Hydrogels for dermal and transdermal drug delivery.

A painless and non-invasive method to deliver drugs using dermal and transdermal administration routes has been expanding for more than 30 years as it reduces the risk of drug overdoses that can be associated with oral administrations or injections. To understand the particularities of this drug delivery pathway, we will present a rapid review of the skin, including its structure and the parameters that influence drug diffusion into it, and then discuss the strategies that improve dermal drug delivery. Of the multitude of existing systems used for topical dermal and transdermal applications, this review will focus on the breakthroughs in drug delivery systems made of hydrogels. Specifically, we will firstly present the use of hydrogels as innovative drug delivery vehicles to carry the active ingredient and penetrate the skin barrier. We will discuss the structure of hydrogels and the physicochemical parameters to master for improving drug delivery, as well as the drug encapsulation and release processes from hydrogels. In the last part, we will review the use of hydrogels as pharmaceutical forms associated with other vehicles - as emulsions, lipid nanoparticles, vesicles, capsules and polymeric or inorganic nanoparticles - suitable for skin penetration enhancement and drug protection, as well as side effects that may limit their use.

Sealing hyaluronic acid microgels with oppositely-charged polypeptides: A simple strategy for packaging hydrophilic drugs with on-demand release.

A simple route to deliver on demand hydrosoluble molecules such as peptides, packaged in biocompatible and biodegradable microgels, is presented. Hyaluronic acid hydrogel particles with a controlled structure are prepared using a microfluidic approach. Their porosity and their rigidity can be tuned by changing the crosslinking density. These negatively-charged polyelectrolytes interact strongly with positively-charged linear peptides such as poly-l-lysine (PLL). Their interactions induce microgel deswelling and inhibit microgel enzymatic degradability by hyaluronidase. While small PLL penetrate the whole volume of the microgel, PLL larger than the mesh size of the network remain confined at its periphery. They make a complexed layer with reduced pore size, which insulates the microgel inner core from the outer medium. Consequently, enzymatic degradation of the matrix is fully inhibited and non-affinity hydrophilic species can be trapped in the core. Indeed, negatively-charged or small neutral peptides, without interactions with the network, usually diffuse freely across the network. By simple addition of large PLL, they are packaged in the core and can be released on demand, upon introduction of an enzyme that degrades selectively the capping agent. Single polyelectrolyte layer appears as a simple generic method to coat hydrogel-based materials of various scales for encapsulation and controlled delivery of hydrosoluble molecules.