Hallyosite Nanotubes Hollow Microspheres Prepared By Assembly Technique And Their Application In Control Release

Hollow micro/nano-structures with void space and shell in the scale range ofnanometers to micrometers, have attracted continuous interest in chemistry andscience, owing to their large surface areas, lower density, high stability, goodpermeation and compatibilities with other materials, and widespread applications incatalysis, sensors, fillers, drug delivery and lithium ion batteries.Here we fabricated hollow microsphere via the layer-by-layer(LBL) assemblytechnique based on colloidal templates，consecutively assembling hallyosite nanotube(HNTs) and chitosan(CHI) polyelectrolyte onto polystyrene microspheres (PSt) andsubsequently removing the PSt templates either by calcination. In order to improvebiocompatibility, the surface modification of the hollow hybrid microspheres is need.In this article, dopamine was used to prepare modified hollow hybrid microspheres(DHHMs). Both the hollow hybrid microspheres and modified hollow microspheres,were served as drug carriers to load and and control release of ibuprofen. Meanwhilewe used glutaraldehyde to cross-link chitosan which belong to shell materials and toimpove the stability of the core–shell structure so that the integrated hollow structurecan be obtained after removing the PSt templates by exposure to tetrahydrofuran. Weobtain the following results：(1) Preparation of Polystyrene Microspheres (PSt) templateDispersion polymerization of styrene had been carried out to fabricated uniformdispersion polystyrene microspheres (PSt) in ethanol with poly(N-vinyl pyrrolidone)(PVP) as a stabilizer and2,2`-Azobisisobutyronitrile(AIBN) as a initiator. Theinfluence factors on the size and size distribution were investigated. Monodispersepolystyrene microspheres in the size of3.5μm with smooth surface were preparedwhen the stabilizer PVP is0.65%，the monomer concentration is22%, initiatorAIBN is0.32%and reaction temperature is70℃.(2) Preparation of core-shell composite microspheres by LBL technologyThe sizes of2.1μm,3.5μm,18.3μm PSt microspheres were chosen as templates.And at first, the PSt microspheres were sulfonated by dispersing into sulfuric acid(98%) at50oC for8h, and after dilution with water, the product was neutralized withNaOH aqueous solution. Then the sulfonated PSt templates was first deposited on a precursor polyelectrolyte CHI/PSS/CHI there-layer film to provide a uniformlycharged surface and to facilitate subsequent HNTs adsorption. And then the core-shellstructure was fabricated via the layer-by-layer (LBL) assembly technique by theelectrostatic interaction between the polycation chitosan (CHI) and the anion HNTs onPSt templates. Meanwhile we also investigated the effects of the assembled numbersof bilayers (HNT/CHI) on the morphologies of core-shell structures. The resultsshowed that with an increase of the cycle numbers, the HNTs coverage increasesdramatically. And also the larger size of the PSt, the better spheres morphologies ofcore-shell structures.(3) Preparation of hollow structuresFirst, the4μm hollow hybrid microspheres (HHMs) were obtained bycalcination the core-shell microspheres to remove the PSt templates at250oC for6h.And then the HHMs was coated with polydopamine films (DHHMs) byself-polymerization of dopamine in an aqueous solution (4mg/mL). We also usedtetrahydrofuran to etch the PSt template. To obtain the complete hollow structure, thecore-shell microspheres should be cross-linked by50%(v/v) glutaraldehyde, beforeexposure to tetrahydrofuran.(4) In Vitro Loading and Release of ibuprofenMoreover the HHMs and DHHMs can be used as drug delivery carriers, anddrug storage/release properties were investigated using ibuprofen as the model drug.Especially, we used nonpolar hexane as solvents to load ibuprofen, and the releasebehaviors of ibuprofen in phosphate buffer saline (PBS, pH≈7.4) at37oC under140rpm were studied. The results showed that the maximal loading amount of ibuprofenin HHMs was approached to210mg/g, at10oC, under100rpm for shaking24h. Theibuprofen loaded systems showed a burst release of about50%within0.5h, andfollowed by a relatively slow release of nearly80%within6h. But, with the aid ofultrasonication, the ibuprofen-release rate increased dramatically, nearly90%within9min. Moreover, the DHHMs were also used as drug delivery carriers. The resultsshowed that the maximal loading amount of ibuprofen can reach400mg/g，and therelease of ibuprofen can be reach76.8%with192h.In summary, the hollow microspheres were fabricated by consecutivelyassembling HNTs and CHI polyelectrolyte onto PSt microsphere and subsequentlyremoving the PSt core by calcination. And then the hollow structure was modified bydopamine. Finally, these hollow spheres were used as drug carriers, and ibuprofen was chosen as a model molecule. As a result, both of them have high loading amount, butthe dopamine modified microspheres (DHHMs) have a better controlled release ofdruges.