低频超声刺激对无机空心纳米微球药物释放影响的体外研究
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摘要
目的研究低频超声对无机空心纳米微球携载药物释放的影响,并探讨无机空心纳米载体用作超声靶向药物治疗载体的可行性。方法以植酸为调控剂,钙盐和亚硒酸盐为反应物,在水热条件下制备无机空心纳米微球。然后以牛血清白蛋白(BSA)为模型药物,载入无机空心纳米微球中,并给予低频超声刺激,测定BSA的释放量。结果水热条件下成功制备了分散性良好的无机空心纳米微球,低频超声刺激下有利于加速纳米空心微球中BSA的释放,且BSA的释放率随低频超声功率的增加而加快。结论本方法制备无机纳米空心微球简单、快速,且制备的微球分散良好。低频超声刺激有利于加速无机空心纳米微球中的药物释放速率。该微球有望用作低频超声靶向药物治疗载体。
Objective To study the effects of low frequency ultrasound on the drug release from inorganic hollow nanospheres and investigate the possibility of inorganic hollow nanospheres as the carrier of ultrasound targeted drug delivery system. Methods Using phytic acid as the modifier and calcium salt and selenite as reagent, inorganic hollow nanospheres were synthesized under hydrothermal condition. Then, bovine serum albumin as the model drug were loaded into the nanospheres and stimulated by low frequency ultrasound. The BSA release amount was measured under the low frequency ultrasound stimulus. Results Inorganic hollow nanospheres with good dispensability were successfully synthesized under hydrothermal condition. BSA release was facilated under ultrasound stimulus and BSA release rate increased with the ultrasound power. Conclusion This method is simple and effective to synthesize inorganic hollow nanospheres with good dispensability. Moreover, low frequency ultrasound stimulus is benefit to facilate drug release from inorganic hollow nanospheres. The inorganic hollow nanospheres could be a potent carrier of low frequency ultrasound targeted drug delivery system.
Objective To study the effects of low frequency ultrasound on the drug release from inorganic hollow nanospheres and investigate the possibility of inorganic hollow nanospheres as the carrier of ultrasound targeted drug delivery system. Methods Using phytic acid as the modifier and calcium salt and selenite as reagent, inorganic hollow nanospheres were synthesized under hydrothermal condition. Then, bovine serum albumin as the model drug were loaded into the nanospheres and stimulated by low frequency ultrasound. The BSA release amount was measured under the low frequency ultrasound stimulus. Results Inorganic hollow nanospheres with good dispensability were successfully synthesized under hydrothermal condition. BSA release was facilated under ultrasound stimulus and BSA release rate increased with the ultrasound power. Conclusion This method is simple and effective to synthesize inorganic hollow nanospheres with good dispensability. Moreover, low frequency ultrasound stimulus is benefit to facilate drug release from inorganic hollow nanospheres. The inorganic hollow nanospheres could be a potent carrier of low frequency ultrasound targeted drug delivery system.
引文
[1] Yoon HJ,Lee HS,Jung JH,et al.Photothermally amplified therapeutic liposomes for effective combination treatment of cancer[J].ACS Applied Materials & Interfaces,2018,10(7):6118-6123.
[2] Lee SJ,Kim HJ,Huh YM,et al.Functionalized magnetic PLGA nanospheres for targeting and bioimaging of breast cancer[J].Journal of Nanoscience and Nanotechnology,2018,18(3):1542-1547.
[3] Jatupaiboon N,Wang Y,Wu H,et al.A facile microemulsion template route for producing hollow silica nanospheres as imaging agents and drug nanocarriers[J].Journal of Materials Chemistry B,2015,3(16):3130-3133.
[4] McDannold N,Clement GT,Black P,et al.Transcranial magnetic resonance imaging-guided focused ultrasound surgery of brain tumors:initial findings in 3 patients[J].Neurosurgery,2010,66(2):323-332.
[5] Dallapiazza RF,Timbie KF,Holmberg S,et al.Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound[J].Journal of Neurosurgery,2017,128(3):875-884.
[6] Kotopoulis S,Dimcevski G,Mc Cormack E,et al.Ultrasound-and microbubble-enhanced chemotherapy for treating pancreatic cancer:A phase I clinical trial[J].The Journal of the Acoustical Society of America,2016,139(4):2092-2092.
[7] Schroeder A,Avnir Y,Weisman S,et al.Controlling liposomal drug release with low frequency ultrasound:mechanism and feasibility[J].Langmuir,2007,23(7):4019-4025.
[8] Jin Z,Choi Y,Ko SY,et al.Experimental and simulation studies on focused ultrasound triggered drug delivery[J].Biotechnology and Applied Biochemistry,2017,64(1):134-142.
[9] Uskokovi V,Uskokovi DP.Nanosized hydroxyapatite and other calcium phosphates:chemistry of formation and application as drug and gene delivery agents[J].Journal of Biomedical Materials Research Part B:Applied Biomaterials,2011,96(1):152-191.
[10] Lafon JP,Champion E,Bernache-Assollant D.Processing of AB-type carbonated hydroxyapatite Ca10-x(PO4)6-x(CO3)x(OH)2-x-2y(CO3)y ceramics with controlled composition[J].Journal of the European Ceramic Society,2008,28(1):139-147.
[11] 王艳华.硒掺杂羟基磷灰石材料的制备及其抗癌效应的实验研究[D].武汉:华中科技大学,2014,5-122.
[12] 张昔玉,葛圣松,邵谦,等.酵母菌模板法制备CeO2空心微球及其光催化性能[J].无机化学学报,2016,32(9):1535-1542.
[13] Wang Y,Yu L,Lou XW.Synthesis of highly uniform molybdenum-glycerate spheres and their conversion into hierarchical MoS2 hollow nanospheres for lithium-ion batteries[J].Angewandte Chemie International Edition,2016,55(26):7423-7426.
[14] Xu A W,Yu Q,Dong W F,et al.Stable amorphous CaCO3 microparticles with hollow spherical superstructures stabilized by phytic acid[J].Advanced Materials,2005,17(18):2217-2221.
[15] Xiao D,Tan Z,Fu Y,et al.Hydrothermal synthesis of hollow hydroxyapatite microspheres with nano-structured surface assisted by inositol hexakisphosphate[J].Ceramics International,2014,40(7):10183-10188.
[16] 张丽果,汲振余,赫培远,等.超声刺激对海藻酸钠微球机械特性和释放特性的影响[J].北京工业大学学报,2015,41(9):1302-1307.
[17] 梁士利,韩冬,徐美玲,等.超声药物释放空化动力学行为研究[J].发光学报,2012,33(2):182-186.
[18] Boissenot T,Bordat A,Fattal E,et al.Ultrasound-triggered drug delivery for cancer treatment using drug delivery systems:from theoretical considerations to practical applications[J].Journal of Controlled Release,2016,241(2016):144-163.
[19] Pamornpathomkul B,Duangjit S,Laohapatarapant S,et al.Transdermal delivery of fluorescein isothiocyanate-dextrans using the combination of microneedles and low-frequency sonophoresis[J].Asian Journal of Pharmaceutical Sciences,2015,10(5):415-424.
[20] Prather JL,Tummel EK,Patel AB,et al.Prospective randomized controlled trial comparing the effects of noncontact low-frequency ultrasound with standard care in healing split-thickness donor sites[J].Journal of the American College of Surgeons,2015,221(2):309-318.
[2] Lee SJ,Kim HJ,Huh YM,et al.Functionalized magnetic PLGA nanospheres for targeting and bioimaging of breast cancer[J].Journal of Nanoscience and Nanotechnology,2018,18(3):1542-1547.
[3] Jatupaiboon N,Wang Y,Wu H,et al.A facile microemulsion template route for producing hollow silica nanospheres as imaging agents and drug nanocarriers[J].Journal of Materials Chemistry B,2015,3(16):3130-3133.
[4] McDannold N,Clement GT,Black P,et al.Transcranial magnetic resonance imaging-guided focused ultrasound surgery of brain tumors:initial findings in 3 patients[J].Neurosurgery,2010,66(2):323-332.
[5] Dallapiazza RF,Timbie KF,Holmberg S,et al.Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound[J].Journal of Neurosurgery,2017,128(3):875-884.
[6] Kotopoulis S,Dimcevski G,Mc Cormack E,et al.Ultrasound-and microbubble-enhanced chemotherapy for treating pancreatic cancer:A phase I clinical trial[J].The Journal of the Acoustical Society of America,2016,139(4):2092-2092.
[7] Schroeder A,Avnir Y,Weisman S,et al.Controlling liposomal drug release with low frequency ultrasound:mechanism and feasibility[J].Langmuir,2007,23(7):4019-4025.
[8] Jin Z,Choi Y,Ko SY,et al.Experimental and simulation studies on focused ultrasound triggered drug delivery[J].Biotechnology and Applied Biochemistry,2017,64(1):134-142.
[9] Uskokovi V,Uskokovi DP.Nanosized hydroxyapatite and other calcium phosphates:chemistry of formation and application as drug and gene delivery agents[J].Journal of Biomedical Materials Research Part B:Applied Biomaterials,2011,96(1):152-191.
[10] Lafon JP,Champion E,Bernache-Assollant D.Processing of AB-type carbonated hydroxyapatite Ca10-x(PO4)6-x(CO3)x(OH)2-x-2y(CO3)y ceramics with controlled composition[J].Journal of the European Ceramic Society,2008,28(1):139-147.
[11] 王艳华.硒掺杂羟基磷灰石材料的制备及其抗癌效应的实验研究[D].武汉:华中科技大学,2014,5-122.
[12] 张昔玉,葛圣松,邵谦,等.酵母菌模板法制备CeO2空心微球及其光催化性能[J].无机化学学报,2016,32(9):1535-1542.
[13] Wang Y,Yu L,Lou XW.Synthesis of highly uniform molybdenum-glycerate spheres and their conversion into hierarchical MoS2 hollow nanospheres for lithium-ion batteries[J].Angewandte Chemie International Edition,2016,55(26):7423-7426.
[14] Xu A W,Yu Q,Dong W F,et al.Stable amorphous CaCO3 microparticles with hollow spherical superstructures stabilized by phytic acid[J].Advanced Materials,2005,17(18):2217-2221.
[15] Xiao D,Tan Z,Fu Y,et al.Hydrothermal synthesis of hollow hydroxyapatite microspheres with nano-structured surface assisted by inositol hexakisphosphate[J].Ceramics International,2014,40(7):10183-10188.
[16] 张丽果,汲振余,赫培远,等.超声刺激对海藻酸钠微球机械特性和释放特性的影响[J].北京工业大学学报,2015,41(9):1302-1307.
[17] 梁士利,韩冬,徐美玲,等.超声药物释放空化动力学行为研究[J].发光学报,2012,33(2):182-186.
[18] Boissenot T,Bordat A,Fattal E,et al.Ultrasound-triggered drug delivery for cancer treatment using drug delivery systems:from theoretical considerations to practical applications[J].Journal of Controlled Release,2016,241(2016):144-163.
[19] Pamornpathomkul B,Duangjit S,Laohapatarapant S,et al.Transdermal delivery of fluorescein isothiocyanate-dextrans using the combination of microneedles and low-frequency sonophoresis[J].Asian Journal of Pharmaceutical Sciences,2015,10(5):415-424.
[20] Prather JL,Tummel EK,Patel AB,et al.Prospective randomized controlled trial comparing the effects of noncontact low-frequency ultrasound with standard care in healing split-thickness donor sites[J].Journal of the American College of Surgeons,2015,221(2):309-318.