title: Revisiting the nanoformulation design approach for effective delivery of topotecan in its stable form: an appraisal of its in vitro Behavior and tumor amelioration potential.
abstract: Topotecan (TPT) is indicated against a variety of solid tumors, but has restricted clinical use owing to associated pharmaceutical caveats. This study is focused at formulating a successful TPT PLGA nanosystem which ameliorates the rapid conversion of active lactone form of drug to its inactive carboxylate form and consequently improvises its efficacy. TPT PLGA nanoparticles were formulated by a double emulsion-solvent evaporation technique with sequential optimization to obtain desired particle size, PDI, zeta potential, and entrapment efficiency. Stability of TPT was ensured by maintaining an acidic pH in the drug-containing phase and the system was evaluated for in vitro-in vivo performance including cytotoxic potency. The optimized nanosystem had a particle size of 187.33 ± 7.50 nm, a PDI of 0.179 ± 0.05, and an entrapment efficiency of 56 ± 1.2%. Low pH in the interior of nanoparticles stabilized the drug to remain in its active lactone form and revealed a biphasic release pattern till 15 d. Additionally, an in vitro cytotoxicity testing as well as in vivo antitumor efficacy demonstrated a significant potential of higher proliferation inhibition as compared with neat drug (TPT). Thus, the investigation summarized an innovative simple tool for developing stable TPT NPs for effective delivery for treating solid tumors.
authors.affiliation: a Department of Pharmaceutics , Faculty of pharmacy Jamia Hamdard , New Delhi , India.|b Product Development Cell-II, National Institute of Immunology , New Delhi , India.
authors.forename: Santwana
authors.initials: S
authors.lastname: Padhi
authors.affiliation: c Sun Pharm India Limited , Gurgaon , India , and.
authors.forename: Mohd Aamir
authors.initials: MA
authors.lastname: Mirza
authors.affiliation: a Department of Pharmaceutics , Faculty of pharmacy Jamia Hamdard , New Delhi , India.
authors.forename: Devina
authors.initials: D
authors.lastname: Verma
authors.affiliation: a Department of Pharmaceutics , Faculty of pharmacy Jamia Hamdard , New Delhi , India.
authors.forename: Tahir
authors.initials: T
authors.lastname: Khuroo
authors.affiliation: b Product Development Cell-II, National Institute of Immunology , New Delhi , India.
authors.forename: Amulya K
authors.initials: AK
authors.lastname: Panda
authors.affiliation: a Department of Pharmaceutics , Faculty of pharmacy Jamia Hamdard , New Delhi , India.
authors.forename: Sushama
authors.initials: S
authors.lastname: Talegaonkar
authors.affiliation: d BSAnangpuria Institute of Pharmacy , Faridabad , Haryana , India.
authors.forename: Roop Krishen
authors.initials: RK
authors.lastname: Khar
authors.affiliation: a Department of Pharmaceutics , Faculty of pharmacy Jamia Hamdard , New Delhi , India.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D019772:Topotecan / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D019772:Topotecan
keywords: Cytotoxicity; PLGA nanoparticles; lactone–carboxylate; lung cancer cells; topotecan