pH Responsive 5-Fluorouracil Loaded Biocompatible Nanogels For Topical Chemotherapy of Aggressive Melanoma.

pH Responsive 5-Fluorouracil Loaded Biocompatible Nanogels For Topical Chemotherapy of Aggressive Melanoma.

Publication date: Feb 01, 2019

Combating melanoma via topical route is a highly challenging task due to low selectivity, poor efficacy and impeding biological environment of the skin. In the present study, we engineered a chitosan based pH responsive biodegradable nanogel (FCNGL), encapsulated with 5-FU that was effective even at very low drug doses (0.2% w/v) against melanoma. The FCNGL was synthesized by ion gelation technique exhibited nano-size particle distribution and sustained drug release kinetics. Hemolysis and coagulation analysis revealed high safety whereas MTT and apoptosis assays exhibited the efficacy of FCNGL. DMBA-Croton oil Swiss albino mice model was employed for in vivo assessment followed by gamma scintigraphic screening. Tumor burden and pharmacokinetic antioxidant stress levels along with whole-body gamma scintigraphy imaging using 99 mTc labelled nanogel exhibited selective accumulation in melanoma tumor nodules. The pH responsive behaviour of the nanogels resulted in triggered release of 5-FU in slightly acidic microenvironment, resulting in selective drug accumulation at the melanoma site. Immunohistochemistry (IHC) analysis of tumor showed improvement of subcutaneous layer alignment and regeneration of the epithelial skin layer when compared with standard 5% 5-FU and control mice group. Overall our preclinical data using the FCNGL portends to be a promising platform for efficient and sustained delivery of 5-FU for topical chemotherapy that can result in high efficacy, patient compliance and safety in the clinical set up.

Sahu, P., Kashaw, S.K., Sau, S., , Kushwah, Jain, S., Agrawal, R.K., and Iyer, A.K. pH Responsive 5-Fluorouracil Loaded Biocompatible Nanogels For Topical Chemotherapy of Aggressive Melanoma. 23680. 2019 Colloids Surf B Biointerfaces (174):

Concepts Keywords
99mTc Oil
Albino Control
Antioxidant Chemotherapy
Apoptosis Medicine
Biodegradable RTT
Chemotherapy Clinical medicine
Chitosan Cancer
Coagulation Oncology
Control Group Cancer treatments
Epithelial Organofluorides
Fluorouracil Chemotherapy
Hemolysis Melanoma
Immunohistochemistry Antimetabolite
Ion Fluorouracil
Kinetics Apoptosis
Loaded Chemotherapy
Melanoma
Microenvironment
Nodules
Pharmacokinetic
Scintigraphic
Scintigraphy
Stress
Subcutaneous
Swiss
Topical
Topical Chemotherapy
Tumor
Vivo

Semantics

Type Source Name
disease MESH Neoplasms Experimental
gene UNIPROT SET
disease MESH Tumor
pathway BSID Apoptosis
disease MESH Hemolysis
pathway BSID Release
gene UNIPROT KCNK3
pathway BSID Melanoma
disease DOID Melanoma
disease MESH Melanoma
drug DRUGBANK Fluorouracil

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