RESUMO

Staphylococcus aureus infections and its biofilm removal is an important concern in health care management. Methicillin-resistant S. aureus is responsible for severe morbidity and mortality worldwide. The extensive use of disinfectants against biofilms has led to negative environmental impacts. Developing new and more potent biofilm eradication agents with minimal detrimental effects on human and environmental health is currently on the agenda. The alkyl esters of L-ascorbic acid (ASCn) are antioxidant amphiphiles, which show antimicrobial capacity against methicillin-sensitive and resistant S. aureus strains. ASC12 and ASC14 formulations are able to kill the persister cells of the deepest layers of the biofilm. We tested the hypothesis that the antimicrobial and antibiofilm capacity found for the ASCn emerges from a combined effect of its amphiphilic and their redox capacity. This mechanism appears related to: I) a larger diffusion capacity of the ASC12 micelles than ASC14 and ASC16 microstructures; II) the neutralization of the ASCn acid hydroxyl when the amphiphile reaches the surface of an anionic surface, followed by a rapid insertion; III) the disruption of cell membrane by alteration of membrane tension and structure and IV) ASCn accumulation in the cell membrane or biofilm extracellular matrix surfaces, reducing functional chemical groups and affecting its biological function.

Assuntos

Antibacterianos , Ácido Ascórbico , Biofilmes , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Biofilmes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Ácido Ascórbico/química , Ácido Ascórbico/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/química , Tensoativos/química , Tensoativos/farmacologia

RESUMO

The E6 and E7 oncoproteins of high-risk types of human papillomavirus (HR-HPV) are crucial for the development of cervical cancer (CC). Small interfering RNAs (siRNAs) are explored as novel therapies that silence these oncogenes, but their clinical use is hampered by inefficient delivery systems. Modification (pegylation) with polyethylene glycol (PEG) of liposomal siRNA complexes (siRNA lipoplexes) may improve systemic stability. We studied the effect of siRNA targeting HPV16 E6, delivered via cationic liposomes (lipoplexes), on cellular processes in a cervical carcinoma cell line (CaSki) and its potential therapeutic use. Lipoplexes-PEG-HPV16 E6, composed of DOTAP, Chol, DOPE, and DSPE-PEG2000 were prepared. The results showed that pegylation (5% DSPE-PEG2000) provided stable siRNA protection, with a particle size of 86.42 ± 3.19 nm and a complexation efficiency of over 80%; the siRNA remained stable for 30 days. These lipoplexes significantly reduced HPV16 E6 protein levels and restored p53 protein expression, inhibiting carcinogenic processes such as proliferation by 25.74%, migration (95.7%), and cell invasion (97.8%) at concentrations of 20 nM, 200 nM, and 80 nM, respectively. In conclusion, cationic lipoplexes-PEG-HPV16 E6 show promise as siRNA carriers for silencing HPV16 E6 in CC.

RESUMO

BACKGROUND: Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats. METHODS: Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs' antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis. RESULTS: According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration. CONCLUSION: The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy.

Assuntos

Autofagia , Diabetes Mellitus Experimental , Neuropatias Diabéticas , Estresse do Retículo Endoplasmático , Flavonoides , Lipossomos , Animais , Flavonoides/farmacologia , Flavonoides/administração & dosagem , Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Ratos , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/prevenção & controle , Polietilenoglicóis/farmacologia , Aloxano , Ratos Wistar , Ratos Sprague-Dawley

RESUMO

BACKGROUND AND PURPOSE: Head and neck cancer patients frequently develop radiation dermatitis (RD) during radiotherapy. We compared liposomal gel with and without chamomile extract for the prevention and management of RD in head and neck cancer patients undergoing radiotherapy. MATERIALS AND METHODS: Sixty participants undergoing radiotherapy for the first time for head and neck cancer were recruited in a double-blind randomized clinical trial. Primary outcomes were the occurrence of dry desquamation and the cumulative dose of ionizing radiation at the first occurrence of dry desquamation. Secondary outcomes were the occurrence of erythema, moist desquamation, global RD, and participant self-reported symptoms. RESULTS: Dry desquamation occurred in 76.9 % (95 % CI: 57.9, 89.0) of participants in the chamomile liposomal gel group and in 88.9 % (95 % CI: 71.9, 96.1) in the liposomal gel group (p = 0.43). The median cumulative dose of ionizing radiation when dry desquamation occurred was 48.0 Gy in the chamomile liposomal gel group and 40.0 Gy in the liposomal gel group. Fewer symptoms were reported in the chamomile liposomal gel group. CONCLUSION: No statistically significant differences in outcomes were found between the two groups, though the chamomile liposomal gel group presented with lower grades of RD than the liposomal gel group. In addition, when compared to the literature on other topical interventions to manage RD, our results show that chamomile liposomal gel has potential for better management and prevention of RD in this population, which should be further tested. This study provides crucial information to design future studies. Clinical Trials Registration (REBEC): RBR-92cts3.

Assuntos

Camomila , Géis , Neoplasias de Cabeça e Pescoço , Lipossomos , Radiodermite , Humanos , Radiodermite/prevenção & controle , Radiodermite/etiologia , Neoplasias de Cabeça e Pescoço/radioterapia , Feminino , Pessoa de Meia-Idade , Masculino , Método Duplo-Cego , Idoso , Extratos Vegetais/uso terapêutico , Extratos Vegetais/administração & dosagem , Adulto

RESUMO

Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to develop and characterize liposomes and nanocapsules containing paroxetine hydrochloride and evaluate their antidepressant-like effect using the open field and tail suspension tests in mice. Liposomes and nanocapsules were prepared using the reverse-phase evaporation and nanoprecipitation methods, respectively. The particle size of the formulation ranged from 121.81 to 310.73 nm, the polydispersity index from 0.096 to 0.303, the zeta potential from -11.94 to -34.50 mV, the pH from 5.31 to 7.38, the drug content from 80.82 to 94.36 %, and the association efficiency was 98 %. Paroxetine hydrochloride showed slower release when associated with liposomes (43.82 %) compared to nanocapsules (95.59 %) after 10 h. In Vero cells, in vitro toxicity showed a concentration-dependent effect for paroxetine hydrochloride nanostructures. Both nanostructures decreased the immobility time in the TST at 2.5 mg/kg without affecting the number of crossings in the open field test, suggesting the antidepressant-like effect of paroxetine. In addition, the nanocapsules decreased the number of groomings, reinforcing the anxiolytic effect of this drug. These results suggest that the nanostructures were effective in preserving the antidepressant-like effect of paroxetine hydrochloride even at low doses.

Assuntos

Lipossomos , Nanocápsulas , Paroxetina , Animais , Paroxetina/administração & dosagem , Paroxetina/farmacologia , Paroxetina/química , Nanocápsulas/química , Camundongos , Chlorocebus aethiops , Masculino , Células Vero , Tamanho da Partícula , Liberação Controlada de Fármacos , Depressão/tratamento farmacológico , Elevação dos Membros Posteriores , Antidepressivos/administração & dosagem , Antidepressivos/química , Antidepressivos/farmacologia , Antidepressivos de Segunda Geração/administração & dosagem , Antidepressivos de Segunda Geração/química , Antidepressivos de Segunda Geração/farmacologia , Comportamento Animal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos

RESUMO

Drug delivery selectivity is a challenge for cancer treatment. A hybrid pegylated pH-sensitive liposome-extracellular vesicle isolated from human breast cancer cell MDA-MB-231 was developed to investigate its in vitro activity against breast cancer cells of different molecular profiles to overcome this inconvenience. The hybrid nanosystem was produced by film hydration, and doxorubicin (DOX) was encapsulated in this system using the ammonium sulfate gradient method. The characterization of this hybrid nanosystem revealed a mean diameter of 140.20 ± 2.70 nm, a polydispersity index of 0.102 ± 0.033, an encapsulation efficiency of doxorubicin of 88.9% ± 2.4, and a great storage stability for 90 days at 4 °C. The fusion of extracellular vesicles with liposomes was confirmed by nanoflow cytometry using PE-conjugated human anti-CD63. This hybrid nanosystem demonstrated cytotoxicity against human breast cancer cell lines with different molecular subtypes, enhanced anti-migration properties, and exhibited similar cellular uptake to the free DOX treatment. Preliminary acute toxicity assessments using Balb/C female mice indicated a median lethal dose of 15-17.5 mg/kg, with no evidence of splenic, liver, heart, bone marrow, and renal damage at a dose of 15 mg/kg. These findings suggest the hybrid formulation as a versatile nanocarrier for the treatment of various breast cancer subtypes.

RESUMO

Chloraluminium phthalocyanine (ClAlPc) has potential therapeutic effect for the treatment of cancer; however, the molecule is lipophilic and may present self-aggregation which limits its clinical success. Thus, nanocarriers like liposomes can improve ClAlPc solubility, reduce off-site toxicity and increase circulation time. For this purpose, developing suitable liposomes requires the evaluation of different lipid compositions. Herein, we aimed to develop liposomes containing soy phosphatidylcholine (SPC), 1,2-distearoyl-sn-glycero- 3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPEPEG2000), cholesterol and oleic acid loaded with ClAlPc using the surface response methodology and the Box-Behnken design. Liposomes with particle size from 110.93 to 374.97 nm and PdI from 0.265 to 0.468 were obtained. The optimized formulation resulted in 69.09 % of ClAlPc encapsulated, with particle size and polydispersity index, respectively, at 153.20 nm and 0.309, providing stability and aggregation control. Atomic force microscopy revealed vesicles in a spherical or almost spherical shape, while the analyzes by Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) suggested that the drug was adequately incorporated into the lipid bilayer of liposomes, in its amorphous state or molecularly dispersed. In vitro studies conducted in breast cancer cells (4T1) showed that liposome improved phototoxicity compared to the ClAlPc solution. ClAlPc-loaded liposomes also enhanced the production of ROS 3-fold compared to the ClAlPc solution. Finally, confocal microscopy and flow cytometry demonstrated the ability of the liposomes to enter cells and deliver the fluorescent ClAlPc photosensitizer with dose and time-dependent effects. Thus, this work showed that Box-Behnken factorial design was an effective strategy for optimizing formulation development. The obtained ClAlPc liposomes can be applied for photodynamic therapy in breast cancer cells.

Assuntos

Neoplasias da Mama , Indóis , Lipossomos , Compostos Organometálicos , Tamanho da Partícula , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Indóis/química , Indóis/administração & dosagem , Feminino , Compostos Organometálicos/química , Compostos Organometálicos/administração & dosagem , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Polietilenoglicóis/química , Fosfatidiletanolaminas/química , Fosfatidilcolinas/química , Colesterol/química , Ácido Oleico/química

RESUMO

Sunscreen products are essential for shielding the skin from ultraviolet (UV) radiation, a leading cause of skin cancer. While existing products serve this purpose, there is a growing need to enhance their efficacy while minimizing potential systemic absorption of UV filters and associated toxicological risks. Liposomal-based formulations have emerged as a promising approach to address these challenges and develop advanced photoprotective products. These vesicular systems offer versatility in carrying both hydrophilic and lipophilic UV filters, enabling the creation of broad-spectrum sunscreens. Moreover, their composition based on phospholipids, resembling that of the stratum corneum, facilitates adherence to the skin's surface layers, thereby improving photoprotective efficacy. The research discussed in this review underscores the significant advantages of liposomes in photoprotection, including their ability to limit the systemic absorption of UV filters, enhance formulation stability, and augment photoprotective effects. However, despite these benefits, there remains a notable gap between the potential of liposomal systems and their utilization in sunscreen development. Consequently, this review emphasizes the importance of leveraging liposomes and related vesicular systems as innovative tools for crafting novel and more efficient photoprotective formulations.

RESUMO

Chagas disease (CD) is the most important endemic parasitosis in South America and represents a great socioeconomic burden for the chronically ill and their families. The only currently available treatment against CD is based on the oral administration of benznidazole, an agent, developed in 1971, of controversial effectiveness on chronically ill patients and toxic to adults. So far, conventional pharmacological approaches have failed to offer more effective and less toxic alternatives to benznidazole. Nanomedicines reduce toxicity and increase the effectiveness of current oncological therapies. Could nanomedicines improve the treatment of the neglected CD? This question will be addressed in this review, first by critically discussing selected reports on the performance of benznidazole and other molecules formulated as nanomedicines in in vitro and in vivo CD models. Taking into consideration the developmental barriers for nanomedicines and the degree of current technical preclinical efforts, a prospect of developing nanomedicines against CD will be provided. Not surprisingly, we conclude that structurally simpler formulations with minimal production cost, such as oral nanocrystals and/or parenteral nano-immunostimulants, have the highest chances of making it to the market to treat CD. Nonetheless, substantive political and economic decisions, key to facing technological challenges, are still required regarding a realistic use of nanomedicines effective against CD.