Dataset Information

Preparation and characterization of BSA-loaded liraglutide and platelet fragment nanoparticle delivery system for the treatment of diabetic atherosclerosis.

ABSTRACT:

Background

Diabetic atherosclerosis is one of the main causes of morbidity and mortality worldwide, but its therapeutic options are limited. Liraglutide (LIR), a synthetic analog of GLP-1 approved as an anti-obesity drug by the FDA, has been reported as a promising drug for diabetic atherosclerosis. However, the main problem with LIR is its use that requires regular parenteral injections, which necessitates the improvement of drug delivery for increased efficiency and minimization of injection numbers.

Results

The objective of our present study was to prepare and characterize nanoparticles (BSA@LIR-PMF) for targeted drug delivery using LIR-encapsulated platelet membrane fragments (PMF) coated bovine serum albumin (BSA). We used various methods to characterize the prepared nanoparticles and evaluated their efficiency on diabetes-induced atherosclerosis in vitro and in vivo. The results showed that the nanoparticles were spherical and had good stability and uniform size with intact membrane protein structure. The loading and encapsulation rates (LR and ER) of BSA@LIR-PMF were respectively 7.96% and 85.56%, while the cumulative release rate was around 77.06% after 24 h. Besides, we also examined the impact of BSA@LIR-PMF on the proliferation, migration, phagocytosis, reactive oxygen species (ROS) levels, oxidative phosphorylation, glycolysis, lactate and ATP levels, and lipid deposition in the aortas. The results indicated that BSA@LIR-PMF could effectively inhibit ox-LDL-stimulated abnormal cell proliferation and migration, reduce the level of ROS and lactate concentration, and enhance the level of ATP, thereby improving oxidative phosphorylation in ox-LDL-treated cells.

Conclusion

BSA@LIR-PMF significantly inhibited diabetes-induced atherosclerosis. It was anticipated that the BSA@LIR-PMF nanoparticles might be used for treating diabetes-associated cardiovascular complications.

SUBMITTER: He M

PROVIDER: S-EPMC11342552 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Preparation and characterization of BSA-loaded liraglutide and platelet fragment nanoparticle delivery system for the treatment of diabetic atherosclerosis.

He Mingping M Fang Ming M Fan Limin L Maimaitijiang Alimujiang A

Journal of nanobiotechnology 20240823 1

<h4>Background</h4>Diabetic atherosclerosis is one of the main causes of morbidity and mortality worldwide, but its therapeutic options are limited. Liraglutide (LIR), a synthetic analog of GLP-1 approved as an anti-obesity drug by the FDA, has been reported as a promising drug for diabetic atherosclerosis. However, the main problem with LIR is its use that requires regular parenteral injections, which necessitates the improvement of drug delivery for increased efficiency and minimization of inj ...[more]

PMID: 39180102

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Project description:Diabetes and periodontitis exhibit a bidirectional relationship, posing significant challenges for the treatment of periodontitis in patients with diabetes. Our previous studies showed that the hypoglycemic agent liraglutide (LIRA), together with glycemic control, had favorable therapeutic effects on diabetic periodontitis (DP), achieving a "two birds with one stone" effect. Therefore, exploration of the topical application of LIRA for treating DP is warranted. In this study, nanoparticles were loaded with LIRA using poly (lactic-co-glycolic acid) (PLGA), and their morphology, particle size, encapsulation efficiency, drug loading, and drug release profiles were characterized. These nanoparticles were further encapsulated with hyaluronic acid (HA) to form a LIRA@PLGA/HA sustained-release system. The cytotoxicity of LIRA@PLGA/HA was analyzed using CCK-8 assays, and its anti-inflammatory and osteogenic effects on periodontitis in diabetic rats were evaluated by histology, ELISA, and micro-CT analysis, while its influence on necroptosis-related factors was assessed using qRT-PCR and Western blotting. The results indicated that LIRA@PLGA (30000 Da) exhibited an encapsulation efficiency of 86.2 %, a drug loading capacity of 4.3 %, and a cumulative release of LIRA reaching approximately 60 % after 8 days, thereby meting the requirement for sustained release. Following 24 h of stimulation with various concentrations (0-20 mg/ml) of LIRA@PLGA/HA, the viability of human periodontal ligament cells (HPDLCs) remained above 85 %. Topical application for four weeks significantly inhibited the expression of the inflammatory factors TNF-α and IL-1β in gingival crevicular fluid and serum, reduced inflammatory cell infiltration in periodontal tissues, and attenuated alveolar bone resorption while improving alveolar bone microstructure, showing therapeutic effects similar to the commercial drug PERIOCLINE® (PERIO). Furthermore, LIRA@PLGA/HA reduced the expression of necroptosis-related factors RIPK1, RIPK3, and MLKL. In conclusion, these results suggest that topical application of LIRA@PLGA/HA is effective for the treatment of DP through inhibition of necroptosis, representing a promising treatment strategy.

Dataset Information

Preparation and characterization of BSA-loaded liraglutide and platelet fragment nanoparticle delivery system for the treatment of diabetic atherosclerosis.

Background

Results

Conclusion

Publications

Preparation and characterization of BSA-loaded liraglutide and platelet fragment nanoparticle delivery system for the treatment of diabetic atherosclerosis.

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