Photocytotoxicity studies of polyamidoamine (PAMAM) dendrimer and its glucoheptoamidated derivative as delivery drug systems in local PUVA photochemotherapy

8-methoxypsoralen (8-MOP) given topically in local PUVA photochemotherapy poorly penetrates through the skin to its deeper layers which restricts its effectiveness. Poly(amidoamine) (PAMAM) dendrimers enhanced 8-MOP permeation through the skin. The aim of this study was to investigate photocytotoxicity of the third generation PAMAM dendrimer (G3) and its glucoheptoamidated derivative (GD), a new delivery drug systems in local PUVA photochemotherapy. PAMAM dendrimer third generation (G3) as well as its glucoheptoamidated derivative (GD) were synthesized and used as macromolecular host to encapsulate 8-MOP. In our study, this is the first time we investigated the potential cytotoxicity of 8-MOP encapsulated in GD (4MOP@GD) to NIH-3T3 cells by a colorimetric method MTT compared to cytotoxicity of 4MOP@G3, 8-MOP and G3. The 4MOP@GD may be used as pharmaceutical substances applied systemically or topically which is why we tested the photoreactivity and estimated the phototoxic potential by the method based on the protocol of the validated NIH-3T3 NRU phototoxicity test. We confirmed our suspicions of lower toxicity 4MOP@GD compared to others testing substances. Increasing the concentration of the 4MOP@GD 200 times more than 4MOP@G3 maintains the cell viability at identical level. We are convinced that the use of the 4MOP@GD have a significant importance in the therapy by increasing the concentration of 8-MOP in the application site, together with increase safety for the patient. Using 8-MOP encapsulated in glycodendrimer at 4:1 stoichiometry (4MOP@GD) in local photochemotherapy with long-wavelength radiation makes possible to decrease dose UVA irradiation. The lower dose of local UVA results reducing risk of side effects like photocarcinogenesis. The 4MOP@GD is less cytotoxic than the encapsulate of 8-MOP in PAMAM G3 dendrimer (4MOP@G3). 4MOP@GD makes it possible to achieve concentrations five times higher than 4MOP@G3 in local PUVA photochemotherapy.