Electron beam crosslinking of polyethylene glycol for the developing an hydrogel- and peptidomimetic-based antimicrobial drug

Introduction. Currently, the search for alternatives to conventional antibiotics, as well as for materials that do not exert an irritating effect on the body but can serve as a depot for antimicrobial substances, is highly relevant. The idea of developing a composition of a modified polyethylene glycol-based gel and an antimicrobial peptidomimetic is considered promising.

Aim. To study the physico-chemical processes of electron beam crosslinking of polyethylene glycol (PEG) in order to obtain a hydrogel with required properties and develop a depot-matrix for an antimicrobial peptidomimetic based on this technology.

Materials and methods . PEGs with a molecular weight of 400–40 000 Da was exposed to radiation, which involves polymer degradation and crosslinking. Their properties were studied, and a composition based on PEG and the antimicrobial peptidomimetic CAMP-1 (tripeptide H-Arg-Tbt-Arg-NH-C2H4-Ph) was developed.

Results . The gel was obtained using low-molecular-weight PEG and a radiation dose of 1,5–3 Mrad or high-molecular-weight PEG (over 4000 Da) and a radiation dose of 0,25 Mrad. To achieve gel formation by crosslinking, we used low-molecular-weight PEG (1,500 Da) and a radiation dose of 2 Mrad. The antibacterial peptidomimetic CAMP-1 was implanted into the gel obtained without technological complexity using a rotary homogenizer. An increase in the radiation dose led to a proportional decrease in gel flowability.

Conclusion. Varying the electron beam exposure parameters and PEG concentration allows to obtain hydrogels with the required properties for a depot-matrix intended to implant pharmacologically active agents. CAMP-1 is retained in a gel-like depot-matrix, and the diffusion of this peptidomimetic into the aqueous phase occurs at low intensity. Developing this technology of an antimicrobial drug makes it possible to produce prototypes of finished dosage forms for topical use.

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