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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.
Eur J Pharm Sci. 2021 Oct 01; 165:105938.EJ

Abstract

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.

Authors+Show Affiliations

Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India.Faculty of Pharmacy and Pharmaceutical Sciences, Katz Group Centre for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta, Canada.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.Department of Pharmaceutics, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, India.Department of Pharmacology, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India; Faculty of Medical Sciences, Arunachal University Studies, Namasi, Arunachal Pradesh, India.Department of Pharmacology, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India.Department of Pharmaceutical Analysis, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India.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.Department of Pharmaceutics, Frederic and Mary Wolfe Center 114J, University of Toledo, United States.Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India. Electronic address: sansunv@yahoo.co.in.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34256103

Citation

Karuppaiah, Arjunan, et al. "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." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 165, 2021, p. 105938.
Karuppaiah A, Babu D, Selvaraj D, et al. 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. Eur J Pharm Sci. 2021;165:105938.
Karuppaiah, A., Babu, D., Selvaraj, D., Natrajan, T., Rajan, R., Gautam, M., Ranganathan, H., Siram, K., Nesamony, J., & Sankar, V. (2021). 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. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 165, 105938. https://doi.org/10.1016/j.ejps.2021.105938
Karuppaiah A, et al. 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. Eur J Pharm Sci. 2021 Oct 1;165:105938. PubMed PMID: 34256103.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Karuppaiah,Arjunan, AU - Babu,Dinesh, AU - Selvaraj,Divakar, AU - Natrajan,Tamilselvan, AU - Rajan,Ravikumar, AU - Gautam,Mrinmoy, AU - Ranganathan,Hariprasad, AU - Siram,Karthik, AU - Nesamony,Jerry, AU - Sankar,Veintramuthu, Y1 - 2021/07/10/ PY - 2021/02/27/received PY - 2021/06/28/revised PY - 2021/06/29/accepted PY - 2021/7/14/pubmed PY - 2021/8/13/medline PY - 2021/7/13/entrez KW - Breast cancer KW - Chitosan nanoparticles KW - Design of experiment KW - Gemcitabine KW - Optimization KW - Silver nanoparticles KW - pH-stimuli SP - 105938 EP - 105938 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 165 N2 - 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. SN - 1879-0720 UR - https://www.unboundmedicine.com/medline/citation/34256103/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. L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928-0987(21)00241-4 DB - PRIME DP - Unbound Medicine ER -