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

作者：Tenci Marika; Rossi Silvia^*; Bonferoni Maria Cristina; Sandri Giuseppina; Mentori Irene; Boselli Cinzia; Cornaglia Antonia Icaro; Daglia Maria; Marchese Anna; Caramella Carla; Ferrari Franca

来源：International Journal of Pharmaceutics, 2017, 516(1-2): 266-277.

DOI：10.1016/j.ijpharm.2016.10.050

• DoE approach
• Pectin
• Chitosan glutamate
• Hyaluronic acid
• Wound healing

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.

• 出版日期2017-1-10