Lyophilization and nebulization of pulmonary surfactant-coated nanogels for siRNA inhalation therapy.

Lyophilization and nebulization of pulmonary surfactant-coated nanogels for siRNA inhalation therapy.
Eur J Pharm Biopharm. 2020 Oct 03;:
Authors: Merckx P, Lammens J, Nuytten G, Bogaert B, Guagliardo R, Maes T, Vervaet C, De Beer T, De Smedt SC, Raemdonck K
Abstract
RNA interference (RNAi) enables highly specific silencing of potential target genes for treatment of pulmonary pathologies. The intracellular RNAi pathway can be activated by cytosolic delivery of small interfering RNA (siRNA), inducing sequence-specific gene knockdown on the post-transcriptional level. Although siRNA drugs hold many advantages over currently applied therapies, their clinical translation is hampered by inefficient delivery across cellular membranes. We previously developed hybrid nanoparticles consisting of an siRNA-loaded nanosized hydrogel core (nanogel) coated with Curosurf®, a clinically used pulmonary surfactant (PS). The latter enhances both particle stability as well as intracellular siRNA delivery, which was shown to be governed by the PS-associated surfactant protein B (SP-B). Despite having a proven in vitro and in vivo siRNA delivery potential when prepared ex novo, clinical translation of this liquid nanoparticle suspension requires the identification of a long-term preservation strategy that maintains nanoparticle stability and potency. In addition, to achieve optimal pulmonary deposition of the nanocomposite, its compatibility with state-o...

Source: European Journal of Pharmaceutics and Biopharmaceutics - October 2, 2020 Category: Drugs & Pharmacology Authors: Merckx P, Lammens J, Nuytten G, Bogaert B, Guagliardo R, Maes T, Vervaet C, De Beer T, De Smedt SC, Raemdonck K Tags: Eur J Pharm Biopharm Source Type: research