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Design of Methylprednisolone Biodegradable Microspheres Intended for Intra-articular Administration

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Abstract

This study aimed to design methyprednisolone (MP)-loaded poly(d,l lactide-co-glycolide) (PLGA) microspheres (MS) intended for intra-articular administration. MP was encapsulated in four different types of PLGA by using an S/O/W technique. The effects of β-irradiation at the dose of 25 kGy were evaluated on the chemical and physicochemical properties of MS and the drug release profiles. The S/O/W technique with hydroxypropylmethylcellulose (HPMC) as surfactant allowed obtaining MS in the tolerability size (7–50 µm) for intra-articular administration. The MP encapsulation efficiency ranged 56–60%. HPMC traces were evidenced in the loaded and placebo MS by attenuated total reflectance Fourier transform infrared spectroscopy. MS made of the capped PLGA DL5050 2M (MS 2M) and uncapped PLGA DL5050 3A (MS 3A) prolonged the release of MP over a 2- to 3-month period with a triphasic (burst release–dormant period–second release pulse) and biphasic release pattern, respectively. The β-irradiation did not significantly alter the morphology, chemical, and physicochemical properties of MS. The only variation was evidenced in the drug release for MS 2M in term of shorting of the dormant period. The minimal variations in the properties of irradiated PLGA MS, which are in disagreement with literature data, may be attributed to a radioprotecting effect exerted by HPMC.

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Acknowledgments

This research project was supported by the grant “Ricerca 2006 sui farmaci, sulle sostanze e sulle pratiche mediche utilizzabili a fini doping nelle attività sportive” from the Ministero della Salute (Rome, Italy). The authors would like to acknowledge Dr. Silvio Faragò of Centro Sperimentale della Seta (Milan, Italy) for the SEM investigations.

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Authors and Affiliations

  1. Istituto di Chimica Farmaceutica e Tossicologica “P. Pratesi”, Università degli Studi di Milano, Via Mangiagalli, 14, 20133, Milan, Italy

    Francesco Cilurzo, Francesca Selmin, Paola Minghetti & Luisa Montanari

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  1. Francesco Cilurzo
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  2. Francesca Selmin
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  3. Paola Minghetti
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  4. Luisa Montanari
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Correspondence to Francesco Cilurzo.

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Cilurzo, F., Selmin, F., Minghetti, P. et al. Design of Methylprednisolone Biodegradable Microspheres Intended for Intra-articular Administration. AAPS PharmSciTech 9, 1136–1142 (2008). https://doi.org/10.1208/s12249-008-9158-1

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