Studies on the particle size control of gelatin microspheres

A series of gelatin microspheres (GMs) were prepared through emulsification-coacervation method in water-in-oil (w/o) emulsions. The influence of preparation parameters on particle size, surface morphology, and dispersion of GMs was examined. The studied preparation parameters include concentration of gelatin solutions, concentration of the emulsifier, w/o ratio, emulsifying time, stirring speed, and so on. The surface morphology, dispersion, and particle sizes of GMs were determined by the scanning electron microscopy (SEM), SemAfore 4 Demo software, and particle size distribution graphic charts. The experimental results indicated that increasing the concentration of gelatin solution would increase the particle size of GMs. When the solution concentration increased from 0.050 to 0.200 g/mL gradually, the particle size increased correspondingly. The relationship between the two quantities was linear. On the contrary, increasing the concentration of the emulsifier would decrease the particle size of GMs. Furthermore, the particle size reduced quickly at initial time and slowed down latterly. With the increase of emulsifier concentration from 0 to 0.020 g/mL, themean diameters ofGMsdecreased from 17.32 to 5.38 μm. However, the particle size dwindled slowly when emulsifier concentration was higher than 0.020 g/mL. The excellent result was obtained with the condition of 0.050 g/mL of emulsifier concentration, 0.100 g/mL of gelatin solution concentration, 1/5 of w/o ratio, 10 min of emulsifying time, and 900 r/min of the stirring speed. The GMs prepared at this condition had the smallest sizes, the narrowest size distribution, the best spherical shape, and fluidity. The w/o ratio has the same influence on particle size of GMs as that of gelatin solution concentration. With the increase of w/o ratio, the average particle sizes increased linearly, and the surface of microspheres become smoother as well. It is supposed that w/o ratio can be used to change the diameters and surface morphologies of GMs. The emulsifying time has little influence on the mean diameters of GMs, but it affects the dispersion of GMs apparently. When the emulsifying time was shorter than 5 min, the GMs had bad dispersion. After increasing the emulsifying time to 13 min, the dispersion of GMs changed greatly, whereas the dispersion of GMs became bad again when the emulsifying time was longer than 13 min. According to the experimental results, 13 min was considered to be the best emulsifying time. The stirring speed has the similar influence on GMs’ morphologies as that of emulsifying time. Slow stirring rate made large size distribution and bad spherical shape of GMs; excessive stirring speed results in aggregation among GMs likewise. The smaller size distribution and better spherical shape of GMs were observed under the stirring rate between 500 and 1500 r/min by SEM. In conclusion, increasing the concentration of gelatin solution or w/o ratio would increase the particle sizes of GMs, increasing the concentration of the emulsifier would decrease the sizes of GMs at proper emulsifying time, and stirring speed would get the best spherical shape of GMs. These are the basic laws governing the design and manufacture of the GMs. __________ Translated from Acta Polymerica Sinica, 2008, 8 (in Chinese)     

Self-assembly and morphology control of new L-glutamic acid-based amphiphilic random copolymers: giant vesicles, vesicles, spheres, and honeycomb film

New amphiphilic random copolymers containing hydrophobic dodecyl (C12) chain and hydrophilic L-glutamic acid were synthesized, and their self-assembly in solution as well as on the solid surfaces was investigated. The self-assembly behavior of these polymers are largely dependent on their hydrophilic and hydrophobic balances. The copolymer with a more hydrophobic alkyl chain (～90%) self-assembled into giant vesicles with a diameter of several micrometers in a mixed solvent of ethanol and water. When the hydrophobic ratio decreased to ca. 76%, the polymer self-assembled into conventional vesicles with several hundred nanometers. The giant vesicles could be fused in certain conditions, while the conventional vesicles were stable. When the content of the hydrophilic part was further increased, no organized structures were formed. On the other hand, when the copolymer solutions were directly cast on solid substrates such as silicon plates, films with organized nanostructures could also be obtained, the morphology of which depended on solvent selection. When ethanol or methanol was used, spheres were obtained. When dichloromethane was used as the solvent, honeycomb-like morphologies were obtained. These results showed that through appropriate molecular design, random copolymer could self-assemble into various organized structures, which could be regulated through the hydrophobic/hydrophilic balance and the solvents.     

Synthesis and morphology control of raspberry-like poly(ethylene terephthalate)/polyacrylonitrile microspheres

The fabrication of raspberry-like poly(ethylene terephthalate)/polyacrylonitrile (PET/PAN) microspheres by γ-ray radiation-induced polymerization of acrylonitrile on micron-sized PET microspheres were first reported in this work. A PET emulsion was firstly prepared by dispersing a PET solution with 1,1,2,2-tetrachloroethane/phenol mixture as the solvent into an aqueous solution of sodium dodecyl sulfate. Then, PET microspheres were formed by precipitating the PET emulsion droplets from ethanol. The influence of the PET solvent and the weight ratio of ethanol to PET emulsion on the morphology of the PET microspheres had been investigated. After the surface of the prepared PET microspheres was grafted with poly(acrylic acid), the grafting polymerization of AN also had been successfully initiated by γ-ray radiation to form PAN microspheres with a size of about 100 nm on the PET microspheres. This work provides a new method to fabricate micron-sized PET microspheres, and further expands the functionalization of PET and its application fields.     

The encapsulation of an amphiphile into polystyrene microspheres of narrow size distribution

ABSTRACT: Encapsulation of compounds into nano- or microsized organic particles of narrow size distribution is of increasing importance in fields of advanced imaging and diagnostic techniques and drug delivery systems. The main technology currently used for encapsulation of molecules within uniform template particles while retaining their size distribution is based on particle swelling methodology, involving penetration of emulsion droplets into the particles. The swelling method, however, is efficient for encapsulation only of hydrophobic compounds within hydrophobic template particles. In order to be encapsulated, the molecules must favor the hydrophobic phase of an organic/aqueous biphasic system, which is not easily achieved for molecules of amphiphilic character.The following work overcomes this difficulty by presenting a new method for encapsulation of amphiphilic molecules within uniform hydrophobic particles. We use hydrogen bonding of acid and base, combined with a pseudo salting out effect, for the entrapment of the amphiphile in the organic phase of a biphasic system. Following the entrapment in the organic phase, we demonstrated, using fluorescein and (antibiotic) tetracycline as model molecules, that the swelling method usually used only for hydrophobes can be expanded and applied to amphiphilic molecules.     

Organic-inorganic hybrid mesoporous silicas: functionalization, pore size, and morphology control

Topological design of mesoporous silica materials, pore architecture, pore size, and morphology are currently major issues in areas such as catalytic conversion of bulky molecules, adsorption, host-guest chemistry, etc. In this sense, we discuss the pore size-controlled mesostructure, framework functionalization, and morphology control of organic-inorganic hybrid mesoporous silicas by which we can improve the applicability of mesoporous materials. First, we explain that the sizes of hexagonal- and cubic-type pores in organic-inorganic hybrid mesoporous silicas are well controlled from 24.3 to 98.0 A by the direct micelle-control method using an organosilica precursor and surfactants with different alkyl chain lengths or triblock copolymers as templates and swelling agents incorporated in the formed micelles. Second, we describe that organic-inorganic hybrid mesoporous materials with various functional groups form various external morphologies such as rod, cauliflower, film, rope, spheroid, monolith, and fiber shapes. Third, we discuss that transition metals (Ti and Ru) and rare-earth ions (Eu(3+) and Tb(3+)) are used to modify organic-inorganic hybrid mesoporous silica materials. Such hybrid mesoporous silica materials are expected to be applied as excellent catalysts for organic reactions, photocatalysis, optical devices, etc.     

Iron hydroxyl phosphate microspheres: Microwave-solvothermal ionic liquid synthesis, morphology control, and photoluminescent properties

A variety of iron hydroxyl phosphate (NH₄Fe₂(PO₄)₂OH·2H₂O) nanostructures such as solid microspheres, microspheres with the core in the hollow shell, and double-shelled hollow microspheres were synthesized by a simple one-step microwave-solvothermal ionic liquid method. The effects of the experimental parameters on the morphology and crystal phase of the resultant materials were investigated. Structural dependent photoluminescence was observed from the double-shelled hollow microspheres and the underlying mechanisms were discussed.     

Controlling morphology and particle size of hollow poly(styrene-divinylbenzene) microspheres fabricated by template-based method

Hollow poly(styrene–divinylbenzene) (P(S-DVB)) microspheres were fabricated via template-based method including synthesis of silica particles by sol-gel method, preparation of silica/P(S-DVB) particles by dispersion polymerization and chemical etching of silica cores by NaOH solution. TEM, FTIR and TG analyses confirmed that the hollow P(S-DVB) microspheres were successfully obtained. The morphology of hollow P(S-DVB) microspheres could be controlled by adjusting the amounts of DVB, AIBN and VTES, and the round-ball-like hollow P(S-DVB) microspheres were fabricated when the amount of DVB, AIBN and VTES was 30.0?wt%, 5.0?wt% and 30.0?vol% respectively. Both the size of silica particles and amount of monomers were regarded as the two key factors to control the particle size of the round-ball-like hollow P(S-DVB) microspheres.     

PVA-g-PS复合微球的制备与粒径控制研究

由链转移自由基聚合与端基置换反应法,合成了苯乙稀基单封端的聚醋酸乙烯酯(PVAc)大分子单体,使其与苯乙烯在乙醇/水的混合介质中进行自由基分散共聚,得到了表面以PVAc为接枝链的聚苯乙烯(PVAc-g-PSt)微球。将所得微球在碱性条件下醇解,形成了以亲水性聚乙烯醇(PVA)为壳、聚苯乙烯为核的复合微球(PVAc-g-PSt)。用核磁共振对聚合物的结构进行表征,定出了PVAc末端双键的含量;并用激光光散射、扫描电子显微镜对微球的粒径与形态进行了表征。研究结果表明,在共聚反应体系中大分子单体的分子量与浓度、苯乙烯浓度、引发剂浓度及溶剂的组成对微球的形态和粒径大小有明显影响。     

Recognition-induced polymersomes: structure and mechanism of formation

Random polystyrene copolymers grafted with complementary recognition elements were combined in chloroform producing vesicular aggregates, that is, recognition-induced polymersomes (RIPs). Reflection interference contrast microscopy (RICM) in solution, coupled with optical microscopy (OM) and atomic force microscopy (AFM) on solid substrates, were used to determine the wall thickness of the RIPs. Rather than a conventional mono- or bilayer structure (approximately 10 or approximately 20 nm, respectively) the RIP membrane was 43+/-7 nm thick. Structural arrangement of the polymer chains on the RIP wall were characterized by using angle-resolved X-ray photoelectron spectroscopy (AR-XPS). The interior portion of the vesicle membrane was found to be more polar, containing more recognition units, than the exterior part. This gradient suggests that a rapid self-sorting of polymers takes place during the formation of RIPs, providing the likely mechanism for vesicle self-assembly.     

Fabrication and morphology control of hollow polymer particles by altering core particle size

Particles with various morphologies were fabricated by changing the size of carboxyl-containing core particles and performing seeded emulsion polymerization as well as alkali posttreatment. The distribution of carboxyl groups, size, and morphology of the resultant particles were characterized with conductometric titration, dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Results indicated that the size of carboxyl-containing core latex particles could be varied from 95 to 240 nm by adjusting the concentration of sodium dodecyl sulfate (SDS). The percentage of carboxyl groups buried inside particles increased clearly along with the encapsulation of core by interlayer and shell polymers, and seeded emulsion copolymerization performed smoothly except the system using core particles with size less than 99 nm. After alkali posttreatment, the morphologies of corresponding particles showed porous, hollow, and bowl-like structure, respectively. Moreover, the relationship between core particle size and alkali-treated particle morphology was elucidated briefly.     

Reversible size of shear-induced multi-lamellar vesicles

We have investigated the reversibility in the shear-induced multi-lamellar vesicle (MLV) size during stepwise cycling of the shear rate by employing common rheometry, polarized light microscopy and rheo-optic techniques. We thus address the question whether there is a true MLV steady state, irrespective of history. The system studied, was the nonionic surfactant triethylene glycol decyl ether (C₁₀E₃) with a concentration of 40 wt.% in D₂O and a constant temperature of 25°C. It was found that the MLV size varies reversibly with varying shear rate, and hence there exists a true steady state in the presence of shear flow. The experimental observations of reversibility are however restricted to higher shear rates. Because the transformation of the size results from the shear strain, the process is very slow at lower shear rates, where the steady state cannot be reached within a reasonable experimental time.     

Entropic stabilization and equilibrium size of lipid vesicles

We have studied the phase behavior of zwitterionic phospholipid dioleoylphosphatidylcholine (DOPC) vesicles (membranes) and interpreted our results using scaling arguments in combination with molecular realistic self-consistent field (SCF) calculations. DOPC membranes acquire a partial negative charge per lipid molecule at intermediate NaBr concentrations. As a result of this, dilute DOPC solutions form stable unilamellar vesicles. Both at low and high salt concentrations phase separation into a lamellar and a vesicular phase is observed. The vesicle radius decreases as a power law with decreasing lipid concentration. This power-law concentration dependence indicates that the vesicle phase is entropically stabilized; the size of the DOPC vesicles result from a competition between the bending energy and translation and undulation entropy. This scaling behavior breaks down for very small vesicles. This appears to be consistent with SCF predictions that point to the fact that in this regime the mean bending modulus kc increases with curvature. The SCF theory predicts that, at low ionic strength, the membrane stability improves when there is more charge on the lipids. Upon a decrease of the ionic strength, lipids with a full negative charge form vesicles that grow exponentially in size because the mean bending modulus increases with decreasing ionic strength. At the same time the Gaussian bending modulus becomes increasingly negative such that the overall bending energy tends to zero. This indicates that small micelles become the dominant species. The SCF theory thus predicts a catastrophic break down of giant vesicles in favor of small micelles at sufficiently low ionic strength and high charge density on the lipids.     

Dielectric behavior of lipid vesicles: the case of L-alpha-dipalmitoylphosphatidylcholine vesicles as a function of size and temperature

We present an extensive set of radio wave dielectric relaxation spectroscopy measurements of aqueous suspensions of different size unilamellar L-alpha-dipalmitoylphosphatidylcholine (DPPC) vesicles, in a temperature range between 15 and 55 C, where the lipidic bilayer experiences structural transitions from the gel to the rippled phase (at the pretransition temperature) and from the rippled to the liquid phase (at the main transition temperature). The dielectric spectra have been analyzed in the light of the Cole-Cole relaxation function, and the main dielectric parameters-the dielectric increment Deltaepsilon and the mean relaxation frequency omega(0)--have been evaluated as a function of temperature. These parameters display a very complex phenomenology, depending on the structural arrangement of the lipid-water interface. The structural parameters that govern the dielectric behavior of these systems associated with the lipid bilayer have been recognized within a recent dynamic mean-field model we have proposed, aimed to predict the dipolar relaxation of an array of strongly interacting dipoles anchored to a flat or corrugated surface. They are the prefactor A(T) of the distance-dependent part of the effective dipolar interaction energy, the term Gamma(vis), that takes into account the damping of the dipolar motion, the average dipolar distance related to the area a(0) per polar head, and the bilayer thickness. The present analysis furnishes, from a phenomenological point of view, the dependence of these parameters on the temperature and on the vesicle size.     

Temperature-responsive phase transition of polymer vesicles: real-time morphology observation and molecular mechanism

Novel thermosensitive polymer vesicles with controlled temperature-responsive phase transition at the lower critical solution temperature (LCST) varying from 8 to 81 degrees C were prepared via self-assembly of amphiphilic hyperbranched star copolymers having a hydrophobic hyperbranched poly[3-ethyl-3-(hydroxymethyl)oxetane] (HBPO) core and many hydrophilic polyethylene oxide (PEO) arms. Real-time optical microscopic observation revealed that the polymer vesicles have undergone sequential morphology changes including enrichment, aggregation, fusion, and vesicle-to-membrane transformation near the LCST. Molecular-level investigation indicates that the LCST transition results from the decreasing water solubility of the polymer vesicles with increasing temperature based on the partial dehydration of the PEO vesicle corona. On the basis of these results, a LCST transition mechanism, in view of the molecular configuration, balance of hydrophilic and hydrophobic moieties, and the vesicle morphology transformations, was proposed. As far as we know, the work presented here is the first demonstration of thermosensitive vesicles based on PEO, and the finding may be useful to design the thermosensitive core-shell structures by introducing the PEO segments.     

Surfactant mediated control of pore size and morphology for molecularly ordered ethylene-bridged periodic mesoporous organosilica

A series of ethylene-containing mesoporous organosilica materials were fabricated via surfactant-mediated assembly of 1,2-bis(triethoxysilyl)ethylene (BTEE) organosilica precursor using alkyltrimethylammonium bromide (CnTAB) surfactants with different alkyl chain length (n=12, 14, 16, 18) as supramolecular templates. The presence of molecularly ordered ethylene groups in the resulting periodic mesoporous organosilica (PMO) materials was confirmed by XRD data along with 29Si and 13C MAS NMR analysis. Additional characterization techniques, namely nitrogen sorption, TEM, and TGA, confirmed the structural ordering and thermal stability of the molecularly ordered ethylene-bridged PMOs. The PMOs exhibit molecular-scale ordering (with a periodicity of 5.6 A) within the organosilica framework and tunable pore size, which depending on the alkyl chain length of the surfactant templates, varied in the range 23-41 A. Furthermore, depending on the alkyl chain length of the templates, the particle morphology of the PMOs gradually changed from monodisperse spheres (for C12TAB) to rod or cakelike particles (for C14TAB) and elongated ropelike particles for longer chain surfactants. Variations in the surfactant chain length therefore allowed control of both the pore size and particle morphology without compromising molecular-scale or structural ordering. The reactivity of ethylene groups was probed by bromination, which demonstrated the potential for further functionalization of the PMOs.     

Uniform molecularly imprinted microspheres and nanoparticles prepared by precipitation polymerization: the control of particle size suitable for different analytical applications

Molecularly imprinted polymers (MIPs) are being increasingly used as selective adsorbents in different analytical applications. To satisfy the different application purposes, MIPs with well controlled physical forms in different size ranges are highly desirable. For examples, MIP nanoparticles are very suitable to be used to develop binding assays and for microfluidic separations, whereas MIP beads with diameter of 1.5-3 μm can be more appropriate to use in new analytical liquid chromatography systems. Previous studies have demonstrated that imprinted microspheres and nanoparticles can be synthesized using a simple precipitation polymerization method. Despite that the synthetic method is straightforward, the final particle size obtained has been difficult to adjust for a given template. In this work, we initiated to study new synthetic conditions to obtain MIP beads with controllable size in the nano- to micro-meter range, using racemic propranolol as a model template. Varying the composition of the cross-linking monomer allowed the particle size of the MIP beads to be altered in the range of 130 nm to 2.4 μm, whereas the favorable binding property of the imprinted beads remained intact. The chiral recognition sites were further characterized with equilibrium binding analysis using tritium-labeled (S)-propranolol as a tracer. In general, the imprinted sites displayed a high chiral selectivity: the apparent affinity of the (S)-imprinted sites for (S)-propranolol was 20 times that of for (R)-propranolol. Compared to previously reported irregular particles, the chiral selectivity of competitive radioligand binding assays developed from the present imprinted beads has been increased by six to seven folds in an optimized aqueous solvent.     

交联剂加入方式对聚苯乙烯微球形貌和分散性能的影响

以醇水混合液为分散介质,偶氮二异丁腈为引发剂,聚乙烯吡咯烷酮为稳定剂,二乙烯基苯为交联剂,采用分散聚合法一步制备了粒径约为1μm的单分散交联聚苯乙烯微球;采用扫描电镜和激光粒度仪等分析微球表面形貌及粒径分布,研究了滴加交联剂开始时间、交联剂浓度、引发剂浓度等对微球形貌和分散性能的影响.结果表明,在实验进行4h时加入交联剂,且交联剂滴加持续时间为2h的条件下,可制得平均粒径为1μm左右的交联聚苯乙烯微球,其具有较好的单分散性和球形度,且表面光滑.     

Concise synthesis of NaTi2(PO4)3 nanocrystals with size and morphology control

NaTi_2 (PO_4)_3 (NTP) nanocrystals with high room-temperature ionic conductivity of 1.1×10~3 S/cm were prepared by a concise solvothermal method at 140 ℃ for 3 h, and the aspect ratios of all the NTP nanocrystals are the closest to 0.7. It implies a moderate size-distribution of NTP nanocrystals obtained at 140 ℃ for 3 h is helpful for increasing packing density, and the packing density is the larger, so its conductivity is the higher. The controllability over size and morphology of the NTP nanocrystals via solvothermal temperature and time were investigated. The results suggest that our method is of great potential in synthesizing NTP nanocrystals with high room-temperature ionic conductivity at low cost.     

Shape and size of giant unilamellar phospholipid vesicles containing cardiolipin

The effect of cardiolipin content on the shape and size of giant palmitoyloleylphosphatidylcholine/cardiolipin vesicles was studied. Unilamellar vesicles were prepared in sugar solution by the method of electroformation, from mixtures containing up to 50% weight ratio of cardiolipin. At room temperature the vesicles containing cardiolipin exhibited abrupt changes in the curvature of the vesicle contour indicating regions of phase separation. The deviations from the spherical shape were larger if vesicles were made from mixtures with a higher content of cardiolipin. Numerous vesicles with soft fluctuating walls were observed. The estimated size of the vesicles containing cardiolipin was found to be smaller than the size of pure palmitoyloleylphosphatidylcholine vesicles.