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Papain decorated multi‐functional polymeric micelles for the targeted intracellular delivery of paclitaxel
Author(s) -
Razzaq Sobia,
Rauf Aisha,
Raza Abida,
Tabish Tanveer A.,
RaufulHassan Muhammad,
Shahnaz Gul
Publication year - 2021
Publication title -
polymers for advanced technologies
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.61
H-Index - 90
eISSN - 1099-1581
pISSN - 1042-7147
DOI - 10.1002/pat.5330
Subject(s) - paclitaxel , cytotoxicity , micelle , hyaluronic acid , drug delivery , biophysics , nanocarriers , penetration (warfare) , materials science , intracellular , chemistry , zeta potential , in vitro , nanotechnology , nanoparticle , biochemistry , chemotherapy , organic chemistry , medicine , biology , surgery , operations research , aqueous solution , engineering , anatomy
Mucopermeating nanocargoes being able to overcome mucosal, as well as extracellular barrier leads to enhance penetration of poorly soluble anticancer drugs at its target site. We developed an innovative means to bring amphiphilic mucopermeating functional micelles to tumors. Papain (Pap) grafted thiolated hyaluronic acid‐pluronic F 127 ‐lithocholic acid triblock (Pap‐THA‐g‐F 127 ‐SS‐LCA) was synthesized in this study. As‐prepared formulation yielded Pap functionalized thiolated redox micelles (PT‐R‐Ms). Mucolytic and tumor extracellular matrix‐degrading property of Pap enzyme facilitated the diffusion of paclitaxel loaded PT‐R‐Ms. Moreover, PT‐R‐Ms exhibited glutathione‐triggered release serving as a mimic for the tumor microenvironment yielding enhanced intracellular tumor penetration thereby leading to high tumor cytotoxicity. PT‐R‐Ms were spherical with a particle size of 80 nm, the negative zeta potential of −29 ± 3.85, and high encapsulation efficiency, that is, 80 ± 3.29% of paclitaxel. In‐vitro anticancer activity demonstrated higher cytotoxicity of PT‐R‐Ms against all HCT‐116, Hep‐2, and RD cancerous cell lines in comparison to free paclitaxel. PT‐R‐Ms indicated the highest penetration in tumor tissue in terms of maximum fluorescence. Briefly, this delivery system addresses the existing clinical challenges by enabling as‐prepared nanocargoes to release paclitaxel when reaching the site of a target (where it is the most needed), thereby minimizing off‐target toxic effects. Targeted delivery of drug using nanocargoes has the potential to propel the field of drug delivery in solving real‐world clinical problems.