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Development and Characterization of Biocompatible Mannose Functionalized Mesospheres: an Effective Chemotherapeutic
Laxmikant Gautam1, Rajeev Sharma1, Priya Shrivastava1
1Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, M.P., 470003, India.
AAPS Pharmscitech
|July 15, 2020
Summary
Surface engineered mesospheres loaded with doxorubicin hydrochloride (DOX) show potential for lung targeting. Mannose-modified gelatin-DOX-mesospheres (M2) demonstrated enhanced cytotoxicity and lung accumulation, suggesting targeted delivery for lung cancer treatment with reduced side effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Pharmacology
Background:
- Lung cancer remains a leading cause of cancer-related deaths globally.
- Effective drug delivery to the lungs is crucial for improving treatment outcomes.
- Current treatments often suffer from systemic toxicity and poor targeting efficiency.
Purpose of the Study:
- To engineer gelatin-based mesospheres for targeted lung delivery of doxorubicin hydrochloride (DOX).
- To surface-modify mesospheres with mannose to enhance lung targeting.
- To evaluate the physicochemical properties, in vitro drug release, cytotoxicity, and lung accumulation of the engineered mesospheres.
Main Methods:
- Preparation of gelatin-DOX-mesospheres (M1) and gelatin-mannosylated-DOX-mesospheres (M2) using steric stabilization.
- Characterization of mesospheres for particle size, polydispersity index, zeta potential, and entrapment efficiency.
- In vitro drug release studies, cytotoxicity assays on A-549 lung cancer cell lines, and hemolytic toxicity assessment.
- Evaluation of lung accumulation of DOX after administration of mesosphere formulations.
Main Results:
- Mesospheres M1 and M2 exhibited favorable physicochemical properties, with M2 showing a slightly larger particle size and lower polydispersity.
- In vitro drug release was sustained for both formulations, with M1 showing higher cumulative release than M2.
- Mannose-modified mesospheres (M2) demonstrated significantly higher cytotoxicity against A-549 cells compared to M1 and free DOX, with maximal lung accumulation.
- Minimal hemolytic toxicity was observed for both mesosphere formulations.
Conclusions:
- Surface-engineered gelatin-mannosylated-DOX-mesospheres (M2) show significant potential for targeted lung cancer therapy.
- The mannose modification enhances specific targeting and cytotoxic efficacy in the lungs.
- These mesospheres offer a promising platform for sustained and targeted delivery of doxorubicin hydrochloride to the lungs, potentially minimizing systemic side effects.
