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Published on: December 21, 2019
Liposomal pemetrexed: formulation, characterization and in vitro cytotoxicity studies for effective management of
Noha Essam Eldin1, Hanan Mohamed Elnahas, Mahmoud Abd-Elghany Mahdy
1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University 44 519, Egypt; Department of Pharmacokinetics and Biopharmaceutics, Institute of Health Biosciences, University of Tokushima.
Abstract:
Pemetrexed (PMX) is a newly developed multi-targeted anti-folate with promising clinical activity in many solid tumors including malignant pleural mesothelioma (MPM). However, PMX does not show sufficient anti-tumor activity in vivo when used alone either due to inefficient delivery of adequate concentrations to tumor tissue or dose-limiting side effects. In order to overcome these problems and to achieve potent anti-tumor activity, PMX was encapsulated into a liposomal delivery system. In the present study, various formulations of liposomal PMX were prepared. The effect of formulation parameters on the encapsulation efficiency of PMX within liposomes was evaluated. In addition, the influence of drug release rate on the in vitro cytotoxicity was investigated. Encapsulation of PMX within liposomes was remarkably increased by the incorporation of cholesterol within liposomal membranes and by increasing the total lipid concentration. Encapsulation efficiency was found to be unaffected by the type of phospholipid used or the inclusion of a cation lipid, DC-6-14. Interestingly, encapsulation of PMX within "fluid" liposomes was found to allow efficient release of PMX from liposomes resulting in a potent in vitro cytotoxicity against MPM MSTO-211H cell line. On the other hand, entrapment of PMX within "solid" liposomes substantially hindered PMX release from liposomes, and thus PMX failed to exert any in vitro cytotoxicity. These results suggest that encapsulation of PMX within "fluid" liposomes might represent a novel strategy to enhance the therapeutic efficacy of PMX while minimizing the side effect encountered by the non selective delivery of free PMX to various body tissues.
Insights
Liposomal pemetrexed (PMX) enhances anti-tumor activity for malignant pleural mesothelioma (MPM). Fluid liposomes improve drug release and cytotoxicity, offering a novel therapeutic strategy.
Area of Science:
- Oncology
- Nanomedicine
- Drug Delivery
Background:
- Pemetrexed (PMX) is a multi-targeted anti-folate with clinical activity in solid tumors like malignant pleural mesothelioma (MPM).
- PMX exhibits limited in vivo anti-tumor efficacy due to poor tumor delivery and dose-limiting side effects.
- Liposomal encapsulation is explored to improve PMX delivery and therapeutic outcomes.
Purpose of the Study:
- To develop and characterize liposomal formulations of Pemetrexed (PMX).
- To evaluate the impact of formulation parameters on PMX encapsulation efficiency.
- To investigate the correlation between drug release rate and in vitro cytotoxicity of liposomal PMX.
Main Methods:
- Preparation of various liposomal PMX formulations.
- Assessment of encapsulation efficiency influenced by cholesterol and lipid concentration.
- Evaluation of in vitro cytotoxicity against MPM MSTO-211H cell line.
Main Results:
- Cholesterol incorporation and increased lipid concentration significantly enhanced PMX encapsulation.
- Lipid composition did not affect encapsulation efficiency.
- Fluid liposomes facilitated efficient PMX release and potent in vitro cytotoxicity.
- Solid liposomes hindered PMX release, resulting in no observed cytotoxicity.
Conclusions:
- Liposomal encapsulation of PMX can overcome limitations of free drug administration.
- Fluid liposomal formulations enhance PMX release and in vitro anti-tumor activity.
- This strategy holds potential for improved MPM therapy with reduced side effects.
