N-acetyl-d-glucosamine-conjugated PAMAM dendrimers as dual receptor-targeting nanocarriers for anticancer drug delivery.

N-acetyl-d-glucosamine-labelled dendrimers (NAG-Dend) were synthesized for the targeted delivery of camptothecin (CPT) to A549 human lung adenocarcinoma cells, which overexpress glucose transporters and lectin receptors. CPT loaded, NAG-Dend (NAG-Dend-CPT) exhibited more rapid and higher cellular uptake than the unlabelled dendrimer formulation (Dend-CPT), leading to enhanced cytotoxicity. Compared with native CPT, NAG-Dend-CPT was 4.5 times more toxic to A549 cells. The anticancer activity of the different CPT formulations was dose and time dependent. NAG-Dend-CPT also increased reactive oxygen species generation, induced higher apoptosis and showed greater inhibition of A549 cell migration than Dend-CPT. The selective accumulation of NAG-Dend in the lungs of tumour-bearing mice confirmed that the NAG-based dendrimer system can target lung metastasis tumours in a biological system. Overall, our results show that NAG-conjugated dendrimers could be a promising nanocarrier system for the delivery of anticancer drugs, including CPT, to human lung cancer cells.

Design of multifunctional peptide collaborated and docetaxel loaded lipid nanoparticles for antiglioma therapy.

Glioblastoma multiforme (GBM) is one of the most encountered gliomas of the central nervous system. The chemotherapeutic drugs used in the treatment of GBM suffer from poor blood brain barrier penetration, severe systemic toxicities and lack of specificity towards tumor cells. There is an urgent need to explore novel drug delivery systems specifically designed for targeting GBM. Solid lipid nanoparticles (SLN) are biocompatible vehicle with less toxicity issues compared to other drug delivery systems and serve the purpose of obviating the limitations posed by existing anti-cancer drugs for GBM. In this study, angiopep-2, a ligand for the lipoprotein receptor related protein 1 (LRP 1) receptor over expressed in endothelial cells of both brain and glioma, was grafted on the surface of solid lipid nanoparticles for the delivery of docetaxel. The peptide grafted nanoparticles (A-SLN) showed increased cytotoxicity, enhanced cellular internalization and prominent apoptosis than that of unconjugated nanoparticles against U87MG human glioblastoma and GL261 mouse glioma cells. A significant dual targeting effect of A-SLN (p < 0.0001) was confirmed in in-vivo studies by real time fluorescence imaging studies in glioblastoma induced C57BL/6 mice model. Pharmacokinetic and tissue distribution studies showed selective targeting with higher accumulation of A-SLN in brain compared to Taxtotere, a marketed formulation of docetaxel. After treatment with A-SLN, the mean animal survival time of the animals was significantly enhanced to 39 days from 24 days of plain docetaxel. Collectively, this study indicated that solid lipid nanoparticles decorated with angiopep-2 can be an excellent option as targeted drug delivery system for antiglioma therapy.

Enhanced oral bioavailability and anticancer efficacy of fisetin by encapsulating as inclusion complex with HPßCD in polymeric nanoparticles.

Fisetin (FST), a potent anticancer phytoconstituent, exhibits poor aqueous solubility and hence poor bioavailability. The aim of the present study is to improve the oral bioavailability of FST by encapsulating into PLGA NPs (poly-lactide-co-glycolic acid nanoparticles) as a complex of HPßCD (hydroxyl propyl beta cyclodextrin) and to assess its anti-cancer activity against breast cancer cells. FST-HPßCD inclusion complex (FHIC) was prepared and the supramolecular complex formation was characterized by FTIR, DSC, PXRD and 1H NMR. FHIC encapsulated PLGA nanoparticles (FHIC-PNP) were prepared and were studied for in vitro anticancer activity, cellular uptake, apoptosis and reactive oxygen species generation in MCF-7 human breast cancer cells. Comparative bioavailability of FST was determined after oral administration in C57BL6 mice as pure FST and FHIC-PNP. The results revealed that FHIC-PNP not only enhanced the anti-cancer activity and apoptosis of FST against MCF-7 cells but also improved its oral bioavailability, as demonstrated by increased peak plasma concentration and total drug absorbed.