Abstract
A modified facile biomimetic Temozolomide Chitosan nanogel (TCNL) was developed offering pH responsive, charge attracted and microenvironment dependent tumor targeting nanotherapy. USFDA approved chemotherapeutic TMZ (Temozolomide) was encapsulated in a cationic biocompatible chitosan nanogel subsequently surface modified with nonionic Transcutol by inotropic gelation method and evaluated for its combined anti-metastatic and antitumor efficiency. The in-vitro results authenticated that TMZ encapsulated TCNL was effectively uptake and distributed in HaCaT cell line inducing high apoptosis and necrosis of tumor cells prior to the electron microscopic (TEM & SEM) and thermal evaluations (DSC, DTA & TG) suggesting spherical and thermo-stable nanogel system. An accelerated sustained release pattern of TMZ from TCNL was displayed in mildly acidic conditions (pH 6) signifying ultra-sensitivity of TCNL. In-vivo evaluation over 16 week DMBA/croton oil tumor induced mice model showed noteworthy tumor targeting with down regulation of overexpressed COX-2, cytokines and nuclear factors on western blot analysis. Moreover, advanced gamma scintigraphy analysis displayed significant drug accommodation and expressing potent tumor accumulation, suppression and metastasis effect on carcinogenic mice. The TCNL outcomes displayed effective tumor targeting on transdermal delivery for operative nanotherapy against skin cancer.
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