Design of methylprednisolone biodegradable microspheres intended for intra-articular administration

Francesco Cilurzo1, Francesca Selmin, Paola Minghetti

  • 1Istituto di Chimica Farmaceutica e Tossicologica "P. Pratesi", Università degli Studi di Milano, Via Mangiagalli 14, 20133 Milan, Italy. francesco.cilurzo@unimi.it

AAPS Pharmscitech
|November 15, 2008
PubMed

Insights

This study developed methyprednisolone (MP)-loaded poly(D,L lactide-co-glycolide) (PLGA) microspheres for joint injections. Beta-irradiation minimally affected microsphere properties, with HPMC potentially offering radioprotection.

Area of Science:

  • Biomaterials Science
  • Drug Delivery Systems
  • Polymer Chemistry

Background:

  • Intra-articular administration requires specialized drug delivery systems.
  • Poly(D,L lactide-co-glycolide) (PLGA) microspheres are suitable for sustained drug release.
  • Methyprednisolone (MP) is a corticosteroid used for inflammatory conditions.

Purpose of the Study:

  • To design and characterize methyprednisolone (MP)-loaded poly(D,L lactide-co-glycolide) (PLGA) microspheres for intra-articular administration.
  • To evaluate the impact of beta-irradiation on the properties and drug release of these microspheres.

Main Methods:

  • Microspheres were prepared using the oil-in-water (O/W) emulsion technique with hydroxypropylmethylcellulose (HPMC) as a surfactant.
  • Four types of PLGA with varying properties were used for encapsulation.
  • Beta-irradiation (25 kGy) was applied to assess its effects on microsphere characteristics and drug release profiles.
  • Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was used to confirm HPMC presence.

Main Results:

  • The O/W technique with HPMC yielded microspheres of appropriate size (7-50 microm) for intra-articular injection.
  • Encapsulation efficiency for MP ranged from 56-60%.
  • Microspheres made from capped (MS 2M) and uncapped (MS 3A) PLGA demonstrated prolonged MP release over 2-3 months, exhibiting triphasic and biphasic patterns, respectively.
  • Beta-irradiation showed minimal impact on microsphere morphology and physicochemical properties, with a slight reduction in the dormant release period for MS 2M.

Conclusions:

  • PLGA microspheres loaded with methyprednisolone are feasible for intra-articular delivery, providing sustained release over several months.
  • Beta-irradiation at 25 kGy does not significantly alter the critical properties of these PLGA microspheres.
  • The presence of HPMC may confer a radioprotective effect on the PLGA microspheres, explaining the minimal changes observed post-irradiation, which contrasts with existing literature.

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