PVP Hydrogels containing Nanosilver for the treatment of venous ulcers

1. Gustavo H. C. Varca1, Maria J.A. de Oliveira1, Jorge G.S. Batista1, , Vinicius S. Carvalho1, Gabriela A. Dos Santos1, Talita R. Cardoso2, Albeliggia B. Vicentine2,Ademar B. Lugão1 varca@usp.br 1Instituto de Pesquisas Energéticas e Nucleares – IPEN-CNEN/SP, SP, Brazil; 2Instituto Tocantinense Presidente Antônio Carlos – ITPAC Porto Nacional, TO, Brazil. Research Approach Hydrogels comprise crosslinked polymeric matrices of renowned applications in distinct biotechnological areas, which may be synthesized by several techniques. In general and although very effective, many techniques required the need of monomers or solvents which require careful washing processes in order to be removed from the systems. On this aspect the synthesis of hydrogels developed by exposition to ionizing radiation offers advantages over the conventional methods, such as no need of monomers or toxic solvents, being also capable of sterilizing the product inside final packaging. In this work we report the loading and release of silver nanoparticles into radiation synthesized hydrogels to be applied as dressing for wound healing, from development stages to initial clinical evaluation in (Ethics Committee Reg TO 161/2013) patients with venous ulcers. Figure 1. PVP basedHydrogels containing nanosilver obtained by simultaneous crosslinking and sterilization induced by gamma radiation. PVP Hydrogels containing Nanosilver for the treatment of venous ulcers PVP Hydrogel & Nanosilver • Hydrogel Synthesis Clinical trial – The case of Venous Ulcers Simultaneous Polymer crosslinking & sterilization 1st day Hydrogel Formulation • Gamma Irradiation dose • (25 kGy) • Patient with 8.706 cm2 venous ulcer (7 years) • Dead tissue; • Dressings removal (every 6h) • Intense pain and odor • bleeding • 8% PVP • 1% PEG • 1.5% Agar • 22ppm Nanosilver* Polymer crosslinking & Sterilization *Commercially available nanosilver solution (22 ppm) from KHEMIA® • Mechanical Properties Figure 6. PatientVenous ulcer on the 1st day of treatment with the dressing. 5th day • Significantly reduced odor; • Reduced exudate formation; • Dressings removal (every 12h) • Reduced Sensitivity and pain Figure 2. Hydrogel handling & usage. PVP hydrogel containing nanosilver • WOUND DRESSING • Suitable Mechanical properties • No cell adherence • Antibacterial properties (nanosilver) PVP hydrogel Figure 7. PatientVenous ulcer during treatment (5thday). 10th day • Reduced odor • Dressings removal (every 24h) • No pain • No bleeding • Reduced venous ulcer size • Increase in revitalized tissue Figure 3. Mechanical Properties of the hydrogels. Swelling Properties & Nanosilver Release Figure 8. Venous ulcer during treatment (10th day). Exudate absorption Conclusions Figure 4. Swelling properties of the hydrogel - (a) lyophilized form (b) regular form. The membrane producedpresented suitable mechanical properties to be applied as wound dressings. The Patient ulcer treated with the dressings presented increased healing process and better aspects which were identified on the 5th day. On the 10th day, the lesions were significantly smaller, with reduced odor and no report of pain. Thus the initial trials indicated that such dressing may be effectively applied for the treatment of venous ulcers, being capable of significantly reducing pain, odor and exudate formation. Nanosilver release up to 48 hours Figure 5. Nanosilver Release Profile -ICP-MS. Gel Fraction Band gel PVP ± 69 % PVP / Ag+± 75% References Acknowledgments Oliveira, M.J.A.; Amato, V.S. ; Lugão, A.B. ; Parra, D.F. Radiat. Phys. chem. v. 81, p. 1471-1474, 2012. Ferraz, C.C; Varca, G.H.C.; Lopes, P.S.; Mathor, M.B.; Lugao. Radiat. Phys. chem. v. 94, p. 186-189, 2014.