Cellulose-Derived Gels for Topical Delivery: HPMC as a Functional Matrix for Porphyrinic Photosensitizers

Hydroxypropyl methylcellulose (HPMC) is a biocompatible polymer widely used in topical formulations due to its suitable rheological behavior, film-forming capacity, and good compatibility with different active pharmaceutical ingredients. The present study demonstrates the potential of HPMC-based gels for dermal delivery of porphyrinic photosensitizers, aiming to enhance the efficiency of photodynamic therapy (PDT) in potential skin cancer applications. HPMC-based gel incorporating two previously synthesized porphyrinic photosensitizers, named 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2), was developed and carefully characterized regarding its rheological behavior, texture, and in vitro activity. Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), atomic force microscopy (AFM), fluorescence, and UV-Vis spectroscopy were carried out to evaluate the structural and morphological changes induced by the incorporation of the porphyrins in the HPMC gel matrix. The gels were subsequently evaluated by pharmacotechnical analysis, including pH (7.2 for both HPMC-P2.1 and HPMC-P2.2), viscosity, spreadability, texture profile analysis, and drug content uniformity. Rheological behavior confirmed the pseudoplastic behavior, suggesting a structured system with a gel-like consistency, while physical measurements demonstrated the stability and preserved functionality of the photosensitizers within the HPMC matrix. In vitro studies revealed an efficient cellular internalization of selected porphyrins into human epidermoid carcinoma cells, a critical requirement for topical PDT applications. The study highlights the capability of HPMC gels to serve as effective delivery platforms for porphyrin-based photosensitizers, supporting their application in localized skin cancer treatment through PDT.