Improved In vitro and In vivo Cutaneous Delivery of Protoporphyrin IX from PLGA-based Nanoparticles

We report the development of d, l lactic co‐glycolic acid) (PLGA)‐based nanoparticles (NPs) for topical delivery of protoporphyrin IX (PpIX), a photosensitizer (PS), in treatments like photodynamic therapy (PDT) of skin cancers. PpIX‐NPs were obtained in ~75.0% yield, encapsulation efficiency of 67.7%, drug content of 50.3 μg mg−1, average diameter of 290 nm maintained up to 30 days and a zeta potential of 32.3 mV. Sustained in vitro release of PpIX through artificial membranes following Higuchi kinetics was kept up to 10 days. In vitro retentions of PpIX both in stratum corneum (SC) and epidermis + dermis ([EP + D]) were higher from NPs (23.0 and 10.0 times, respectively) compared to control solutions at all times. Quantification of PpIX by extraction, after in vivo skin application of NPs‐PpIX on hairless mice, showed higher retention of the PS both in SC and in [EP + D] (3.0 and 2.0 times, respectively) compared to control solutions. Taken together, the results indicate that NPs are suitable for PpIX encapsulation showing minimal permeation through the skin and a localized effect, characteristics of a potential and promising delivery system for PDT‐associated treatments of skin cancers, photodiagnosis and their off‐label uses. Polymeric Nanoparticles (Nps) are emerging as an effective drug delivery system for hydrophobic photosensitizers in photodynamic therapy (PDT). In brief, PpIX‐loaded NPs could improve (in vitro and in vivo) drug residence in deeper skin (i.e. EP + D), the target tissue for PDT in cutaneous tumors, without increasing transdermal transport. These NPs may be potential for topical application of PpIX as photosensitizer for PDT of skin cancers. In a typical scheme of cutaneous PDT, after application of photosensitizer‐loaded Np and laser light source, the conversion of the triplet singlet oxygen into singlet will cause desired tumor destruction.