Biodistribution and Pharmacokinetic Study of Gemcitabine Hydrochloride Loaded Biocompatible Iron-Based Metal Organic Framework
- Authors
- Kush, Preeti; Bajaj, Tania; Kaur, Manjot; Madan, Jitender; Jain, Upendra Kumar; Kumar, Parveen; Deep, Akash; Kim, Ki-Hyun
- Issue Date
- Aug-2020
- Publisher
- SPRINGER
- Keywords
- Gemcitabine hydrochloride; Biocompatibility; Metal-organic frameworks; Pancreatic cancer; Hemolysis; Half life; Biodistribution; Pharmacokinetics
- Citation
- JOURNAL OF INORGANIC AND ORGANOMETALLIC POLYMERS AND MATERIALS, v.30, no.8, pp.2827 - 2841
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF INORGANIC AND ORGANOMETALLIC POLYMERS AND MATERIALS
- Volume
- 30
- Number
- 8
- Start Page
- 2827
- End Page
- 2841
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/9019
- DOI
- 10.1007/s10904-019-01417-4
- ISSN
- 1574-1443
- Abstract
- This study was designed to improve bioavailability and therapeutic efficacy of Gemcitabine (GEM) with reduced side effects using MOF MIL-100 as cargo. MIL-100 was synthesized, and characterized by microscopic and spectroscopic techniques. Impregnation approach was used for encapsulation of GEM inside the MIL-100 (i.e., MIL100-GEM). In-vitro release studies of MIL100-GEM was carried out in different media (PBS, deionized water and Tris buffer, pH = 7.4, 9.5 mM) to find out the drug release mechanism. Cytotoxicity and apoptosis assays were evaluated using MTT and fluorescence-activated cell sorting (FACS) assay in MiaPaCa-2 pancreatic cancer cell lines. Biocompatibility, pharmacokinetic and biodistribution studies of MIL100-GEM were assessed in Wistar rats. MIL100-GEM exhibited high encapsulation efficiency (78.6 +/- 0.5%) and maximum payload (23.6 +/- 1%). PXRD confirmed crystallinity of MIL-100, and did not show any effect on its structural integrity after encapsulation of GEM. In-vitro release studies revealed a biphasic release pattern in PBS buffer which followed Higuchi diffusion kinetics. In-vitro cytotoxicity studies showed low IC(50)value for MIL100-GEM (3.50 +/- 1.33 mu g/ml) compared to GEM (6.22 +/- 1.55 mu g/ml), ensuring adequate cell proliferation after 72 h. Hemolysis study showed that MIL100-GEM (14.54 +/- 1.3%) had better biocompatibility than the native GEM (30.52 +/- 1.67%). Furthermore, pharmacokinetic and biodistribution studies exhibited similar to 17-fold increased bioavailability, similar to 20-fold increased distribution half-life and similar to 15-folds elimination half-life of GEM with less accumulation of drug in the kidneys. MIL-100 MOF was synthesized and characterized to address the metabolic degradation issue of GEM. Biocompatible, MIL100-GEM demonstrated efficient drug (GEM) loading and enhanced cytotoxic activity in pancreatic cancer cell line with augmented bioavailability, providing MIL-100 a promising drug cargo. Graphic MIL-100 was synthesized using a microwave-assisted method. The anticancer drug Gemcitabine Hydrochloride (GEM) was loaded into the MIL-100 using the impregnation method. Encapsulation protected the drug from its metabolic inactivation to enhance bioavailability in target organs and reduce side effects.
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