首页|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

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

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  • NSTL
  • Elsevier
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)-2,5diphenyltetrazolium 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 CSNPs 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.

Breast cancerChitosan nanoparticlesDesign of experimentGemcitabineOptimizationpH-stimuliSilver nanoparticles

Karuppaiah, Arjunan、Babu, Dinesh、Selvaraj, Divakar、Natrajan, Tamilselvan、Rajan, Ravikumar、Gautam, Mrinmoy、Ranganathan, Hariprasad、Siram, Karthik、Nesamony, Jerry、Sankar, Veintramuthu

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PSG Coll Pharm, Dept Pharmaceut, Coimbatore, Tamil Nadu, India

Univ Alberta, Fac Pharm & Pharmaceut Sci, Katz Grp, Ctr Pharm & Hlth Res, Edmonton, AB, Canada

JSS Acad Higher Educ & Res, JSS Coll Pharm, Dept Pharmacol, Nilgiris, Tamil Nadu, India

KMCH Coll Pharm, Dept Pharmaceut, Coimbatore, Tamil Nadu, India

PSG Coll Pharm, Dept Pharmacol, Coimbatore, Tamil Nadu, India

PSG Coll Pharm, Dept Pharmaceut Anal, Coimbatore, Tamil Nadu, India

Univ Toledo, Dept Pharmaceut, Freder & Mary Wolfe Ctr 114J, Toledo, OH USA

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2021

10.1016/j.ejps.2021.105938

European journal of pharmaceutical sciences

European journal of pharmaceutical sciences

ISTP
ISSN：0928-0987
年,卷(期)：2021.165
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