title: Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment.
abstract: 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, pH7.4) and acetate buffer (AB, pH4.3), 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.
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: Sujata
authors.initials: S
authors.lastname: Sundara Rajan
authors.affiliation: School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: Yevgeniy
authors.initials: Y
authors.lastname: Turovskiy
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: Yashveer
authors.initials: Y
authors.lastname: Singh
authors.affiliation: School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Chikindas
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA. Electronic address: sinko@rci.rutgers.edu.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Sinko
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004777:Environment; D004847:Epithelial Cells / Q000187:drug effects; D005079:Excipients / Q000737:chemistry; D005260:Female; D006194:Gardnerella vaginalis / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D007773:Lactates / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D012212:Rheology; D016585:Vaginosis, Bacterial / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D004337:Drug Carriers; D005079:Excipients; D020100:Hydrogels; D007773:Lactates; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols
keywords: Bacterial vaginosis; Controlled release; Hydrogel; Lactic acid; Poly(ethylene glycol)