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Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles
Published on: August 28, 2015
Injectable methotrexate loaded polycaprolactone microspheres: Physicochemical characterization, biocompatibility, and
Mukesh Dhanka1, Chaitra Shetty1, Rohit Srivastava1
1Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
Abstract:
In this study, bare polycaprolactone microspheres (PCL MPs) and methotrexate (MTX) loaded PCL microspheres (MTX-PCL MPs) have been developed by oil-in-water emulsion solvent evaporation method using hydroxypropyl methylcellulose (HPMC) as an emulsifier. Encapsulation efficiency and loading capacity of methotrexate were found to be 51.28%±0.52 and 2.8%±0.06 respectively. Environmental scanning electron microscopy showed the PCL MPs and MTX-PCL MPs to have a spherical shape and smooth surface morphology. The mean size of microspheres (23μm) was found within injectability criteria. High-Resolution X-ray diffraction of microspheres revealed that PCL retained its semi-crystalline nature after processing in microspheres, but the drug looses its crystallinity. Fourier transmittance infrared spectroscopy and thermogravimetry analysis of the microspheres indicated that no physicochemical modification occurred. In vitro, MTX release study from MTX-PCL MPs in phosphate buffer saline (pH7.4) showed controlled release profile and only 31% of MTX released in 306h. The microspheres in lyophilized form are physicochemically stable for 8months. Furthermore, L929 cells treated with microspheres showed cell viability >80%. The different concentrations of microspheres found hemocompatible and did not affect the biconcave shape of red blood cells (RBCs). The physiochemical and biological evaluation of microspheres suggests their further use for drug delivery application.
Insights
Polycaprolactone microspheres loaded with methotrexate were developed for drug delivery. These microspheres show controlled drug release, good stability, and biocompatibility, suggesting potential for pharmaceutical applications.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Polymer Chemistry
Background:
- Polycaprolactone (PCL) microspheres are a promising platform for controlled drug delivery.
- Methotrexate (MTX) is a widely used chemotherapeutic agent requiring effective delivery systems.
- Developing stable and biocompatible MTX-loaded microspheres is crucial for therapeutic efficacy.
Purpose of the Study:
- To develop and characterize polycaprolactone microspheres (PCL MPs) loaded with methotrexate (MTX).
- To evaluate the physicochemical properties, in vitro drug release, stability, and biocompatibility of MTX-PCL MPs.
- To assess the potential of these microspheres for future drug delivery applications.
Main Methods:
- Oil-in-water emulsion solvent evaporation method using hydroxypropyl methylcellulose (HPMC) as an emulsifier.
- Characterization using environmental scanning electron microscopy (ESEM), High-Resolution X-ray diffraction (HRXRD), Fourier transmittance infrared spectroscopy (FTIR), and thermogravimetry analysis (TGA).
- In vitro drug release studies in phosphate buffer saline (PBS, pH 7.4), stability testing, L929 cell viability assays, and hemocompatibility tests with red blood cells (RBCs).
Main Results:
- Methotrexate encapsulation efficiency of 51.28%±0.52 and loading capacity of 2.8%±0.06 were achieved.
- Microspheres exhibited spherical morphology with smooth surfaces and a mean size of 23μm, suitable for injection.
- PCL retained its semi-crystalline nature, while MTX lost crystallinity; no physicochemical modifications were observed. Controlled MTX release (31% in 306h) and good physicochemical stability for 8 months.
- High cell viability (>80%) and hemocompatibility were confirmed, with no adverse effects on RBCs.
Conclusions:
- Developed MTX-PCL MPs demonstrate favorable physicochemical properties and controlled drug release kinetics.
- The microspheres exhibit excellent stability and biocompatibility, indicating a low risk of adverse biological reactions.
- These findings support the potential of MTX-PCL MPs as a viable drug delivery system for therapeutic applications.
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