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In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) copolymer.

Gong CY, Shi S, Dong PW, Zheng XL, Fu SZ, Guo G, Yang JL, Wei YQ, Qian ZY - BMC Biotechnol. (2009)

Bottom Line: Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients.A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition.The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China. chygong14@yahoo.com.cn

ABSTRACT

Background: Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy.

Results: A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and in vitro drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 microg per well. Vitamin B12 (VB12), honokiol (HK), and bovine serum albumin (BSA) were used as model drugs to investigate the in vitro release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate.

Conclusion: The results showed that composite hydrogel prepared in this paper were biocompatible with low cell cytotoxicity, and the drugs in this work could be released slowly from composite hydrogel in an extended period, which suggested that the composite hydrogel might have great potential applications in biomedical fields.

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SEM photograph of composite hydrogel before and after drug release. S1 hydrogel before (A) and after (B) drug release for 8 hours. S3 hydrogel before (C) and after (D) drug release for 8 hours.
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Figure 8: SEM photograph of composite hydrogel before and after drug release. S1 hydrogel before (A) and after (B) drug release for 8 hours. S3 hydrogel before (C) and after (D) drug release for 8 hours.

Mentions: Interior morphology of composite hydrogel before and 8 hours after drug released was investigated by SEM. The composite hydrogels were frozen in liquid nitrogen and lyophilized for 72 h before the test. According to Fig. 8, all the hydrogel samples showed porous three-dimension structure, but the shape and mesh size of pores in the hydrogel were different. As shown in Fig. 8–A, S1 hydrogel before drug release presented approximately spherical pore with small mesh size. S3 hydrogel (Fig. 8–C), composed of 60% PECE hydrogel and 40% Pluronic F127 hydrogel, also showed spherical pores, but have larger mesh size compared to S1 hydrogel. The morphology of S1 and S3 hydrogel suggested that the composition of composite hydrogel have great influence on their interior structure, which dramatically affected the drug release behavior of composite hydrogel. Eight hours after drug released, S1 hydrogel could maintain its integrity, but the hydrogel surface eroded (Fig. 8–B). In Fig. 8–D, S3 hydrogel after immersed in PBS for 8 hours showed large pores and cracks, due to the fast-eroding of Pluronic F127 from the composite hydrogel.


In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) copolymer.

Gong CY, Shi S, Dong PW, Zheng XL, Fu SZ, Guo G, Yang JL, Wei YQ, Qian ZY - BMC Biotechnol. (2009)

SEM photograph of composite hydrogel before and after drug release. S1 hydrogel before (A) and after (B) drug release for 8 hours. S3 hydrogel before (C) and after (D) drug release for 8 hours.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2654890&req=5

Figure 8: SEM photograph of composite hydrogel before and after drug release. S1 hydrogel before (A) and after (B) drug release for 8 hours. S3 hydrogel before (C) and after (D) drug release for 8 hours.
Mentions: Interior morphology of composite hydrogel before and 8 hours after drug released was investigated by SEM. The composite hydrogels were frozen in liquid nitrogen and lyophilized for 72 h before the test. According to Fig. 8, all the hydrogel samples showed porous three-dimension structure, but the shape and mesh size of pores in the hydrogel were different. As shown in Fig. 8–A, S1 hydrogel before drug release presented approximately spherical pore with small mesh size. S3 hydrogel (Fig. 8–C), composed of 60% PECE hydrogel and 40% Pluronic F127 hydrogel, also showed spherical pores, but have larger mesh size compared to S1 hydrogel. The morphology of S1 and S3 hydrogel suggested that the composition of composite hydrogel have great influence on their interior structure, which dramatically affected the drug release behavior of composite hydrogel. Eight hours after drug released, S1 hydrogel could maintain its integrity, but the hydrogel surface eroded (Fig. 8–B). In Fig. 8–D, S3 hydrogel after immersed in PBS for 8 hours showed large pores and cracks, due to the fast-eroding of Pluronic F127 from the composite hydrogel.

Bottom Line: Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients.A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition.The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China. chygong14@yahoo.com.cn

ABSTRACT

Background: Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy.

Results: A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and in vitro drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 microg per well. Vitamin B12 (VB12), honokiol (HK), and bovine serum albumin (BSA) were used as model drugs to investigate the in vitro release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate.

Conclusion: The results showed that composite hydrogel prepared in this paper were biocompatible with low cell cytotoxicity, and the drugs in this work could be released slowly from composite hydrogel in an extended period, which suggested that the composite hydrogel might have great potential applications in biomedical fields.

Show MeSH