Locust bean gum hydrogels are bioadhesive and improve indole-3-carbinol cutaneous permeation: influence of the polysaccharide concentration

Abstract The locust bean gum (LBG) is a polysaccharide with thickening, stabilizing and gelling properties and it has been used in the preparation of pharmaceutical formulations. Hydrogels (HGs) are obtained from natural or synthetic materials that present interesting properties for skin application. This study aimed to develop HGs from LBG using indole-3-carbinol (I3C) as an asset model for cutaneous application. HGs were prepared by dispersing LBG (2%, 3% and 4% w/v) directly in cold water. The formulations showed content close to 0.5 mg/g (HPLC) and pH ranging from 7.25 to 7.41 (potentiometry). The spreadability factor (parallel plate method) was inversely proportional to LBG concentration. The rheological evaluation (rotational viscometer) demonstrated a non-Newtonian pseudoplastic flow behavior (Ostwald De Weale model), which is interesting for cutaneous application. The HET-CAM evaluation showed the non-irritating characteristic of the formulations. The bioadhesive potential demonstrated bioadhesion in a concentration-dependent manner. Permeation in human skin using Franz cells showed that the highest LBG concentration improved the skin distribution profile with greater I3C amounts in the viable skin layers. The present study demonstrated the feasibility of preparing HGs with LBG and the formulation with the highest polymer concentration was the most promising to transport active ingredients through the skin.

Development and clinical application of hydrogel formulations containing papain and urea for wound healing

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.

Development and Evaluation of a Hydrogel containing Momordica cochinchinensis Spreng Extract for Topical Applications

Abstract The purpose of this research was to develop a hydrogel containing the extract of Gac fruit (Momordica cochinchinensis Spreng) with appropriate physicochemical properties and good dermatological efficacy. The Gac aril fruit was extracted by maceration in dichloromethane, and its antioxidant activity was determined through a DPPH assay. The very low water-solubility of the Gac extract is responsible for its incompatibility with the hydrogel. To overcome this drawback, LabrafacTM PG and Tween 60 were used to develop the hydrogel due to their potent potential for solubilizing the Gac extract. The prepared hydrogels displayed good physical properties, a homogenous orange gel, appropriate pH, and viscosity. After storage in an accelerated condition for six months, the hydrogels of the Gac extract had physical stability and high remaining amounts of beta-carotene and lycopene within the range of 90.25 - 94.61%. The skin efficacy of hydrogel containing the Gac fruit extract was found using 14 healthy female volunteers over a 30-day period of daily application. Topical application of the hydrogel containing the Gac fruit extract, which contains antioxidants, significantly moisturizes the skin and enhanced its elasticity (p ≤ 0.05; ANOVA). This makes it suitable for use as a skin care product

Synthesis and characterization of chitosan-PVA hydrogel containing PEGylated recombinant epidermal growth factor on cell culture for wound healing substitute

Abstract The aim of the current study was to assess the physicochemical characteristics and wound healing activity of chitosan-polyvinyl alcohol (PVA) crosslinked hydrogel containing recombinant human epidermal growth factor (rh-EGF) or recombinant mouse epidermal growth factor (rm-EGF). The hydrogels were prepared and analyses were made of the morphological properties, viscosity, water absorption capacity, mechanical and bio-adhesive properties. The viscosity of the formulations varied between 14.400 - 48.500 cPs, with the greatest viscosity values determined in K2 formulation. F2 formulation showed the highest water absorption capacity. According to the studies of the mechanical properties, H2 formulation (0.153±0.018 N.mm) showed the greatest adhesiveness and E2 (0.245±0.001 mj/cm2) formulation, the highest bio-adhesion values. Hydrogels were cytocompatible considering in vitro cell viability values of over 76% on human keratinocyte cells (HaCaT, CVCL-0038) and of over 84% on human fibroblast cells (NIH 3T3, CRL-1658) used as a model cell line. According to the BrdU cell proliferation results, B1 (197.82±2.48%) formulation showed the greatest NIH 3T3 and C1 (167.43±5.89%) formulation exhibited the highest HaCaT cell proliferation ability. In addition, the scratch closure assay was performed to assess the wound healing efficiency of formulation and the results obtained in the study showed that F2 formulation including PEGylated rh-EGF had a highly effective role.

Development and Characterization of a Hydrogel Containing Silver Sulfadiazine for Antimicrobial Topical Applications. Part II: Stability, Cytotoxicity and Silver Release Patterns

Abstract Hydrogels are interesting for use in the treatment of topical wounds due to their virtually zero toxicity, and capacity for extended release of pharmaceuticals. Silver sulfadiazine (SSDZ) is the drug of choice in the treatment of skin burns. The aim of the study was to determine cytotoxicity, antimicrobial activity and stability of a PVA hydrogel with integrated silver sulfadiazine. SSDZ-hydrogels were prepared using 10% (w/w) PVA (either 89% or 99% hydrolyzed) and 1% (w/w) silver sulfadiazine. Cellular viability was assessed via MTS assays, antimicrobial activity via disk-diffusion and accelerated stability tests were carried out with analysis at 0, 30, 60, 90 and 180 days of storage at 40 ± 2 °C and a relative humidity of 75 ± 5%. The parameters evaluated included organoleptic characteristics, moisture, swelling ability, mechanical strength, FTIR, XRD, TGA and DSC, and silver release patterns via XRD and potentiometry. Cell viability tests indicated some cytotoxicity, although within acceptable levels. After 90 days of storage, SSDZ hydrogel samples exhibited a brown coloration, probably due to the formation of Ag or Ag2O nanoparticles. The SSDZ-loaded hydrogels suffered visual and physical changes; however, these changes did not compromise its use as occlusive wound dressings or its antimicrobial properties.

Safe-by-design development of a topical patch for drug delivery

Few topical products have been developed specifically to treat acute and chronic arthritis and inflammation, using non-steroidal anti-inflammatory drugs (NSAIDs). The lack of dosing accuracy commonly found in locally applied semisolid products for cutaneous use is a critical issue that leads to treatment failure. The aim of the present work is to develop a differentiated and innovative topical patch based on a monolithic hydrogel for ibuprofen skin delivery, in order to provide a safer and accurate way of drug administration along with improved treatment compliance. Topical patches based on hydroxypropylmethylcellulose (HPMC) were optimized in composition, in terms of enhancer and adhesive, supported on a systematic assessment of in vitro release and permeation behavior and adhesion properties. Several mathematical models were used to scrutinize the release mechanisms from the patches. In vitro release kinetics was shown to be mainly driven by diffusion. However, other mechanisms seemed to be also present, supporting the feasibility of using patches for sustained drug delivery. PEG 200 provided the best permeation rate, with a permeation enhancement ratio of ca. 3 times higher, than the commercial reference. The addition of Eudragit L30D 55 to the formulation led to the best adhesion profile, thus achieving a successful development based on a safe-by-design concept.

Appraisal of acute oral toxicity of glucuronoxylan hydrogel from Mimosa pudica seeds

Glucuronoxylan hydrogel (GXH) isolated from M. pudica seeds was assessed for acute toxicology in albino mice that were alienated into four groups. Three groups, i.e., II, III and IV received GXH at a dose of 1, 2 and 5 g/kg, respectively while group I was retained untreated and provided routine diet. After administering GXH, mice were examined for vomiting, diarrhea, allergy and tremors for 8 h. All animals were carefully observed for food and water consumption at 1, 2, 3, 7 and 14 day after administering GXH. At the end of studies, blood samples were drawn for investigation of hematological and biochemical parameters. All animals were sacrificed, relative body weight of vital organs was calculated and their histopathology was studied. It was concluded that there was insignificant difference in body weight, behavioral pattern, food and water intake among treated and control groups. Haematology and biochemistry of blood samples from all groups were found analogous. Histopathological evaluation of vital body organs exhibited no lesions in all groups. Ocular, cardiac and dermal safety of GXH was also established on albino rabbits.

Avaliação da peroxidação lipídica no plasma de ratos submetidos à lesão tecidual e tratados com hidrogel de poliamido de mandioca / Evaluación de la peroxidación de lípidos en plasma de ratas sometidas a lesión tisular y tratadas con hidrogel de poliamida de yuca / Evaluación de la peroxidación de lípidos en plasma de ratas sometidas a lesión tisular y tratadas con hidrogel de poliamida de yuca

As espécies reativas ao oxigênio (EROS) são produzidas como mecanismo de defesa celular, participando dos processos de cicatrização celular. Entretanto, altos níveis de EROS podem causar danos como a peroxidação lipídica (PL). O presente estudo teve como objetivo, verificar os níveis de PL por meio da determinação das substâncias reativas ao ácido tiobarbitúrico (TBARS) no plasma de ratos com lesão tecidual induzida. Foram utilizados 32 ratos machos, Rattus norvegicus albinus da linhagem Wistar, os quais foram pesados e da média ± 10% do peso foram distribuídos em quatro grupos: A ­ controle negativo; B - Vetaglós®; C ­ hidrogel de poliamido de mandioca+ Vetaglós®; D ­ Hidrogel de poliamido de mandioca. Após 21 dias, todos os animais foram anestesiados com isoflurano e foi feita a coleta de sangue por punção cardíaca, e os plasmas foram obtidos após centrifugação, na sequência por superdosagem do anestésico foi realizada a eutanásia. Os níveis de PL nos plasmas dos ratos foram determinados pelo método do TBARS. Não houve diferença significativa entre os grupos em relação à PL, indicando um equilíbrio entre as defesas antioxidantes celulares e os níveis de EROS produzidos durante o processo de cicatrização celular. Essa ausência nos diferentes grupos experimentais, em relação à PL, deixa claro a importância de se contemplar estudos de parâmetros de bioindicadores de estresse oxidativo em protocolos experimentais.

Reactive oxygen species (ROS) are produced as a cellular defense mechanism, participating in the processes of cellular healing. However, high levels of ROS can cause damages such as lipid peroxidation (LPO). This study aimed to verify the levels of LPO through the determination of reactive substances to thiobarbituric acid (TBARS) in rat plasma with induced tissue injury. A total of 32 Rattus norvegicus albinus Wistar were used, with a mean weight ± 10%. They were divided into four groups: A ­ negative control; B - Vetaglós®; C - Polyamide cassava; D - Polyamide cassava + Vetaglós®. After 21 days, all animals were anesthetized with isoflurane and blood was collected by cardiac puncture. Plasma was obtained after centrifugation. Euthanasia was performed with administration of an overdose of inhalational anesthetic previously used. The LPO levels in rat plasma were determined using the TBARS method. There was no significant difference between the groups in relation to LPO, indicating a balance between antioxidant defenses and cellular levels of ROS produced during the cellular healing process. This absence in the different experimental groups in relation to LPO emphasizes the importance of further studies related to the bio-indicator parameters for oxidative stress in experimental protocols.

Las especies reactivas al oxígeno (EROS) se producen como mecanismo de defensa celular, que participan en los procesos de curación celulares. Sin embargo, los altos niveles de EROS pueden causar daños como la peroxidación lipídica (PL). Este estudio tuvo como objetivo verificar los niveles de peroxidación lipídica por sustancias reactivas al ácido tiobarbitúrico (TBARS) en el plasma de ratas con lesión tisular inducida. Se han utilizado 32 ratas machos, Rattus norvegicus albinus de linaje Wistar, que se pesaron y la media ± 10% en peso, y se dividieron en cuatro grupos: A ­ control negativo; B - Vetaglós®; C ­ hidrogel de poliamida de yuca + Vetaglós®; D ­ Hidrogel de poliamida de yuca. Después de 21 días, todos los animales fueron anestesiados con isoflurano y se hizo la extracción de sangre por punción cardiaca, y se obtuvieron los plasmas después de la centrifugación, enseguida con sobredosis de anestésico se realizó la eutanasia. Los niveles de PL en los plasmas de las ratas se determinaron por el método de TBARS. No hubo diferencia significativa entre los grupos en relación a la peroxidación lipídica, lo que indica un equilibrio entre las defensas antioxidantes celulares y los niveles de EROS producidos durante el proceso de curación celular. Esa ausencia en los diferentes grupos experimentales, en relación a la PL, pone de manifiesto la importancia de contemplarse estudios de parámetros de bioindicadores de estrés oxidativo en los protocolos experimentales.

Curativo imediato com hidrogel à base de água, óleo de melaleuca alternifolia e emulsificantes após queimaduras / Burns immediate dressing with water, oil of melaleuca and emulsificants

Introdução: O Burnshield® (United Medical, Brasil) é uma opção de curativo imediato paraqueimaduras que visa à hidratação e ao resfriamento da ferida, sendo objetivo deste trabalhoavaliar sua eficácia. Método: Estudo experimental controlado cego, com 36 ratos Wistardivididos em 3 grupos de 12: (A) tratados com Burnshield®, (B) tratados com água correntepor 15 minutos e (C) não tratados. Metade dos animais de cada grupo foi sacrificada com 30minutos após queimadura, e a outra metade com 24 horas de evolução. O critério de avaliaçãofoi a maior profundidade de lesão encontrada em cada animal. Resultados: O grupo Capresentou as queimaduras mais profundas em relação aos demais, com 30 minutos e 24 horas.Não houve diferença entre os grupos A e B com 30 minutos, porém houve melhor resultadosignificativo no grupo A nas 24 horas de evolução. Conclusão: O Burnshield® mostroueficácia comparável à água corrente no tratamento inicial de queimaduras, com melhoresresultados depois de 24 horas de evolução. Apresenta como maior vantagem a praticidade,podendo ser usado enquanto o paciente é deslocado até o centro de tratamento especializado.

Introduction: Burnshield® (United Medical, Brazil) is an option of immediate dressing forburns aimed at hydrating and cooling the wound. Purpose: Investigate, histopathologically,the efficacy of Burnshield® as initial treatment for thermal burns. Method: Blind controlledexperimental study, with 36 Wistar rats divided into 3 groups of 12 rats: (A) treated withBurnshield®, (B) treated with running water for 15 minutes and (C) not treated. Half of theanimals of each group were sacrificed 30 minutes after the burn and the other half, within 24of evolution. The assessment criterion was the extension of lesion found in each animal.Results: Group C showed the deepest burns compared to the others, within 30 minutes and24 hours. There was no difference between groups A and B within 30 minutes; however, groupA showed better and significant results within 24 hours of evolution. Conclusion:Burnshield® showed efficacy comparable to running water at the initial treatment of burns,with better results after 24 hours of evolution. Its main advantage is its practicality, once itcan be used while the patient is carried up to the center of specialized treatment.

Hidrogéis de PVP e blendas de PVP/polianidridos como potenciais curativos para feridas crônicas / PVP hydrogels and PVP/Polyanhydride blends as potential materials for chronic wounds dressings

Hidrogéis compreendem uma importante classe de materiais poliméricos adequados à aplicação como curativos de feridas e queimaduras. A estrutura tridimensional hidrofílica dos hidrogéis permite que estes mantenham a umidade ideal no leito das feridas, absorvam o exsudato e não causem danos ao novo tecido durante as trocas dos curativos. No caso dos hidrogéis, essas trocas podem ser menos frequentes. Além disso, curativos que auxiliem na remoção de tecidos necrosados e ainda sejam capazes de oferecer tratamentos extras que acelerem o processo de cicatrização são desejáveis. Este trabalho apresenta a produção de materiais à base de hidrogel capazes de auxiliar neste processo de diferentes maneiras. Primeiramente, são apresentados hidrogéis formados a partir de nanofibras de poli(N-vinil-2-pirrolidona) (PVP) produzidas por eletrofiação, seguido da reticulação através da utilização de radiação UV-C ou reação de Fenton. A utilização da eletrofiação como técnica auxiliar na formação dos hidrogéis permitiu o controle da porosidade através da formação de fibras de diferentes diâmetros. A evidência de tal propriedade foi constatada através da produção de materiais que apresentam diferentes perfis de liberação da proteína modelo albumina de soro bovino (BSA). O hidrogel de PVP nanoestruturado foi capaz de liberar e manter a atividade da colagenase, uma importante enzima aplicada no tratamento de feridas via desbridamento enzimático, durante as 48 horas em que foi avaliado. Além disso, hidrogéis bactericidas nanoestruturados foram produzidos a partir de nanocompósitos de PVP e nanopartículas de prata (AgNP) produzidos por eletrofiação. Esses hidrogéis apresentaram propriedades térmicas semelhantes aos hidrogéis sem AgNP, diminuindo, contudo, a sua capacidade de intumescimento. Esses hidrogéis mostraram-se ativos contra bactérias gram-positivas e gram-negativas a partir de 100 ppm de AgNPs. Adicionalmente, foi estudada a formação de um hidrogel modelo composto PVP/AgNP/Imidazol, almejando-se a produção de um material bactericida-fungicida a base de hidrogel. Este hidrogel apresentou atividade conta três espécies de Candida a partir de 500 ppm de imidazol no material. Embora exista a formação de um complexo estável entre AgNP e Imidazol, cálculos teóricos e a constatação da atividade fungicida corroboram com o fato de que derivados imidazólicos podem ser liberados a partir deste hidrogel híbrido. A produção de hidrogéis físicos compostos por blendas de PVP/Polianidridos sintetizados a partir de derivados de hidroxicinamatos e ácido salicílico, capazes de liberar moléculas de interesse biológico quando parcialmente degradados hidroliticamente, também é descrita neste trabalho. Os resultados indicam que interações hidrofóbicas entre a PVP e os polianidridos sintetizados podem ser responsáveis pela formação dos hidrogéis físicos e pela miscibilidade das blendas produzidas. Os hidrogéis físicos de PVP/Polianidridos foram obtidos na forma de filmes por evaporação do solvente. Micro- e nanofibras também foram obtidas por eletrofiação. Desta maneira, o presente trabalho contribui com o desenvolvimento de uma geração de curativos multifuncionais aplicados no tratamento de feridas crônicas e queimaduras

Hydrogels comprise an important class of polymeric materials that finds application as wound and burn dressings. The hydrophilic three-dimensional structure of hydrogels helps to provide the ideal humidity at the wound bed, to remove exsudates and to prevent damages to the new tissue during dressing substitution. Furthermore, these wound dressings are able to remove necrotic tissues and, therefore, capable to offer extra treatments that would benefit the healing processes. This work describes the production of hydrogel based materials that are able to act in wound healing by different ways. First, it is presented hydrogels composed of poly(N-vinyl-2-pyrrolidone) (PVP) nanofibers produced by electrospinning, followed by its crosslinking using UV-C radiation or Fenton reaction. The use of electrospinning in the hydrogel formation allowed porosity control by obtaining fibers of different diameters. This was evidenced by achieving materials that present different release profiles of the model protein bovine serum albumin (BSA). The nanostructured PVP hydrogel was capable of releasing and maintaining collagenase activity during 48 hour of evaluation. This is an important enzyme that find application in wound healing based on enzymatic debridement. Moreover, nanostructured bactericidal hydrogels were produced from PVP and silver nanoparticles (AgNP) composite through electrospinning, resulting in hydrogels with thermal properties similar to those hydrogels without AgNP, decreasing its swelling ability. These hydrogels were active against gram-positives and gram-negatives bacteria starting from 100 ppm of AgNP. In addition, the production of a model hydrogel composed by PVP/AgNP/Imidazole was investigated, aiming at a bactericidal-fungicidal hydrogel based material. This hydrogel was active against three Candida having 500 ppm of imidazole into the structure. In spite of the formation of a stable complex between AgNP and imidazole, theoretic calculations and the observed fungicidal activity corroborate with the fact that imidazoles derivatives can be released from this hybrid hydrogel. Physical hydrogels composed of PVP/Polyanhydrides blends were synthesized from hydroxycinammates derivatives and salicylic acid. These materials which were capable of releasing molecules with biological potential upon hydrolysis, are also described in this work. The results indicate that hydrophobic interactions between PVP and the synthesized polyanhydrides could be responsible for the hydrogel formation and blend miscibility as well. PVP/Polyanhydride physical hydrogels were obtained from cast films. Micro- and nanofibers were also obtained by electrospinning. Thus, the present work contributes with the development of the new generation of smart dressings for wound and burn healing