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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: 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.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.

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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Sol-gel-sol transition phase diagram of composite hydrogel.
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Figure 3: Sol-gel-sol transition phase diagram of composite hydrogel.

Mentions: PECE and Pluronic F127 copolymers are both amphiphilic in nature, whose aqueous solution individually presented sol-gel-sol transition behavior. The composite hydrogel prepared in this work were composed of the two copolymers. As presented in Table 1, composite hydrogel based on PECE and Pluronic F127 copolymers from S1 to S6 all showed temperature-dependent reversible sol-gel-sol phase transition. The composite hydrogel flowed freely at lower temperature, but became a non-flowing gel at body temperature about 37°C (Fig. 2). Fig. 3 presented the sol-gel-sol phase transition diagrams of prepared composite hydrogel. When the copolymer concentrations are above the critical gelation concentration (CGC), aqueous solutions of composite hydrogel changed from "sol" phase to "gel" phase with increase in temperature to the lower critical gelation temperature (LCGT). With further increase of temperature to upper critical gelation temperature (UCGT), the sol phase occurs.


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)

Sol-gel-sol transition phase diagram of composite hydrogel.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Sol-gel-sol transition phase diagram of composite hydrogel.
Mentions: PECE and Pluronic F127 copolymers are both amphiphilic in nature, whose aqueous solution individually presented sol-gel-sol transition behavior. The composite hydrogel prepared in this work were composed of the two copolymers. As presented in Table 1, composite hydrogel based on PECE and Pluronic F127 copolymers from S1 to S6 all showed temperature-dependent reversible sol-gel-sol phase transition. The composite hydrogel flowed freely at lower temperature, but became a non-flowing gel at body temperature about 37°C (Fig. 2). Fig. 3 presented the sol-gel-sol phase transition diagrams of prepared composite hydrogel. When the copolymer concentrations are above the critical gelation concentration (CGC), aqueous solutions of composite hydrogel changed from "sol" phase to "gel" phase with increase in temperature to the lower critical gelation temperature (LCGT). With further increase of temperature to upper critical gelation temperature (UCGT), the sol phase occurs.

Bottom Line: 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.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.

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
Related in: MedlinePlus