SummaryNanoparticles (NP) of poly(lactic-co-glycolic acid) (PLGA) represent a promising biodegradable drug delivery system. We suggest here a two-step release system of PLGA nanoparticles with a pH-tunable polymeric shell, providing an initial pH-triggered step, releasing a membrane-toxic cationic compound. PLGA nanoparticles are coated by polyelectrolytes using the layer-by-layer self-assembly technique, employing poly(acrylic acid) (PAA) as a pH-sensitive component and poly(diallyldimethylammonium chloride) (PDADMAC) as the releasable polycation. The pH during multilayer deposition plays a major role and influences the titration curve of the layer system. The pH-tunability of PAA is intensively investigated with regard to the pH region, in which the particle system becomes uncharged. The isoelectric point can be shifted by employing suitable deposition pH values. The release is investigated by quantitative 1H NMR, yielding a pH-dependent release curve. A release of PDADMAC is initiated by a decrease of the pH value. The released amount of polymer, as quantified by 1H NMR analysis, clearly depends on the pH value and thus on the state of deprotonation of the pH-sensitive PAA layer. Subsequent incubation of the nanoparticles with high concentrations of sodium chloride shows no further release and thus demonstrates the pH-driven release to be quantitative.

This prospective, open-label, multicentre, multinational, randomised trial investigated the non-inferiority of treatment with a vaginal hormone-free moisturising cream compared to a vaginal estriol (0.1%) cream in a panel of post-menopausal women suffering from symptoms of vulvovaginal dryness in a parallel group design. In total, 172 post-menopausal women were randomly allocated to either one of the two treatments, each administered for 43 days. The primary endpoint was the total severity score of subjective symptoms (dryness, itching, burning and pain unrelated to sexual intercourse) of the respective treatment period. Secondary endpoints were severity of single subjective symptoms (including dyspareunia if sexually active), impairment of daily life, Vaginal Health Index, as well as assessment of safety. In both groups, women treated with hormone-free moisturising cream and those treated with estriol cream, total severity score improved significantly compared to baseline by 5.0 (from 6.1 to 1.1) and by 5.4 (from 6.0 to 0.6), respectively, after 43 days of treatment (p < 0.0001). One-sided test of baseline differences (for a clinically relevant difference Δ = 1.5) confirmed the hormone-free moisturising cream to be non-inferior to the estriol cream. Severity of dyspareunia as well as impairment of daily life due to subjective symptoms, significantly improved for both treatment groups (p<0.0001). Subgroup analysis of women with mild or moderate impairment of daily life at baseline caused by “vaginal dryness” symptoms benefited from both creams, while women with severe impairment showed a significantly greater benefit from the estriol cream (p = 0.0032). Both treatments were well tolerated with no serious adverse events occurring. This study provides clinical evidence that a hormone-free vaginal moisturising cream cannot only improve vaginal dryness compared to an 0.1% estriol cream but also can relieve dyspareunia as well as improve woman’s impairment of daily life, justifying its use as a first choice for mild or moderate vulvovaginal dryness symptoms.

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