Preparation and verification of dezocine polylactic acid-glycolic acid block copolymer microspheres / 中华麻醉学杂志

ABSTRACT

Objective:To prepare and preliminary verify dezocine polylactic acid-glycolic acid block copolymer (PLGA) microspheres.Methods:Preparation of dezocine PLGA microspheres Dezocine 120 mg, PLGA 0.1 g and the solubilizing additive poloxamer 0.1 g were dispersed in tetrahydrofuran solvent to form an organic phase solution. Sodium chloride and polyethylene glycol were dissolved in water for injection to form an inner aqueous phase solution and an outer aqueous phase solution. After the organic phase solution 20 ml was mixed with the inner aqueous phase solution 20 ml to form a water/oil colostrum, the water/oil colostrum was added to the outer aqueous phase solution to form a water/oil/water multiple emulsion, which was fully mixed with lyophilized powder protective agent and freeze-dried to prepare dezocine PLGA microspheres. Verification Eighteen clean-grade healthy male Sprague-Dawley rats, aged 10-12 weeks, weighing 220-260 g, were divided into 3 groups ( n=6 each) by a random number table method: control group (group C), dezocine ordinary preparation group (group D 1) and dezocine PLGA microspheres group (group D 2). Normal saline, dezocine injectio (dose 1 mg) and dezocine PLGA microsphere injectio (dose 0.2 μg) 0.2 ml were intramuscularly injected in C, D 1 and D 2 groups, respectively. The concentrations of dezocine in plasma were measured at 30 min and 1, 2, 3, 4, 5, 6, 7 and 8 h after administration, and thermal paw withdrawal latency was measured at T 1-T 3, T 5 and T 9. Tissues from the injection site were obtained on day 7 after intramuscular injection, and the inflammatory response was observed after HE staining. Results:Compared with group C, the thermal paw withdrawal latency was significantly prolonged at T 1-T 3 in group D 1 and at T 1-T 3, T 5 and T 9 in group D 2 ( P<0.05). Compared with group D 1, the thermal paw withdrawal latency was significantly prolonged at T 5 and T 9, and the plasma concentrations of dezocine were increased at T 6-T 9 in group D 2 ( P<0.05). Compared with the values at T 2, the plasma concentrations of dezocine were significantly decreased at T 4-T 9 in group D 1 ( P<0.05), and no significant change was found in the plasma concentrations of dezocine at T 3-T 9 in group D 2 ( P>0.05). On 7 days after injection, no inflammation was found in the local tissues in C, D 1 and D 2 groups, and no significant difference was found among the three groups. Conclusions:The sustained-release formulation of dezocine PLGA microspheres is successfully prepared, and it can maintain stable blood concentrations, effectively prolongs the action time of the drug and has significant sustained-release effect in rats.