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.

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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