RESUMO
The purpose is to estimate the oxygen diffusion coefficient and the relaxation time of the cornea with respect to the oxygen tension at the cornea-tears interface. Both findings are discussed. From the experimental data provided by Bonanno et al., the oxygen tension measurements in vivo for human cornea-tears-contact lens (CL), the relaxation time of the cornea, and their oxygen diffusion coefficient were obtained by numerical calculation using the Monod-kinetic model. Our results, considering the relaxation time of the cornea, observe a different behavior. At the time less than 8 s, the oxygen diffusivity process is upper-diffusive, and for the relaxation time greater than 8 s, the oxygen diffusivity process is lower-diffusive. Both cases depend on the partial pressure of oxygen at the entrance of the cornea. The oxygen tension distribution in the cornea-tears interface is separated into two different zones: one for conventional hydrogels, which is located between 6 and 75 mmHg, with a relaxation time included between 8 and 19 s, and the other zone for silicone hydrogel CLs, which is located at high oxygen tension, between 95 and 140 mmHg, with a relaxation time in the interval of 1.5-8 s. It is found that in each zone, the diffusion coefficient varies linearly with the oxygen concentration, presenting a discontinuity in the transition of 8 s. This could be interpreted as an aerobic-to-anaerobic transition. We attribute this behavior to the coupling formalism between oxygen diffusion and biochemical reactions to produce adenosine triphosphate. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:14-21, 2020.
Assuntos
Lentes de Contato Hidrofílicas , Córnea/metabolismo , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Modelos Biológicos , Oxigênio/metabolismo , Córnea/patologia , Difusão , Humanos , LágrimasRESUMO
Although phenytoin is an antiepileptic drug used in the oral treatment of epilepsy, its off-label use as a cutaneous healing agent has been studied in recent years due to the frequent reports of gingival hyperplasia after oral administration. However, the cutaneous topical application of phenytoin should prevent percutaneous skin permeation. Therefore, the aim of this study was to evaluate the in vitro skin permeation/retention and in vivo effects of nanocapsules and nanoemulsions loaded with phenytoin and formulated as chitosan hydrogels on the healing process of cutaneous wounds in rats. The hydrogels had adequate pH values (4.9-5.6) for skin application, drug content of 0.025% (w/w), and non-Newtonian pseudoplastic rheological behaviour. Hydrogels containing nanocapsules and nanoemulsions enabled improved controlled release of phenytoin and adhesion to skin, compared with hydrogels containing non-encapsulated phenytoin. In vitro skin permeation studies showed that phenytoin permeation to the receptor compartment, and consequently the risk of systemic absorption, may be reduced by nanoencapsulation without any change in the in vivo performance of phenytoin in the wound healing process in rats.
Assuntos
Quitosana , Hidrogel de Polietilenoglicol-Dimetacrilato , Nanocápsulas , Fenitoína , Absorção Cutânea/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Administração Tópica , Animais , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacocinética , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Masculino , Nanocápsulas/química , Nanocápsulas/uso terapêutico , Fenitoína/química , Fenitoína/farmacocinética , Fenitoína/farmacologia , Ratos , Ratos Wistar , Suínos , Ferimentos e Lesões/metabolismoRESUMO
Objective of this study was to evaluate the efficacy of the autolytic debridement promoted by hydrogel with sodium alginate enriched with fatty acids and vitamins A and E in the healing of foot wounds in diabetic patients. A clinical study was conducted at an outpatient clinic of medical specialties. The sample comprised 8 patients supervised for a 3-month period, from April to July 2017, by means of a clinical history, photographic record, planimetry, and classification of the wound severity by the Pressure Ulcer Scale for Healing (PUSH) system. Of the 8 patients supervised, 1 dropped out and 7 were followed up for 12 weeks. Only 2 had complete wound healing, but all presented a reduction of the lesion area of approximately 22.2% and PUSH score of 9.8 to 6.6. This study found that hydrogel showed good results for the treatment of diabetic feet, reducing the area and overall PUSH score of the wounds.
Assuntos
Alginatos/farmacologia , Complicações do Diabetes/terapia , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Cicatrização/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Alginatos/uso terapêutico , Bandagens , Diabetes Mellitus/fisiopatologia , Feminino , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/uso terapêutico , Masculino , Pessoa de Meia-IdadeRESUMO
Chitosan (CH) is a biopolymer that exhibits a number of interesting properties such as anti-inflammatory and antibacterial activity and is also a promising platform for the incorporation of photosensitizing agents. This study aimed to evaluate the efficacy of antimicrobial activity of chitosan hydrogel formulation alone and in combination with the methylene blue (MB) associated with antimicrobial photodynamic therapy (aPDT) against planktonic and biofilm phase of Propionibacterium acnes. Suspensions were sensitized with 12.5, 25.0, 37.5, 50.0 µg/mL of MB for 10 min and biofilms to 75, 100 and 150 µg/mL for 30 min then exposed to red light (660 nm) at 90 J/cm² and 150 J/cm² respectively. After treatments, survival fractions were calculated by counting the number of colony-forming units. The lethal effect of aPDT associated with CH hydrogel in planktonic phase was achieved with 12.5 µg/mL MB and 1.9 log10 biofilm reduction using 75 µg/mL MB. Rheological studies showed that formulations exhibited pseudoplastic non-Newtonian behavior without thixotropy. Bioadhesion test evidenced that the formulations are highly adhesive to skin and the incorporation of MB did not influence the bioadhesive force of the formulations.
Assuntos
Anti-Infecciosos/química , Quitosana/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Propionibacterium acnes/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Quitosana/farmacologia , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Azul de Metileno/química , Fotoquimioterapia , Propionibacterium acnes/patogenicidade , ReologiaRESUMO
As úlceras neuropáticas ou pé diabético compreendem ulcerações que são definidas pela Organização Mundial de Saúde (OMS) como infecções destruições dos tecidos moles, que ocorrem concomitantemente com alterações neurológicas de diversos graus, devido à doença arterial periférica (DAP) localizada nos membros inferiores. O estudo objetivou avaliar a capacidade cicatrizante de uma formulação tópica contendo a fração proteolítica (P1G10) de látex de Vasconcellea cundinamarcensis, quando administrada em úlceras neuropáticas de pacientes diabéticos. Trata-se de um ensaio clínico, randomizado, controlado, duplo-mascarado. A população deste estudo foi composta por adultos (idade ≥ 18 anos), de ambos os sexos, usuárias de um serviço de referência em tratamento de feridas do município de Belo Horizonte Minas Gerais. A aplicação de fina camada da formulação sobre o leito da ferida, recobrindo toda a sua extensão, foi realizada em cada paciente, totalizando 48 aplicações. As feridas foram avaliadas por meio de medidas das suas dimensões: comprimento, largura, profundidade e área. O efeito da intervenção foi estimado pela incidência acumulativa de cicatrização (até 80 e 100% da ferida) usando o método de Kaplan-Meier. As técnicas estatísticas foram realizadas com o auxílio do programa Stata. A população estudada foi composta de 50 indivíduos. A taxa de incidência de cicatrização total em indivíduos tratados com a fração proteolítica P1G10 foi de 5,15/ 1000 pessoas-dia (IC 95% = 2,85 9,3). Pacientes que foram submetidos ao tratamento com P1G10 apresentaram uma taxa de incidência de cicatrização 2,95 (IC 95% = 1,0257- 8,51) vezes maior que os do grupo tratado com Hidrogel. Os resultados contribuem para ampliar o potencial de indicações terapêuticas das enzimas proteolítica de Vasconcelles Cundinamarcensis. Sugere-se a continuidade do ensaio clinico de fase III com estudo multicêntrico com maior número de participantes.
Neuropathic ulcers or diabetic foot ulcers are defined by the World Health Organization (WHO) as soft tissue infections and destruction, occurring concomitantly with neurological disorders of varying degrees due to peripheral arterial disease (PAD) located in lower members. The study aimed to evaluate the healing capacity of a topical formulation containing the proteolytic fraction (P1G10) of latex of Vasconcellea cundinamarcensis, when administered in neuropathic ulcers of diabetic patients. It is a double-masked, randomized, controlled, clinical trial. The population of this study was composed of adults (age ≥ 18 years) of both sexes, users of a referral service in the treatment of wounds in the city of Belo Horizonte - Minas Gerais. The application of a thin layer of the formulation over the wound bed, covering all its extension, was performed in each patient, totalizing 48 applications. The wounds were evaluated by means of measures of their dimensions: length, width, depth and area. The effect of the intervention was estimated by the cumulative incidence of healing (up to 80 and 100% of the wound) using the Kaplan-Meier method. Statistical techniques were performed with the help of the Stata program. The study population consisted of 50 individuals. The incidence rate of total healing in subjects treated with the proteolytic fraction P1G10 was 5.15 / 1000 person-days (95% CI = 2.85-9.3). Patients who underwent P1G10 treatment had an incidence rate of 2.95 (95% CI: 1.0257-8.51) greater than that of the group treated with Hydrogel. The results contribute to increase the potential of therapeutic indications of proteolytic enzymes of Vasconcelles Cundinamarcensis. We suggest the continuity of the phase III clinical trial with a multicenter study with a larger number of participants for its use in the this patholy.
Assuntos
Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Carica , Cicatrização , Peptídeo Hidrolases/uso terapêutico , Pé Diabético/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Inquéritos e QuestionáriosRESUMO
Development and optimization of a hydrogel with impregnated silver sulfadiazine was pursued, for antimicrobial topical applications. The selected hydrogel exhibited a homogeneous appearance, with whitish colloration and devoid of any fractures or cracks. The content in impregnated silver sulfadiazine was within established limits (1%, w/w) with a standard deviation of up to 1.28%. The hydrogel presented a good characteristic in relation to release of the active antimicrobial principle, verified through swelling tests and antimicrobial activity. The swelling tests indicated a higher increase in weight during the first 6 h of contact with a moist environment, with a maximum value of 266.00 ± 0.81, and with maintenance of the original shape of the hydrogel. The impregnated silver sulfadiazine presented antimicrobial activity, as expected, indicating a prolonged release of the drug. The infrared spectra of the hydrogel with impregnated silver sulfadiazine indicated that the drug did not engage in any bonds with the polymeric matrix, which otherwise could have reduced its antimicrobial activity. The mechanical resistance tests produced good results, indicating that the hydrogels may be utilized in different locations of the human body with skin lesions.
Assuntos
Antibacterianos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Sulfadiazina de Prata/química , Prata/química , Antibacterianos/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Prata/farmacologia , Sulfadiazina de Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacosRESUMO
PURPOSE: To evaluate the biocompatibility and local sensibility reaction to bacterial cellulose hydrogel (0.8%) implanted in subcutaneous tissue of rabbits. METHODS: Fifteen New Zeland rabbits were randomly allocated into three groups: T1, 7 days, T2, 21 days, and T3, 84 days. The new material was implanted in the subcutaneous tissue of the ear; on the scalp over the periosteum; and on the outer and inner surfaces of the thighs, in the aponeurosis of the muscle. At 7, 21 and 84 postoperative days, the material was collected for histological study. The clinical signs, inflammatory response, angiogenesis and fibrogenesis were variables used for analysis of the biocompatibility and biological reactivity to BCH. Analyses were performed with an AXIO(r) Imager. The statistical tests were performed using the GraphPad Prism 5.0 program(r) RESULTS: The intensity of the inflammatory infiltrate, considering the different cell types (PMN, LMN and GC), was statistically significant, with group T1 different from groups T2 and T3 (p = 0.0124 and p <0.0001, respectively) and T2 different from the T3 group (p = 0.0007). Fibrogenesis grade 1 was the most prevalent in groups T1 (55.4%) and T2 (44.6%). The formation of neovascularization in the group was identified in 84.4% of samples. CONCLUSION: Bacterial cellulose hydrogel (0.8%) is biocompatible, integrating with the subcutaneous tissue of rabbits and inducing tissue remodeling.
Assuntos
Bactérias/química , Materiais Biocompatíveis/farmacologia , Celulose/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Tela Subcutânea/efeitos dos fármacos , Animais , Masculino , Teste de Materiais , Coelhos , Distribuição Aleatória , Reprodutibilidade dos Testes , Tela Subcutânea/patologia , Fatores de TempoRESUMO
This study examined caprine follicular development in different concentrations of alginate matrix to determine the optimal conditions for culture. Caprine preantral follicles were cultured in a two-dimensional system (control) or a three-dimensional encapsulated system in 0.25%, 0.5%, or 1% alginate (ALG 0.25, ALG 0.5, and ALG 1, respectively). A higher percentage of morphologically normal follicles developed in ALG 0.5 and ALG 1 than in ALG 0.25 or the control (P < 0.05). The rate of antrum formation, however, was higher in ALG 0.25 than in ALG 0.5 and ALG 1 conditions (P < 0.05), but similar to the control. Follicles cultured in ALG 0.25 had higher growth rates and meiotic resumption than those cultured in ALG 0.5, ALG 1, or the control (P < 0.05). Moreover, follicles cultured in ALG 0.25 had higher levels of estradiol and progesterone than those cultured in ALG 0.5, ALG 1, or the control, as well as higher levels of CYP19A1 and HSD3B mRNA. In conclusion, a three-dimensional system that uses ALG 0.25 fosters the in vitro development of caprine preantral follicles and increases the rate of meiotic resumption.
Assuntos
Alginatos/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Folículo Ovariano/crescimento & desenvolvimento , 3-Hidroxiesteroide Desidrogenases/análise , 3-Hidroxiesteroide Desidrogenases/genética , 3-Hidroxiesteroide Desidrogenases/metabolismo , Alginatos/química , Animais , Aromatase/análise , Aromatase/genética , Aromatase/metabolismo , Técnicas de Cultura de Células , Feminino , Cabras , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Oócitos/efeitos dos fármacos , Oócitos/crescimento & desenvolvimento , Folículo Ovariano/efeitos dos fármacosRESUMO
Bromelina é um nome coletivo para enzimas proteolíticas encontradas no talo, fruto e folhas do abacaxi (Ananas comosus Merr). A bromelina possui propriedades anti-inflamatórias, de debridamento, entre outras. Para a produção da bromelina deve-se, preferencialmente, usar resíduos do abacaxi, visto que os produtos do fruto têm aplicação comercial. Este trabalho teve como objetivo a extração de bromelina a partir de cascas de abacaxi através de sistema de duas fases aquosas (SDFA), e sua aplicação em hidrogel polimérico. Foram realizados estudos de estabilidade da bromelina comercial, em que se observou maior estabilidade em pH 5,0 com menor perda da atividade relativa em todas as temperaturas estudadas (20, 30, 40 e 50°C). O estudo da extração da bromelina em SDFA formado por polietileno glicol (PEG) e ácido poliacrílico (PAA) (com auxílio da análise de variância de parâmetros como rendimento, fator de purificação e coeficiente de partição) proporcionou rendimento de 335% e fator de purificação de 25,8. Os hidrogéis poliméricos à base de PEG estudados apresentaram-se flexíveis, com pouca elasticidade e taxa de absorção superior a 1000%. Hidrogel carreado de bromelina pelo método de turgescência proporcionou a maior liberação da enzima, assim como a maior atividade (80% da bromelina liberada em 24 h e 278 ± 89 U/mL)
Bromelain is a collective name for the proteolytic enzymes found in the stem, fruit and leaves of pineapple (Ananas comosus Merr.). Bromelain possesses anti-inflammatory properties, debridement, among others. For bromelain production one should preferably use the waste materials, whereas pineapple fruit products have commercial application. This study aimed to extract bromelain from pineapple peels using aqueous two-phase system (ATPS), and its application in polymeric hydrogels. Stability studies of commercial bromelain were performed, which found greater stability at pH 5.0 with minor loss of relative activity at all temperatures studied. The study of bromelain extraction in ATPS composed by polyethylene glycol (PEG) and poly acrylic acid (PAA) (with assistance of variance analysis of parameters such as yield, purification factor and partition coefficient) showed yield 335% and purification factor of 25.8. The PEG-based hydrogels studied presented flexibility, low elasticity and swelling ratio higher than 1000%. Hydrogel containing bromelain, loading by embedding (solvent sorption) method, yielded the highest enzyme release, as well as the highest activity (80% bromelain released over 24 h and 278 ± 89 U / mL)
Assuntos
Bromelaínas/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Ananas/anatomia & histologia , Biotecnologia , Tecnologia FarmacêuticaRESUMO
We aimed to develop an alginate hydrogel (AH) modified with nano-/microfibers of titanium dioxide (nfTD) and hydroxyapatite (nfHY) and evaluated its biological and chemical properties. Nano-/microfibers of nfTD and nfHY were combined with AH, and its chemical properties were evaluated by FTIR spectroscopy, X-ray diffraction, energy dispersive X-Ray analysis, and the cytocompatibility by the WST-1 assay. The results demonstrate that the association of nfTD and nfHY nano-/microfibers to AH did not modified the chemical characteristics of the scaffold and that the association was not cytotoxic. In the first 3 h of culture with NIH/3T3 cells nfHY AH scaffolds showed a slight increase in cell viability when compared to AH alone or associated with nfTD. However, an increase in cell viability was observed in 24 h when nfTD was associated with AH scaffold. In conclusion our study demonstrates that the combination of nfHY and nfTD nano-/microfibers in AH scaffold maintains the chemical characteristics of alginate and that this association is cytocompatible. Additionally the combination of nfHY with AH favored cell viability in a short term, and the addition of nfTD increased cell viability in a long term.