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Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery.

Xiao H, Wang L - Int J Nanomedicine (2015)

Bottom Line: To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized.Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method.Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People's Republic of China.

ABSTRACT
To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized. The formation of nanomicelles was proved with respect to the blue shift of the emission fluorescence as well as the fluorescent intensity increase of coumarin 6-loaded particles. The X-shaped polymers exhibited a smaller critical micelle concentration value and possessed higher micellar stability in comparison with those of linear ones. The size of X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles (XNMs) was much smaller than that of nanomicelles prepared with linear polymers. The reduction sensitivity of polymers was confirmed by the increase of micellar sizes as well as the in vitro drug release profile of DTX-loaded XNMs (DTX/XNMs). Cytotoxicity assays in vitro revealed that the blank XNMs were nontoxic against A2780 cells up to a concentration of 50 µg/mL, displaying good biocompatibility. DTX/XNMs were more toxic against A2780 cells than other formulations in both dose- and time-dependent manners. Cellular uptake assay displayed a higher intracellular drug delivery efficiency of XNMs than that of nanomicelles prepared with linear polymers. Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method. Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.

No MeSH data available.


Related in: MedlinePlus

(A) Typical SEM images of DTX/XNMs (insert: typical appearance of DTX/XNMs suspension). (B) Typical TEM images of DTX/XNMs. (C) In vitro drug release profile of DTX/XNMs. (D) Changes of particle size, PDI, and drug remaining percentage of DTX/XNMs in process of time.Abbreviations: DTX, docetaxel; XNMs, X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles; TEM, transmission electron microscopy; PDI, polydispersity index; PLGA, poly(lactic-co-glycolic acid); PEG, poly(ethylene glycol).
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f7-ijn-10-5309: (A) Typical SEM images of DTX/XNMs (insert: typical appearance of DTX/XNMs suspension). (B) Typical TEM images of DTX/XNMs. (C) In vitro drug release profile of DTX/XNMs. (D) Changes of particle size, PDI, and drug remaining percentage of DTX/XNMs in process of time.Abbreviations: DTX, docetaxel; XNMs, X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles; TEM, transmission electron microscopy; PDI, polydispersity index; PLGA, poly(lactic-co-glycolic acid); PEG, poly(ethylene glycol).

Mentions: As shown in Figure 7A, the DTX/XNMs suspension with milky-blue opalescence was obtained. The hydrodynamic size of nanomicelles was 77.38 nm with a PDI of 0.118, which were characterized by DLS. SEM and TEM were used to images to show the particle sizes as well as the morphology of nanomicelles (Figure 7B). No pores were observed on the surface of DTX/XNMs. In vitro drug release of DTX/XNMs was performed using a membrane dialysis apparatus. As shown in Figure 7C, a typical biphasic release pattern of DTX/XNMs was obtained under conditions without the addition of reducing agents, which included an initial burst release of approximately 33% during the first 4 hours followed by a sustained release of approximately 45% up to 120 hours. However, the release of DTX increased obviously in the presence of DTT in dialysis media (10 mmol/L). During the first 4 hours, approximately 45% of DTX was released from nanomicelles. In Figure 7D, the changes in particle size, PDI, and percentage of drug remaining of DTX/XNMs were analyzed. No obviously changes in both size and PDI were observed after 2 weeks, and the percentage of drug remaining of DTX/XNMs exhibited negligible decreases during the first week and declined to 85% from approximately 95% after another week, indicating the good physical stability of DTX/XNMs.


Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery.

Xiao H, Wang L - Int J Nanomedicine (2015)

(A) Typical SEM images of DTX/XNMs (insert: typical appearance of DTX/XNMs suspension). (B) Typical TEM images of DTX/XNMs. (C) In vitro drug release profile of DTX/XNMs. (D) Changes of particle size, PDI, and drug remaining percentage of DTX/XNMs in process of time.Abbreviations: DTX, docetaxel; XNMs, X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles; TEM, transmission electron microscopy; PDI, polydispersity index; PLGA, poly(lactic-co-glycolic acid); PEG, poly(ethylene glycol).
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f7-ijn-10-5309: (A) Typical SEM images of DTX/XNMs (insert: typical appearance of DTX/XNMs suspension). (B) Typical TEM images of DTX/XNMs. (C) In vitro drug release profile of DTX/XNMs. (D) Changes of particle size, PDI, and drug remaining percentage of DTX/XNMs in process of time.Abbreviations: DTX, docetaxel; XNMs, X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles; TEM, transmission electron microscopy; PDI, polydispersity index; PLGA, poly(lactic-co-glycolic acid); PEG, poly(ethylene glycol).
Mentions: As shown in Figure 7A, the DTX/XNMs suspension with milky-blue opalescence was obtained. The hydrodynamic size of nanomicelles was 77.38 nm with a PDI of 0.118, which were characterized by DLS. SEM and TEM were used to images to show the particle sizes as well as the morphology of nanomicelles (Figure 7B). No pores were observed on the surface of DTX/XNMs. In vitro drug release of DTX/XNMs was performed using a membrane dialysis apparatus. As shown in Figure 7C, a typical biphasic release pattern of DTX/XNMs was obtained under conditions without the addition of reducing agents, which included an initial burst release of approximately 33% during the first 4 hours followed by a sustained release of approximately 45% up to 120 hours. However, the release of DTX increased obviously in the presence of DTT in dialysis media (10 mmol/L). During the first 4 hours, approximately 45% of DTX was released from nanomicelles. In Figure 7D, the changes in particle size, PDI, and percentage of drug remaining of DTX/XNMs were analyzed. No obviously changes in both size and PDI were observed after 2 weeks, and the percentage of drug remaining of DTX/XNMs exhibited negligible decreases during the first week and declined to 85% from approximately 95% after another week, indicating the good physical stability of DTX/XNMs.

Bottom Line: To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized.Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method.Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People's Republic of China.

ABSTRACT
To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized. The formation of nanomicelles was proved with respect to the blue shift of the emission fluorescence as well as the fluorescent intensity increase of coumarin 6-loaded particles. The X-shaped polymers exhibited a smaller critical micelle concentration value and possessed higher micellar stability in comparison with those of linear ones. The size of X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles (XNMs) was much smaller than that of nanomicelles prepared with linear polymers. The reduction sensitivity of polymers was confirmed by the increase of micellar sizes as well as the in vitro drug release profile of DTX-loaded XNMs (DTX/XNMs). Cytotoxicity assays in vitro revealed that the blank XNMs were nontoxic against A2780 cells up to a concentration of 50 µg/mL, displaying good biocompatibility. DTX/XNMs were more toxic against A2780 cells than other formulations in both dose- and time-dependent manners. Cellular uptake assay displayed a higher intracellular drug delivery efficiency of XNMs than that of nanomicelles prepared with linear polymers. Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method. Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.

No MeSH data available.


Related in: MedlinePlus