PMID- 34256103 OWN - NLM STAT- MEDLINE DCOM- 20210812 LR - 20221207 IS - 1879-0720 (Electronic) IS - 0928-0987 (Linking) VI - 165 DP - 2021 Oct 1 TI - Building and behavior of a pH-stimuli responsive chitosan nanoparticles loaded with folic acid conjugated gemcitabine silver colloids in MDA-MB-453 metastatic breast cancer cell line and pharmacokinetics in rats. PG - 105938 LID - S0928-0987(21)00241-4 [pii] LID - 10.1016/j.ejps.2021.105938 [doi] AB - The pH-stimuli release behavior of nanoformulations may enhance the success rate of chemotherapeutic drugs in cancers by site-specific delivery of drugs to cancer tissues. The aim of the present study was to prepare chitosan (CS) nanoparticles (NPs) with previously synthesized folic acid (FA) capped silver nanoparticles (AgNPs) loaded with the anti-cancer drug gemcitabine (GEM) (FA-GEM-AgNPs). The CS-FA-GEM-AgNPs (CS-NPs) were characterized with dynamic light scattering (DLS), transmission electron microscopy (TEM), energy dispersive x-ray analysis (EDAX), selected area electron diffraction (SAED), and differential scanning calorimetric (DSC) analyses. The in-vitro drug release of GEM was evaluated in media of different pH. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to determine the cytotoxic effects of the prepared nanoformulations in media with various pH. The time- and pH-dependent apoptotic cell death induced by CS-NPs with MDA-MB-453 human breast cancer cell line was observed using acridine orange (AO)/ethidium bromide (EtBr) staining. The pharmacokinetic parameters were studied with high-performance liquid chromatography (HPLC) and atomic absorption spectroscopy (AAS). Two batches of CS-NPs formulations were prepared, one with AgNPs of particle size 143 nm and the other with 244 nm. The particle size for CS-NPs-I (FA-GEM-AgNPs-143 nm) and CS-NPs-II (FA-GEM-AgNPs-244 nm) was found to be 425 and 545 nm, respectively. The zeta potential was found to be 36.1 and 37.5 mV for CS-NPs-I and CS-NPs-II, respectively. CS-NPs-I and CS-NPs-II showed a polydispersity index (PDI) of 0.240 and 0.261, respectively. A TEM study confirmed the spherical nature of the NPs. The nanoformulations exerted pH-dependant effect against MDA-MB-453 cells with relatively higher cytotoxicity at the lower pH than at higher pH levels. The pharmacokinetic profile and tissue distribution of CS-NPs in rats exerted drug release in a pH-dependent manner with enhanced excretion of Ag(+). An optimized nanoformulation for pH-stimuli responsive release of GEM was successfully developed for future therapeutic exploration. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Karuppaiah, Arjunan AU - Karuppaiah A AD - Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India. FAU - Babu, Dinesh AU - Babu D AD - Faculty of Pharmacy and Pharmaceutical Sciences, Katz Group Centre for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta, Canada. FAU - Selvaraj, Divakar AU - Selvaraj D AD - Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India; Department of Pharmacology, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India. FAU - Natrajan, Tamilselvan AU - Natrajan T AD - Department of Pharmaceutics, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, India. FAU - Rajan, Ravikumar AU - Rajan R AD - Department of Pharmacology, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India; Faculty of Medical Sciences, Arunachal University Studies, Namasi, Arunachal Pradesh, India. FAU - Gautam, Mrinmoy AU - Gautam M AD - Department of Pharmacology, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India. FAU - Ranganathan, Hariprasad AU - Ranganathan H AD - Department of Pharmaceutical Analysis, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India. FAU - Siram, Karthik AU - Siram K AD - Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India; Department of Biomedical and Pharmaceutical Sciences, Center for Translational Medicine, Skaggs School of Pharmacy, University of Montana, United States. FAU - Nesamony, Jerry AU - Nesamony J AD - Department of Pharmaceutics, Frederic and Mary Wolfe Center 114J, University of Toledo, United States. FAU - Sankar, Veintramuthu AU - Sankar V AD - Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India. Electronic address: sansunv@yahoo.co.in. LA - eng PT - Journal Article DEP - 20210710 PL - Netherlands TA - Eur J Pharm Sci JT - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JID - 9317982 RN - 0 (colloidal silver) RN - 0W860991D6 (Deoxycytidine) RN - 3M4G523W1G (Silver) RN - 9012-76-4 (Chitosan) RN - 935E97BOY8 (Folic Acid) RN - 0 (Gemcitabine) SB - IM MH - Animals MH - *Breast Neoplasms/drug therapy MH - Cell Line MH - Cell Line, Tumor MH - *Chitosan MH - Deoxycytidine/analogs & derivatives MH - Female MH - Folic Acid MH - Humans MH - Hydrogen-Ion Concentration MH - *Metal Nanoparticles MH - *Nanoparticles MH - Particle Size MH - Rats MH - Silver MH - Gemcitabine OTO - NOTNLM OT - Breast cancer OT - Chitosan nanoparticles OT - Design of experiment OT - Gemcitabine OT - Optimization OT - Silver nanoparticles OT - pH-stimuli EDAT- 2021/07/14 06:00 MHDA- 2021/08/13 06:00 CRDT- 2021/07/13 20:11 PHST- 2021/02/27 00:00 [received] PHST- 2021/06/28 00:00 [revised] PHST- 2021/06/29 00:00 [accepted] PHST- 2021/07/14 06:00 [pubmed] PHST- 2021/08/13 06:00 [medline] PHST- 2021/07/13 20:11 [entrez] AID - S0928-0987(21)00241-4 [pii] AID - 10.1016/j.ejps.2021.105938 [doi] PST - ppublish SO - Eur J Pharm Sci. 2021 Oct 1;165:105938. doi: 10.1016/j.ejps.2021.105938. Epub 2021 Jul 10.