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. 2023 Jun 9;28(12):4659.
doi: 10.3390/molecules28124659.

Preparation, Properties and Therapeutic Effect of a TPL Nanoparticle Thermosensitive Gel for Intra-Articular Injection

Affiliations

Preparation, Properties and Therapeutic Effect of a TPL Nanoparticle Thermosensitive Gel for Intra-Articular Injection

Lijuan Wang et al. Molecules. .

Abstract

Most injectable preparations for the articular cavity are solution-type preparations that are frequently administered because of rapid elimination. In this study, triptolide (TPL), an effective ingredient in the treatment of rheumatoid arthritis (RA), was prepared in the form of a nanoparticle thermosensitive gel (TPL-NS-Gel). The particle size distribution and gel structure were investigated by TEM, laser particle size analysis and laser capture microdissection. The effect of the nanoparticle carrier material PLGA on the phase transition temperature was investigated by 1H variable temperature NMR and DSC. The tissue distribution, pharmacokinetic behavior, four inflammatory factors and therapeutic effect were determined in a rat RA model. The results suggested that PLGA increased the gel phase transition temperature. The drug concentration of the TPL-NS-Gel group in joint tissues was higher than that in other tissues at different time points, and the retention time was longer than that of the TPL-NS group. After 24 days of administration, TPL-NS-Gel significantly improved the joint swelling and stiffness of the rat models, and the improvement degree was better than that of the TPL-NS group. TPL-NS-Gel significantly decreased the levels of hs-CRP, IL-1, IL-6 and TNF-α in serum and joint fluid. There was a significant difference between the TPL-NS-Gel and TPL-NS groups on Day 24 (p < 0.05). Pathological section results showed that inflammatory cell infiltration was lower in the TPL-NS-Gel group, and no other obvious histological changes were observed. Upon articular injection, the TPL-NS-Gel prolonged drug release, reduced the drug concentration outside the articular tissue and improved the therapeutic effect in a rat RA model. The TPL-NS-Gel can be used as a new type of sustained-release preparation for articular injection.

Keywords: intra-articular injection; nanoparticle; therapeutic effect; thermosensitive gel; triptolide.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
TPL-NS-Gel ((A). the uniform emulsion of TPL-NS with blue opalescence as shown by the arrow; (B). the particle size of the microspheres measured by TEM; (C). The size distribution of the microspheres measured by the Malvern laser particle size analyzer; (D). the transition of TPL-NS-Gel from 4 °C to body temperature; (E). the internal structures of TPL-NS-Gel from 4 °C to 35 °C were detected with laser capture microdissection system).
Figure 2
Figure 2
The effect of PLGA on the phase transition temperature of poloxamer gel measured by 1H variable temperature NMR. ((A). the hydrogen NMR spectra of poloxamer thermosensitive gel; (B). the chemical shifts of PO-CH3 and PO-CH2- at 18 °C, 25 °C, 32 °C; (C). the change of chemical shift in PO-CH3 and PO-CH2- for TPL-NS-Gel containing 1%, 5% and 10% TPL at 18 °C, 20 °C, 22 °C, 24 °C, 26 °C, 28 °C, 30 °C and 32 °C).
Figure 3
Figure 3
The effect of PLGA on the phase transition temperature of poloxamer gel measured by DSC ((A). the poloxamer gel without PLGA nanoparticle; (B). the poloxamer gel with 5% PLGA nanoparticle).
Figure 4
Figure 4
The photographs of the diseased joint in three groups after administration. (A). TPL-NS-Gel group (before administration); (B). TPL-NS-Gel group (24 days after administration); (C). TPL-NS group (before administration); (D). TPL-NS group (24 days after administration); (E). Control group (before administration); (F). Control group (24 days after administration).
Figure 5
Figure 5
The standard curves and R2 of hs-CRP, IL-1, IL-6 and TNF-α in serum and articular fluid were determined by ELISA ((A). hs-CRP, (B). IL-1, (C). IL-6, (D). TNF-α).
Figure 6
Figure 6
The mean plasma concentration–time curve for TPL-NS-Gel group (A) and TPL-NS group (B) after articular cavity administration at 10 mg/kg in RA rats (Mean ± SD, n = 3). Blood samples were collected at 30 min, 8 h, 1 d, 2 d, 3 d, 5 d, 8 d, 12 d, 16 d, and 24 d after dosing.
Figure 7
Figure 7
The histological view of different tissues in Rat RA models after administration (HE staining, 20×).

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