It was also confirmed that the formulation was non-irritant to the eye. Conclusion: The developed formulation was found to be a better alternative to the conventional ophthalmic formulations.

Background: Eclipta alba Hassk. (Family: Compositae) contains coumestans useful in liver problems. The present work is aimed to develop a new formulation of plant-derived coumestans in combination with the soya-phosphatidylcholine (PC) and it is expected to improve the absorption of coumestans. The study also examines the protective effect of coumestans-phosphatidylcholine complex (C-PC) on carbon tetrachloride (CCl4) induced acute liver injury in rats. Method: Coumestans (C) were characterized in the ethyl acetate fraction of methanolic extract (EFME). The C-PC was characterized by DSC and FTIR spectroscopy. In vitro drug release from EFME and C-PC through egg-membrane was measured using a UVVisible spectrophotometer. The hepatoprotective activity of C-PC (equivalent to 5.35 and 10.7 mg/kg body weight of EFME), ME 250 mg/kg and EFME 5.35 mg/kg was analyzed by assessing the level of various enzymes. Conclusion: C-PC significantly (P<0.001) provided better protection to the liver by normalizing the levels of enzymes SGPT, SGOT, ALP and total bilirubin when compared to CCl4 group. The histopathological study showed that C-PC showed improvement in rat’s liver as compared to ME and EFME at similar doses as they showed regeneration of hepatocytes, central vein, intact cytoplasm and nucleus.

Aim: One major challenge associated with the design of transdermal drug delivery systems is to overcome the barrier of the skin. Hence, current study aimed at hydrogel based nanoemulsion (HNE) of lercanidipine for enhanced transdermal delivery and investigation for its rheology, bioadhesion, droplet size, transmission electron microscopy (TEM), and skin permeation mechanism. Main Methods: Flow behavior of HNE was studied by conducting the controlled stress rate study using R/S CPS plus Rheometer and Bio-adhesive strength was measured by texture analyzer. Skin permeation mechanism across rat skin was determined by differential scanning calorimeter (DSC) study, activation energy (Ea) determination, histopathological examination, confocal laser scanning microscopy (CLSM). Moreover, we have used TEM and Biovis IP2000 software for microscopic analysis. Key Finding: The formulation exhibited HershelBulkley flow with good bioadhesion (43N/mm). A uniform droplets distribution under TEM image with size of 80.18±0.315nm inside gel network was found. DSC, Ea and histopathological examination revealed that HNE might have dissolved intercellular lipid and separated corneocytes from each other to weaken the barrier function of SC for enhancing the skin permeation. CLSM result dictated a distributed droplets throughout the skin layers with high depth of penetration (>150.0 μm). Significance: The formulation has a good perspective to safe and effective delivery of lercanidipine for enhanced transdermal application.

Objective: This study aims to investigate the in vivo toxicological profile and pre-clinical safety of surface modified self-nanoemulsifying formulations (SNEFs) for oral delivery of a broad spectrum, anti-bacterial agent, gentamicin. Method: SNEFs which were surface modified using PEG 4000, were formulated through water titration method using appropriate mixtures of soybean oil, a combination of Kolliphor ® EL and Kolliphor® P188 as surfactants, and Transcutol® HP as co-surfactant, and encapsulating gentamicin. SNEFs were characterized by measuring the droplet sizes, size distribution and surface charges using a Zetasizer. The effects of the SNEFs on body weight, haematological, biochemical, and histopathological factors of rats after oral administration were determined. Results: Physicochemical characterization showed that the nanoformulations had droplet sizes ranging from 96 - 121 nm with surface charges of -32 to -36 mV. SNEFs did not show net suppression of body weights of rats. There were no clear indications of haematologic, hepatic and renal injuries in the study rats due to flip-flops in the levels of haematologic, hepatic and nephritic biomarkers evaluated. Histopathological organ examinations corroborated findings from the effect of SNEFs on the liver and kidney but revealed possible induction of astrocytosis in the cerebral cortex of rats. Conclusion: Results of the study indicate that surface modified SNEFs of gentamicin have a promising pre-clinical safety potential with minimum toxicity effects.