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  • Title: Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery.
    Author: Alex AT, Joseph A, Shavi G, Rao JV, Udupa N.
    Journal: Drug Deliv; 2016 Sep; 23(7):2144-2153. PubMed ID: 25544603.
    Abstract:
    CONTEXT: The study was aimed to develop a polymeric nanoparticle formulation of anticancer drug carboplatin using biodegradable polymer polycaprolactone (PCL). The formulation is intended for intranasal administration to treat glioma anticipating improved brain delivery as nasal route possess direct access to brain and nanoparticles have small size to overcome the mucosal and blood-brain barrier. OBJECTIVE: Development and evaluation of carboplatin-PCL nanoparticles for brain delivery by nasal route. METHODOLOGY: Carboplatin-loaded PCL nanoparticles (CPCs) were prepared by double emulsion-solvent evaporation technique and characterized by particle size, zeta potential, entrapment efficiency, scanning electron microscopy and differential scanning calorimetry. The CPCs were assessed for in vitro release kinetics, ex vivo permeation and in situ nasal perfusion. Cytotoxic potential of CPCs in vitro was evaluated on LN229 human glioblastoma cells. RESULTS AND DISCUSSION: The optimized formulation of carboplatin-PCL nanoparticle CPC-08 with particle size of 311.6 ± 4.7 nm and zeta potential -16.3 ± 3.7 mV exhibited percentage entrapment efficiency of 27.95 ± 4.21. In vitro drug release showed initial burst release followed by slow and continues release indicating biphasic pattern. The ex vivo permeation pattern through sheep nasal mucosa also exhibited a similar release pattern as for in vitro release studies. In situ nasal perfusion studies in Wistar rats demonstrate that CPCs show better nasal absorption than carboplatin solution. In vitro cytotoxicity studies on LN229 cells showed an enhancement in cytotoxicity by CPCs compared to carboplatin alone. CONCLUSION: CPC-08 effectively improves nasal absorption of carboplatin and can be used for intranasal administration of carboplatin for improved brain delivery.
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