title: pH-Sensitive Biocompatible Nanoparticles of Paclitaxel-Conjugated Poly(styrene-co-maleic acid) for Anticancer Drug Delivery in Solid Tumors of Syngeneic Mice.
abstract: In the present study, we have synthesized poly(styrene-co-maleic anhydride), a biocompatible copolymer that was further conjugated with paclitaxel (PTX) via ester linkage and self-assembled to form poly(styrene-co-maleic acid)-paclitaxel (PSMAC-PTX) nanoparticles (NPs). The in vitro release of PTX from PSMAC-PTX NPs showed a higher release at lower pH than at the physiological pH of 7.4, confirming its pH-dependent release. The cell viability of PSMAC-PTX nanoparticles was evaluated using MTT assay. IC50 values of 9.05-18.43 ng/mL of PTX equivalent were observed in various cancer cell lines after 72 h of incubation. Confocal microscopy, Western blotting, and Flow cytometry results further supported that the cellular uptake and apoptosis of cancer cells with PSMAC-PTX NPs. Pharmacokinetic studies revealed that the conjugation of PTX to the PSMAC co-polymer not only increased the plasma and tumor C(max) of PTX but also prolonged its plasma half-life and retention in tumor via enhanced permeability and retention (EPR) effect. Administration of PSMAC-PTX NPs showed significant tumor growth inhibition with improved apoptosis effects in vivo on Ehrlich Ascites Tumor (EAT)-bearing BALB/c syngeneic mice in comparison with Taxol, without showing any cytotoxicity. On the basis of preliminary results, no subacute toxicity was observed in major organs, tissues and hematological system up to a dosage of 60 mg/kg body weight in mice. Therefore, PSMAC-PTX NPs may be considered as an alternative nanodrug delivery system for the delivery of PTX in solid tumors.
authors.affiliation: Centre for Biomedical Engineering, Indian Institute of Technology , Hauz Khas, New Delhi-110016, India.|Biomedical Engineering Unit, All India Institute of Medical Sciences, AIIMS , New Delhi, Ansari Nagar, New Delhi-110029, India.
authors.forename: Manu
authors.initials: M
authors.lastname: Dalela
authors.affiliation: Department of Reproductive Biomedicine, National Institute of Health & Family Welfare , Delhi-110067, India.
authors.forename: T G
authors.initials: TG
authors.lastname: Shrivastav
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School , Boston, Massachusetts 02215, United States.
authors.forename: Surender
authors.initials: S
authors.lastname: Kharbanda
authors.affiliation: Centre for Biomedical Engineering, Indian Institute of Technology , Hauz Khas, New Delhi-110016, India.|Biomedical Engineering Unit, All India Institute of Medical Sciences, AIIMS , New Delhi, Ansari Nagar, New Delhi-110029, India.
authors.forename: Harpal
authors.initials: H
authors.lastname: Singh
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D019540:Area Under Curve; D001672:Biocompatible Materials / Q000737:chemistry*; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D004705:Endocytosis / Q000187:drug effects; D004903:Erythrocyte Aggregation / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D020287:In Situ Nick-End Labeling; D020128:Inhibitory Concentration 50; D053208:Kaplan-Meier Estimate; D008298:Maleates / Q000737:chemistry*; D020714:Maximum Tolerated Dose; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011137:Polystyrenes / Q000737:chemistry*; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D008298:Maleates; D011137:Polystyrenes; C024074:styrene-maleic acid polymer; C030272:maleic acid; D017239:Paclitaxel
keywords: BALB/c mice; EAT; paclitaxel; pharmacokinetics; poly(styrene-co-maleic acid)