- Email: [email protected]
In situ self-assembled chitosan microspheres for controlled anti-cancer drug release
e30
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
viability was higher than 80 %, confirming that this formulation does not affect cell viability. DXI-loaded NSs were able to partially cross the BBB within one hour. After this time, 32 % of the NSs remain inside the cells releasing the drug from there or crossing later trough the barrier. In addition, NSs do not disrupt the BBB. In vitro transport across the BBB shows that DXI-loaded NSs increased drug permeation. To conclude, DXI-loaded NSs could be a suitable and safe strategy for potential AD prevention. Keywords: nanoparticlesm, dexibuprofen, nanospheres, brain, cells Acknowledgements This work was supported by the Spanish Ministry (MAT201459134-R projects).
Keywords: 5-Fluorouracil, chitosan, drug delivery, self-assembly, pharmacokinetics References [1] X. Wu, C. He, Y. Wu, X. Chen, Synergistic therapeutic effects of Schiff's base crosslinked injectable hydrogels for local co-delivery of metformin and 5-fluorouracil in a mouse colon carcinoma model, Biomaterials 75 (2016) 148-162. [2] E. Lepeltier, B. Loretz, D. Desmaële, J. Zapp, J. Herrmann, P. Couvreur, C.M. Lehr, Squalenoylation of chitosan: a platform for drug delivery, Biomacromolecules 16 (2015) 2930-2939. [3] R.M. Raftery, E.G. Tierney, C.M. Curtin, S.A. Cryan, F.J. O'Brien, Development of a gene-activated scaffold platform for tissue engineering applications using chitosanpDNA nanoparticles on collagen-based scaffolds, J. Control. Release 210 (2015) 84-94.
doi:10.1016/j.jconrel.2017.03.087
Reference [1] J. Folch, D. Petrov, M. Ettcheto, S. Abad, E. Sánchez-López, M.L. García, J. Olloquequi, C. Beas-zarate, C. Auladell, A. Camins, Current Research Therapeutic Strategies for Alzheimer’ s Disease Treatment, Neural Plast.2016 (2016) 1-15.
doi:10.1016/j.jconrel.2017.03.086
In situ self-assembled chitosan microspheres for controlled anti-cancer drug release Elon Ishmael Cadoga⁎, Ching-Hwa Lee⁎ Department of Environmental Engineering, 168 University Rd., Dacun, Changhua 51591, China ⁎Corresponding authors. E-mail addresses: [email protected] (E.I. Cadoga), [email protected] (C.-H. Lee) 5-Fluroruracil (5FU) is used as a chemotherapeutic agent in modern medicine. However, due to its low solubility at physiological pH, inclusion complexes of chitosan (CS) with 5FU was used to improve the efficacy of 5FU [1]. The CS-5FU inclusion complexes were prepared as 5FU loaded CS microspheres via an in situ self-assembly method (Fig. 1). CS is a cationic copolymer obtained by deacetylation of chitin. CS shows good biocompatibility, biodegradability and non-toxicity [2], which renders it a promising drug delivery material. With a hydrophilic nature, CS is crosslinked with glutaraldehyde to achieve sustained release of 5FU [3]. Our results showed that the amine groups of CS interacted with the 5FU, the semi-crystalline morphology had an increase in lmax from ~1.2 nm to ~1.9 nm, and the size of the agglomerated microspheres ranged from 70-90 μm. The fabrication of the inclusion complex had an efficiency of 39%. The binding mechanism of 5FU and CS was investigated via the Hill model. The in vitro release studies showed sustained release of 5FU for up to 36 hours. The mechanism of drug release was investigated by different models. Moreover, the optimum drug delivery formulation was also studied in vivo on adult zebra fish. These CS-5FU inclusion complex exhibited a low toxicity and improved delivery of 5FU. The inclusion-complex approach can be used in the future to improve the efficacy of 5FU.
Fig. 1. Preparation of CS-5FU inclusion complex.
Coaxial double-walled microspheres for combined release of cytochrome c and doxorubicin Fang Fenga,b,⁎, Kar Yee Neoha, Pooya Davoodia, Chi-Hwa Wanga,⁎⁎ a Department of Chemical and Biomolecular Engineering, National University of Singapore, 117585, Singapore b School of Chemistry, Biology and Materials Engineering, Suzhou University of Science and Technology, Suzhou 215009, China ⁎Correspondence to: F. Feng, Department of Chemical and Biomolecular Engineering, National University of Singapore, 117585, Singapore. ⁎⁎Corresponding author. E-mail addresses: [email protected] (F. Feng), [email protected] (C.-H. Wang) Co-axial electrohydrodynamic atomization (CEHDA) can be adapted to fabricate core/shell microspheres with narrow size distribution in a single step for controlled and sustained release of therapeutic drugs [1]. Our previous studies evaluated the advantages of CEHDA for the encapsulation of BSA and hepatocyte growth factor, where it mitigated denaturation of bioactive compounds during fabrication process and subsequent release from biodegradable polymeric microparticles [2, 3]. In the present study (Fig. 1), we examined the versatile application of core/shell microspheres for co-encapsulating a therapeutic protein (cytochrome c, CC) and an anticancer drug (doxorubicin, DOX), which provide a synergistic chemotherapeutic effect upon co-delivery at target tissue. DOX, a FDA approved chemotherapeutic drug which can induce apoptosis in various cancer cells was used in combination with CC, which plays an important role in programmed cell death. The coreshell microparticles ranging from 1 to 9 μm were successfully fabricated using CEHDA technique. Two PLGA solutions (two different molecular weights with inherent viscosities of 0.26-0.54 dL/g and 0.65-0.85 dL/g, respectively) were used to study their effects on particle size and in vitro drug release. Additionally, the stability of CC was confirmed by ABTS assay and circular dichroism (CD). The CEHDA technique reduced the loss of potentially expensive solutes (94% encapsulation efficiency for CC), hence protecting the protein drug structure. Zero-order release of CC has been observed regardless of the formulations used. Combination
Fig. 1. Fig. 1. Coaxial double-walled microspheres for combined release of cytochrome c and doxorubicin.
Abstracts / Journal of Controlled Release 259 (2017) e5–e195
viability was higher than 80 %, confirming that this formulation does not affect cell viability. DXI-loaded NSs were able to partially cross the BBB within one hour. After this time, 32 % of the NSs remain inside the cells releasing the drug from there or crossing later trough the barrier. In addition, NSs do not disrupt the BBB. In vitro transport across the BBB shows that DXI-loaded NSs increased drug permeation. To conclude, DXI-loaded NSs could be a suitable and safe strategy for potential AD prevention. Keywords: nanoparticlesm, dexibuprofen, nanospheres, brain, cells Acknowledgements This work was supported by the Spanish Ministry (MAT201459134-R projects).
Keywords: 5-Fluorouracil, chitosan, drug delivery, self-assembly, pharmacokinetics References [1] X. Wu, C. He, Y. Wu, X. Chen, Synergistic therapeutic effects of Schiff's base crosslinked injectable hydrogels for local co-delivery of metformin and 5-fluorouracil in a mouse colon carcinoma model, Biomaterials 75 (2016) 148-162. [2] E. Lepeltier, B. Loretz, D. Desmaële, J. Zapp, J. Herrmann, P. Couvreur, C.M. Lehr, Squalenoylation of chitosan: a platform for drug delivery, Biomacromolecules 16 (2015) 2930-2939. [3] R.M. Raftery, E.G. Tierney, C.M. Curtin, S.A. Cryan, F.J. O'Brien, Development of a gene-activated scaffold platform for tissue engineering applications using chitosanpDNA nanoparticles on collagen-based scaffolds, J. Control. Release 210 (2015) 84-94.
doi:10.1016/j.jconrel.2017.03.087
Reference [1] J. Folch, D. Petrov, M. Ettcheto, S. Abad, E. Sánchez-López, M.L. García, J. Olloquequi, C. Beas-zarate, C. Auladell, A. Camins, Current Research Therapeutic Strategies for Alzheimer’ s Disease Treatment, Neural Plast.2016 (2016) 1-15.
doi:10.1016/j.jconrel.2017.03.086
In situ self-assembled chitosan microspheres for controlled anti-cancer drug release Elon Ishmael Cadoga⁎, Ching-Hwa Lee⁎ Department of Environmental Engineering, 168 University Rd., Dacun, Changhua 51591, China ⁎Corresponding authors. E-mail addresses: [email protected] (E.I. Cadoga), [email protected] (C.-H. Lee) 5-Fluroruracil (5FU) is used as a chemotherapeutic agent in modern medicine. However, due to its low solubility at physiological pH, inclusion complexes of chitosan (CS) with 5FU was used to improve the efficacy of 5FU [1]. The CS-5FU inclusion complexes were prepared as 5FU loaded CS microspheres via an in situ self-assembly method (Fig. 1). CS is a cationic copolymer obtained by deacetylation of chitin. CS shows good biocompatibility, biodegradability and non-toxicity [2], which renders it a promising drug delivery material. With a hydrophilic nature, CS is crosslinked with glutaraldehyde to achieve sustained release of 5FU [3]. Our results showed that the amine groups of CS interacted with the 5FU, the semi-crystalline morphology had an increase in lmax from ~1.2 nm to ~1.9 nm, and the size of the agglomerated microspheres ranged from 70-90 μm. The fabrication of the inclusion complex had an efficiency of 39%. The binding mechanism of 5FU and CS was investigated via the Hill model. The in vitro release studies showed sustained release of 5FU for up to 36 hours. The mechanism of drug release was investigated by different models. Moreover, the optimum drug delivery formulation was also studied in vivo on adult zebra fish. These CS-5FU inclusion complex exhibited a low toxicity and improved delivery of 5FU. The inclusion-complex approach can be used in the future to improve the efficacy of 5FU.
Fig. 1. Preparation of CS-5FU inclusion complex.
Coaxial double-walled microspheres for combined release of cytochrome c and doxorubicin Fang Fenga,b,⁎, Kar Yee Neoha, Pooya Davoodia, Chi-Hwa Wanga,⁎⁎ a Department of Chemical and Biomolecular Engineering, National University of Singapore, 117585, Singapore b School of Chemistry, Biology and Materials Engineering, Suzhou University of Science and Technology, Suzhou 215009, China ⁎Correspondence to: F. Feng, Department of Chemical and Biomolecular Engineering, National University of Singapore, 117585, Singapore. ⁎⁎Corresponding author. E-mail addresses: [email protected] (F. Feng), [email protected] (C.-H. Wang) Co-axial electrohydrodynamic atomization (CEHDA) can be adapted to fabricate core/shell microspheres with narrow size distribution in a single step for controlled and sustained release of therapeutic drugs [1]. Our previous studies evaluated the advantages of CEHDA for the encapsulation of BSA and hepatocyte growth factor, where it mitigated denaturation of bioactive compounds during fabrication process and subsequent release from biodegradable polymeric microparticles [2, 3]. In the present study (Fig. 1), we examined the versatile application of core/shell microspheres for co-encapsulating a therapeutic protein (cytochrome c, CC) and an anticancer drug (doxorubicin, DOX), which provide a synergistic chemotherapeutic effect upon co-delivery at target tissue. DOX, a FDA approved chemotherapeutic drug which can induce apoptosis in various cancer cells was used in combination with CC, which plays an important role in programmed cell death. The coreshell microparticles ranging from 1 to 9 μm were successfully fabricated using CEHDA technique. Two PLGA solutions (two different molecular weights with inherent viscosities of 0.26-0.54 dL/g and 0.65-0.85 dL/g, respectively) were used to study their effects on particle size and in vitro drug release. Additionally, the stability of CC was confirmed by ABTS assay and circular dichroism (CD). The CEHDA technique reduced the loss of potentially expensive solutes (94% encapsulation efficiency for CC), hence protecting the protein drug structure. Zero-order release of CC has been observed regardless of the formulations used. Combination
Fig. 1. Fig. 1. Coaxial double-walled microspheres for combined release of cytochrome c and doxorubicin.