Lipid Based Aqueous Core Nanocapsules (ACNs) for Encapsulating Hydrophillic Vinorelbine Bitartrate: Preparation, Optimization, Characterization and In vitro Safety Assessment for Intravenous Administration.

BACKGROUND: Vinorelbine bitartrate (VRL) is an antimitotic agent approved by FDA for breast cancer and non-small cell lung cancer (NSCLC) in many countries. However, high aqueous solubility and thermo degradable nature of VRL limited the availability of marketed dosage forms. OBJECTIVES: The current work is focused on the development of lipid based aqueous core nanocapsules which can encapsulate the hydrophilic VRL in the aqueous core of nanocapsules protected with a lipidic shell which will further provide a sustained release. METHODS: The ACNs were prepared by double emulsification technique followed by solvent evaporation. Box Behnken Design was utilized to optimize the formulation and process variables. Thirteen batches were generated utilizing lipid concentration, surfactant concentration and homogenizer speed as dependent variables (at three levels) and particle size and encapsulation efficiency as critical quality attributes. The ACNs were characterized for particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, morphology by Transmission Electron Microscopy (TEM) and in vitro release. The ACNs were further evaluated for safety against intravenous administration by haemocompatibility studies. RESULTS: Results demonstrated that lipidic nanocapsules enhanced the entrapment efficiency of VRL up to 78%. Transmission Electron Microscopy revealed spherical shape of ACNs with core-shell structure. The GMS-VRL-ACNs showed that release followed Korsemeyer peppas kinetics suggesting Fickian diffusion. Moreover, the compliance towards haemocompatibility studies depicted the safety of prepared nanocapsules against intravenous administration. CONCLUSION: ACNs were found to be promising in encapsulating high aqueous soluble anticancer drugs with enhanced entrapment and safety towards intravenous administration.

Cell proliferation influenced by matrix compliance of gelatin grafted poly(d,l-Lactide) three dimensional scaffolds.

Surface and mechanical properties of the biomaterials are determinants of cellular responses. In our previous study, star-shaped poly(d,l-Lactide)-b-gelatin (ss-pLG) was reported for possessing improved cellular adhesion and proliferation. Here, we extended our investigation to establish the cellular compatibility of gelatin-grafted PDLLA with respect to mechanical properties of biological tissues. In this view, linear PDLLA-b-gelatin (l-pLG) was synthesized and tissue-level compatibility of 1-pLG and ss-pLG against fibroblasts (L929), myoblasts (C2C12) and preosteoblasts (MG-63) was examined. The cell proliferation of C2C12 was significantly higher within l-pLG scaffolds, whereas L929 showed intensified growth within ss-pLG scaffolds. The difference in cell proliferation may be attributed to the varying mechanical properties of scaffolds; where the stiffness of l-pLG scaffolds was notably higher than ss-pLG scaffolds, most likely due to the variable levels of gelatin grafting on the backbone of PDLLA. Therefore, gelatin grafting can be used to modulate mechanical property of the scaffolds and this study reveals the significance of the matrix stiffness to produce the successful 3D scaffolds for tissue engineering applications.

Catechin-loaded Eudragit microparticles for the management of diabetes: formulation, characterization and in vivo evaluation of antidiabetic efficacy.

Catechin (CT) is natural molecule proved for antidiabetic activity. Clinical application of CT is highly restricted because of its low bioavailability and ineffectiveness in in vivo conditions. Therefore, the main objective of the present investigation was to formulate CT-loaded Eudragit RS 100 microparticles and evaluated for its potential against diabetes. CT microparticles showing highest entrapment efficiency of 92.3 ± 6.5% and higher percentage yield of 63.46 ± 4.3% was selected as optimised formulation. CT microparticles treated rats showed significantly lower blood glucose, cholesterol, LDL, free fatty acid and triglyceride concentrations in comparison to pristine CT-treated rats. The glucose and lipid profiles of microparticle formulation were akin to normal rats. Moreover, CT microparticles did not produce obesity even after 60 days which is a comment side effect of antidiabetic drugs. These results indicate that the CT microparticles can be applied as potential and safe carrier for the treatment of diabetes.

Pharmacokinetics, biodistribution, in vitro cytotoxicity and biocompatibility of Vitamin E TPGS coated trans resveratrol liposomes.

The clinical application of trans resveratrol (RSV) in glioma treatment is largely limited because of its rapid metabolism, fast elimination from systemic circulation and low biological half life. Therefore, the objectives of this study were to enhance the circulation time, biological half life and passive brain targeting of RSV using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) coated liposomes (RSV-TPGS-Lipo). In addition to basic liposomal characterizations, in vitro anticancer potential against C6 glioma cell lines and cellular internalization of liposomes were carried out by MTT assay and confocal laser scanning microscopy (CLSM), respectively. Pharmacokinetics and tissue distribution studies were also carried out after intravenous administration in Charles Foster rats. RSV-TPGS-Lipo 2 showed significantly higher cytotoxicity than RSV-Lipo (uncoated liposomes) and RSV. Both uncoated and TPGS coated liposomes showed excellent cellular uptake. RSV, RSV-Lipo and RSV-TPGS-Lipo 2 were found to be haemocompatible and safe after i.v. administration. Area under the curve (AUC) and plasma half life (t1/2) after i.v. administration of RSV-TPGS-Lipo 2 was found to be approximately 5.73 and 6.72 times higher than that of RSV-Lipo as well as 29.94 and 29.66 times higher than that of RSV, respectively. Thus, the outcome indicates that RSV-TPGS-Lipo 2 is a promising carrier for glioma treatment with improved pharmacokinetic parameters. Moreover, brain accumulation of RSV-Lipo and RSV-TPGS-Lipo 2 was found to be significantly higher than that of RSV (P<0.05). Results are suggesting that both RSV-Lipo and RSV-TPGS-Lipo 2 are the promising tools of RSV for the treatment of brain cancer.