Machado Ana Carolina Henriques Ribeiro, Marinheiro Laís Júlio, Benson Heather Ann Elizabeth, Grice Jeffrey Ernest, Martins Tereza da Silva, Lan Alexandra, Lopes Patricia Santos, Andreo-Filho Newton, Leite-Silva Vania Rodrigues
Programa de Pós-Graduação em Medicina Translacional, Universidade Federal de São Paulo, Rua Pedro de Toledo, 720, Sao Paulo 04039-002, SP, Brazil.
Departamento de Ciências Farmacêuticas, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Rua São Nicolau, 210, Diadema 09913-030, SP, Brazil.
Pharmaceutics. 2023 Dec 17;15(12):2793. doi: 10.3390/pharmaceutics15122793.
This study aimed to develop a holobiont tablet with rapid dispersibility to provide regulation of the microbiota, virucidal activity, and skin barrier protection.
A 2 factorial experiment was planned to define the best formulation for the development of the base tablet, using average weight, hardness, dimensions, swelling rate, and disintegration time as parameters to be analyzed. To produce holobiont tablets, the chosen base formulation was fabricated by direct compression of prebiotics, postbiotics, and excipients. The tablets also incorporated solid lipid nanoparticles containing postbiotics that were obtained by high-pressure homogenization and freeze-drying. The in vitro virucidal activity against alpha-coronavirus particles (CCoV-VR809) was determined in VERO cell culture. In vitro analysis, using monolayer cells and human equivalent skin, was performed by rRTq-PCR to determine the expression of interleukins 1, 6, 8, and 17, aquaporin-3, involucrin, filaggrin, FoxO3, and SIRT-1. Antioxidant activity and collagen-1 synthesis were also performed in fibroblast cells. Metagenomic analysis of the skin microbiome was determined in vivo before and after application of the holobiont tablet, during one week of continuous use, and compared to the use of alcohol gel. Samples were analyzed by sequencing the V3-V4 region of the 16S rRNA gene.
A handrub tablet with rapid dispersibility was developed for topical use and rinse off. After being defined as safe, the virucidal activity was found to be equal to or greater than that of 70% alcohol, with a reduction in interleukins and maintenance or improvement of skin barrier gene markers, in addition to the reestablishment of the skin microbiota after use.
The holobiont tablets were able to improve the genetic markers related to the skin barrier and also its microbiota, thereby being more favorable for use as a hand sanitizer than 70% alcohol.
本研究旨在开发一种具有快速分散性的全生物片剂，以调节微生物群、具有杀病毒活性并提供皮肤屏障保护。
计划进行一项二因素实验，以确定基础片剂开发的最佳配方，将平均重量、硬度、尺寸、溶胀率和崩解时间作为待分析参数。为生产全生物片剂，通过直接压片益生元、后生元和辅料来制备所选的基础配方。片剂还包含通过高压均质和冷冻干燥获得的含有后生元的固体脂质纳米颗粒。在VERO细胞培养中测定对α冠状病毒颗粒（CCoV-VR809）的体外杀病毒活性。使用单层细胞和人体等效皮肤进行体外分析，通过逆转录定量聚合酶链反应（rRTq-PCR）来确定白细胞介素1、6、8和17、水通道蛋白-3、兜甲蛋白、丝聚蛋白、叉头转录因子O3（FoxO3）和沉默信息调节因子1（SIRT-1）的表达。还在成纤维细胞中进行抗氧化活性和I型胶原蛋白合成实验。在连续使用一周期间，在体内应用全生物片剂前后测定皮肤微生物群的宏基因组分析，并与使用酒精凝胶进行比较。通过对16S rRNA基因的V3-V4区域进行测序来分析样本。
开发了一种用于局部使用和冲洗的具有快速分散性的洗手液片剂。在被确定为安全后，发现其杀病毒活性等于或大于70%酒精，可降低白细胞介素水平，并维持或改善皮肤屏障基因标志物，此外使用后皮肤微生物群得以重建。
全生物片剂能够改善与皮肤屏障及其微生物群相关的基因标志物，因此作为洗手液比70%酒精更具优势。
