Multivesicular liposomal depot system for sustained delivery of risperidone: development, characterization, and toxicity assessment

Abstract

Objective

Considering the limitations of conventional risperidone (RSP) therapies, the present research characterizes the usefulness of multivesicular liposomes (MVLs) as an efficient controlled-release carrier for this widely used antipsychotic drug, to be employed for the treatment of schizophrenia.

Methods

A 2³ full factorial design based on three independent variables was implemented to plan the experiments: the molar ratios of lipid to the drug, triolein to phospholipid, and cholesterol to phospholipid. The impacts of these parameters on the risperidone encapsulation efficiency and its release pattern within the first 24 and 48 h were investigated as dependent variables. Then, the optimized liposomal system was further in-depth analyzed in terms of size, morphological and structural features, release profile over 15 days, biocompatibility, and stability.

Results

Optimized formulation parameters gave rise to MVLs possessing a spherical morphology with a median diameter of about 8 μm, a relatively narrow size distribution (span value of 1.49), and an encapsulation efficiency of 57.6%. These carriers not only exhibited a sustained-release behavior in vitro, lasting until the end of the 15 days but also underwent a negligible change in their size and RSP incorporation over two months at refrigerator condition. Furthermore, in vitro cytotoxicity and hemolysis assessments revealed that the optimized MVL formulation is biocompatible.

Conclusion

This study revealed the potential of MVLs as a promising system for the delivery of RSP and could open a new vista for the successful management of schizophrenia.

Keywords:

• Risperidone
• multivesicular liposomes
• local delivery
• sustained release
• factorial design

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

National Institutes for Medical Research Development (NIMAD) Research reported in this publication was supported by Elite Researcher Grant Committee under award number [963625] from the National Institutes for Medical Research Development (NIMAD), Tehran, Iran.