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Journal of Peking University(Health Sciences) ›› 2018, Vol. 50 ›› Issue (6): 1070-1077. doi: 10.3969/j.issn.1671-167X.2018.06.023

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Preparation and evaluation of blank and doxorubicin loaded poly (acrylic acid) microspheres for embolization

Li-ying GUO1,Xiao-xin LIU1,Zi-yuan LI1,Xiao-ya QIN1,Ze-yang FAN2,Zhen-zhen LI2,Hai-tao GUAN2,Li SONG2,Ying-hua ZOU2,Tian-yuan FAN1,△()   

  1. 1. The State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University School of Pharmaceutical Sciences, Beijing 100191, China
    2. Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing 100034, China
  • Received:2018-05-02 Online:2018-12-18 Published:2018-12-18
  • Contact: Tian-yuan FAN E-mail:tianyuan_fan@bjmu.edu.cn
  • Supported by:
    Supported by the National Natural Science Foundation of China(81571779)

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Abstract:

Objective: To prepare ion exchange doxorubicin-loaded poly (acrylic acid) microspheres (DPMs) and evaluate the properties of these chemoembolic agents.Methods:Poly (acrylic acid) microspheres (PMs) without drug were prepared by inverse suspension polymerization method and then doxorubicin was loaded by ion exchange mechanism to prepare DPMs. Optical microscope was used to investigate the morphology and particle size distribution of PMs and DPMs; fluorescence microscope and confocal microscope were used to observe the distribution of doxorubicin after drug loading. Elasticities of both the microspheres were evaluated by texture analyzer. High performance liquid chromatography (HPLC) method was established to determine the drug loading behavior of PMs and releasing behavior of DPMs. The in vivo embolic property was evaluated by embolizing the hepatic artery of a rabbit with 0.1 mL of DPMs.Results:PMs and DPMs were both spherical in shape, smooth in surface and dispersed well. Doxorubicin was mainly in the outer area inside of DPMs and distributed evenly. The average particle size of PMs and DPMs were (283±136) μm and (248±149) μm, respectively. PMs and DPMs both had good compression ability with the Young’s modulus of (62.63±1.65) kPa and (93.94±1.10) kPa separately. PMs reached the drug loading balance at 12 h, and the entrapment efficiency was greater than 99%. Drug loading of PMs in doxorubicin solution at the concentration of 5.0 g/L and 12.5 g/L was (19.78±0.27) g/L and (49.45±0.37) g/L, respectively. Doxorubicin released slowly from DPMs in PBS and the accumulative release percentages of DPMs with corresponding drug loading were 6.82%±0.02% and 2.83%±0.10% after 24 h, respectively. Arterial angiograms showed that the hepatic artery of the rabbit was successfully embolized with DPMs.Conclusion:DPMs with good performance of loading doxorubicin could be a potential embolic agent for transcatheter arterial chemoembolization.

Key words: Microspheres, Chemoembolization, therapeutic, Ion exchange, Doxorubicin, Sustained release

CLC Number: 

  • R94

Figure 1

Drug loading (A) and entrapment efficiency (B) of PMs in different concentrations of doxorubicin"

Figure 2

PMs (A) and DPMs (B) under optical microscope (×64)"

Figure 3

DPMs under fluorescent microscope (×100)"

Figure 4

DPMs under confocal laser scanning microscope, showing progressive sections from outside inwards (A-D)"

Figure 5

Size distribution of PMs and DPMsPMs, poly (acrylic acid) microspheres; DPMs, doxorubicin-loaded poly (acrylic acid) microspheres."

Table 1

Young’s modulus, relaxation half time and residual force, percentage of failure deformation, failure stress, springiness,cohesiveness and resilience of PMs and DPMs (n=3)"

Microspheres PMs DPMs
Young’s modulus/kPa 62.63±1.65 93.94±1.10#
RHT/s 37.45±1.90 15.42±0.71#
Residual force/% 71.68±6.15 41.54±3.73#
Percentage of failure deformation/% 94.0±1.7 99.4±0.31#
Failure stress/N 0.43±0.13 0.70±0.04*
Springiness 0.73±0.02 0.69±0.02
Cohesiveness 0.74±0.04 0.61±0.08
Resilience 0.51±0.04 0.35±0.06*

Figure 6

Accumulative release of doxorubicin from DPMs with different drug loading (n=3)"

Figure 7

Arterial angiograms of hepatic artery before (A) and immediately after (B) embolization of a rabbit"

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