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具有延长人生长激素释放功能的二氧化硅-胶原蛋白纳米制剂

Silica-collagen nanoformulations with extended human growth hormone release.

作者信息

Villarruel Luis A, Brie Belén, Municoy Sofía, Becú-Villalobos Damasia, Desimone Martín F, Catalano Paolo N

机构信息

Instituto de Nanociencia y Nanotecnología (CNEA - CONICET), Nodo Constituyentes, Av. Gral.Paz 1499 (B1650KNA), San Martín, Buenos Aires, Argentina; Departamento de Micro y Nanotecnología, Gerencia de Desarrollo Tecnológico y Proyectos Especiales, Gerencia de Área de Investigación y Aplicaciones No Nucleares, Centro Atómico Constituyentes, Comisión Nacional de Energía Atómica, Av. Gral. Paz 1499 (B1650KNA), San Martín, Buenos Aires, Argentina.

Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490 (C1428ADN), Buenos Aires, Argentina.

出版信息

Int J Pharm. 2023 Mar 5;634:122662. doi: 10.1016/j.ijpharm.2023.122662. Epub 2023 Feb 1.

Abstract

Growth hormone deficiency has been treated by the daily administration of recombinant human growth hormone (hGH) for decades. Patient compliance to this treatment is generally incomplete due to challenges including dose frequency and lack of perceived benefits. This stimulates the research on new formulations to reduce the number of periodic administrations. In this study silica nanoparticles and silica-collagen nanocomposites were evaluated for hGH loading and release. Bare nanoparticles showed higher hGH adsorption capacity than thiol- and isobutyl-bearing particles of similar diameters. Monitoring of bound protein conformation changes indicated hGH structure retention when adsorbed on bare silica nanoparticles and suggested no alterations on protein activity. Protein-loaded particles incorporated into collagen matrices (silica-collagen nanocomposites) showed a progressive protein release profile different from the observed for hGH-loaded silica nanoparticles and hGH-loaded collagen matrices. While both the collagen and the silica nanoparticle systems reached a 100 % release after 4 and 7 days respectively, silica-collagen nanocomposites showed a bi-phasic prolonged hGH release reaching approximately an 80 % after 15 days. These findings suggest that biocompatible silica-collagen nanocomposites could be used as vehicles for the prolonged delivery of hGH which could lead to a potential reduction in the number of periodic administrations.

摘要

几十年来,生长激素缺乏症一直通过每日注射重组人生长激素(hGH)进行治疗。由于包括给药频率和缺乏明显疗效等挑战,患者对这种治疗的依从性通常并不理想。这激发了对新制剂的研究,以减少定期给药的次数。在本研究中,评估了二氧化硅纳米颗粒和二氧化硅 - 胶原蛋白纳米复合材料对hGH的负载和释放情况。与具有相似直径的含硫醇和异丁基的颗粒相比,裸露的纳米颗粒表现出更高的hGH吸附能力。对结合蛋白构象变化的监测表明,hGH吸附在裸露的二氧化硅纳米颗粒上时其结构得以保留,且表明蛋白活性未发生改变。掺入胶原蛋白基质中的载蛋白颗粒(二氧化硅 - 胶原蛋白纳米复合材料)显示出一种渐进性的蛋白释放曲线,这与载hGH的二氧化硅纳米颗粒和载hGH的胶原蛋白基质所观察到的不同。虽然胶原蛋白和二氧化硅纳米颗粒系统分别在4天和7天后达到了100%的释放,但二氧化硅 - 胶原蛋白纳米复合材料显示出双相延长的hGH释放,在15天后达到约80%。这些发现表明,生物相容性二氧化硅 - 胶原蛋白纳米复合材料可用作hGH长效递送的载体,这可能会导致定期给药次数的潜在减少。

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