RESUMEN
BACKGROUND: The complex etiology and pathogenesis underlying Chronic Non-Bacterial Prostatitis (CNP), coupled with the existence of a Blood Prostate Barrier (BPB), contribute to a lack of specificity and poor penetration of most drugs. Emodin (EMO), a potential natural compound for CNP treatment, exhibits commendable anti-inflammatory, anti-oxidant, and anti-fibrosis properties but suffers from the same problems as other drugs. METHODS: By exploiting the recognition properties of lactoferrin (LF) receptors that target intestinal epithelial cells (NCM-460) and prostate epithelial cells (RWPE-1), a pathway is established for the transrectal absorption of EMO to effectively reach the prostate. Additionally, hyaluronic acid (HA) is employed, recognizing CD44 receptors which target macrophages within the inflamed prostate. This interaction facilitates the intraprostatic delivery of EMO, leading to its pronounced anti-inflammatory effects. A thermosensitive hydrogel (CS-Gel) prepared from chitosan (CS) and ß-glycerophosphate disodium salt (ß-GP) was used for rectal drug delivery with strong adhesion to achieve effective drug retention and sustained slow release. Thus, we developed a triple-targeted nanoparticle (NPs)/thermosensitive hydrogel (Gel) rectal drug delivery system. In this process, LF, with its positive charge, was utilized to load EMO through dialysis, producing LF@EMO-NPs. Subsequently, HA was employed to encapsulate EMO-loaded LF nanoparticles via electrostatic adsorption, yielding HA/LF@EMO-NPs. Finally, HA/LF@EMO-NPs lyophilized powder was added to CS-Gel (HA/LF@EMO-NPs Gel). RESULTS: Cellular assays indicated that NCM-460 and RWPE-1 cells showed high uptake of both LF@EMO-NPs and HA/LF@EMO-NPs, while Raw 264.7 cells exhibited substantial uptake of HA/LF@EMO-NPs. For LPS-induced Raw 264.7 cells, HA/LF@EMO-NPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways. Tissue imaging corroborated the capacity of HA/LF-modified formulations to breach the BPB, accumulating within the gland's lumen. Animal experiments showed that rectal administration of HA/LF@EMO-NPs Gel significantly reduced inflammatory cytokine expression, oxidative stress levels and fibrosis in the CNP rats, in addition to exerting anti-inflammatory effects by inhibiting the NF-κB signaling pathway without obvious toxicity. CONCLUSION: This triple-targeted NPs/Gel rectal delivery system with slow-release anti-inflammatory, anti-oxidant, and anti-fibrosis properties shows great potential for the effective treatment of CNP.
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Quitosano , Emodina , Nanopartículas , Prostatitis , Humanos , Masculino , Ratas , Animales , Hidrogeles , Emodina/farmacología , Emodina/uso terapéutico , Prostatitis/tratamiento farmacológico , Antioxidantes , FN-kappa B , Sistemas de Liberación de Medicamentos/métodos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Portadores de FármacosRESUMEN
OBJECTIVES: Stress urinary incontinence is a common disease with many therapeutic ways, but it lacks long-term follow-up. This study aims to conduct a retrospective study on the long-term efficacy of women with mild and moderate stress urinary incontinence after pelvic floor rehabilitation treatment for 3-years so as to provide a more effective treatment plan for this disease. METHODS: Data were collected from 279 female patients, who were diagnosed with stress urinary incontinence at the Pelvic Floor Rehabilitation Center of the Third Xiangya Hospital of Central South University from January 2017 to January 2019. All patients received health education and were instructed to perform Kegel exercises for 20 min daily at home. According to the treatment pattern, patients were divided into 3 groups as A, B, and C. Group A (n=94) received pelvic floor biofeedback, electrical stimulation and electroacupuncture; Group B (n=99) received pelvic floor biofeedback and electrical stimulation; Group C (n=86) only got pelvic floor function examinations and did not receive any pelvic floor treatment. The pelvic floor functional examinations included a pelvic floor electrophysiological test, pelvic organ prolapse quantitive examination (POP-Q), and stress urinary incontinence severity assessment. All patients were followed up with questionnaire consisting of the International Committee on Urinary Incontinence Questionnaire-Short Form (ICI-Q-SF) and the Quality of Life questionnaire of Urinary Incontinence (I-QOL) before and after the treatment, as well as at 1-, 2-, and 3-years after the treatment (5 times in total). Among the patients who received the treatment, 43 returned to the hospital, including 21 in group A (Group Areturn) and 22 in group B (Group Breturn). Pelvic floor electrophysiological test and POP-Q were performed on the 2 groups. RESULTS: For the leakage rate at the end of the treatment and the following 1-, 2-, and 3-years: Group A
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Prolapso de Órgano Pélvico , Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Humanos , Femenino , Incontinencia Urinaria de Esfuerzo/terapia , Calidad de Vida , Diafragma Pélvico , Estudios Retrospectivos , Terapia por Ejercicio , Resultado del TratamientoRESUMEN
The damping coefficient serves to quantify the energy dissipation in particle collisions and constitutes a crucial parameter in discrete element simulations. Nevertheless, the factors influencing the damping coefficient remain unclear, and the damping coefficients of the majority of materials have not been precisely determined. In this investigation, the damping coefficients of eight representative particles were studied using the acoustic frequency sampling method, and the correlations between these coefficients and collision velocity, material density, and elastic modulus were analyzed. The findings indicate that damping coefficients exhibit insensitivity to velocity in strongly elastic and moderately elastic material particles. Conversely, for weakly elastic material particles, damping coefficients demonstrate an increase with rising velocity. The damping coefficient of metallic particles exhibits a linear relationship with material density and elastic modulus.
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Herein, a ß-1,3-D-glucan based yeast cell wall loaded with co-loaded nanoparticles of Rhein (RH) and Emodin (EMO), was developed for the combined treatment of ulcerative colitis (UC) by modulating gut microbiota and the Th17/Treg cell balance. This was achieved through an oral "nano-in-micro" advanced drug delivery system. Specifically, RH was grafted onto the HA chain via disulfide bonds to synthesize a reduction-sensitive carrier material and then used to encapsulate EMO to form nanoparticles with a specific drug ratio (denoted as HA-RH/EMO NPs). As anticipated, HA-RH/EMO NPs were encased within the "nests"-yeast cell wall microparticles (YPs), efficiently reach the colon and then released gradually, this occurs mainly due to the degradation of ß-1,3-D-glucan by ß-glucanase. Additionally, HA-RH/EMO NPs demonstrated a significant reduction-sensitive effect in GSH stimulation evaluations and a remarkable ability to target macrophages in in vitro cell uptake studies. Notably, HA-RH/EMO NYPs reduced inflammatory responses by inhibiting the PI3K/Akt signaling pathway. Even more crucially, the oral delivery and drug combination methods significantly enhanced the regulatory effects of HA-RH/EMO NYPs on gut microbiota and the Th17/Treg balance. Overall, this research marks the first use of YPs to encapsulate two components, RH and EMO, presenting a promising therapeutic strategy for UC.
Asunto(s)
Antraquinonas , Colitis Ulcerosa , Emodina , Microbiota , Nanopartículas , Proteoglicanos , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Emodina/farmacología , Emodina/química , Glucanos/uso terapéutico , Saccharomyces cerevisiae , Fosfatidilinositol 3-Quinasas , Nanopartículas/químicaRESUMEN
In the pharmaceutical industry, linear die filling is widely employed in R&D, while rotary die filling is very common in commercial production. It is not clear if powder die filling behaviour in a linear die filling system is representative of the flow performance in a rotary tablet press. In this study, a linear die filling system and a rotary die filling system were used to examine flow behaviours of both poor-flowing and free-flowing powders. It was found that the performance of poor-flowing powder in the linear die filling system is slightly better than that in the rotary die filling system, while the performance of free-flowing powders in the linear die filling system is similar to that in the rotary die filling system. Hence, it is suitable to use the linear die filling system to estimate the flow behaviour during rotary die filling with free-flowing powders, but caution needs to be taken when poor-flowing powders are used.