Water-responsive gel extends drug retention and facilitates skin penetration for curcumin topical delivery against psoriasis

Psoriasis is a chronic inflammatory skin disease characterized by erythema,scaling,and skin thickening.Topical drug application is recommended as the first-line treatment.Many formulation strategies have been developed and explored for enhanced topical psoriasis treatment.However,these preparations usually have low viscosity and limited retention on the skin surface,resulting in low drug delivery efficiency and poor patient satisfaction.In this study,we developed the first water-responsive gel(WRG),which has a distinct water-triggered liquid-to-gel phase transition property.Specifically,WRG was kept in a solution state in the absence of water,and the addition of water induced an immediate phase transition and resulted in a high viscosity gel.Curcumin was used as a model drug to investigate the potential of WRG in topical drug delivery against psoriasis.In vitro and in vivo data showed that WRG formulation could not only extend skin retention but also facilitate the drug permeating across the skin.In a mouse model of psoriasis,curcumin loaded WRG(CUR-WRG)effectively ameliorated the symptoms of psoriasis and exerted a potent anti-psoriasis effect by extending drug retention and facilitating drug penetration.Further mechanism study demonstrated that the anti-hyperplasia,anti-inflammation,anti-angiogenesis,anti-oxidation,and immunomodulation properties of curcumin were amplified by enhanced topical drug delivery efficiency.Notably,neglectable local or systemic toxicity was observed for CUR-WRG application.This study suggests that WRG is a promising formulation for topically psoriasis treatment.

Film-Forming Systems in Topically Administered Pharmaceutical Formulations

The skin is the most extensive and outermost organ in the body and can be greatly exploited both from the point of view of alternative routes of systemic drug delivery and treatment of dermatological diseases. Because of its main function as a barrier against harmful external agents, it also becomes a barrier to drug administration, but there are strategies to reduce this limitation of this promising route of administration. The development of polymer-based film-forming formulations is extensively studied for this purpose, since the formation of a film on the skin increases the contact time of the drug, for this being characterized as a controlled release reservoir system. There are a multitude of possible polymers to compose these formulations and their choice must be made according to the purpose of each application. This work, therefore, aims to study the state of the art of film forming systems for topical application of pharmaceutical formulations.

Metal alginates for polyphenol delivery systems: Studies on crosslinking ions and easy-to-use patches for release of protective flavonoids in skin

Incorporation of bioactive natural compounds like polyphenols is an attractive approach for enhanced functionalities of biomaterials.In particular flavonoids have important pharmacological activities,and controlled release systems may be instrumental to realize the full potential of these phytochemicals.Alginate presents interesting attributes for dermal and other biomaterial applications,and studies were carried here to support the development of polyphenol-loaded alginate systems.Studies of capillary viscosity indicated that ionic medium is an effective strategy to modulate the polyelectrolyte effect and viscosity properties of alginates.On gelation,considerable differences were observed between alginate gels produced with Ca^2+,Ba^2+,Cu^2+,Fe^2+,Fe^3+and Zn^2+as crosslinkers,especially concerning shrinkage and morphological regularity.Stability assays with different polyphenols in the presence of alginate-gelling cations pointed to the choice of calcium,barium and zinc as safer crosslinkers.Alginate-based films loaded with epicatechin were prepared and the kinetics of release of the flavonoid investigated.The results with calcium,barium and zinc alginate matrices indicated that the release dynamics is dependent on film thicknesses,but also on the crosslinking metal used.On these grounds,an alginate-based system of convenient use was devised,so that flavonoids can be easily loaded at simple point-of-care conditions before dermal application.This epicatechin-loaded patch was tested on an ex-vivo skin model and demonstrated capacity to deliver therapeutically relevant concentrations on skin surface.Moreover,the flavonoid released was not modified and retained full antioxidant bioactivity.The alginate-based system proposed offers a multifunctional approach for flavonoid controllable delivery and protection of skin injured or under risk.