Objective Encapsulation of esculetin into DSPE-MPEG2000 carrier was performed to improve its water solubility and oral bioavailability, as well as enhance its anti-inflammatory effect on a mouse model of ulcerative colitis that was induced with dextran sulphate sodium (DSS).Methods We determined the in-vitro and in-vivo high-performance liquid chromatographic (HPLC) analysis method of esculetin; Esculetin-loaded nanostructure lipid carrier (Esc-NLC) was prepared using a thin-film dispersion method, wherein a particle size analyser was used to measure the particle size (PS) and zeta potential (ZP) of the Esc-NLC, while a transmission electron microscope (TEM) was employed to observe its morphology. Also, HPLC was used to measure its drug loading (DL), encapsulation efficiency (EE) and the in-vitro release of the preparation, as well as investigate the pharmacokinetic parameters. In addition, its anti-colitis effect was evaluated via histopathological examination of HE-stained sections and detection of the concentrations of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (β), and IL-6 in serum with ELISA kits.Results The PS of Esc-NLC was 102.29 ± 0.63 nm with relative standard deviation (RSD) of 1.08% (with poly-dispersity index-PDI of 0.197 ± 0.023), while the ZP was −15.67 ± 1.39 mV with RSD of 1.24%. Solubility of esculetin was improved coupled with prolonged release time. Its pharmacokinetic parameters were compared with that of free esculetin, wherein the maximum concentration of the drug in plasma was increased by 5.5 times. Of note, bioavailability of the drug was increased by 1.7 times, while the half-life was prolonged by 2.4 times. In the anti-colitis efficacy experiment, the mice in Esc and Esc-NLC groups exhibited significantly reduced levels of TNF-α, IL-1β, and IL-6 in their sera comparable to the DSS group. Colon histopathological examination revealed that mice with ulcerative colitis in both Esc and Esc-NLC groups displayed improved inflammation, amid the Esc-NLC groups having the best prophylactic treatment effect.Conclusion Esc-NLC could ameliorate DSS-induced ulcerative colitis by improving bioavailability, prolonging drug release time and regulating cytokine release. This observation confirmed the potential of Esc-NLC to reduce inflammation in ulcerative colitis, albeit the need for follow-up research to verify the application of this strategy to clinical treatment of ulcerative colitis.
Li Chenglong,Lu Guanting,Jiang Yue,Su Huaiyu,Li Chen
Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the
global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no
known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor
on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic
distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant
role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune
response and inflammatory cytokine production.
Aim: The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions
(NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared
by high-pressure homogenization method and modified with DSPE-mPEG2000 and Ca(OH)2.
Methods: A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To
decrease aggregation and load EN, DSPE-mPEG2000 and Ca(OH)2 were successively decorated on the
surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were
investigated by using a laser particle size analyzer and transmission electron microscopy, respectively.
The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation.
In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development
of the mouse arthritis model.
Results: Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had
no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA)
mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as,
anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic
score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory
cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN.
Conclusion: NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work
provides an experimental foundation for expanding the clinical application of EN.
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