Abstract
Aim- The goal of this study is to optimization and evaluation of dopamine-loaded NLC (NLC-DOPA) for achieve dopamine concentrations into brain for treatment of Parkinson's disease which causes progressive neuronal death. Method- NLC-DOPA prepared by homogenization method using solid lipids (Cholesterol and Soya lecithin), liquid lipid (Oleic acid) and surfactant (Poloxamer- 188) as major excipients, optimized by central composite design using design expert-13 software. The optimized formulations were characterized by particle size, zeta potential, entrapment efficiency, SEM, TEM, FTIR, DSC, XRD, stability study and in-vitro drug release. The histopathology of rat brain tissues and goat nasal tissues were performed. The ex-vivo (permeability and nasal ciliotoxicity study) and in vivo pharmacodynamics study were also accomplished to determine its efficacy and potency of NLC. Result- The NLC-DOPA formulations were optimized in particle size and (EE)% with range from 85.53 ± 0.703 to 106.11 ± 0.822 nm and 82.17 ± 0.794 to 95.45 ± 0.891%, respectively. The optimized formulation F11 showing best goodness-fitted model kinetic, followed by Korsmeyer-Peppas equation and zero order kinetic. The SEM and TEM confirmed the spherical and smooth morphology of formulation. FTIR and DSC spectra were given compatibility of compound and XRD diffractograms confirmed the amorphous nature. An ex-vivo study was showed the high permeability coefficient (6.67*10−4 cm/min, which is twice, compare to pure drug) and there was no damage in nasal mucosa, confirmed by the ciliotoxicity study. In-vivo study was shown significant effects of optimized NLC-DOPA on locomotor activity, force-swimming test and neurochemical assessment using rotenone induced Parkinson’s model on Albino wistar rats. Conclusion- NLC-DOPA was prepared and optimized successfully with increased bioavailability of drug from the NLC into brain with reduce toxicity in effective treatment of Parkinson’s disease.
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