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1.
Macromol Biosci ; 24(4): e2300465, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38111343

RESUMO

Combination therapy through colon-targeted oral delivery of multiple drugs presents a promising approach for effectively treating ulcerative colitis (UC). However, the codelivery of drugs with diverse physicochemical properties in a single formulation remains a formidable challenge. Here, microcapsules are designed based on hydroxyethyl starch-curcumin (HES─CUR) conjugates to enable the simultaneous delivery of hydrophobic dexamethasone acetate (DA) and hydrophilic cefazolin sodium (CS), yielding multiple drug-loaded microcapsules (CS/DA-loaded HES─CUR microcapsules, CDHC-MCs) tailored for colon-targeted therapy of UC. Thorough characterization confirms the successful synthesis and exceptional biocompatibility of CDHC-MCs. Biodistribution studies demonstrate that the microcapsules exhibit an impressive inflammatory targeting effect, accumulating preferentially in inflamed colons. In vivo experiments employing a dextran-sulfate-sodium-induced UC mouse model reveal that CDHC-MCs not only arrest UC progression but also facilitate the restoration of colon length and alleviate inflammation-related splenomegaly. These findings highlight the potential of colon-targeted delivery of multiple drugs within a single formulation as a promising strategy to enhance UC treatment, and the CDHC-MCs developed in this study hold great potential in developing novel oral formulations for advanced UC therapy.


Assuntos
Colite Ulcerativa , Curcumina , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Curcumina/química , Distribuição Tecidual , Cápsulas/metabolismo , Colo/metabolismo , Amido/farmacologia , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças
2.
Adv Healthc Mater ; 13(9): e2303379, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38211342

RESUMO

Hydrogel dressings capable of infection monitoring and precise treatment administration show promise for advanced wound care. Existing methods involve embedd ingorganic dyes or flexible electronics into preformed hydrogels, which raise safety issues and adaptability challenges. In this study, an injectable hydrogel based smart wound dressing is developed by integrating food-derived anthocyanidin as a visual pH probe for infection monitoring and poly(L-lactic acid) microcapsules as ultrasound-responsive delivery systems for antibiotics into a poly(ethylene glycol) hydrogel. This straightforwardly prepared hydrogel dressing maintains its favorable properties for wound repair, including porous morphology and excellent biocompatibility. In vitro experiments demonstrated that the hydrogel enabled visual assessment of pH within the range of 5 âˆ¼ 9.Meanwhile, the release of antibiotics could be triggered and controlled by ultrasound. In vivo evaluations using infected wounds and diabetic wounds revealed that the wound dressing effectively detected wound infection by monitoring pH levels and achieved antibacterial effects through ultrasound-triggered drug release. This led to significantly enhanced wound healing, as validated by histological analysis and the measurement of inflammatory cytokine levels. This injectable hydrogel-based smart wound dressing holds great potential for use in clinical settings to inform timely and precise clinical intervention and in community to improve wound care management.


Assuntos
Bandagens , Hidrogéis , Hidrogéis/química , Cápsulas , Antibacterianos/farmacologia , Antibacterianos/química , Materiais Biocompatíveis , Concentração de Íons de Hidrogênio
3.
Int J Biol Macromol ; 266(Pt 1): 131107, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38527677

RESUMO

Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.


Assuntos
Anti-Inflamatórios , Colite Ulcerativa , Curcumina , Microbioma Gastrointestinal , Derivados de Hidroxietil Amido , Microesferas , Estresse Oxidativo , Curcumina/farmacologia , Curcumina/química , Animais , Colite Ulcerativa/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Derivados de Hidroxietil Amido/química , Derivados de Hidroxietil Amido/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Colo/microbiologia , Inflamação/tratamento farmacológico , Modelos Animais de Doenças , Portadores de Fármacos/química , Masculino
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