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超细的介孔生物活性玻璃纤维的制备和药物传递

Fabrication and Drug Delivery of Ultrathin Mesoporous Bioactive Glass Hollow Fibers#
 

Abstract: In this paper we describe a kind of ultrathin mesoporous bioactive glass hollow fibers
(MBGHFs) which are fabricated using an electrospinning technique and combing a phase
separation-induced agent, polyethylene oxide. The rapid solvent evaporation during electrospinning
and the polyethylene oxide-induced phase separation process demonstrated play vital roles in the
formation of the ultrathin bioactive glass fibers with hollow cores and mesoporous walls. An
immersion of the MBGHFs in simulated body fluid rapidly develops a layer of enamel-like apatite
mesocrystals at the fiber surfaces and that there also are apatite nanocrystals to generate inside the
hollow cores. The drug loading and release experiments indicate that the drug loading capacity and
drug release behavior of the MBGHFs strongly depend on the fiber length. The MBGHFs with the fiber
length > 50 um can become excellent carriers for drug delivery. The shortening of the fiber length
reduces the drug loading amounts and accelerates the drug release. The MBGHFs reported here
possessing such sophisticated structure, high bioactivity, and good drug delivery capability can be a
 promising scaffold for hard tissue repair and wound healing when organized into three-dimensional
macroporous membranes.
 

Keywords: bioactive glass; hollow fibers; drug delivery; electrospinning

0 Introduction
Bioactive glasses (BGs) are a kind of biomaterials whose performances and applications
strongly depend on their morphological and structural properties.[1-3] Tailoring BGs into right
structures can largely improves their bioactivity even extends their applications. For example, the
existence of nanoporosities in the BG matrixes and high surface area accelerate greatly the
deposition process of hydroxycarbonate apatite (HCA) as demonstrated by Zhao et al.[2] At the
30 same time, BGs possessing three-dimensional (3D) structure with the interconnected macroporous
network at macroscopic scale is in particular favorable for bone tissue engineering scaffold.[3]

Nowadays, many techniques have been explored to process BGs, and a variety of BG
building blocks with various structures have been created, involving mesoporous particles,[4]
macroporous scaffolds,[3,5] hierarchical porous scaffolds,[3,5] and nanofibrous nonwovens.[6]
Among these building blocks, of particular interest to us is its nanofiber form fabricated via an
electrospinning technique as reported by Kim et al and Xia et al.[6] These BG nanofibers present
two distinct advantages. At microscopic scale, the BG nanofibers with ultrathin diameter show
high specific surface areas. Due to its super-long length (The electrospun fibers are continuous
long), at macroscopic scale, the nanofibers can be assembled into 3D membranes with
interconnected macroporous network. Such BG membrane demonstrated both possesses high
bioactivity and is an excellent scaffold of bone repair.[6] Nevertheless, the reported BG nanofibers
are not optimal in structures. For example, these fibers are solid, lacking nanoporosities in the
fiber textures. Therefore, continuous efforts into designing BGs towards more sophisticated
structure are significant. Recently, we reported a kind of nanoporous BG fibers.[7] Because of
abundant porosities in the fiber matrixes, the BG fibers are endowed high bioactivity and other functions.

Alternatively, in this work, we describe another structural BGs, i.e., ultrathin mesoporous BG
hollow fibers (MBGHFs), which are easily fabricated via an electrospinning technique and using
high molecular polyethylene oxide (PEO, Mn: 2,000,000) as phase separation agents. The rapid
solvent evaporation during electrospinning and the PEO-induced 50 phase separation process
demonstrated played vital roles in the formation of the ultrathin BG fibers with hollow core and
mesoporous wall. According to our knowledge, this is the first example of tailoring BGs into the
ultrathin tubular structures. Furthermore, experiments also demonstrated that the fabricated
MBGHFs had high bioactivity and the hollow cores of the MBGHFs could be interestingly
exploited as drug delivery systems for drug loading and release.

3 Conclusion
In summary, the MBGHFs could be easily prepared using the electrospinning technique and
employing the high molecular PEO as phase separation agents. The rapid solvent evaporation
during electrospinning and phase separation induced by electrospinning played vital roles to
facilitate the formation of hollow cores and mesoporosities in the ultrathin BG fibers. The
 transformation of the MBGHFs from the bamboo-like hollow fibers to the completely tubular
structures demonstrated strongly depended on the ratio of the co-solvent. This method of
fabricating the mesoporous hollow fibers can be extended to tailor other functional ceramics, e.g.,
TiO2, ZrO2, etc.

The SBF immersion experiments demonstrated that the MBGHFs had good bioactivities.
After the MBGHFs were immersed for 24 h, abundant enamel-like HCA mesocrystals were grown
at the fiber outer surfaces and that there also were the HCA particles to be yielded inside the
hollow cores. Experiments indicated that the drug loading capacity and drug release behavior of
the MBGHFs were length-dependent. The MBGHFs with the fiber length > ~50 μm could become
good carriers for drug delivery. The decrease of the MBGHF length reduced the drug loading
amounts and accelerated extremely 405 the drug release.

Because the MBGHFs can be well organized into 3D macroporous membranes at
macroscopic scale by electrospinning, the MBGHF membranes with high bioactivity and drug
delivery capability have potential applications on hard tissue repair and wound healing. Especially,
after drug loading, these membranes can cooperatively administrate wound and hard tissue with
drug.

References
[1] RAMILA A, BALAS F, VALLET-REGI M. Synthesis Routes for Bioactive Sol−Gel Glasses: Alkoxides
versus Nitrates[J].Chem. Mater., 2002, 14(2): 542~548.
[2] YAN X, YU C, ZHOU X, TANG J, ZHAO D. Highly Ordered Mesoporous Bioactive Glasses with Superior In
Vitro Bone-Forming Bioactivities[J]. Angew. Chem. Int. Ed., 2004, 43(44): 5980~5984.
[3] HENCH L L. The story of Bioglass[J]. J. Mater. Sci. Med., 2006, 17(11): 967~978.
[4] SHI Q.WANG J, ZHANG J, FAN J, STUCKY G D. Rapid-Setting Mesoporous Bioactive Glass Cements That
Induce Accelerated In Vitro Apatite Formation[J]. Adv. Mater., 2006, 18(8): 1038~1042.
[5] LI X, WANG X, CHEN H, JIANG P, DONG X, SHI J. Hierarchically Porous Bioactive Glass Scaffolds
Synthesized with a PUF and P123 Cotemplated Approach[J]. Chem. Mater., 2007, 19(17): 4322~4326.
[6] KIM H W, KIM H E, KNOWLES J C. Production and Potential of Bioactive Glass Nanofibers as a
Next-Generation Biomaterial[J]. Adv. Funct. Mater., 2006, 16(12): 1529~1535.
[7] HONG Y, CHEN X, JING X, FAN H, GUO B, GU Z, ZHANG X. Preparation, Bioactivity and Drug Release
of Hierarchical Nanoporous Bioactive Glass Ultrathin Fibers[J]. Adv. Mater., 2010, 22(6): 754~758.
[8] DAYAL P, KYU T. Porous Fiber Formation in a Polymer-Solvent System undergoing Solvent Evaporation[J].
J. Appl. Phys., 2006, 100(4): 043512.
[9] POLVERARI M, VAN DE VEN T G M. Dilute aqueous Poly(ethylene oxide) solutions: Clusters and single
molecules in thermodynamic equilibrium[J]. J. Phys. Chem., 1996, 100(32): 13687~13695.
[10] K. Nakanishi, N. Tanaka, Sol-gel with phase separation. Hierarchically porous materials optimized for
high-performance liquid chromatography separations[J]. Acc. Chem. Res., 2007, 40(9): 863~873.
[11] GREENSPAN D C, WEST J K. Composition and method for acceleration of wound and burn healing[P]. US
Patent 5834008, 1998.
[12] TAO J, PAN H, ZENG Y, XU X, TANG R. Roles of Amorphous Calcium Phosphate and Biological
Additives in the Assembly of Hydroxyapatite Nanoparticles[J]. J. Phys. Chem. B, 2007, 111(47): 13410~13418.
[13] HIGUCHI T. Mechanism of Sustained Action Medication: Theoretical Analysis of Rate of Release of Solid
Drugs Dispersed in Solid Matrices[J]. J. Pharm. Sci., 1963, 52(12): 1145~1149.
[14] KIM H, FASSIHI R. Application of binary polymer system in drug release rate modulation I. Characterization
of release mechanism[J]. J Pharmaceutical Sci., 1997, 86(3): 316~322.
[15] KOSMIDIS K, ARGYRAKIS P, MACHERAS P. Fractal kinetics in drug release from finite fractal matrices
[J]. J. Chem. Phys., 2003, 119(12): 6373~6377.
[16] XIA W, CHANG J. Well-ordered mesoporous bioactive glasses (MBG): a promising bioactive drug delivery
system[J]. J. Controlled Release, 2006, 110(3): 522~530.

 

超细的介孔生物活性玻璃纤维的制备和药物传递
 

摘要:本文描述了使用静电纺丝技术结合相分离试剂PEO 制备一种介孔生物活性玻璃超细中
空纤维(MBGHFs)。这些MBGHFs 在模拟体液中浸泡后在纤维表面和中空纤维内表面形成了
类似牙釉结构磷灰石层。药物装载和释放试验展示药物装载量和释放行为和纤维长度紧密相
关。纤维长度> 50 um 能很好的作为药物载体。在此长度范围内,缩短纤维长度会降低药物
装载量并加速药物释放速度。由于MBGHFs 具有高的生物相容性、高级的结构、以及药物传
递的功能,该MBGHFs 具有极大的用于骨组织支架的潜能。
 

关键词:生物活性玻璃;中空纤维;药物传递;静电纺丝

 


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