Development and Characterization of Core Shell Nanoparticle for Enhanced Drug Delivery to Treat Solid Tumor: Preparation and In-Vitro Assessment

Mortalities from cancer in the world are projected to continue rising, with an estimated 9 million and 11.4 million people dying from cancer in 2015 and 2030, respectively. Rates are rising as more people live to an old age and as mass lifestyle changes occur in the developing world. With present treating regimen for cancer, dose-limited toxicity is a big reason that reduces the efficacy of cancer treatments. In search for more effective cancer treatments, nanosized drug delivery systems, those are capable of delivering their drug payload selectively to cancer cells such as nanoparticles, solid lipid nanoparticles, liposomes are among the most promising approaches. Core shell nanoparticles are one of the investigated moieties in recent years that are seeking much attention nowadays for biomedical applications including the field of oncology.The present work aims at developing a core shell nanoparticle comprising Poly (D, L –lactide –co –glycolide) (PLGA) core and polyethyleneimine (PEI) shell loaded with anticancer bioactive docetaxel (DTX) for passive targeting of the tumor tissue. It is expected that incorporation of PEI will improve the uptake and subsequent release of the drug in the cytosol due to endosomal escape phenomenon. Keywords: Solid tumor; nanotechnology; nanoparticle; PLG

Novel Gemcitabine Conjugated Albumin Nanoparticles: a Potential Strategy to Enhance Drug Efficacy in Pancreatic Cancer Treatment

Purpose: The present study reports a novel conjugate of gemcitabine (GEM) with bovine serum albumin (BSA) and thereof nanoparticles (GEM-BSA NPs) to potentiate the therapeutic efficacy by altering physicochemical properties, improving cellular uptake and stability of GEM. Methods: The synthesized GEM-BSA conjugate was extensively characterized by NMR, FTIR, MALDI-TOF and elemental analysis. Conjugation mediated changes in structural conformation and physicochemical properties were analysed by fluorescence, Raman and CD spectroscopy, DSC and contact angle analysis. Further, BSA nanoparticles were developed from BSA-GEM conjugate and extensively evaluated against in-vitro pancreatic cancer cell lines to explore cellular uptake pathways and therapeutic efficacy. Results: Various characterization techniques confirmed covalent conjugation of GEM with BSA. GEM-BSA conjugate was then transformed into NPs via high pressure homogenization technique with particle size 147.2 ± 7.3, PDI 0.16 ± 0.06 and ZP -19.2 ± 1.4. The morphological analysis by SEM and AFM revealed the formation of smooth surface spherical nanoparticles. Cellular uptake studies in MIA PaCa-2 (GEM sensitive) and PANC-1 (GEM resistant) pancreatic cell lines confirmed energy dependent clathrin internalization/endocytosis as a primary mechanism of NPs uptake. In-vitro cytotoxicity studies confirmed the hNTs independent transport of GEM in MIA PaCa-2 and PANC-1 cells. Moreover, DNA damage and annexin-V assay revealed significantly higher apoptosis level in case of cells treated with GEM-BSA NPs as compared to free GEM. Conclusions: GEM-BSA NPs were found to potentiate the therapeutic efficacy by altering physicochemical properties, improving cellular uptake and stability of GEM and thus demonstrated promising therapeutic potential over free drug

Advances in oral delivery of anti-cancer prodrugs

<p><b>Introduction</b>: Most anticancer drugs have poor aqueous solubility and low permeability across the gastrointestinal tract. Furthermore, extensive efflux by P-glycoproteins (P-gp) in the small intestine also limits the efficient delivery of anticancer drugs via oral route.</p> <p><b>Area covered</b>: This review explores the prodrug strategy for oral delivery of anticancer drugs. Different categories of oral anticancer prodrugs along with recent clinical studies have been comprehensively reviewed here. Furthermore, novel anticancer prodrugs such as polymer-prodrugs and lipid-prodrugs have been discussed in detail. Finally, various nanocarrier-based approaches employed for oral delivery of anticancer prodrugs have also been discussed.</p> <p><b>Expert opinion</b>: Premature degradation of anticancer prodrugs in the gastrointestinal tract could lead to variable pharmacokinetics and undesired toxicity. Despite their increased aqueous solubility, the oral bioavailability of several anticancer prodrugs are limited by their poor permeability across the gastrointestinal tract. These limitations can be overcome by the use of functional excipients (polymers, lipids, amino acids/dipeptides), which are specifically absorbed via transporters and receptor-mediated endocytosis. Oral delivery of anticancer prodrugs using nanocarrier-based drug delivery system is a recent development; however it should be justified based on the comparative advantages of encapsulating prodrug in a nanocarrier versus the use of anticancer prodrug molecule itself.</p