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1.
Curr Pharm Des ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38963114

RESUMO

INTRODUCTION: Luteolin (LUT), a naturally occurring flavonoid found in vegetables, fruits, and herbal medicines, has been extensively studied for its pharmacological activities, including anti-proliferative and anticancer effects on various cancer lines. It also exhibits potent antioxidant properties and pro-apoptotic activities against human cancers. However, its therapeutic potential is hindered by its poor solubility in water (5 µg/ml at 45°C) and low bioavailability. This research on the development of luteolin-loaded nanocarrier aims to overcome these limitations, thereby opening up new possibilities in cancer treatment. METHODS: This paper covers several nanoformulations studied to increase the solubility and bioavailability of LUT. The physicochemical characteristics of the nanoformulation that influence luteolin's solubility and bioavailability have been the subject of more in-depth investigation. Furthermore, it examines how LUT's anti-inflammatory and antioxidant properties aid in lessening the side effects of chemotherapy. RESULTS: Most nanoformulations, including phytosomes, lipid nanoparticles, liposomes, protein nanoparticles, polymer micelles, nanoemulsions, and metal nanoparticles, have shown promising results in improving the solubility and bioavailability of LUT. This is a significant step forward in enhancing the therapeutic potential of LUT in cancer treatment. Furthermore, the study found that LUT's ability to scavenge free radicals can significantly reduce the side effects of cancer treatment, further highlighting its potential to improve patient outcomes. CONCLUSION: Nanoformulations, because of their unique surface and physiochemical properties, improve the solubility and bioavailability of LUT. However, poor in-vitro and in-vivo correlation and scalability of nanoformulations need to be addressed to achieve good clinical performance of LUT in oncology.

2.
AAPS PharmSciTech ; 25(5): 106, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724834

RESUMO

The primary factor underlying the virulence of Candida albicans is its capacity to form biofilms, which in turn leads to recurrent complications. Over-the-counter antifungal treatments have proven ineffective in eliminating fungal biofilms and the inflammatory cytokines produced during fungal infections. Chitosan nanoparticles offer broad and versatile therapeutic potential as both antifungal agents and carriers for antifungal drugs to combat biofilm-associated Candida infections. In our study, we endeavoured to develop chitosan nanoparticles utilising chitosan and the antifungal crosslinker phytic acid targeting C. albicans. Phytic acid, known for its potent antifungal and anti-inflammatory properties, efficiently crosslinks with chitosan. The nanoparticles were synthesised using the ionic gelation technique and subjected to analyses including Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential analysis. The synthesised nanoparticles exhibited dimensions with a diameter (Dh) of 103 ± 3.9 nm, polydispersity index (PDI) of 0.33, and zeta potential (ZP) of 37 ± 2.5 mV. These nanoparticles demonstrated an antifungal effect with a minimum inhibitory concentration (MIC) of 140 ± 2.2 µg/mL, maintaining cell viability at approximately 90% of the MIC value and reducing cytokine levels. Additionally, the nanoparticles reduced ergosterol content and exhibited a 62% ± 1.2 reduction in biofilm susceptibility, as supported by colony-forming unit (CFU) and XTT assays-furthermore, treatment with nanoparticles reduced exopolysaccharide production and decreased secretion of aspartyl protease by C. albicans. Our findings suggest that the synthesised nanoparticles effectively combat Candida albicans infections. In vivo studies conducted on a mouse model of vaginal candidiasis confirmed the efficacy of the nanoparticles in combating fungal infections in vivo.


Assuntos
Anti-Inflamatórios não Esteroides , Antifúngicos , Biofilmes , Candida albicans , Candidíase Vulvovaginal , Quitosana , Reagentes de Ligações Cruzadas , Nanopartículas , Ácido Fítico , Biofilmes/efeitos dos fármacos , Ácido Fítico/química , Ácido Fítico/farmacologia , Ácido Fítico/uso terapêutico , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/farmacologia , Reagentes de Ligações Cruzadas/uso terapêutico , Quitosana/química , Quitosana/farmacologia , Quitosana/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico , Antifúngicos/química , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Testes de Sensibilidade Microbiana , Citocinas/imunologia , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Feminino , Animais , Camundongos , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/metabolismo , Vagina/microbiologia
3.
AAPS PharmSciTech ; 25(4): 85, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605158

RESUMO

Cervical cancer (CC) is the fourth leading cancer type in females globally. Being an ailment of the birth canal, primitive treatment strategies, including surgery, radiation, or laser therapy, bring along the risk of infertility, neonate mortality, premature parturition, etc. Systemic chemotherapy led to systemic toxicity. Therefore, delivering a smaller cargo of therapeutics to the local site is more beneficial in terms of efficacy as well as safety. Due to the regeneration of cervicovaginal mucus, conventional dosage forms come with the limitations of leaking, the requirement of repeated administration, and compromised vaginal retention. Therefore, these days novel strategies are being investigated with the ability to combat the limitations of conventional formulations. Novel carriers can be engineered to manipulate bioadhesive properties and sustained release patterns can be obtained thus leading to the maintenance of actives at therapeutic level locally for a longer period. Other than the purpose of CC treatment, these delivery systems also have been designed as postoperative care where a certain dose of antitumor agent will be maintained in the cervix postsurgical removal of the tumor. Herein, the most explored localized delivery systems for the treatment of CC, namely, nanofibers, nanoparticles, in situ gel, liposome, and hydrogel, have been discussed in detail. These carriers have exceptional properties that have been further modified with the aid of a wide range of polymers in order to serve the required purpose of therapeutic effect, safety, and stability. Further, the safety of these delivery systems toward vital organs has also been discussed.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias do Colo do Útero , Feminino , Recém-Nascido , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Lipossomos , Hidrogéis
4.
AAPS PharmSciTech ; 24(7): 196, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37783948

RESUMO

Despite having a wide range of therapeutic advantages, glycyrrhizin (GL) has few commercial applications due to its poor aqueous solubility. In this study, we combined the benefits of hydroxypropyl ß-cyclodextrin (HP-ßCD) supramolecular inclusion complexes and electrospun nanofibers to improve the solubility and therapeutic potential of GL. A molecular inclusion complex containing GL and HP-ßCD was prepared by lyophilization at a 1:2 molar ratio. GL and hydroxypropyl ß-cyclodextrin inclusion complexes were also incorporated into hyaluronic acid (HA) nanofibers. Prepared NF was analyzed for physical, chemical, thermal, and pharmaceutical properties. Additionally, a rat model of carrageenan-induced hind paw edema and macrophage cell lines was used to evaluate the anti-inflammatory activity of GL-HP-ßCD NF. The DSC and XRD analyses clearly showed the amorphous state of GL in nanofibers. In comparison to pure GL, GL-HP-ßCD NF displayed improved release (46.6 ± 2.16% in 5 min) and dissolution profiles (water dissolvability ≤ 6 s). Phase solubility results showed a four-fold increase in GL solubility in GL-HP-ßCD NF. In vitro experiments on cell lines showed that inflammatory markers like IL-1ß, TNF-α, and IL-6 were significantly lower in GL-HP-ßCD NF compared to pure GL (p < 0.01 and p < 0.05). According to in vivo results, the prepared nanofiber exhibits a better anti-inflammatory effect than pure GL (63.4% inhibition vs 53.7% inhibition). The findings presented here suggested that GL-HP-ßCD NF could serve as a useful strategy for improving the therapeutic effects of GL.


Assuntos
Ácido Glicirrízico , Nanofibras , Ratos , Animais , 2-Hidroxipropil-beta-Ciclodextrina/química , Solubilidade , Ácido Glicirrízico/farmacologia , Nanofibras/química , Anti-Inflamatórios/farmacologia
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