Preparation of long-acting microspheres loaded with octreotide for the treatment of portal hypertensive

Abstract

The purpose of this study was to optimize the preparation method of injectable Octreotide microspheres. To explore the correlation between the solvent system and the general properties of microspheres to reduce burst release and enable them to be used for portal hypertension. Octreotide microspheres were prepared by modified double emulsion solution evaporation method after optimizing preparation conditions. The results showed that Octreotide microspheres had a particle size of 57.48 ± 15.24 μm, and the initial release was significantly reduced. In vitro release and in vivo pharmacokinetic data indicated that Octreotide was released stably within 1200 h. The effects on portal vein pressure, liver tissue morphology and other related indexes were observed after administration. As obvious results, injection of Octreotide microspheres could significantly reduce portal vein pressure and reduce the portal vein lumen area in experimental cirrhotic portal hypertensive rats. The optimized Octreotide PLGA microsphere preparation has been proved to have a good effect on PHT in vivo after detecting aminotransferase (AST) and alanine aminotransferase (ALT) activity, liver tissue hydroxyproline (Hyp) content, serum and liver tissue malondialdehyde (MDA) levels, plasma prostacyclin (PGI 2 ) levels, and liver tissue tumor necrosis factor (TNFα) content. In addition, serum and liver tissue superoxide dismutase (SOD) activity and liver tissue glutathione (GSH) content, plasma thromboxane (TXA 2 ), serum nitric oxide (NO), liver tissue nitric oxide synthase (NOS), and plasma and liver tissue endothelin (ET) were significantly increased.

Clinical efficacy of total laparoscopic splenectomy for portal hypertension and its influence on hepatic hemodynamics and liver function

“…Therefore, the debate regarding the best treatment for PH has been ongoing worldwide but remains controversial[ 13 ]. It has been suggested previously that conventional treatment and surgery for PH cannot prevent emergencies or pain and that long-acting medications offer the opportunity to improve the patient’s quality of life[ 14 ]. However, some evidence suggests that this treatment may compromise hemodynamic stability[ 15 ].…”

Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization: in vitro and in vivo evaluation

“…NAR-ME and NAR-Susp were immersed in a system of a fixed volume (100 mL) and in a closed and relatively static environment, respectively. However, while in vitro release tests can provide important parameters for in vivo research to a certain extent, they can never replace in vivo tests (Han et al., 2021 ). The drug release curves were fitted to different models, and for NAR-ME, the correlation coefficient R 2 of the Higuchi release model was the highest.…”

Structural Evolution of the Pharmaceutical Peptide Octreotide upon Controlled Relative Humidity and Temperature Variation

“…Additionally, studies have delved into octreotide's pharmacokinetic profile, encompassing aspects such as ADME characteristics essential for optimizing dosing regimens and predicting therapeutic outcomes [29][30][31]. Furthermore, formulation strategies for octreotide have been explored to enhance its stability, bioavailability, and duration of action through novel delivery systems and formulations [32][33][34]. Notably, oral capsules have been developed to enable the oral delivery of octreotide, demonstrating promising stability and desired bioavailability in preclinical and clinical studies [24].…”