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

Autor: Varun Kushwah, Ashish Kumar Agrawal, Sanyog Jain, Ramesh C. Gupta, David Mallinson, Dimitrios A. Lamprou, Chander Parkash Dora
Rok vydání: 2017
Předmět:
medicine.medical_specialty
endocrine system diseases
Cell Survival
Surface Properties
media_common.quotation_subject
Pharmaceutical Science
Antineoplastic Agents
Apoptosis
02 engineering and technology
Conjugated system
Endocytosis
Deoxycytidine
Clathrin
03 medical and health sciences
0302 clinical medicine
Annexin
Cell Line
Tumor
Internal medicine
medicine
Animals
Humans
Pharmacology (medical)
Particle Size
Bovine serum albumin
Cytotoxicity
Internalization
media_common
Pharmacology
biology
Chemistry
Organic Chemistry
Serum Albumin
Bovine
021001 nanoscience & nanotechnology
Gemcitabine
Pancreatic Neoplasms
Drug Liberation
Endocrinology
Drug Resistance
Neoplasm
030220 oncology & carcinogenesis
Biophysics
biology.protein
Nanoparticles
Molecular Medicine
Cattle
0210 nano-technology
Biotechnology
Conjugate
Zdroj: Pharmaceutical Research. 34:2295-2311
ISSN: 1573-904X
0724-8741
Popis: 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.
Databáze: OpenAIRE
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