Dermal Microdialysis Technique to Evaluate the Trafficking of Surface-Modified Lipid Nanoparticles upon Topical Application

Abstract

Purpose The central objective of the current study was to evaluate the skin pharmacokinetics and tissue distribution of cell penetrating peptides (CPP) modified nano-structured lipid carrier (NLC) using an in vivo dermal microdialysis (MD) technique. Methods Celecoxib (Cxb) encapsulated NLCs (CXBN), CPP modified CXBN (CXBN-CPP) and Cxb-Solution (CXBS) formulations were prepared and tested for in vitro skin distribution. MD was used to assess pharmacokinetic parameters of Cxb after topical application of Cxb formulations. The effect of pre-treatment with Cxb formulations was evaluated for expression of prostaglandin-E2 (PGE2) and Interleukin-6 (IL-6) after exposure of xylene using MD. Allergic contact dermatitis (ACD) model was used to confirm in vivo therapeutic response of Cxb formulations. Results The cumulative permeation of Cxb in MD dialysate after 24 h for CXBN-CPP was significantly higher (p<0.001) than CXBN and CXBS. Further, pre-treatment with CXBN-CPP significantly inhibited PGE2 and IL-6 expression compared to CXBS and CXBN (p<0.001). In ACD model, CXBN-CPP showed significant reduction (p<0.001) in ear thickness compared to controls. Conclusions Surface modification of NLC with CPPs can enhance the skin permeation of Cxb and MD can be used to investigate pharmacokinetics of Cxb nanoparticles in the skin.

Topical delivery of anti-TNFα siRNA and capsaicin via novel lipid-polymer hybrid nanoparticles efficiently inhibits skin inflammation in vivo

“…The particle size and zeta potential of Blank-CyLiPn, C-CyLiPn, S-CyLiPn and CS-CyLiPn were measured using Nicomp 380 ZLS as explained previously [16–19]. The assay was performed by dissolving 100 µl of CyLiPn in 900 µl of ethanol.…”

“…While the siTNFα content was measured by the Quant-iT™ RiboGreen® RNA Kit (Molecular Probes, Inc., Eugene, OR, USA) according to the manufacturer’s instructions and the fluorescence was measured using Tecan® 200 PRO microplate reader (Männedorf, Switzerland). The entrapment efficiency of Cap in the C-CyLiPn and CS-CyLiPn was determined by using vivaspin columns as explained earlier [16]. Each sample was analyzed in triplicate.…”

“…Use of nanoparticle has shown great potential as novel drug delivery systems. [15–16]. Moreover, it offers the advantage of delivering multi therapeutic agents simultaneously [17–19].…”

Novel Gefitinib Formulation with Improved Oral Bioavailability in Treatment of A431 Skin Carcinoma

“…The solubility and dissolution of Gef can be improved by complexation with cyclodextrins (CDs) (18). There are several approaches to improve the solubility and oral bioavailability of poorly water soluble drugs among which the spray drying (SD) solid dispersions posses several advantages (19–23). SD has gained lot of importance owing to its relative simplicity, low cost and large scalability.…”

Microemulsion based gel for topical dermal delivery of pseudolaric acid B: In vitro and in vivo evaluation

“…SD rats were anesthetized with intraperitoneal injection of 0.25% urethane and placed on a temperature controlled heating pad (37 ± 2 o C) with the back facing the pad. MD was performed according to the previously reported (Desai et al, 2012;Zhang et al, 2015). In brief, a CMA 30 linear MD probe was implanted into the abdomen skin of the rat with the help of the needle introducer.…”