One-pot and gram-scale synthesis of biodegradable polyglycerols under ambient conditions: nanocarriers for intradermal drug delivery

Hyperbranched polyglycerols (hPGs) have a variety of biomedical applications due to their unique physicochemical properties such as biocompatibility and multi-functionality. However, their lack of biodegradability under physiological conditions hampers their in vivo applications. Therefore, the development of straightforward methods for the synthesis of biodegradable hyperbranched polyglycerols is of great importance. In this work, caprolactone segments were incorporated into the backbone of polyglycerols by a one-pot, ring-opening copolymerization of glycidol and e-caprolactone under ambient conditions. While the synthesized polyglycerols were susceptible to enzymatic cleavage, they were stable under neutral and acidic conditions. In spite of their high cellular uptake that was proven by laser scanning confocal microscopy (LSCM), the MTT assay did not show a significant toxicity against HaCaT cells up to 1000 mu g ml(-1). The biodegradability and biocompatibility of the synthesized polymers together with their ability to form nanoparticles in aqueous solutions and loading of hydrophobic guest molecules encourage us to evaluate their application as intradermal delivery systems. Ex vivo skin penetration tests showed that the synthesized polymers enhanced the Nile red penetration into the skin upon enzymatic degradation. While polymers stayed at the superficial stratum corneum, the released cargo penetrated into the deeper layers of the skin.