Skip to main content
Kent Academic Repository

Novel Gemcitabine Conjugated Albumin Nanoparticles: a Potential Strategy to Enhance Drug Efficacy in Pancreatic Cancer Treatment

Kushwah, Varun, Agrawal, Ashish Kumar, Dora, Chander Parkash, Mallinson, David, Lamprou, Dimitrios A., Gupta, Ramesh C., Jain, Sanyog (2017) Novel Gemcitabine Conjugated Albumin Nanoparticles: a Potential Strategy to Enhance Drug Efficacy in Pancreatic Cancer Treatment. Pharmaceutical Research, 34 . pp. 2295-2311. ISSN 0724-8741. E-ISSN 1573-904X. (doi:10.1007/s11095-017-2238-8) (KAR id:62653)

Abstract

Purpose: The present study reports a novel conjugate of gemcitabine (GEM) with bovine serum albumin (BSA) and thereof nanoparticles (GEM-BSA NPs) to potentiate the therapeutic efficacy by altering physicochemical properties, improving cellular uptake and stability of GEM. Methods: The synthesized GEM-BSA conjugate was extensively characterized by NMR, FTIR, MALDI-TOF and elemental analysis. Conjugation mediated changes in structural conformation and physicochemical properties were analysed by fluorescence, Raman and CD spectroscopy, DSC and contact angle analysis. Further, BSA nanoparticles were developed from BSA-GEM conjugate and extensively evaluated against in-vitro pancreatic cancer cell lines to explore cellular uptake pathways and therapeutic efficacy. Results: Various characterization techniques confirmed covalent conjugation of GEM with BSA. GEM-BSA conjugate was then transformed into NPs via high pressure homogenization technique with particle size 147.2 ± 7.3, PDI 0.16 ± 0.06 and ZP -19.2 ± 1.4. The morphological analysis by SEM and AFM revealed the formation of smooth surface spherical nanoparticles. Cellular uptake studies in MIA PaCa-2 (GEM sensitive) and PANC-1 (GEM resistant) pancreatic cell lines confirmed energy dependent clathrin internalization/endocytosis as a primary mechanism of NPs uptake. In-vitro cytotoxicity studies confirmed the hNTs independent transport of GEM in MIA PaCa-2 and PANC-1 cells. Moreover, DNA damage and annexin-V assay revealed significantly higher apoptosis level in case of cells treated with GEM-BSA NPs as compared to free GEM. Conclusions: GEM-BSA NPs were found to potentiate the therapeutic efficacy by altering physicochemical properties, improving cellular uptake and stability of GEM and thus demonstrated promising therapeutic potential over free drug.

Item Type: Article
DOI/Identification number: 10.1007/s11095-017-2238-8
Uncontrolled keywords: BSA nanoparticles, conjugate, gemcitabine, MIA PaCa-2, PANC-1
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Dimitrios Lamprou
Date Deposited: 14 Aug 2017 07:50 UTC
Last Modified: 09 Dec 2022 05:51 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/62653 (The current URI for this page, for reference purposes)

University of Kent Author Information

Lamprou, Dimitrios A..

Creator's ORCID: https://orcid.org/0000-0002-8740-1661
CReDIT Contributor Roles:
  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.