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: Manu Dalela, T G Shrivastav, Surender Kharbanda, Harpal Singh
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 7 Issue 48 Pg. 26530-48 (Dec 09 2015) ISSN: 1944-8252 [Electronic] United States
• PMID: 26528585 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Biocompatible Materials
• Maleates
• Polystyrenes
• styrene-maleic acid polymer
• maleic acid
• Paclitaxel

Topics

• Administration, Intravenous
• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacokinetics, pharmacology, therapeutic use)
• Area Under Curve
• Biocompatible Materials (chemistry)
• Blood Cell Count
• Body Weight (drug effects)
• Carcinoma, Ehrlich Tumor (drug therapy, pathology)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Delivery Systems
• Drug Liberation
• Drug Stability
• Endocytosis (drug effects)
• Erythrocyte Aggregation (drug effects)
• Hemolysis (drug effects)
• Hydrogen-Ion Concentration
• In Situ Nick-End Labeling
• Inhibitory Concentration 50
• Kaplan-Meier Estimate
• Maleates (chemistry)
• Maximum Tolerated Dose
• Mice, Inbred BALB C
• Nanoparticles (chemistry, ultrastructure)
• Paclitaxel (chemistry, pharmacokinetics, pharmacology, therapeutic use)
• Polystyrenes (chemistry)
• Tissue Distribution (drug effects)