Design and evaluations of a nanostructured lipid carrier loaded with dopamine hydrochloride for intranasal bypass drug delivery in Parkinson’s disease

Abstract

Aim

The goal of this study is to optimisation 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 homogenisation method using solid lipids (Cholesterol and Soya lecithin), liquid lipid (Oleic acid) and surfactant (Poloxamer- 188) as major excipients, optimised by central composite design using design expert-13 software. The optimised formulations were characterised 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 optimised 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 optimised 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*1 0 ⁻⁴cm/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 optimised 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 optimised successfully with increased bioavailability of drug from the NLC into brain with reduce toxicity in effective treatment of Parkinson’s disease.

Keywords:

• Parkinson’s disease
• dopamine hydrochloride
• nanostructured lipid carrier
• homogenisation
• particle size
• entrapment efficiency
• Ciliotoxicity

Acknowledgement

The authors would like to thank Delhi Institute of pharmaceutical science and research, New Delhi, India for providing research facilities and SAIF Department at Punjab University, Chandigarh, India for FTIR, SEM, TEM analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was funded by the senior research fellowship through Indian council of medical research (ICMR, New Delhi).