Nanosized dendritic polyguanidilyated translocators for enhanced solubility, permeability, and delivery of gatifloxacin.

Purpose: Dendrimeric polyguanidilyated translocators (DPTs) are nanosized novel dendrimers that efficiently translocate molecules across biological barriers. The purpose of this study was to develop a DPT that could serve as an ophthalmic delivery vehicle for gatifloxacin and to evaluate its in vitro and in vivo delivery after topical application.

Methods: The gatifloxacin (GFX) solubility-enhancing property of a six-guanidine group-containing dendrimer (g6 DPT) was investigated as a function of pH and dendrimer concentration.

First-in-human mutation-targeted siRNA phase Ib trial of an inherited skin disorder.

The rare skin disorder pachyonychia congenita (PC) is an autosomal dominant syndrome that includes a disabling plantar keratoderma for which no satisfactory treatment is currently available. We have completed a phase Ib clinical trial for treatment of PC utilizing the first short-interfering RNA (siRNA)-based therapeutic for skin. This siRNA, called TD101, specifically and potently targets the keratin 6a (K6a) N171K mutant mRNA without affecting wild-type K6a mRNA.