Abstract
Gliomas are one of the prominent cancers of the central nervous system with limited therapeutic modalities. The present investigation evaluated the synergistic effect of paclitaxel (PAX) and resveratrol (RESV)-loaded Soluplus polymeric nanoparticles (PNPs) against glioma cell lines along with in vivo pharmacokinetics and brain distribution study. PAX-RESV-loaded PNPs were prepared by the thin film hydration technique and optimized for different dependent and independent variables by using DoE (Design-Expert) software. The in vitro physiochemical characterization of prepared PAX-RESV-loaded PNPs exhibited appropriate particle size, PDI and % encapsulation efficiency. Cytotoxicity assay revealed that PTX-RESV loaded PNPs had a synergistic antitumor efficacy against C6 glioma cells compared with single and combined pure drugs. Finally, the pharmacokinetic and brain distribution studies in mice demonstrated that the PNPs significantly enhanced the bioavailability of PTX-RESV PNPs than pure PAX and RESV. Thus, the study concluded that PAX-RESV PNPs combination could significantly enhance anti-glioma activity, and this could be developed into a potential glioma treatment strategy.
Highlights
Central nervous system tumors and malignancies showed 45% and 77% occurrence of gliomas, respectively [1]
PAX is activating the production of reactive oxygen species found in many cancer cells including glioblastoma [6]
Soluplus was utilized as a carrier to encapsulate PAX and RESV and TPGS1000 was used to decorate the drug loaded nano carrier by employing thin film hydration technique
Summary
Central nervous system tumors and malignancies showed 45% and 77% occurrence of gliomas, respectively [1]. Radiotherapy, chemotherapy and resection are the common treatment strategy for gliomas [3], but these therapies were considered inefficient in managing cancer because the survival rate was less than 15 months [4]. This insufficiency to combat the disease was due to the resistance and toxic effect of anti-neoplastic drugs. PAX is activating the production of reactive oxygen species (oxidative stress) found in many cancer cells including glioblastoma [6]. The high mortality rate of cells could lead to the unknown molecular pathways of PAX resistance. The poor blood–brain tumor barrier (BBTB) and blood–brain barrier (BBB) permeation of the active
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