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用于治疗慢性细菌性前列腺炎的靶向环丙沙星纳米载体的制备与应用

Fabrication and application of targeted ciprofloxacin nanocarriers for the treatment of chronic bacterial prostatitis.

作者信息

Mohammad Sahar I, Aldosari Basmah Nasser, Mehanni Magda M, El-Gendy Ahmed O, Hozayen Walaa G, Afzal Obaid, Zaki Randa Mohammed, Sayed Ossama M

机构信息

Biotechnology and Life Science Department, Faculty of Postgraduate Studies for Advanced Science, Beni-Suef University, Beni-Suef, Egypt.

Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

出版信息

Int J Pharm X. 2024 Apr 18;7:100247. doi: 10.1016/j.ijpx.2024.100247. eCollection 2024 Jun.

DOI:10.1016/j.ijpx.2024.100247
PMID:38706465
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11066576/
Abstract

Pathogenic bacteria cause chronic bacterial prostatitis (CBP). CPB is characterized by urinary tract infection and persistence of pathogenic bacteria in prostatic secretion. Owing to poor blood supply to the prostate gland and limited drug penetration, CBP treatment is difficult. Transferosomes are ultradeformable vesicles for nanocarrier applications, which have become an important area of nanomedicine. Such carriers are specifically targeted to the pathological area to provide maximum therapeutic efficacy. It consists of a lipid bilayer soybean lecithin phosphatidylcholine (PC), an edge activator Tween 80 with various ratios, and a chloroform/methanol core. Depending on the lipophilicity of the active substance, it can be encapsulated within the core or among the lipid bilayer. Due to their exceptional flexibility, which enables them to squeeze themselves through narrow pores that are significantly smaller than their size, they can be a solution. One formulation (Cipro5 PEG) was selected for further in vitro analysis and was composed of phosphatidylcholine (PC), Tween 80, and polyethylene glycol-6 stearate (PEG-6 stearate) in a ratio of 3:3:1 in a chloroform/methanol mixture (1:2 /v). In vitro, the results showed that PEGylated transferosomes had faster drug release, higher permeation, and increased bioavailability. The transferosomes were quantified with a particle size of 202.59 nm, a zeta potential of-49.38 mV, and a drug entrapment efficiency of 80.05%. The aim of this study was to investigate drug targeting. Therefore, Monoclonal antibody IgG was coupled with Cipro5 PEG, which has specificity and selectivity for conjugated nanoparticles. In vivo, a total of twenty-five adult Wistar rats were obtained and randomly divided into 5 groups, each of 5 rats at random: the control group, blank group, positive control group, Cipro 5PEG group, and Cipro 5PEG coupled with IgG antibody group. The cytokines levels (IL-1β, IL-8, and TNF-α) in the serum were detected by analysis kits. Compared with the control group, treatment with Cipro 5PEG coupled with the IgG antibody could significantly inhibit cytokines, according to histological analysis. Cipro 5PEG, coupled with the IgG antibody group, reduced prostate tissue inflammation. Hence, our results show a promising approach to delivering antibiotics for the targeted therapy of CBP.

摘要

致病性细菌可引发慢性细菌性前列腺炎(CBP)。CBP的特征为尿路感染以及致病性细菌在前列腺分泌物中的持续存在。由于前列腺的血液供应较差且药物渗透有限,CBP的治疗颇具难度。传递体是用于纳米载体应用的超可变形囊泡,已成为纳米医学的一个重要领域。此类载体可特异性靶向病理区域以提供最大治疗效果。它由脂质双层大豆卵磷脂磷脂酰胆碱(PC)、不同比例的边缘活化剂吐温80以及氯仿/甲醇核心组成。根据活性物质的亲脂性,其可被包裹在核心内或脂质双层之间。因其具有非凡的柔韧性,能够使自身挤过比其尺寸小得多的狭窄孔隙,所以它们可能是一种解决方案。选择一种制剂(Cipro5 PEG)进行进一步的体外分析,其由磷脂酰胆碱(PC)、吐温80和聚乙二醇-6硬脂酸酯(PEG-6硬脂酸酯)以3:3:1的比例在氯仿/甲醇混合物(1:2 /v)中组成。体外实验结果表明,聚乙二醇化传递体具有更快的药物释放、更高的渗透率以及更高的生物利用度。所制备的传递体粒径为202.59 nm,zeta电位为 -49.38 mV,药物包封率为80.05%。本研究的目的是研究药物靶向性。因此,将单克隆抗体IgG与Cipro5 PEG偶联,其对偶联纳米颗粒具有特异性和选择性。在体内实验中,总共获取了25只成年Wistar大鼠并随机分为5组,每组5只大鼠:对照组、空白组、阳性对照组、Cipro 5PEG组以及Cipro 5PEG与IgG抗体偶联组。通过分析试剂盒检测血清中的细胞因子水平(IL-1β、IL-8和TNF-α)。组织学分析表明,与对照组相比,Cipro 5PEG与IgG抗体联合治疗可显著抑制细胞因子。Cipro 5PEG与IgG抗体偶联组减轻了前列腺组织炎症。因此,我们的结果显示了一种为CBP靶向治疗递送抗生素的有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/769394fb8b14/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/213bc5876c27/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/1c592df05c5f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/8c01f91a2b24/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/62f4f5228f24/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/568c008fad8b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/06e2dedc0971/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/769394fb8b14/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/213bc5876c27/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/1c592df05c5f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/8c01f91a2b24/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/62f4f5228f24/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/568c008fad8b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/06e2dedc0971/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f697/11066576/769394fb8b14/gr6.jpg

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本文引用的文献

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