Application of DoE approach in the development of mini-capsules, based on biopolymers and manuka honey polar fraction, as powder formulation for the treatment of skin ulcers

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• 作者：Marika Tenci^a ; Silvia Rossi^a ; ^{silvia.rossi@unipv.it} ; Maria Cristina Bonferoni^a ; Giuseppina Sandri^a ; Irene Mentori^a ; Cinzia Boselli^a ; Antonia Icaro Cornaglia^b ; Maria Daglia^a ; Anna Marchese^c ; Carla Caramella^a ; Franca Ferrari^a
• 关键词：DoE approach ; Pectin ; Chitosan glutamate ; Hyaluronic acid ; Wound healing
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：10 January 2017
• 年：2017
• 卷：516
• 期：1-2
• 页码：266-277
• 全文大小：2531 K
• 卷排序：516

文摘

The aim of the present work was the development of a powder formulation for the delivery of manuka honey (MH) bioactive components in the treatment of chronic skin ulcers. In particular pectin (PEC)/chitosan glutamate (CS)/hyaluronic acid (HA) mini-capsules were obtained by inverse ionotropic gelation in presence of calcium chloride and subsequently freeze-dried. Optimization of unloaded (blank) formulation was performed using DoE approach. In a screening phase, the following three factors were investigated at two levels: CS (0.5–1% w/w), PEC (0.5–1% w/w) and HA (0.3–0.5% w/w) concentrations. For the optimization phase a “central composite design” was used. The response variables considered were: particle size, buffer (PBS) absorption and mechanical resistance. In a previously work two different MH fractions were investigated, in particular MH fraction 1 (Fr1), rich in polar substances (sugars, methylglyoxal (MGO), dicarbonyl compounds, …), was able to enhance human fibroblasts in vitro proliferation. In the present work, the loading of MH Fr1 into mini-capsules of optimized composition determined a significant increase in cell proliferation in comparison with the unloaded ones. Loaded particles showed antimicrobial activity against Staphylococcus aureus and Streptococcus pyogenes; they were also able to improve wound healing in vivo on a rat wound model.