Ciprofloxacin-lidocaine-based hydrogel: development, characterization, and in vivo evaluation in a second-degree burn model

被引:16
|
作者
Florencia Sanchez, Maria [1 ,2 ]
Andrea Breda, Susana [3 ]
Andres Soria, Elio [4 ,5 ]
Ignacio Tartara, Luis [1 ,2 ]
Hilario Manzo, Ruben [1 ,2 ]
Eugenia Olivera, Maria [1 ,2 ]
机构
[1] Univ Nacl Cordoba, Fac Ciencias Quim, CONICET, Unidad Invest & Desarrollo Tecnol Farmaceut UNITE, RA-5000 Cordoba, Argentina
[2] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Ciencias Farmaceut, RA-5000 Cordoba, Argentina
[3] Univ Nacl Cordoba, Hosp Nacl Clin, Fac Ciencias Med, Farm Cent, Cordoba, Argentina
[4] Univ Nacl Cordoba, CONICET, Inst Invest Ciencias Salud INICSA, Cordoba, Argentina
[5] Univ Nacl Cordoba, Fac Ciencias Med, Cordoba, Argentina
关键词
Polymeric drug delivery systems; Skin; Birefringence; Rheology; Aesthesiometric evaluation; Pain; SILVER SULFADIAZINE; CONTROLLED-RELEASE; EUDRAGIT E100; CARBOMER; HYDROCHLORIDE; FORMULATIONS; VITRO; SENSITIVITY; PROPOLIS; COLLAGEN;
D O I
10.1007/s13346-018-0523-7
中图分类号
TH7 [仪器、仪表];
学科分类号
0804 ; 080401 ; 081102 ;
摘要
The purpose of this work was to develop an effective carbomer hydrogel to be used to treat second-degree burns that combined ciprofloxacin and lidocaine (CbCipLid hydrogel). Its antibiotic and anesthetic efficacy and the physical and chemical properties of the CbCipLid hydrogel (release rate and kinetics, rheology, appearance, and drug content) were evaluated both before and after a sterilization cycle and also after 6 months of storage. For the in vivo studies, second-degree burns were developed in a rat model. Animals were divided into three groups: CbCipLid hydrogel, silver sulfadiazine cream (reference), and carbomer hydrogel (as control). The treatments were applied daily for 21 days, and the healing was monitored by macroscopic observation and histologic evaluation. The anesthetic effect was evaluated through the corneal touch threshold in a rabbit eye model. The CbCipLid hydrogel obtained is transparent and allows the loading of ciprofloxacin above its solubility at a neutral pH, with a rheology which is convenient for topical administration. Its physical and chemical properties remained unchanged after sterilization and for at least six additional months. Both ciprofloxacin and lidocaine are reversibly released from the CbCipLid hydrogel with a kinetics fitting the Higuchi model. The presence of a biologic-like fluid increased the rate of drug delivery through an ionic exchange mechanism. Treatment with the CbCipLid hydrogel decreased the wound-healing period, compared with the reference, and was associated with a greater number of fibroblasts and a faster rate of epithelialization and dermis reconstruction. These differences were assigned to the moist environment provided by the hydrogel and also to the presence of a therapeutic concentration of ciprofloxacin. Moreover, CbCipLid hydrogel provides an immediate anesthetic effect, which is significantly more intense than that of the reference. Based on these results, it is believed that the CbCipLid hydrogel could be a potential candidate in the prophylaxis/treatment of second-degree burns.
引用
收藏
页码:1000 / 1013
页数:14
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