RESUMEN
Abstract Hydrogels are used for wound treatment, as they may contain one or more active components and protect the wound bed. Papain is one of the active substances that have been used with this purpose, alongside urea. In this paper, carboxypolymethylene hydrogels containing papain (2% and 10% concentrations) and urea (5% concentration) were produced. Physical-chemical stability was performed at 0, 7, 15 and 30 days at 2-8ºC, 25ºC and 40ºC, as well as the rheological aspects and proteolytic activity of papain by gel electrophoresis. Clinical efficacy of the formulations in patients with lower limb ulcers was also evaluated in a prospective, single-center, randomized, double-blind and comparative clinical trial. The results showed 7-day stability for the formulations under 25ºC, in addition to approximately 100% and 15% of protein activity for 10% and 2% papain hydrogel, respectively. The rheological profile was non-Newtonian for the 10% papain hydrogel tested. There were no significant differences regarding the mean time for healing of the lesions, although 10% papain presented a better approach to be used in all types of tissue present in the wound bed.
Asunto(s)
Urea/efectos adversos , Cicatrización de Heridas/efectos de los fármacos , Papaína/efectos adversos , Hidrogeles/análisis , Heridas y Lesiones/clasificación , Electroforesis/instrumentaciónRESUMEN
Nanotechnology, when applied to PDT's, allows the encapsulation of ZnPc in nanocarriers, producing thus nanoemulsions that permit the use of ZnPc as photosensitizers. The Enterococcus faecalis and methicillin-resistant Staphylococcus aureus (MRSA) are microorganisms present in biofilms which can cause resistant endodontic infections. The objective of this work is the development and characterization of clove essential oil nanoemulsions containing ZnPc. The formulations were developed according to factorial experimental planning and characterized by the determination of the mean drop size, Polydispersity Index (PdI), content, organoleptic characteristics, stability, morphology, cytotoxicity in the dark and evaluation of the photobiological activity. The experimental planning was able to indicate the maximum amount of ZnPc that could be encapsulated in the nanoemulsion while maintaining droplet size <50 nm and PdI < 0.2. The surface plots for the response variables indicated a robust region for the combination of Pluronic® F-127 and clove oil factors. The result of this study was the choice of the nanoemulsion containing ZnPc solution at 5%, clove oil at 5%, Pluronic® F-127 at 10% and will be codified as ZnPc-NE. The nanoemulsion presented a mean diameter of 30.52 nm, PDI < 0.2 and a concentration of 17.5 µg/mL, as well as stability at room temperature for 180 days. TEM showed that the drops are spherical with nanometric size, which corroborates the results of dynamic light scattering. Concerning the photobiological activity, the ZnPc-NE exhibited MIC 1.09 µg/mL for Enterococcus faecalis and 0.065 µg/mL for MRSA (Methicillin-resistant Staphylococcus aureus). ZnPc-NE showed higher photobiological activity than free ZnPc. Besides, cytotoxicity studies showed that blank-NE (nanoemulsions without PS) showed good antimicrobial activity. Thus, clove oil nanoemulsion is an excellent nanocarrier to promote the photobiological activity of the ZnPc against pathogenic microorganisms.
Asunto(s)
Antiinfecciosos/química , Emulsiones/química , Indoles/química , Nanocápsulas/química , Compuestos Organometálicos/química , Fármacos Fotosensibilizantes/química , Administración Oral , Antiinfecciosos/farmacología , Supervivencia Celular/efectos de los fármacos , Aceite de Clavo/química , Composición de Medicamentos , Enterococcus faecalis/efectos de los fármacos , Humanos , Indoles/farmacología , Isoindoles , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Compuestos Organometálicos/farmacología , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Poloxámero/química , Compuestos de ZincRESUMEN
Oral therapy with 8-methoxypsoralen (8-MOP) may cause major side effects, whereas the topical treatment might not be much effective due to the low penetration induced by typical formulations. Therefore, the objectives of this work are the development and characterization of a nanoemulsion (NE) containing 8-MOP together with an ex vivo permeation study, monitored by a validated HPLC-Fluo method, to determine the amount of drug retained in viable skin (epidermis (E) and dermis (D)) and in stratum corneum (SC). The optimized conditions for NE formulation were achieved by full factorial designs (25 and 32): 60â¯s and 60% of ultrasound time and potency, respectively; 10â¯mL of final volume; 2% v/v of oil phase (clove essential oil); and 10% m/v of Poloxamer 407. The NE showed mean droplet diameter of 24.98⯱â¯0.49â¯nm, polydispersity index (PDI) of 0.091⯱â¯0.23, pH values of 6.54⯱â¯0.06, refractive index of 1.3525⯱â¯0.0001 and apparent viscosity of 51.15⯱â¯3.66â¯mPa at 20⯰C. Droplets with nanospherical diameters were also observed by transmission electron microscopy (TEM). Ex vivo permeation study showed that 8.5% of the applied 8-MOP dose permeated through the biological membranes, with flux (J) of 1.35⯵gâ¯cm-2â¯h-1. The drug retention in Eâ¯+â¯D and in SC was 10.15⯱â¯1.36 and 1.95⯱â¯0.71⯵gâ¯cm-2, respectively. Retention in viable skin induced by the NE was almost two-fold higher than a compounded cream (5.04⯱â¯0.30⯵gâ¯cm-2). These results suggested that the developed NE is a promising alternative for 8-MOP topical therapy when compared to commercial formulations.