已发表论文

用聚精氨酸肽修饰的纳米结构脂质载体凝胶改善氯诺昔康经皮给药以治疗角叉菜胶诱导的大鼠足爪水肿

 

Authors Gao S, Tian B, Han J, Zhang J, Shi Y, Lv Q, Li K

Received 14 February 2019

Accepted for publication 12 June 2019

Published 2 August 2019 Volume 2019:14 Pages 6135—6150

DOI https://doi.org/10.2147/IJN.S205295

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Thiruganesh Ramasamy

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun

Background: Nanostructured lipid carriers (NLCs) are emerging as attractive drug carriers in transdermal drug delivery. The surface modification of NLCs with cell-penetrating peptides (CPPs) can enhance the skin permeation of drugs.
Purpose: The objective of the current study was to evaluate the ability of the cell-penetrating peptide (CPP) polyarginine to translocate NLCs loaded with lornoxicam (LN) into the skin layers and to evaluate its anti-inflammatory effect.
Methods: The NLCs were prepared using an emulsion evaporation and low temperature solidification technique using glyceryl monostearates, triglycerides, DOGS-NTA-Ni lipids and surfactants, and then six histidine-tagged polyarginine containing 11 arginine (R11) peptides was modified on the surface of NLCs.
Results: The developed NLCs formulated with LN and R11 (LN-NLC-R11) were incorporated into 2% HPMC gels. NLCs were prepared with a particle size of (121.81±3.61)–(145.72±4.78) nm, and the zeta potential decreased from (−30.30±2.07) to (−14.66±0.74) mV after the modification of R11 peptides. The encapsulation efficiency and drug loading were (74.61±1.13) % and (7.92±0.33) %, respectively, regardless of the surface modification. Cellular uptake assays using HaCaT cells suggested that the NLC modified with R11 (0.02%, w/w) significantly enhanced the cell internalization of nanoparticles relative to unmodified NLCs (<0.05 or <0.01). An in vitro skin permeation study showed better permeation-enhancing ability of R11 (0.02%, w/w) than that of other content (0.01% or 0.04%). In carrageenan-induced rat paw edema models, LN-NLC-R11 gels inhibited rat paw edema and the production of inflammatory cytokines compared with LN-NLC gels and LN gels (<0.01).
Conclusion: In our investigation, it was strongly demonstrated that the surface modification of NLC with R11 enhanced the translocation of LN across the skin, thereby alleviating inflammation.
Keywords: lornoxicam, nanostructured lipid carriers, cell penetrating peptides, transdermal drug delivery, anti-inflammatory effect




Figure 3 Cell uptake of different formulations in HaCaT cells analyzed by flow cytometry.