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Semisolid Wet Sol-Gel Silica/Hydroxypropyl Methyl Cellulose Formulation for Slow Release of Serpin B3 Promotes Wound Healing In Vivo.
Albiero, Mattia; Fullin, Alice; Villano, Gianmarco; Biasiolo, Alessandra; Quarta, Santina; Bernardotto, Simone; Turato, Cristian; Ruvoletto, Mariagrazia; Fadini, Gian Paolo; Pontisso, Patrizia; Morpurgo, Margherita.
Afiliación
  • Albiero M; Department of Medicine, The University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
  • Fullin A; Veneto Institute of Molecular Medicine, Via G. Orus 2, 35129 Padova, Italy.
  • Villano G; Department of Pharmaceutical and Pharmacological Sciences, The University of Padova, Via Marzolo, 5, 35131 Padova, Italy.
  • Biasiolo A; Department of Surgical, Oncological and Gastroenterological Sciences-DISCOG, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
  • Quarta S; Department of Medicine, The University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
  • Bernardotto S; Department of Medicine, The University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
  • Turato C; Department of Pharmaceutical and Pharmacological Sciences, The University of Padova, Via Marzolo, 5, 35131 Padova, Italy.
  • Ruvoletto M; Department of Medicine, The University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
  • Fadini GP; Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy.
  • Pontisso P; Department of Medicine, The University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
  • Morpurgo M; Department of Medicine, The University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
Pharmaceutics ; 14(9)2022 Sep 14.
Article en En | MEDLINE | ID: mdl-36145692
Foot ulcerations are a disabling complication of diabetes and no treatment is currently available based on disease mechanisms. The protein serpin B3 (SB3) was identified as a positive biomarker of successful diabetic wound healing; therefore, its exogenous administration may promote healing. The topical administration of SB3 is challenging due to its protein nature. Physical entrapment in wet sol-gel silica can stabilize the protein's conformation and permit its sustained delivery. However, irreversible syneresis and poor viscoelastic properties hamper wet sol-gel silica application as a semisolid vehicle. To overcome these limits, a sol-gel silica/hydroxypropylmethylcellulose (HPMC) hydrogel blend was developed. SB3 entrapped in 8% SiO2 wet sol-gel silica preserved its structure, was stabilized against denaturation, and was slowly released for at least three days. Blending a silica gel with an HPMC-glycerol (metolose-G) hydrogel permitted spreadability without affecting the protein's release kinetics. When administered in vivo, SB3 in silica/metolose-G-but not in solution or in metolose-G alone-accelerated wound healing in SB3 knockout and diabetic mouse models. The results confirmed that SB3 is a new pharmacological option for the treatment of chronic ulcers, especially when formulated in a slow-releasing vehicle. Silica-metolose-G represents a novel type of semisolid dosage form which could also be applied for the formulation of other bioactive proteins.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceutics Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceutics Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza