Bottom-Up Strategy to Forecast the Drug Location and Release Kinetics in Antitumoral Electrospun Drug Delivery Systems

Electrospun systems are becoming promising devices usable for topical treatments. They are eligible to deliver different therapies, from anti-inflammatory to antitumoral. In the current research, polycaprolactone electrospun membranes loaded with synthetic and commercial antitumoral active substances were produced, underlining how the matrix-filler affinity is a crucial parameter for designing drug delivery devices. Nanofibrous membranes loaded with different percentages of Dacarbazine (the drug of choice for melanoma) and a synthetic derivative of Dacarbazine were produced and compared to membranes loaded with AuM1, a highly active Au-complex with low affinity to the matrix. AFM morphologies showed that the surface profile of nanofibers loaded with affine substances is similar to one of the unloaded systems, thanks to the nature of the matrix-filler interaction. FTIR analyses proved the efficacy of the interaction between the amidic group of the Dacarbazine and the polycaprolactone. In AuM1-loaded membranes, because of the weak matrix-filler interaction, the complex is mainly aggregated in nanometric domains on the nanofiber surface, which manifests a nanometric roughness. Consequently, the release profiles follow a Fickian behavior for the Dacarbazine-based systems, whereas a two-step with a highly prominent burst effect was observed for AuM1 systems. The performed antitumoral tests evidence the high-cytotoxic activity of the electrospun systems against melanoma cell lines, proving that the synthetic substances are more active than the commercial dacarbazine.

Automated summary

Electrospun systems have shown potential in topical treatments, particularly in delivering different therapies such as anti-inflammatory and antitumoral substances. This study focused on producing polycaprolactone electrospun membranes loaded with antitumoral substances and comparing their performance with membranes loaded with a highly active but low affinity complex. The findings highlighted the importance of the matrix-filler affinity in designing effective drug delivery devices. Additionally, the study showed that synthetic derivatives of the antitumoral substance were more active than the commercial dacarbazine.