02817nas a2200289   4500008004100000022001400041245017700055210006900232260000800301300001100309490000800320520181800328653002102146653001502167653002302182653001502205653001602220653001302236100002502249700001802274700002202292700002202314700001902336700002802355700002202383856012202405       2020                        eng d  a0928-493100aLHRH-conjugated, PEGylated, poly-lactide-co-glycolide nanocapsules for targeted delivery of combinational chemotherapeutic drugs Docetaxel and Quercetin for prostate cancer0 aLHRHconjugated PEGylated polylactidecoglycolide nanocapsules for  cSEP  a1110350 v1143 a<p>One of the major challenges in effective cancer chemotherapy is the severe systemic cytotoxicities of anticancer drugs on healthy tissues. The present study reports chemically modified polymeric nanocapsules (NCs) encapsulating combination of chemotherapeutic drugs Docetaxel (DTX) and Quercetin (QU) for its active targeting to prostate cancer (PCa). The active targeting was achieved by conjugating Luteinizing-hormone-releasing hormone (LHRH) ligand to poly-lactide-co-glycolide (PLGA) using polyethylene glycol (PEG) as a spacer. The structure of the conjugates was characterized and confirmed using H-1 NMR and ATR-FTIR. The drug encapsulated NCs showed a homogenous size distribution with their size ranging between 120 and 150 nm, and exhibited a negative zeta potential in the range of - 20 to - 40 mV. The in vitro release studies highlighted the sustained drug release pattern from the respective NCs; while the PEG coating to polymeric NCs provided serum stability to the NCs. The in vitro biological evaluation of the NCs was conducted using PC-3 and LNCaP cell lines. The results of the cellular uptake studies showed a significantly higher untake of the LHRH targeted NCs, while the LHRH-targeted-PEGylated DTX: QU NCs exhibited higher caspase-3 activity. The cell viability assay results showed the enhanced cell inhibition activity of the combinatorial DTX: QU when compared to individual DTX. Further, higher cell cytotoxicity was achieved by LHRH-targeted DTX: QU NCs as compared to their free-form or non-targeted NCs. Finally, the results of in vivo tumor localization and in vivo antitumor activity studies complimented and upheld the in vitro results, demonstrating the beneficial role of PLGA-PEG-LHRH NCs encapsulating combination of DTX and QU in combating prostate cancer (PCa).</p>
10aActive targeting10aAnticancer10aControlled release10aEPR effect10aHydrophobic10aProstate1 aShitole, Ajinkya, A.1 aSharma, Neeti1 aGiram, Prabhanjan1 aKhandwekar, Anand1 aBaruah, Meghna1 aGarnaik, Baijayantimala1 aKoratkar, Santosh  uhttps://library.ncl.res.in/content/lhrh-conjugated-pegylated-poly-lactide-co-glycolide-nanocapsules-targeted-delivery