title: Micelle-assisted combination therapies for effective glioblastoma treatment: an in-vitro assessment.
abstract: Glioblastoma is the most fatal type of brain tumor, requiring a better chemotherapy regime to prolong the survival of the patient. The toxicity associated with a high dose of a single drug can be overcome by a combination of different anticancer drugs. Methoxy poly(ethylene glycol)-poly (ε-caprolactone) block copolymeric micelles loaded with two different anticancer drugs such as curcumin and rapamycin were used to assess their therapeutic efficacy in glioblastoma cell lines. In addition, the combination of curcumin and rapamycin was also encapsulated in micelles for better anticancer activity. The in-vitro cellular uptake studies and cytotoxicity studies showed that the drugs encapsulated in the micelles showed ∼3.3 times more uptake than a mixture of native drugs as well as a single drug. The enhanced mitochondrial membrane potential depolarization by drug-loaded micelles leads to higher cell death compared with native drugs in T98G glioblastoma cell culture experiments. The drug combination downregulates P13/AKT and serine/threonine kinase proteins, and leads to programmed cell death. Thus, curcumin and rapamycin-loaded micelles can be used effectively for the treatment of glioblastoma.
authors.affiliation: Department of Pharmacy, Annamalai University, Tamilnadu, India.
authors.forename: Anjan Kumar
authors.initials: AK
authors.lastname: Mohanty
authors.forename: Guru Prasad
authors.initials: GP
authors.lastname: Mohanta
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008823:Micelles; D016328:NF-kappa B / Q000378:metabolism; D011091:Polyesters / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage; D020123:Sirolimus / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D008823:Micelles; D016328:NF-kappa B; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D003474:Curcumin; D020123:Sirolimus