Development of risperidone liposomes for brain targeting through intranasal route

Abstract

The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (<0.5). The entrapment efficiency of optimized liposomes was between 50 and 60%, functionalized liposomes showed maximum entrapment. The TEM images showed predominantly spherical vesicles with smooth bilayered surface. All formulations showed prolonged diffusion controlled drug release. The in vivo results showed that liposomal formulations provided enhanced brain exposure. Among the formulations studied, PEGylated liposomes (LP-16) had shown greater uptake of risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential.

Intranasal Nanoparticulate Systems as Alternative Route of Drug Delivery

“…Moreover, the fluorescence microscopy studies revealed that the PEG-PLA particles were able to cross the rat's nasal epithelium to the brain [112]. Another study reported that PEGylated liposomes had shown greater uptake of risperidone into the brain in comparison to liposomes and cationic liposomes [113].…”

Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease

“…Direct and brain-targeted drug delivery may allow enhanced therapeutic effects even at a lower drug dose, allow rapid drug absorption at the target site, avoid first-pass elimination, and reduce toxicity (Lalani et al., 2014 ; Gomes et al., 2018 ). Several studies on piperine (Elnaggar et al., 2015 ), tarenflurbil (Muntimadugu et al., 2016 ), risperidone (Narayan et al., 2016 ), glycyrrhizic acid (Ahmad et al., 2019 ) and alginate (Haque et al., 2014 ) have substantiated the theory of nose-to-brain delivery systems. UPLC/ESI-Q-ToF-MS/MS based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency and brain drug-targeting potential studies post intranasal (i.n.)…”

Mixed cationic liposomes for brain delivery of drugs by the intranasal route: The acetylcholinesterase reactivator 2-PAM as encapsulated drug model

“…Their surface can be easily modified to provide them with multiple functions [17]. This has already been demonstrated for improvement of intranasal delivery [18] of rivastigmine [19,20], donepezil [21], zolmitriptan [22].…”