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1.
Int J Pharm ; 650: 123730, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38142014

RESUMO

Skin cancer is considered the fifth most commonly occurring cancer worldwide hampering both health and economy. Piperine had proven efficacy in fighting skin cancer cells. Unfortunately, this natural agent had limited ability to penetrate the skin. The aim of the current study was to formulate piperine-loaded limosomes and hyalurolimosomes incorporating limonene as an edge activator and hyaluronic acid as bioactive gelling agent for managing skin cancer. Titration method followed by homogenization was adopted to prepare the nanoliposomal formulations. Characterization involved size, & zeta potential measurements, examination using transmission electron microscope (TEM) and stability study. Biological evaluation of the antitumor activity of piperine nanoliposomal formulations against Ehrlich's (EAC) solid tumor was also performed. Drug loaded limosomes and hyalurolimosomes had particle size; 346.55 ± 8.55 & 372.70 ± 10.83 nm, respectively. Zeta potential was high enough to ensure their stability. TEM micrographs detected the surrounding layer of Hyaluronic acid formed around the spherical limosomal nano-carrier ensuring the formation of Hyalurolimosomes. All stored formulations showed non-significant differences compared with freshly prepared ones at p < 0.05. In addition, A DAD-HPLC method was developed and validated for Piperine analysis in the skin. Upon application of this method, it was found that hyalurolimosomes deliver double the concentration delivered by limosomes. The piperine hyalurolimosome group showed a significant reduction in tumor size with a smaller AUC compared to piperine gel, which was confirmed by in vivo studies. Consequently, hyalurolimosomes loaded with piperine is considered a promising nanocarrier system and a step forward better management of skin cancer introducing new hope in beating this deadly disease.


Assuntos
Alcaloides , Neoplasias Cutâneas , Humanos , Ácido Hialurônico , Benzodioxóis , Pele , Tamanho da Partícula , Neoplasias Cutâneas/tratamento farmacológico , Lipossomos
2.
BMC Chem ; 17(1): 179, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072975

RESUMO

As a GABA-ß receptor agonist, the central muscle relaxant Baclofen (BAC) has a potential of abuse. Unfortunately, the sense of wellbeing and pleasure is obtained at very high BAC doses. This is associated with many life-threating or even fatal cases due to neurological and respiratory failures. Moreover, having narrow therapeutic index makes BAC a high-risk drug. This is potentiated in case of long-treatment regimen or off-label use in smoking and alcohol cessation protocols. Until now, there is no rapid diagnostic test available for BAC screening. Therefore; It is quite difficult to routinely monitor cases on BAC regimen. On the other hand, smartphone-based colorimetric point of care testing (POCT) is displacing conventional analytical approaches in the detection and assay of abused drugs as well as therapeutic drug monitoring. It offers on-site, rapid, easy, affordable and interpretable analysis. Incorporating smartphone as a portable device facilitates its application, especially in remote areas and low-income countries. For the first time, the current work presents a smartphone-based colorimetric POCT for BAC analysis in urine without interference from urine matrix. It depends on BAC reaction with naphthoquinone sulfonate (NQS) in highly alkaline aqueous medium. The developed color was captured in a customized photo box using smartphone camera. Then, intensity of the blue channel was measured by a software application "Color Analyzer". All parameters were optimized with respect to the colorimetric reaction, photographing and smartphone-based analysis. All parameters were successfully investigated according to FDA guidelines for bioanalytical method validation. Also, all POCT criteria were considered as per WHO requirements. This method could determine BAC, linearly, from 0.02 to 0.21 mmol L-1 in urine. Moreover, LLOQ was lower than the expected BAC therapeutic concentrations in urine. The proposed method proved high reliability and suitability to analyze BAC in urine. This strongly recommends its routine application in screening BAC abusers and BAC therapeutic monitoring.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32947189

RESUMO

As an anticoagulant, Edoxaban (EDX) is a high risk drug that may cause a life-threatening bleeding. Also, it is prescribed as a chronic therapy for atrial fibrillation and venous thromboembolism patients. They are special population that needs appropriate care and optimum dosing of EDX. Hence, its monitoring in the patient plasma is fundamental, especially in emergency and special circumstances. However, such patient mostly receives many drugs of different pharmacological classes, side by side with EDX. This study represents the first attempt to quantify EDX in plasma without interference of the plasma matrix or concomitant medications. An accurate RP-HPLC-DAD method was developed for this purpose. It succeeded to monitor EDX level, selectively, without interference of plasma matrix or 16 of its frequently co-administered drugs. All drugs were extracted from plasma samples by protein precipitation followed by evaporation and concentration. EDX was well resolved from the co-administered drugs on C8 column using linear gradient elution of methanol and phosphate buffer (pH 4), at a flow rate of 1 mL/min. EDX appeared at retention time 9.6 min and was quantified at its λmax (290 nm). It exhibited a linear response over the concentration range of 0.15-2.2 µg/mL plasma which covers the reported therapeutic concentration. The suggested method fulfilled the US FDA guidelines for bioanalytical method validation. The developed method is fully discussed in comparison with the reported techniques. An in vivo study was performed to ensure applicability of the method on real plasma samples without interference from plasma matrix, co-administered drugs or the expected metabolites. It presented a unique selectivity of the method that guarantees accurate laboratory monitoring of EDX in plasma in almost all combined treatments including such novel oral anticoagulant drug.


Assuntos
Anticoagulantes/sangue , Cromatografia Líquida de Alta Pressão/métodos , Piridinas/sangue , Tiazóis/sangue , Administração Oral , Animais , Anticoagulantes/administração & dosagem , Anticoagulantes/isolamento & purificação , Modelos Lineares , Masculino , Piridinas/administração & dosagem , Piridinas/isolamento & purificação , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tiazóis/administração & dosagem , Tiazóis/isolamento & purificação
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