Development and Optimization of Mirabegron Solid Lipid Nanoparticles as an Oral Drug Delivery for Overactive Bladder
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Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles
Published on: August 28, 2015
Prajakta Raut1, Makarand Gambhire1, Dhruvi Panchal1
1Department of Pharmaceutics, Sinhgad College of Pharmacy, Pune, India.
Background:
Mirabegron (MBN), a β-3 adrenergic agent, is used in the treatment of overactive bladder. MBN has alow water solubility, high first-pass metabolism, and low bioavailability, consequently having poor absorption in the gastrointestinal tract.
Objective:
The present study is intended to formulate Mirabegron-loaded solid lipid nanoparticles (MBN-SLN) coated with PEG-400 to bypass hepatic first-pass metabolism and to improve its oral bioavailability.
Methods:
MBN-SLNs were developed using glyceryl monostearate by pre-emulsion-ultrasonication method, which was then optimized applying Box-Behnken Design. The optimized batch of MBN-SLN was selected for surface-modification with PEG-400 (MBN-PEG-SLN) and characterized by photon correlation spectroscopy, DSC, and XRD. Bioavailability studies were conducted in Wistar rats after oral administration of plain MBN dispersion, MBN-SLN, and MBN-PEG-SLN.
Results:
Stable MBN-SLNs and MBN-PEG-SLN of the optimized batch having a mean particle size of 162.7 nm and 149.9 nm; zeta potential of -39.1 mV and -30.9 mV; % entrapment of 89.90% and 90.12%, respectively, were developed. The results of the in vitro drug release studies demonstrated a significant slow release of MBN from MBN-SLN (69.38%) and MBN-PEG-SLN (61.33%) as compared to the dispersion of pure drug (92.10%). The relative bioavailability, as a result of the in vivo studies, of MBN from MBN-PEG-SLN increased by 2-fold, based on the Cmax values, in comparison with the plain MBN dispersion.
Conclusion:
Thus, the study established that the oral bioavailability of MBN could be improved by the administration of MBN-PEG-SLN. The obtained results indicate SLNs as a potential drug delivery system for improving the bioavailability of poorly bioavailable drugs such as MBN by abating the first-pass metabolism.
Insights
This study developed Mirabegron-loaded solid lipid nanoparticles (MBN-SLN) coated with PEG-400 to enhance oral bioavailability. The MBN-PEG-SLN formulation successfully doubled the drug's bioavailability in rats by bypassing liver metabolism.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Nanotechnology
Background:
- Mirabegron (MBN) is a β-3 adrenergic agent for overactive bladder.
- MBN exhibits poor oral absorption due to low water solubility and high first-pass metabolism.
- This limits its therapeutic efficacy and necessitates improved delivery strategies.
Purpose of the Study:
- To formulate Mirabegron-loaded solid lipid nanoparticles (MBN-SLN) coated with PEG-400.
- To enhance oral bioavailability of Mirabegron by bypassing hepatic first-pass metabolism.
- To evaluate the potential of SLNs as a drug delivery system for poorly bioavailable drugs.
Main Methods:
- MBN-SLNs were prepared using glyceryl monostearate via pre-emulsion-ultrasonication and optimized with Box-Behnken Design.
- Optimized MBN-SLN were surface-modified with PEG-400 to create MBN-PEG-SLN.
- Characterization included particle size, zeta potential, entrapment efficiency, in vitro release, and in vivo bioavailability studies in Wistar rats.
Main Results:
- Stable MBN-SLNs and MBN-PEG-SLNs were successfully developed with controlled particle sizes and high entrapment efficiencies.
- In vitro studies showed sustained drug release from MBN-SLN and MBN-PEG-SLN compared to plain MBN dispersion.
- In vivo studies demonstrated a 2-fold increase in MBN bioavailability from MBN-PEG-SLN compared to plain MBN dispersion, based on Cmax.
Conclusions:
- The administration of MBN-PEG-SLN significantly improves the oral bioavailability of Mirabegron.
- Solid lipid nanoparticles (SLNs) represent a promising drug delivery system for enhancing the bioavailability of poorly absorbed drugs.
- PEGylation of SLNs further aids in overcoming pharmacokinetic limitations like first-pass metabolism.
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