title: 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.
abstract: 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.
authors: Department of Drug Science, University of Pavia, Pavia, Italy.
authors: Marika
authors: M
authors: Tenci
authors: Department of Drug Science, University of Pavia, Pavia, Italy. Electronic address: silvia.rossi@unipv.it.
authors: Silvia
authors: S
authors: Rossi
authors: Department of Drug Science, University of Pavia, Pavia, Italy.
authors: Maria Cristina
authors: MC
authors: Bonferoni
authors: Department of Drug Science, University of Pavia, Pavia, Italy.
authors: Giuseppina
authors: G
authors: Sandri
authors: Department of Drug Science, University of Pavia, Pavia, Italy.
authors: Irene
authors: I
authors: Mentori
authors: Department of Drug Science, University of Pavia, Pavia, Italy.
authors: Cinzia
authors: C
authors: Boselli
authors: Department of Public Health, Experimental and Forensic Medicine, Histology and Embryology Unit, University of Pavia, Pavia, Italy.
authors: Antonia Icaro
authors: AI
authors: Cornaglia
authors: Department of Drug Science, University of Pavia, Pavia, Italy.
authors: Maria
authors: M
authors: Daglia
authors: Microbiology Unit, IRCCS-San Martino-IST, DISC, University of Genoa, Italy.
authors: Anna
authors: A
authors: Marchese
authors: Department of Drug Science, University of Pavia, Pavia, Italy.
authors: Carla
authors: C
authors: Caramella
authors: Department of Drug Science, University of Pavia, Pavia, Italy.
authors: Franca
authors: F
authors: Ferrari
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D001704:Biopolymers / Q000737:chemistry*; D002214:Capsules; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000737:chemistry; D006722:Honey; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D008297:Male; D010368:Pectins / Q000737:chemistry; D011208:Powders; D051381:Rats; D017208:Rats, Wistar; D012883:Skin Ulcer / Q000188:drug therapy* / Q000473:pathology; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D013290:Streptococcal Infections / Q000188:drug therapy; D013297:Streptococcus pyogenes / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001704:Biopolymers; D002214:Capsules; D011208:Powders; D018698:Glutamic Acid; D010368:Pectins; D006820:Hyaluronic Acid; D048271:Chitosan
keywords: Chitosan glutamate; DoE approach; Hyaluronic acid; Pectin; Wound healing