Topical delivery of TRPsiRNA-loaded solid lipid nanoparticles confer reduced pain sensation via TRPV1 silencing, in rats.

Abstract:

:Present work describes a novel composition for encapsulating TRPsiRNA (TRPV1-targeting siRNA) within lipid-matrix (4:1::glyceryl behnate:stearic acid) of SLNs, using suitably modified cold high-pressure homogenisation technique. Optimisation of the method and composition conducted using calf-thymus DNA (ctDNA), to avoid cost of TRPsiRNA molecules, resulted in small size (d50 = 50-100 nm) and high entrapment (77.22-98.5%). Complete masking of extreme negative charge of both ctDNA (-34.50 mV) and TRPsiRNA (-23.98 mV) upon encapsulation in SLNs without employing cationic components is reported herein for the first time. Diffusion-controlled release (90.17% at 72 h) from a rigid matrix shifted to porous matrix (at 24 h) due to solubilisation of stearic acid at 37 °C. Efficient in vitro (HEK293 T cells) and in vivo transfection and expression established the proof-of-concept. PEG600 as supporting-surfactant and vitrifying agent promoted small size, effective transfection and rupture of endosomal membrane to affect endosomal escape. Physiological efficacy in terms of significant increase (p < .0001) in paw-withdrawal-latency, following topical and intradermal application of TRPsiRNA-loaded SLNs, in rats, exposed to thermal hyperalgesia (145 and 182%, respectively) and capsaicin-induced pain (155 and 182%, respectively) indicate effective silencing of skin TRPV1. Significant decrease in intensity and duration (one-fifth) of capsaicin-induced nocifensive behaviour was also observed. Naked TRPsiRNA, however, did not show any effect.

journal_name

J Drug Target

authors

Sharma G,Chopra K,Puri S,Bishnoi M,Rishi P,Kaur IP

doi

10.1080/1061186X.2017.1350857

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

135-149

issue

2

eissn

1061-186X

issn

1029-2330

journal_volume

26

pub_type

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