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In Vitro Comparative Study on Oppositely Charged Donepezil-Loaded Intranasal Liposomes.

Elika Valehi1, Gábor Katona1, Dorina Gabriella Dobó1

  • 1Faculty of Pharmacy, University of Szeged, Institute of Pharmaceutical Technology and Regulatory Affairs, Eötvös Str. 6, H-6720 Szeged, Hungary.

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Summary

This study explored using charged liposomes for intranasal drug delivery to the central nervous system (CNS). Negatively charged liposomes improved drug permeability, while positively charged ones enhanced mucoadhesion, both aiding nasal absorption.

Keywords:
dicethyl phosphateliposomenasal administrationstearylamine

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Area of Science:

  • Nanotechnology
  • Pharmacology
  • Drug Delivery

Background:

  • Intranasal delivery offers a direct route for central nervous system (CNS) targeting.
  • Poor nasal mucosal permeability limits the efficacy of many drugs.
  • Liposomes as nanocarriers can enhance nasal drug absorption, with surface charge being critical for uptake.

Purpose of the Study:

  • To formulate and compare oppositely charged liposomes for intranasal delivery of donepezil hydrochloride (DPZ).
  • To evaluate the impact of negatively charged dicetyl phosphate (DCP) and positively charged stearylamine (SA) on liposome properties and nasal applicability.

Main Methods:

  • Liposomes were prepared with phosphatidylcholine (PC) and cholesterol (CH) at a 7:2 molar ratio.
  • The influence of DCP and SA was investigated at varying molar ratios (0.5:2).
  • Key parameters studied included colloidal properties, drug release, in vitro nasal permeability, and mucoadhesion.

Main Results:

  • Liposome vesicle size decreased with increasing DCP concentration and increased with SA concentration.
  • Drug release rates were faster with smaller vesicle sizes.
  • Both DCP and SA improved drug encapsulation efficiency (60-80%).
  • DCP enhanced in vitro nasal permeability, while SA exhibited superior mucoadhesive properties.

Conclusions:

  • Both DCP and SA are effective charge inducers for enhancing nasal absorption of liposomal carriers.
  • Optimal formulation for DCP involved higher concentrations (PC:CH:DCP 7:2:2).
  • Optimal formulation for SA involved lower concentrations (PC:CH:SA 7:2:0.5).