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Skin, the largest organ of the human body, has its integrity compromised after injuries. In severe cases, it can lead to chronic wounds. Chronic wounds show no tendency to heal over a period of 4 - 6 weeks and are highly vulnerable to bacterial infections. A key feature of these infections is the formation of biofilms. Although there are various wound dressings available currently, it is difficult to find a single polymer that meets all the requirements. Usually, polymers need to be chemically or physically functionalized, or specific monomers are used for synthesis to control their intrinsic properties.
The electrospinning technique, often carried out with an electrospinning machine, has great potential in wound treatment due to the high specific surface area, high porosity and other characteristics of nanofibers. Poly(beta-amino) esters (PBAE), as a new class of polymers, can be synthesized from a variety of monomers and possess multiple properties. They were originally used in gene therapy and have potential applications in the field of biomaterials in recent years. However, there are few studies on using PBAE in electrospinning combined with drug delivery systems.
Professor Degoutin's team from the University of Lille published the latest research findings titled "Poly(BETA-AMINO) ester based electrospun membranes with modulated degradation and release kinetics for potential wound dressing applications" in the journal International Journal of Pharmaceutics. The team successfully developed a bioactive membrane loaded with antibiotics (ciprofloxacin) by synthesizing poly(beta-amino) esters (PBAE) with different chain lengths and combining electrospinning technology, which involves the use of an electrospinning machine, and UV cross-linking methods. This achievement provides a new idea for the design of dressings for chronic wound treatment. By adjusting the molecular structure of PBAE, the degradation rate of the membrane and the drug release behavior can be precisely regulated to meet the dual requirements of antibacterial and tissue repair in chronic wound treatment.
The research team synthesized two poly(beta-amino) ester (PBAE) macromers, named Short Unit PBAE (SU-PBAE) and Long Unit PBAE (LU-PBAE), by reacting isobutylamine with two polyethylene glycol diacrylates with different molecular weights (PEGDA-250 and PEGDA-575). These two macromers exhibited different hydrophobicity and crystallinity: SU-PBAE had lower hydrophilicity (contact angle of 62.9°), while LU-PBAE had higher hydrophilicity (contact angle of 43.9°) (see Figs. 2 and 6).
Subsequently, electrospun membranes were successfully prepared by mixing PBAE macromers with polyethylene glycol (PEO) through the electrospinning technique. The electrospinning solution, prepared for use in the electrospinning machine, contained 14.8% PBAE macromers, 5.5% PEO and 0.6% photoinitiator (DMPA), and the spinning was carried out in DMF solvent. The electrospun membranes were further cross-linked by ultraviolet light to enhance their stability and mechanical properties. SEM micrographs showed the fiber morphology and diameter distribution of the electrospun membranes (see Fig. 4).
The physicochemical properties (such as hydrophilicity and crystallinity) of the prepared membranes were similar to those of the constituent PBAE macromers. For example, the SU-PBAE membrane showed lower hydrophilicity, while the LU-PBAE membrane showed higher hydrophilicity. In addition, DSC analysis indicated that the LU-PBAE membrane remained semi-crystalline after UV cross-linking, while the SU-PBAE membrane remained amorphous (see Fig. 5).
Ciprofloxacin (CFX) was successfully loaded into the membranes at a concentration of 1% (relative to the total polymer mass). The actual loading rates of CFX in the SU-PBAE/PEO membrane and the LU-PBAE/PEO membrane reached 90.2% (± 6.0%) and 80.3% (± 7.0%) of the theoretical amount (10.0 mg/g), respectively. Drug release experiments showed that both membranes exhibited an obvious burst release effect, followed by a slow release. The drug release rates of the SU-PBAE membrane and the LU-PBAE membrane reached 98.6% and 83.1% within 96 hours, respectively. Kirby-Bauer diffusion tests and Kill time tests indicated that the released CFX had antibacterial activity against E. coli. After 24 hours of contact, the SU-PBAE/PEO membrane and the LU-PBAE/PEO membrane reduced the number of bacteria by an average of 5.8 Log10 and 3.7 Log10, respectively. Fig. 9 shows the cumulative release curve of CFX, and Figs. 11 and 12 show the antibacterial activity test results, respectively.
This study confirmed the feasibility of preparing electrospun membranes loaded with ciprofloxacin (CFX) using synthesized PBAE macromers with different polymer chain sizes and properties. The use of UV cross-linking successfully overcame the major problem of poor stability of PBAE compounds in water, regardless of the nature of the PBAE membrane. The research indicated that PBAE macromers are ideal materials for preparing electrospun mats with a porous morphology, and their diverse properties can be effectively transferred to the membranes. In this project, only two different macromers were synthesized and electrospun, but these results opened up new prospects for the application of other PBAE compounds in the design of drug delivery systems.
Article source: https://doi.org/10.1016/j.ijpharm.2025.125476