title: P-glycoprotein inhibition of drug resistant cell lines by nanoparticles.
abstract: Several pharmaceutical excipients are known for their ability to interact with cell membrane lipids and reverse the phenomenon of multidrug resistance (MDR) in cancer. Interestingly, many excipients act as stabilizers and are key ingredients in a variety of nano-formulations. In this study, representatives of ionic and non-ionic excipients were used as surface active agents in nanoparticle (NP) formulations to utilize their MDR reversing potential. In-vitro assays were performed to elucidate particle-cell interaction and accumulation of P-glycoprotein (P-gp) substrates-rhodamine-123 and calcein AM, in highly drug resistant glioma cell lines. Chemosensitization achieved using NPs and their equivalent dose of free excipients was assessed with the co-administered anti-cancer drug doxorubicin. Among the excipients used, non-ionic surfactant, Cremophor® EL, and cationic surfactant, cetyltrimethylammonuium bromide (CTAB), demonstrated highest P-gp modulatory activity in both free solution form (up to 7-fold lower IC50) and as a formulation (up to 4.7-fold lower IC50) as compared to doxorubicin treatment alone. Solutol® HS15 and Tween® 80 exhibited considerable chemosensitization as free solution but not when incorporated into a formulation. Sodium dodecyl sulphate (SDS)-based nanocarriers resulted in slightly improved cytotoxicity. Overall, the results highlight and envisage the usage of excipient in nano-formulations in a bid to improve chemosensitization of drug resistant cancer cells towards anti-cancer drugs.
authors.affiliation: a Laboratory of Pharmaceutical Technology and Biopharmaceutics , University of Bonn , Bonn , Germany and.
authors.forename: Manu Smriti
authors.initials: MS
authors.lastname: Singh
authors.affiliation: a Laboratory of Pharmaceutical Technology and Biopharmaceutics , University of Bonn , Bonn , Germany and.|b Laboratory of Pharmaceutical Engineering , University of Franche-Comté , Besançon , France.
authors.forename: Alf
authors.initials: A
authors.lastname: Lamprecht
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005079:Excipients / Q000737:chemistry* / Q000494:pharmacology; D005452:Fluoresceins / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D020128:Inhibitory Concentration 50; D053758:Nanoparticles; D051381:Rats; D020112:Rhodamine 123 / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D005079:Excipients; D005452:Fluoresceins; D013501:Surface-Active Agents; C085925:calcein AM; D020112:Rhodamine 123; D004317:Doxorubicin
keywords: Cancer; MDR; glioblastoma; nanoparticle; surfactants