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Local drug delivery systems based on biodegradable nanofibers for cancer photodynamic therapy PDT

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Chitosan/nanocellulose electrospun fibers with enhanced antibacterial and antifungal activity for wound dressing applications
Publication . Ribeiro, Ana S.; Costa, Sofia M.; Ferreira, Diana P.; Calhelha, Ricardo C.; Barros, Lillian; Stojković, Dejan; Soković, Marina; Ferreira, Isabel C.F.R.; Fangueiro, Raul
The combination of biodegradable fibers at nanoscale with plant-based extracts is attracting increasing attention to produce wound dressing systems. In this work, nanofibers based on chitosan (CS), poly(ethylene oxide) (PEO), cellulose nanocrystals (CNC) and acacia plant-based extract were developed by electrospinning. Firstly, the polymeric formulations and electrospinning parameters were optimized, resulting in nanofibers with average diameters of 80 nm. CNC were successfully introduced into the optimized CS/PEO blend and the membranes were characterized by FESEM, ATR-FTIR, TGA, XRD, WVTR and WCA. The CNC incorporation improved the nanofibers' physical integrity, morphology, diameters, water vapor transmission rate and thermal properties. After acacia introduction into the best CS/PEO/CNC system, the antibacterial effect was relatively maintained while the antifungal activity was enhanced for some fungi, demonstrating its great effect against a wide range of microorganisms, which is crucial to prevent or treat infections. All the developed systems exhibited absence of cytotoxicity in non-tumor cells, suggesting their biocompatibility. Finally, a continuous release of the acacia extract was observed for 24 h, showing its prolonged action, which contributes to the healing process while reduces the frequency of dressing's replacement. Overall, the developed nanofibers are very promising to act as localized drug delivery systems for wound care applications.
Electrospun polycaprolactone membranes functionalized with nanochitin for enhanced bioactivity in localized cancer photodynamic therapy
Publication . Costa, Sofia M.; Mattos, Bruno D.; Calhelha, Ricardo C.; Zhu, Ya; Lima, Eurico; Reis, Lucinda; Rojas, Orlando J.; Fangueiro, Raul; Ferreira, Diana P.
The encapsulation of photosensitizers (PSs) in electrospun membranes has emerged as a promising approach in photodynamic therapy (PDT) on tumor sites, overcoming the drawbacks associated with systemic administration. In this work, localized implants for cancer treatment using PDT were developed by incorporating EL-2 squaraine into poly(epsilon-caprolactone) (PCL) electrospun microfibers. The latter were coated with chitin nanocrystals (ChNC) by electrospraying, which may improve the biocompatibility and bioactivity of the developed membranes, potentially enhancing the clinical outcomes. The developed electrospun membranes were characterized by water contact angle, imaging, and spectroscopy techniques. The uniform encapsulation and distribution of EL-2 within the microfibers were confirmed while ChNC endowed the membranes with surface hydrophilicity. EL-2 alone displayed about 20 times more cytotoxicity after irradiation compared to the dark condition against HeLa cervical carcinoma cells. Meanwhile, the photodynamic action of PCL+EL-2/ChNC membranes promoted a significant inhibition of cancer cells' proliferation under irradiation, achieving 66.25 % of inhibition, compared to only 24.78 % in dark conditions, using the highest concentration of EL-2. Overall, this work introduces a disruptive strategy using electrospinning-electrospraying to design fibrous therapeutic platforms for cancer PDT, taking advantage of electrospun fibers unique features and the localized nature of photodynamic therapy.

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Funding agency

Fundação para a Ciência e a Tecnologia

Funding programme

POR_NORTE

Funding Award Number

SFRH/BD/147517/2019

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