A Novel Melt-Dispersion Technique for Simplistic Preparation of Chlorpromazine-Loaded Polycaprolactone Nanocapsules

Polymers

Thiresen Govender¹  Yahya E. Choonara¹  Pradeep Kumar¹  Lisa C. du Toit¹  Girish Modi³  Dinesh Naidoo²  Viness Pillay¹ 

[1] Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa; E-Mails:;Department of Neurosurgery, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa; E-Mail:;Department of Neurology, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa; E-Mail:

关键词: neurotherapy;    chlorpromazine hydrochloride;    poly-ε-caprolactone;    Polysorbate 80;    melt-dispersion technique;    nanocapsules;    central composite design;   

DOI  :  10.3390/polym7061145

来源: mdpi

【 摘 要 】

The aim of this study was to design, synthesize and optimize chlorpromazine hydrochloride (CPZ)-loaded, poly-ε-caprolactone (PCL) based nanocapsules, intended for site specific delivery to the frontal lobe, using a novel melt-dispersion technique that is non-arduous, inexpensive and devoid of any hazardous organic solvents. Experimental trials using a central composite design were performed on 13 statistically derived formulations of various combinations of PCL (1000–3000 mg) and Polysorbate 80 (2%–5% v/v) on the physicochemical and physicomechanical properties and interactive effects on PCL nanocapsule formulation. Differential scanning calorimetry (DSC), Temperature modulated differential scanning calorimetry (TMDSC) and Fourier transform infrared spectroscopy (FTIR) revealed that there was no thermodegardation of the constituents utilized in the melt dispersion technique. Nanocapsule yields achieved were very high however entrapment of CPZ proved to be relatively low due to the highly hydrophilic nature of CPZ and the processing of the nanocapsules post synthesis. Nanocapsule sizes were in the nanotherapeutic range and varied from 132.7 ± 6.8 nm to 566.6 ± 5.5 nm. Zeta potential ranged from 15.1 ± 0.65 mV to 28.8 ± 0.84 mV revealing capsules that were of incipient to moderate stability. Transmission electron microscopy revealed nanocapsules that were spherical shape, well individualized with a moderate degree of flocculation. In vitro CPZ release was biphasic for all formulations with an initial burst release followed by pseudo-steady controlled release over 30 days. The cytotoxicity of the optimized nanocapsule system on a PC12 neuronal cell line proved to be minimal. Following incorporation of the optimized nanocapsules within a polymeric membrane, in vivo implantation of the device in a New Zealand Albino rabbit model proved the efficacy of the system in achieving prolonged more targeted CPZ levels to the brain. Extensive in vitro testing and optimization and preclinical evaluation supports the application for the use and feasibility of the CPZ-loaded, PCL based nanocapsules for the long-term management of certain psychotropic disorders where the benefits of nanotechnology can be exploited.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.