Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment.
Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment.
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DOI：
10.1016/j.jconrel.2014.08.031
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发表时间：
2014-11-28
期刊：
影响因子：
--
通讯作者：
Sinko PJ
中科院分区：
文献类型：
--
作者：
Sundara Rajan S;Turovskiy Y;Singh Y;Chikindas ML;Sinko PJ
患有细菌性阴道病 (BV) 的女性阴道酸度降低，这使她们容易受到艾滋病毒等相关感染。在当前的研究中，开发了基于聚乙二醇（PEG）纳米载体的可降解水凝胶，用于在 BV 感染女性的阴道中控制乳酸的释放。 PEG-乳酸 (PEG-LA) 纳米载体是通过将乳酸通过可裂解的硫酯键共价连接到 8 臂 PEG-SH 上而制备的。每个分子具有 4 个乳酸拷贝的 PEG-LA 纳米载体可控制乳酸的释放，在磷酸盐缓冲盐水（PBS，pH 7.4）和醋酸盐缓冲液（AB，pH 4.3）中最大释放量分别为 23% 和 47%。基于PEG纳米载体的水凝胶是通过将PEG-LA纳米载体与4臂PEG-NHS通过可降解的硫酯键交联而形成的。基于纳米载体的水凝胶在环境条件下在 20 分钟内形成，并表现出比粘性模量高 100 倍的弹性模量。基于纳米载体的可降解水凝胶可在数小时内控制乳酸的释放；然而，观察到的最大释放量仅为 10%–14%，这可能是由于交联水凝胶中聚合物链的空间位阻所致。相比之下，被动捕获乳酸的水凝胶显示出爆发释放，并在 30 分钟内完全释放。乳酸对主要 BV 病原体阴道加德纳菌具有抗菌活性，最低抑制浓度 (MIC) 为 3.6 mg/ml。此外，被动包埋乳酸的水凝胶显示出保留的抗菌活性，在 48 小时内完全抑制阴道加德纳菌的生长。目前的研究结果共同证明了基于 PEG 纳米载体的水凝胶在阴道给药乳酸以预防和治疗 BV 方面的潜力。
Women with bacterial vaginosis (BV) display reduced vaginal acidity, which make them susceptible to associated infections such as HIV. In the current study, poly(ethylene glycol) (PEG) nanocarrier-based degradable hydrogels were developed for the controlled release of lactic acid in the vagina of BV-infected women. PEG-lactic acid (PEG-LA) nanocarriers were prepared by covalently attaching lactic acid to 8-arm PEG-SH via cleavable thioester bonds. PEG-LA nanocarriers with 4 copies of lactic acid per molecule provided controlled release of lactic acid with a maximum release of 23% and 47% bound lactic acid in phosphate buffered saline (PBS, pH 7.4) and acetate buffer (AB, pH 4.3), respectively. The PEG nanocarrier-based hydrogels were formed by cross-linking the PEG-LA nanocarriers with 4-arm PEG-NHS via degradable thioester bonds. The nanocarrier-based hydrogels formed within 20 min under ambient conditions and exhibited an elastic modulus that was 100-fold higher than the viscous modulus. The nanocarrier-based degradable hydrogels provided controlled release of lactic acid for several hours; however, a maximum release of only 10%–14% bound lactic acid was observed possibly due to steric hindrance of the polymer chains in the cross-linked hydrogel. In contrast, hydrogels with passively entrapped lactic acid showed burst release with complete release within 30 min. Lactic acid showed antimicrobial activity against the primary BV pathogen Gardnerella vaginalis with a minimum inhibitory concentration (MIC) of 3.6 mg/ml. In addition, the hydrogels with passively entrapped lactic acid showed retained antimicrobial activity with complete inhibition G. vaginalis growth within 48 h. The results of the current study collectively demonstrate the potential of PEG nanocarrier-based hydrogels for vaginal administration of lactic acid for preventing and treating BV.
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DOI：
10.1097/qad.0b013e32834541d9
发表时间：
2011-04-24
期刊：
AIDS (London, England)
影响因子：
--
作者：
Abdool Karim SS;Richardson BA;Ramjee G;Hoffman IF;Chirenje ZM;Taha T;Kapina M;Maslankowski L;Coletti A;Profy A;Moench TR;Piwowar-Manning E;Mâsse B;Hillier SL;Soto-Torres L;HIV Prevention Trials Network (HPTN) 035 Study Team
通讯作者：
HIV Prevention Trials Network (HPTN) 035 Study Team
影响因子：
56.3
作者：
Cutler, Blayne;Justman, Jessica
通讯作者：
Justman, Jessica
影响因子：
2.1
作者：
Atassi, Fabrice;Servin, Alain L.
通讯作者：
Servin, Alain L.
影响因子：
14
作者：
Anumolu, SivaNaga S.;DeSantis, Andrea S.;Menjoge, Anupa R.;Hahn, Rita A.;Beloni, John A.;Gordon, Marion K.;Sinko, Patrick J.
通讯作者：
Sinko, Patrick J.
影响因子：
14
作者：
Anumolu, SivaNaga S.;Menjoge, Anupa R.;Deshmukh, Manjeet;Gerecke, Donald;Stein, Stanley;Laskin, Jeffrey;Sinko, Patrick J.
通讯作者：
Sinko, Patrick J.