Stabilization and encapsulation of a staphylokinase variant (K35R) into poly(lactic-co-glycolic acid) microspheres

Jin Tian He, Huabo Su, Guo Ping Li, Xian Mei Tao, Wei Mo, Hou Yan Song

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The aim of this study is to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres containing a staphylokinase variant K35R (DGR) with purpose of preserving the protein stability during both encapsulation and drug release. DGR-loaded microspheres are fabricated using a double-emulsion solvent extraction technique. Prior to encapsulation, the effect of ultrasonication emulsification of DGR solutions with methylene chloride on protein recovery was investigated. Moderate ultrasonic treatment of aqueous DGR/dichloromethane mixtures caused approximately 84% DGR aggregation. Polyvinyl alcohol (PVA) added into aqueous DGR solutions significantly improved DGR recovery to >90%. The effects of co-encapsulated PVA and NaCl in the external aqueous phase on the characteristics of the microspheres were investigated. When 2% PVA was co-encapsulated and 2.5% NaCl was added to the external water phase, DGR encapsulation efficiency was significantly increased from 7.1% to 78.1% and DGR was distributed uniformly throughout the microspheres. In vitro release test showed that DGR was released from PLGA microspheres in a sustained manner over 15 days. A large amount of released DGR was inactive in the absence of co-encapsulated PVA. On the contrary, when 2% PVA was co-encapsulated, the released DGR was almost completely intact within 9 days. In conclusion, PLGA microspheres can be an effective carrier for DGR and form a promising depot system.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
JournalInternational Journal of Pharmaceutics
Volume309
Issue number1-2
DOIs
StatePublished - Feb 17 2006
Externally publishedYes

Fingerprint

Polyvinyl Alcohol
Microspheres
Methylene Chloride
Protein Stability
Emulsions
Ultrasonics
Staphylococcus aureus auR protein
polylactic acid-polyglycolic acid copolymer
Water
Proteins

Keywords

  • Microspheres
  • Polyvinyl alcohol
  • Protein delivery
  • Protein stability
  • Staphylokinase

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Stabilization and encapsulation of a staphylokinase variant (K35R) into poly(lactic-co-glycolic acid) microspheres. / He, Jin Tian; Su, Huabo; Li, Guo Ping; Tao, Xian Mei; Mo, Wei; Song, Hou Yan.

In: International Journal of Pharmaceutics, Vol. 309, No. 1-2, 17.02.2006, p. 101-108.

Research output: Contribution to journalArticle

He, Jin Tian ; Su, Huabo ; Li, Guo Ping ; Tao, Xian Mei ; Mo, Wei ; Song, Hou Yan. / Stabilization and encapsulation of a staphylokinase variant (K35R) into poly(lactic-co-glycolic acid) microspheres. In: International Journal of Pharmaceutics. 2006 ; Vol. 309, No. 1-2. pp. 101-108.
@article{1905c4acb96d437fb37b9ce581c1d30b,
title = "Stabilization and encapsulation of a staphylokinase variant (K35R) into poly(lactic-co-glycolic acid) microspheres",
abstract = "The aim of this study is to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres containing a staphylokinase variant K35R (DGR) with purpose of preserving the protein stability during both encapsulation and drug release. DGR-loaded microspheres are fabricated using a double-emulsion solvent extraction technique. Prior to encapsulation, the effect of ultrasonication emulsification of DGR solutions with methylene chloride on protein recovery was investigated. Moderate ultrasonic treatment of aqueous DGR/dichloromethane mixtures caused approximately 84{\%} DGR aggregation. Polyvinyl alcohol (PVA) added into aqueous DGR solutions significantly improved DGR recovery to >90{\%}. The effects of co-encapsulated PVA and NaCl in the external aqueous phase on the characteristics of the microspheres were investigated. When 2{\%} PVA was co-encapsulated and 2.5{\%} NaCl was added to the external water phase, DGR encapsulation efficiency was significantly increased from 7.1{\%} to 78.1{\%} and DGR was distributed uniformly throughout the microspheres. In vitro release test showed that DGR was released from PLGA microspheres in a sustained manner over 15 days. A large amount of released DGR was inactive in the absence of co-encapsulated PVA. On the contrary, when 2{\%} PVA was co-encapsulated, the released DGR was almost completely intact within 9 days. In conclusion, PLGA microspheres can be an effective carrier for DGR and form a promising depot system.",
keywords = "Microspheres, Polyvinyl alcohol, Protein delivery, Protein stability, Staphylokinase",
author = "He, {Jin Tian} and Huabo Su and Li, {Guo Ping} and Tao, {Xian Mei} and Wei Mo and Song, {Hou Yan}",
year = "2006",
month = "2",
day = "17",
doi = "10.1016/j.ijpharm.2005.11.036",
language = "English (US)",
volume = "309",
pages = "101--108",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Stabilization and encapsulation of a staphylokinase variant (K35R) into poly(lactic-co-glycolic acid) microspheres

AU - He, Jin Tian

AU - Su, Huabo

AU - Li, Guo Ping

AU - Tao, Xian Mei

AU - Mo, Wei

AU - Song, Hou Yan

PY - 2006/2/17

Y1 - 2006/2/17

N2 - The aim of this study is to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres containing a staphylokinase variant K35R (DGR) with purpose of preserving the protein stability during both encapsulation and drug release. DGR-loaded microspheres are fabricated using a double-emulsion solvent extraction technique. Prior to encapsulation, the effect of ultrasonication emulsification of DGR solutions with methylene chloride on protein recovery was investigated. Moderate ultrasonic treatment of aqueous DGR/dichloromethane mixtures caused approximately 84% DGR aggregation. Polyvinyl alcohol (PVA) added into aqueous DGR solutions significantly improved DGR recovery to >90%. The effects of co-encapsulated PVA and NaCl in the external aqueous phase on the characteristics of the microspheres were investigated. When 2% PVA was co-encapsulated and 2.5% NaCl was added to the external water phase, DGR encapsulation efficiency was significantly increased from 7.1% to 78.1% and DGR was distributed uniformly throughout the microspheres. In vitro release test showed that DGR was released from PLGA microspheres in a sustained manner over 15 days. A large amount of released DGR was inactive in the absence of co-encapsulated PVA. On the contrary, when 2% PVA was co-encapsulated, the released DGR was almost completely intact within 9 days. In conclusion, PLGA microspheres can be an effective carrier for DGR and form a promising depot system.

AB - The aim of this study is to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres containing a staphylokinase variant K35R (DGR) with purpose of preserving the protein stability during both encapsulation and drug release. DGR-loaded microspheres are fabricated using a double-emulsion solvent extraction technique. Prior to encapsulation, the effect of ultrasonication emulsification of DGR solutions with methylene chloride on protein recovery was investigated. Moderate ultrasonic treatment of aqueous DGR/dichloromethane mixtures caused approximately 84% DGR aggregation. Polyvinyl alcohol (PVA) added into aqueous DGR solutions significantly improved DGR recovery to >90%. The effects of co-encapsulated PVA and NaCl in the external aqueous phase on the characteristics of the microspheres were investigated. When 2% PVA was co-encapsulated and 2.5% NaCl was added to the external water phase, DGR encapsulation efficiency was significantly increased from 7.1% to 78.1% and DGR was distributed uniformly throughout the microspheres. In vitro release test showed that DGR was released from PLGA microspheres in a sustained manner over 15 days. A large amount of released DGR was inactive in the absence of co-encapsulated PVA. On the contrary, when 2% PVA was co-encapsulated, the released DGR was almost completely intact within 9 days. In conclusion, PLGA microspheres can be an effective carrier for DGR and form a promising depot system.

KW - Microspheres

KW - Polyvinyl alcohol

KW - Protein delivery

KW - Protein stability

KW - Staphylokinase

UR - http://www.scopus.com/inward/record.url?scp=31144447377&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=31144447377&partnerID=8YFLogxK

U2 - 10.1016/j.ijpharm.2005.11.036

DO - 10.1016/j.ijpharm.2005.11.036

M3 - Article

C2 - 16413979

AN - SCOPUS:31144447377

VL - 309

SP - 101

EP - 108

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -