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Published on: December 27, 2013
Preparation and characterization of PLGA microspheres containing a staphylokinase variant (K35R)
Jin-Tian He1, Xian-Mei Tao, Wei Mo
1Key Laboratory of Molecular Medicine of Ministry of Education, Fudan University, Shanghai 200032, China. he_jintian@yahoo.com
Aim:
To produce poly (lactic-co-glycolic acid) (PLGA) microspheres, containing a staphylokinase variant (K35R, DGR) with reduced immunogenecity and antiplatelet aggregation activities, which allowed the preservation of protein stability during both particle processing and drug release.
Methods:
DGR-loaded microspheres were fabricated using a double emulsion-solvent evaporation technique. The effects of preparative parameters, such as stirring rate, polymer concentration, and the excipients of both internal and external aqueous phase (W2), on DGR encapsulation efficiency and microsphere characteristics were investigated. In vitro and in vivo release of DGR were conducted and the cause for instability of DGR during release was also investigated.
Results:
Moderate ultrasonic treatment of aqueous DGR/dichloromethane mixtures caused approximately. Eighty four per cent DGR denaturation. However, the activity recovery of DGR almost amounted to 100% when 2% polyvinyl alcohol (PVA) was addled into the aqueous phase. It was found that NaCl in the external water phase significantly increased DGR encapsulation efficiency. Furthermore, NaCl in the external water phase played a role in determining size and surface morphology of microsphere. In vitro release test showed a burst release of DGR from microspheres, followed by sustained release of 50% total activity over 15 days. In vivo experiments showed that DGR released from microspheres sustained 5 days. Denaturation of DGR within microspheres might be resulted from acidic microclimate.
Conclusion:
The stability of DGR was effectively protected during microencapsulation and a relatively high encapsulation efficiency of DGR was obtained. PLGA microspheres could be an effective carrier for DGR.
Insights
Poly (lactic-co-glycolic acid) microspheres effectively encapsulate a staphylokinase variant (DGR), preserving its stability. These microspheres provide sustained drug release, demonstrating their potential as a viable therapeutic carrier.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Protein Engineering
Background:
- Staphylokinase variants, such as K35R (DGR), offer reduced immunogenicity and antiplatelet activity.
- Protein stability during microencapsulation and release is a critical challenge in developing effective drug delivery systems.
Purpose of the Study:
- To develop poly (lactic-co-glycolic acid) (PLGA) microspheres for encapsulating a staphylokinase variant (DGR).
- To ensure protein stability during particle processing and subsequent drug release.
- To investigate the impact of formulation parameters on DGR encapsulation and microsphere characteristics.
Main Methods:
- Microspheres were fabricated using a double emulsion-solvent evaporation technique.
- The influence of stirring rate, polymer concentration, and aqueous phase excipients on encapsulation efficiency and microsphere properties was examined.
- In vitro and in vivo release studies were performed to assess DGR release profiles and stability.
Main Results:
- Polyvinyl alcohol (PVA) addition aided in near-complete activity recovery of DGR post-processing.
- Sodium chloride (NaCl) in the external aqueous phase significantly enhanced DGR encapsulation efficiency and influenced microsphere size and morphology.
- In vitro release showed an initial burst followed by sustained release over 15 days; in vivo release sustained for 5 days.
Conclusions:
- PLGA microspheres effectively protect DGR stability during microencapsulation, achieving high encapsulation efficiency.
- PLGA microspheres represent a promising carrier system for the delivery of DGR.
