Self-healable and injectable hydrogel platforms for the gynaecological therapies constructed on star-shaped poly(furfuryl glycidyl ether)-block-poly(glyceryl glycerol ether) as an efficient agent for nifuratel solubility enhancement

Vulvovaginitis is one of the most common gynaecological diseases worldwide [1]. The treatment usually involves vaginal suppositories. This treatment, however, suffers from poor adhesive properties and a short retention time of water-insoluble drugs. A drug worth noting due to a broad antimicroorganism activity, i.e., against bacterias, fungi and Trichomonas vaginalis is nifuratel. Polymer platforms for gyneacological therapies seem to be a good candidate to improve the treatment of vaginal infections thanks to prolonging the retention time with mucosa. The properties of polymers allow for the increase in the solubility of the drugs and controlled release [2]. Moreover, hydrogels construction on reversible cross-links assures the shape adjustment to the covered surface, and thus the formation of continuous coverage of infected areas.

The presentation addresses the challenge of the development of improved drug-solubility platforms. For enhancement of nifuratel solubility in water, we managed to synthesize the star-shaped unimolecular micelles by the anionic ring-opening copolymerization of furfuryl glycidyl ether and (1,2-isopropylidene glyceryl) glycidyl ether. The deprotection of the latter gave the hydrophilic 1,2-diols in the shell. The monomers were chosen carefully regarding their molecular structure. The furan containing side groups of the hydrophobic polymer segments, according to the rule: “like dissolves like”, was intended to improve the solubility of nifuratel which also contains the furan moiety in its structure. The 1,2-diol entities in the hydrophilic poly(glyceryl glycerol ether) chain ensured the solubility of the construct in water. Furthermore, it allowed for the formation of boronic esters from boronic acids and 1,2-diols. The cross-linking process assured the self-healing properties of prepared nifuratel-loaded hydrogel platforms.

The micelles exhibited high nifuratel loading capacity, the diffusion-controlled release mechanism revealed in vitro release studies. The micelles showed no cytotoxicity towards HeLa cells. Moreover, it has been noticed that the gel flows under applied stress and can therefore be delivered by a syringe to the afflicted area.

Funding: This work was supported by the National Science Centre, Poland (UMO-2018/30/E/ST5/00576).

References:
[1] Loveless, M.; Myint, O., Best Practice & Research: Clinical Obstetrics & Gynaecology 2018, 48, 14-27.
[2] Palmeira-de-Oliveira, R.; Palmeira-de-Oliveira, A.; Martinez-de-Oliveira, J., Advanced Drug Delivery Reviews 2015, 92, 105-122.