Delivery Of Photosensitizers For Photodynamic Therapy Research Articles

Silk Fibroin/Poly(vinyl Alcohol) Microneedles as Carriers for the Delivery of Singlet Oxygen Photosensitizers.

Photodynamic therapy (PDT) is a medical treatment in which a combination of a photosensitizing drug and visible light produces highly cytotoxic reactive oxygen species (ROS) that leads to cell death. One of the main drawbacks of PDT for topical treatments is the limited skin penetration of some photosensitizers commonly used in this therapy. In this study, we propose the use of polymeric microneedles (MNs) prepared from silk fibroin and poly(vinyl alcohol) (PVA) to increase the penetration efficiency of porphyrin as possible applications in photodynamic therapy. The microneedle arrays were fabricated from mixtures in different proportions (1:0, 7:3, 1:1, 3:7, and 0:1) of silk fibroin and PVA solutions (7%); the polymer solutions were cast in polydimethylsiloxane (PDMS) molds and dried overnight. Patches containing grids of 10 × 10 microneedles with a square-based pyramidal shape were successfully produced through this approach. The polymer microneedle arrays showed good mechanical strength under compression force and sufficient insertion depth in both Parafilm M and excised porcine skin at different application forces (5, 20, 30, and 40 N) using a commercial applicator. We observe an increase in the cumulative permeation of 5-[4-(2-carboxyethanoyl) aminophenyl]-10,15,20-tris-(4-sulphonatophenyl) porphyrin trisodium through porcine skin treated with the polymer microneedles after 24 h. MNs may be a promising carrier for the transdermal delivery of photosensitizers for PDT, improving the permeation of photosensitizer molecules through the skin, thus improving the efficiency of this therapy for topical applications.

Photoactive Pore Matrix for In Situ Delivery of a Photosensitizer in Vascular Smooth Muscle Cells Selective PDT.

In this study we present the porous silica-based material that can be used for in situ drug delivery, offering effective supply of active compounds regardless its water solubility. To demonstrate usability of this new material, three silica-based materials with different pore size distribution as a matrix for doping with Photolon (Ph) and Protoporphyrin IX (PPIX) photosensitizers, were prepared. These matrices can be used for coating cardiovascular stents used for treatment of the coronary artery disease and enable intravascular photodynamic therapy (PDT), which can modulate the vascular response to injury caused by stent implantation—procedure that should be thought as an alternative for drug eluting stent. The FTIR spectroscopic analysis confirmed that all studied matrices have been successfully functionalized with the target photosensitizers. Atomic force microscopy revealed that resulting photoactive matrices were very smooth, which can limit the implantation damage and reduce the risk of restenosis. No viability loss of human peripheral blood lymphocytes and no erythrocyte hemolysis upon prolonged incubations on matrices indicated good biocompatibility of designed materials. The suitability of photoactive surfaces for PDT was tested in two cell lines relevant to stent implantation: vascular endothelial cells (HUVECs) and vascular smooth muscle cells (VSMC). It was demonstrated that 2 h incubation on the silica matrices was sufficient for uptake of the encapsulated photosensitizers. Moreover, the amount of the absorbed photosensitizer was sufficient for induction of a phototoxic reaction as shown by a rise of the reactive oxygen species in photosensitized VSMC. On the other hand, limited reactive oxygen species (ROS) induction in HUVECs in our experimental set up suggests that the proposed method of PDT may be less harmful for the endothelial cells and may decrease a risk of the restenosis. Presented data clearly demonstrate that porous silica-based matrices are capable of in situ delivery of photosensitizer for PDT of VSMC.

Addendum to “Photosensitizer delivery for photodynamic therapy of choroidal neovascularization”: [Adv. Drug Deliv. Rev. 52 (2001) 63–78

Addendum to “Photosensitizer delivery for photodynamic therapy of choroidal neovascularization”: [Adv. Drug Deliv. Rev. 52 (2001) 63–78