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1.
Nanoscale ; 14(10): 3834-3848, 2022 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-35195120

RESUMEN

Psoriasis is a systemic, relapsing, and chronic autoimmune inflammatory disease of the skin. Topical use of betamethasone, a glucocorticoid, in the form of creams is a common treatment for psoriasis. However, topical use of these creams is challenging due to the ineffective entrapment of steroids, burst release of the entrapped drugs, poor skin permeability, and high toxicity. Herein, we present the engineering of a betamethasone-loaded topical hydrogel (B-Gel) that can efficiently entrap steroids with high spreadability, and can also maintain the sustained release of drugs. We used an imiquimod (IMQ) induced ear psoriasis model, and demonstrated that topical application of B-Gel can mitigate the autoimmune inflammation reactions, and leads to a reduction in erythema, induration, scaling, and ear thickness. As interleukin 17 (IL-17) secreting T helper 17 (Th17) cells and γδ+ T cells are responsible for psoriasis, B-Gel treatment witnessed a reduction in the infiltration of leukocytes, CD4+ T cells, Th17 T cells, and dermal γδ+ T cells. We further demonstrated that B-Gel mediated reduction of IL-1ß, IL-17, and K16 (marker for keratinocyte proliferation) is responsible for alleviation of psoriasis. Therefore, the non-greasy nature of the hydrogel with a cooling effect provides an alternative for topical application of steroids.


Asunto(s)
Hidrogeles , Psoriasis , Animales , Autoinmunidad , Modelos Animales de Enfermedad , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Psoriasis/tratamiento farmacológico , Piel , Esteroides
2.
ACS Appl Mater Interfaces ; 13(37): 44041-44053, 2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34491724

RESUMEN

Treatment of chronic wound infections caused by Gram-positive bacteria such as Staphylococcus aureus is highly challenging due to the low efficacy of existing formulations, thereby leading to drug resistance. Herein, we present the synthesis of a nonimmunogenic cholic acid-glycine-glycine conjugate (A6) that self-assembles into a supramolecular viscoelastic hydrogel (A6 gel) suitable for topical applications. The A6 hydrogel can entrap different antibiotics with high efficacy without compromising its viscoelastic behavior. Activities against different bacterial species using a disc diffusion assay demonstrated the antimicrobial effect of the ciprofloxacin-loaded A6 hydrogel (CPF-Gel). Immune profiling and gene expression studies after the application of the A6 gel to mice confirmed its nonimmunogenic nature to host tissues. We further demonstrated that topical application of CPF-Gel clears S. aureus-mediated wound infections more effectively than clinically used formulations. Therefore, cholic acid-derived hydrogels are an efficacious matrix for topical delivery of antibiotics and should be explored further.


Asunto(s)
Antibacterianos/uso terapéutico , Ciprofloxacina/uso terapéutico , Portadores de Fármacos/química , Hidrogeles/química , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infección de Heridas/tratamiento farmacológico , Animales , Antibacterianos/química , Ácidos Cólicos/síntesis química , Ácidos Cólicos/química , Ciprofloxacina/química , Dipéptidos/síntesis química , Dipéptidos/química , Portadores de Fármacos/síntesis química , Liberación de Fármacos , Hidrogeles/síntesis química , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Staphylococcus aureus/efectos de los fármacos
3.
Nanoscale ; 13(31): 13225-13230, 2021 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-34477730

RESUMEN

We present a non-immunogenic, injectable, low molecular weight, amphiphilic hydrogel-based drug delivery system (TB-Gel) that can entrap a cocktail of four front-line antitubercular drugs, isoniazid, rifampicin, pyrazinamide, and ethambutol. We showed that TB-Gel is more effective than oral delivery of the combination of four drugs in reducing the mycobacterial infection in mice. Results show that half the dose of chemotherapeutic drugs is sufficient to achieve a comparable therapeutic effect to that of oral delivery.


Asunto(s)
Antituberculosos , Hidrogeles , Animales , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Etambutol , Isoniazida , Ratones , Pirazinamida
4.
Nanoscale ; 12(35): 18463-18475, 2020 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-32941570

RESUMEN

The release of anticancer drugs in systemic circulation and their associated toxicity are responsible for the poor efficacy of chemotherapy. Therefore, the identification of new chemotherapeutic combinations designed to be released near the tumor site in a sustained manner has the potential to enhance the efficacy and reduce the toxicity associated with chemotherapy. Here, we present the identification of a combination of doxorubicin, a DNA-binding topoisomerase inhibitor, with a naturally occurring triterpenoid, celastrol, that induces a synergistic effect on the apoptosis of colon cancer cells. Hydrogel-mediated sustained release of a combination of doxorubicin and celastrol in a murine tumor model abrogates tumor proliferation, and increases the median survival with enhanced apoptosis and concurrent reduction in proliferation. Sphingolipid profiling (LC-MS/MS) of treated tumors showed that the combination of celastrol and doxorubicin induces global changes in the expression of sphingolipids with an increase in levels of ceramides. We further demonstrate that this dual drug combination induces a significant increase in the expression of ceramide synthase 1, 4, and 6, thereby increasing the level of ceramides that contribute to the synergistic apoptotic effect. Therefore, hydrogel-mediated localized delivery of a combination of celastrol and doxorubicin provides a new therapeutic combination that induces a sphingolipid-mediated synergistic effect against colon cancer.


Asunto(s)
Neoplasias , Triterpenos , Animales , Ceramidas , Cromatografía Liquida , Doxorrubicina/farmacología , Hidrogeles , Ratones , Triterpenos Pentacíclicos , Espectrometría de Masas en Tándem , Triterpenos/farmacología , Regulación hacia Arriba
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