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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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Preparation scheme of demonstrated injectable thermosensitive composite hydrogel. PECE hydrogel solutions were prepared by dissolving PECE copolymers in deionized water at a designated temperature then cooled to 4°C. Then, pluronic F127 were dissolved in icy cold deionized water to a transparent solution. Subsequently, the obtained two solutions were mixed together under mild agitation to obtain homogeneous liquid solution, and then drug were added into the composite hydrogel. The prepared hydrogel containing drug was inhaled into injector and injected into or around the focus of infection in animal. Thus, composite sol turned into gel state and acted as depots for sustained release of drug in situ when the cold sol is warmed to body temperature (37°C)in vivo. At last, for the degradation of the composite hydrogel, the introduced drug delivery system was gradually emanated from body.
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Figure 1: Preparation scheme of demonstrated injectable thermosensitive composite hydrogel. PECE hydrogel solutions were prepared by dissolving PECE copolymers in deionized water at a designated temperature then cooled to 4°C. Then, pluronic F127 were dissolved in icy cold deionized water to a transparent solution. Subsequently, the obtained two solutions were mixed together under mild agitation to obtain homogeneous liquid solution, and then drug were added into the composite hydrogel. The prepared hydrogel containing drug was inhaled into injector and injected into or around the focus of infection in animal. Thus, composite sol turned into gel state and acted as depots for sustained release of drug in situ when the cold sol is warmed to body temperature (37°C)in vivo. At last, for the degradation of the composite hydrogel, the introduced drug delivery system was gradually emanated from body.

Mentions: Preparation scheme of composite hydrogel was described in Fig. 1. Aqueous PECE solutions were prepared by dissolving PECE copolymers in deionized water at a designated temperature then cooled to 4°C. Then, different amounts of Pluronic F127 were dissolved in icy cold deionized water to a transparent solution. Subsequently, the obtained two solutions were mixed together under mild agitation to obtain a homogeneous liquid solution. The final solution contained a given concentration and composition of the two copolymers to form the different composite hydrogel samples. The composite hydrogels prepared in this work were listed in Table 1.


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)

Preparation scheme of demonstrated injectable thermosensitive composite hydrogel. PECE hydrogel solutions were prepared by dissolving PECE copolymers in deionized water at a designated temperature then cooled to 4°C. Then, pluronic F127 were dissolved in icy cold deionized water to a transparent solution. Subsequently, the obtained two solutions were mixed together under mild agitation to obtain homogeneous liquid solution, and then drug were added into the composite hydrogel. The prepared hydrogel containing drug was inhaled into injector and injected into or around the focus of infection in animal. Thus, composite sol turned into gel state and acted as depots for sustained release of drug in situ when the cold sol is warmed to body temperature (37°C)in vivo. At last, for the degradation of the composite hydrogel, the introduced drug delivery system was gradually emanated from body.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Preparation scheme of demonstrated injectable thermosensitive composite hydrogel. PECE hydrogel solutions were prepared by dissolving PECE copolymers in deionized water at a designated temperature then cooled to 4°C. Then, pluronic F127 were dissolved in icy cold deionized water to a transparent solution. Subsequently, the obtained two solutions were mixed together under mild agitation to obtain homogeneous liquid solution, and then drug were added into the composite hydrogel. The prepared hydrogel containing drug was inhaled into injector and injected into or around the focus of infection in animal. Thus, composite sol turned into gel state and acted as depots for sustained release of drug in situ when the cold sol is warmed to body temperature (37°C)in vivo. At last, for the degradation of the composite hydrogel, the introduced drug delivery system was gradually emanated from body.
Mentions: Preparation scheme of composite hydrogel was described in Fig. 1. Aqueous PECE solutions were prepared by dissolving PECE copolymers in deionized water at a designated temperature then cooled to 4°C. Then, different amounts of Pluronic F127 were dissolved in icy cold deionized water to a transparent solution. Subsequently, the obtained two solutions were mixed together under mild agitation to obtain a homogeneous liquid solution. The final solution contained a given concentration and composition of the two copolymers to form the different composite hydrogel samples. The composite hydrogels prepared in this work were listed in Table 1.

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