Preparation and characterization of poly (lactic-co-glycolic acid) microspheres for controlled release of osteogenic growth peptide

Jinhui SONG; Shuqiang MA; Kunzheng WANG; Daocheng WU; Wei WANG; Mingyu ZHANG; Binxiu ZHAO

ABSTRACT

BACKGROUND:

Previous animal studies have revealed that osteogenic growth peptide (OGP) applied locally or systemically could promote fracture healing. But the disadvantages of short in vivo half-life and low oral bioavailability limit its clinical application.

OBJECTIVE:

To study the encapsulation and delivery of synthetic OGP (sOGP) from biodegradable polymeric microspheres in vitro so as to choose better carrier for the future study.

DESIGN:

Grouping observation and comparative trail.

SETTING:

Laboratory of School of Life Science and Technology, Xi'an Jiaotong University.MATERIALS sOGP was synthesized by Xi'an Langene Bio-science Co., Ltd. with Fmoc system. The purity of sOGP after purification was over 98 % identified by reverse phase high performance liquid chromatography, and the molecular weight of sOGP was 1 523 650, which was consistent with the theoretical value (Mr 1 523 750); the result of whole sequence analysis of sOGP was consistent with the theoretical sequence of OGP. Poly (lactic-co-glycolic acid) (PLGA,5050, Mr 30 000; 7525 Mr 80 000) was obtained from Shandong Medical Instrumental Institute (Ji'nan, China)

METHODS:

PLGA with a 5050 or 7525 lactide to glycolide ratio was used for microsphere preparation using a modified double emulsion solvent extraction Water-in-oil-in-water (w/o/w) technique. The surface structure and appearance of microsphere was observed under scanning electron microscope; particle size distribution of microsphere was counted by laser diffraction particle sizer; efficiency of encapsulation, release time and the structural integrity of sOGP released from PLGA were assessed using high performance liquid chromatography (HPLC).

RESULTS:

①Spherical microspheres of sOG-PLGA were formulated successfully. The average particle diameter of the PLGA 5050 microsphere was (19.6±4.5) μm, efficiency of encapsulation (83.9±4.2)% with (83.9±4.2) % drug-loading efficiency, while the PLGA 7525 microspheres showed an average size of (35.8±3.6) μm, efficiency of encapsulation (65.6±6.8)% with (65.6±6.8)% drug-loading efficiency. ②HPLC results indicated that sOGP were not chemically altered,physically aggregated but presented a intact structure as the original sOGP. An initial burst release was observed for both PLGA microspheres, especially from PLGA 7525. sOGP was released from PLGA 5050 microsphere for 56 days,and from PLGA 7525 microspheres for over 70 days. The cumulative release of sOGP from PLGA 5050 for 35 days was significantly lower than from PLGA 7525 (P ＜ 0.05).

CONCLUSION:

The controlled release of sOGP encapsulated within PLGA 5050 is better than the delivery from PLGA 7525. Moreover, the release time could meet the requirements for fracture or bone defect site.