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1.
AAPS PharmSciTech ; 25(7): 203, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237802

RESUMO

Normal skin is the first line of defense in the human body. A burn injury makes the skin susceptible to bacterial infection, thereby delaying wound healing and ultimately leading to sepsis. The chances of biofilm formation are high in burn wounds due to the presence of avascular necrotic tissue. The most common pathogen to cause burn infection and biofilm is Pseudomonas aeruginosa. The purpose of this study was to create a microemulsion (ME) formulation for topical application to treat bacterial burn infection. In the present study, tea tree oil was used as the oil phase, Tween 80 and transcutol were used as surfactants, and water served as the aqueous phase. Pseudo ternary phase diagrams were used to determine the design space. The ranges of components as suggested by the design were chosen, optimization of the microemulsion was performed, and in vitro drug release was assessed. Based on the characterization studies performed, it was found that the microemulsion were formulated properly, and the particle size obtained was within the desired microemulsion range of 10 to 300 nm. The I release study showed that the microemulsion followed an immediate release profile. The formulation was further tested based on its ability to inhibit biofilm formation and bacterial growth. The prepared microemulsion was capable of inhibiting biofilm formation.


Assuntos
Antibacterianos , Biofilmes , Queimaduras , Sistemas de Liberação de Medicamentos , Emulsões , Pseudomonas aeruginosa , Biofilmes/efeitos dos fármacos , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Tamanho da Partícula , Liberação Controlada de Fármacos , Tensoativos/química , Polissorbatos/química , Óleo de Melaleuca/administração & dosagem , Óleo de Melaleuca/química , Óleo de Melaleuca/farmacologia , Química Farmacêutica/métodos , Humanos
2.
Arch Biochem Biophys ; 728: 109375, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35970414

RESUMO

Chitosan is a natural polyfunctional polymer that can be modified to achieve compounds with tailored properties for targeting and treating different cancers. In this study, we report the development and anticancer potential of phosphorylated galactosylated chitosan (PGC). The synthesized compound was characterized by FT-IR, NMR, and mass spectroscopy. The interaction of PGC with asialoglycoprotein receptors (ASGPR) and cellular internalization in HepG2 cells was studied using in silico and uptake studies respectively. PGC was evaluated for its metal chelating, ferric ion reducing, superoxide, and lipid peroxide (LPO) inhibiting potential. Further, anticancer therapeutic potential of PGC was evaluated against N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in a mice model. After development of cancer, PGC was administered to the treatment group (0.5 mg/kg bw, intravenously), once a week for 4 weeks. Characterization studies of PGC revealed successful phosphorylation and galactosylation of chitosan. A strong interaction of PGC with ASGP-receptors was predicted by computational studies and cellular internalization studies demonstrated 98.76 ± 0.53% uptake of PGC in the HepG2 cells. A good metal chelating, ferric ion reducing, and free radical scavenging activity was demonstrated by PGC. The anticancer therapeutic potential of PGC was evident from the observation that PGC treatment increased number of tumor free animals (50%) (6/12) and significantly (p ≤ 0.05) lowered tumor multiplicity as compared to untreated tumor group.


Assuntos
Carcinoma Hepatocelular , Quitosana , Neoplasias Hepáticas , Aminas , Animais , Camundongos , Espectroscopia de Infravermelho com Transformada de Fourier
3.
Asian Pac J Cancer Prev ; 24(4): 1159-1171, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37116137

RESUMO

BACKGROUND: The 5-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an emerging cancer treatment and therapeutic target. Due to the enzyme's complexity and dual nature, it is a confounding target in the treatment strategy. The study aimed to conduct an integrative analysis of the seven subunits and twelve isoforms of AMPK, which is not reported so far in colorectal adenocarcinoma patients. METHODOLOGY: The web-based tools UALCAN, Timer 2.0, KM Plotter, cBioPortal, COSMIC, and STRING were used to investigate the differential expression of AMPK subunits, protein-level Expression, promoter methylation status, survival analyses, Enrichment analysis, and protein-protein interaction. RESULTS: The mRNA expression of AMPK subunits are upregulated in Colorectal Adeno Carcinoma (COAD), while the protein expression is comparatively reduced in colon tumors. The protein-level expression of α2 and ß2 is decreased significantly in COAD patients. The γ3 subunit in colon tumor is hypermethylated. The study also reports that Liver Kinase B1 mutation in 7% of CRC patients, which might be the reason for downregulation of the gene and the protein expression of AMPK subunits in COAD. CONCLUSION: The Overall analysis of the subunits affirms that AMPK expression is beneficial in cancer.


Assuntos
Adenocarcinoma , Neoplasias Colorretais , Humanos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Serina-Treonina Quinases/genética , Isoformas de Proteínas , Neoplasias Colorretais/genética
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