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Mechanisms involved in electrospraying of macromolecules for micro-delivery
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Abstracts / Journal of Controlled Release 213 (2015) e8–e152
[3] X. Ma, A. Gong, L. Xiang, T. Chen, Y. Gao, X. Liang, Z. Shen, A. Wu, Biocompatible composite nanoparticles with large longitudinal relaxivity for targeted imaging and early diagnosis of cancer, J. Mater. Chem. B 1 (2013) 3419–3428. doi:10.1016/j.jconrel.2015.05.249
Mechanisms involved in electrospraying of macromolecules for micro-delivery Zhikai Tan*, Hongjie Wang, Zhenhua Xie, Chunyi Tong, Bin Liu, Yongjun Tan College of Biology, Hunan University, Yuelu District, Changsha 410082, China ⁎Corresponding author. E-mail address: [email protected] (Z. Tan). Electrospraying (ES) is of a great interest in development of biomaterials for controlled delivery [1]. By applying a suitable voltage to a conducting liquid supplied into a capillary, the liquid meniscus will take the form of a cone. Increasing the electric field on the surface of the liquid, which is intended to overcome the surface tension, facilitates the emergence of a controlled micro-sized jet from the tip of the liquid cone, this is called the stable cone-jet mode [2]. The use of micro-sized fine nozzles allows the electrospray to operate at a low flow rate, which accordingly would make the delivery of small volumes and the fabrication of varied sized particles possible [3]. However, the efficiency of materials printing by ES still needs to be improved. This study investigated mechanisms involved in the electrospraying of biological macro-molecules. Hyaluronan (HA) solutions with concentrations ranging from 1 to 5 w/v % were prepared for spraying trials using nozzles with a size of 30 μm. In electrifying HA solutions with a high molecular weight of 2.1 MDa, controllable jets can be achieved only at a lowest concentration of 1 w/v %. Generally, further use of a sonication method to reduce the molecular size, stable cone jets can be obtained relatively easily than using HA solutions of higher concentrations. The improvement of spray stabilities can be attributed to the reduction in viscosity of the solutions after the sonication. Steady microsized jets were observed during the ES process and the jet size was found to increase with the increase of both the molecular size and the concentration. Both parameters can be directly ascribed to the rheological properties of the solutions. A concentration reduction of HA molecules also happens during electrospraying (Fig. 1), which indicates that there is a partial reflection of macromolecules inside the
Fig. 1. Concentration reductions of HA molecules after 20 min spray with different initial concentrations.
Taylor-cone with the fluid motions during the spraying process. The partial reflection process is affected by molecular sizes, solution concentrations and spraying time. This process would reduce the efficiency of materials printing, and needs to be considered for drug delivery and other applications. Keywords: electrospraying, drug delivery, bio-printing, print efficiency, hyaluronan References [1] Z. Ahmad, M. Nangrejo, M. Rasekh, E. Stride, M. Edirisinghe, Novel electrically driven direct-writing methods with managed control on in-situ shape and encapsulation polymer forming, Int. J. Mater. Form. 6 (2013) 281–288. [2] J. Fernández de la Mora, The fluid dynamics of Taylor cones, Annu. Rev. Fluid Mech. 39 (2007) 217–243. [3] J.U. Park, S. Lee, S. Unarunotai, Y. Sun, S. Dunham, T. Song, P.M. Ferreira, A.G. Alleyene, U. Paik, J.A. Rogers, Nanoscale, electrified liquid jets for high-resolution printing of charge, Nano Lett. 10 (2010) 584–591. doi:10.1016/j.jconrel.2015.05.250
Novel redox-sensitive mixed micelle with enhanced antitumor activity Songwei Tan, Mingxing Yin, Qingle Song, Yuling Bao, Zhiping Zhang* Tongji School of Pharmacy & National Engineering Research Center for Nanomedicine, Huazhong University of Science & Technology, Wuhan 430030, China ⁎Corresponding author. E-mail address: [email protected] (Z. Zhang). Nitric oxide (NO) has attracted lots of attention for its antitumor activity and synergistic effects when co-delivered with anticancer agents [1]. However, due to its chemical instability and short halflife, delivering gaseous NO directly to tumors is challenging, let alone co-delivery of NO and antitumor drug into tumor tissue simultaneously. To solve this problem, a novel anti-cancer mixed micelle was prepared here by using D-α-tocopherol polyethylene glycol succinate (TPGS) based redox-sensitive paclitaxel prodrug (TPGS-SS–PTX) and nitric oxide (NO) releasing TPGS derivative (TNO3). This mixed micelle was able to release PTX, TPGS and NO with high concentration and thus reveal a dramatically cytotoxic effect against both A2780 and A2780/T cell line (Fig. 1). The diameters of all the mixed micelles were 100–150 nm with narrow distribution so they can enrich in tumor through EPR effect. Then the disulfide bond
Fig. 1. Schematic illustration of mixed micelles for enhanced tumor treatment.
Abstracts / Journal of Controlled Release 213 (2015) e8–e152
[3] X. Ma, A. Gong, L. Xiang, T. Chen, Y. Gao, X. Liang, Z. Shen, A. Wu, Biocompatible composite nanoparticles with large longitudinal relaxivity for targeted imaging and early diagnosis of cancer, J. Mater. Chem. B 1 (2013) 3419–3428. doi:10.1016/j.jconrel.2015.05.249
Mechanisms involved in electrospraying of macromolecules for micro-delivery Zhikai Tan*, Hongjie Wang, Zhenhua Xie, Chunyi Tong, Bin Liu, Yongjun Tan College of Biology, Hunan University, Yuelu District, Changsha 410082, China ⁎Corresponding author. E-mail address: [email protected] (Z. Tan). Electrospraying (ES) is of a great interest in development of biomaterials for controlled delivery [1]. By applying a suitable voltage to a conducting liquid supplied into a capillary, the liquid meniscus will take the form of a cone. Increasing the electric field on the surface of the liquid, which is intended to overcome the surface tension, facilitates the emergence of a controlled micro-sized jet from the tip of the liquid cone, this is called the stable cone-jet mode [2]. The use of micro-sized fine nozzles allows the electrospray to operate at a low flow rate, which accordingly would make the delivery of small volumes and the fabrication of varied sized particles possible [3]. However, the efficiency of materials printing by ES still needs to be improved. This study investigated mechanisms involved in the electrospraying of biological macro-molecules. Hyaluronan (HA) solutions with concentrations ranging from 1 to 5 w/v % were prepared for spraying trials using nozzles with a size of 30 μm. In electrifying HA solutions with a high molecular weight of 2.1 MDa, controllable jets can be achieved only at a lowest concentration of 1 w/v %. Generally, further use of a sonication method to reduce the molecular size, stable cone jets can be obtained relatively easily than using HA solutions of higher concentrations. The improvement of spray stabilities can be attributed to the reduction in viscosity of the solutions after the sonication. Steady microsized jets were observed during the ES process and the jet size was found to increase with the increase of both the molecular size and the concentration. Both parameters can be directly ascribed to the rheological properties of the solutions. A concentration reduction of HA molecules also happens during electrospraying (Fig. 1), which indicates that there is a partial reflection of macromolecules inside the
Fig. 1. Concentration reductions of HA molecules after 20 min spray with different initial concentrations.
Taylor-cone with the fluid motions during the spraying process. The partial reflection process is affected by molecular sizes, solution concentrations and spraying time. This process would reduce the efficiency of materials printing, and needs to be considered for drug delivery and other applications. Keywords: electrospraying, drug delivery, bio-printing, print efficiency, hyaluronan References [1] Z. Ahmad, M. Nangrejo, M. Rasekh, E. Stride, M. Edirisinghe, Novel electrically driven direct-writing methods with managed control on in-situ shape and encapsulation polymer forming, Int. J. Mater. Form. 6 (2013) 281–288. [2] J. Fernández de la Mora, The fluid dynamics of Taylor cones, Annu. Rev. Fluid Mech. 39 (2007) 217–243. [3] J.U. Park, S. Lee, S. Unarunotai, Y. Sun, S. Dunham, T. Song, P.M. Ferreira, A.G. Alleyene, U. Paik, J.A. Rogers, Nanoscale, electrified liquid jets for high-resolution printing of charge, Nano Lett. 10 (2010) 584–591. doi:10.1016/j.jconrel.2015.05.250
Novel redox-sensitive mixed micelle with enhanced antitumor activity Songwei Tan, Mingxing Yin, Qingle Song, Yuling Bao, Zhiping Zhang* Tongji School of Pharmacy & National Engineering Research Center for Nanomedicine, Huazhong University of Science & Technology, Wuhan 430030, China ⁎Corresponding author. E-mail address: [email protected] (Z. Zhang). Nitric oxide (NO) has attracted lots of attention for its antitumor activity and synergistic effects when co-delivered with anticancer agents [1]. However, due to its chemical instability and short halflife, delivering gaseous NO directly to tumors is challenging, let alone co-delivery of NO and antitumor drug into tumor tissue simultaneously. To solve this problem, a novel anti-cancer mixed micelle was prepared here by using D-α-tocopherol polyethylene glycol succinate (TPGS) based redox-sensitive paclitaxel prodrug (TPGS-SS–PTX) and nitric oxide (NO) releasing TPGS derivative (TNO3). This mixed micelle was able to release PTX, TPGS and NO with high concentration and thus reveal a dramatically cytotoxic effect against both A2780 and A2780/T cell line (Fig. 1). The diameters of all the mixed micelles were 100–150 nm with narrow distribution so they can enrich in tumor through EPR effect. Then the disulfide bond
Fig. 1. Schematic illustration of mixed micelles for enhanced tumor treatment.