Preparation of Uniformly Sized Chitosan Nanospheres by a Premix Membrane Emulsification Technique

Abstract

Chitosan nanospheres have great potential in drug controlled release systems, because they show excellent degradability, biocompatibility, and nontoxicity. The particle size control and size distribution of nanospheres are necessary in order to improve reproducibility, bioavailability, and repeatable release behavior. In order to prepare uniformly sized and size-controllable chitosan nanospheres, in this study, a premix membrane emulsification technique was developed on the basis of direct membrane emulsification, and the uniformly sized chitosan naonospheres were successfully prepared by optimizing preparation conditions. The detail preparation process is as follows: The chitosan aqueous solution was used as a dispersed phase, and the mixture of liquid paraffin and petroleum ether containing emulsifier was used as a continuous phase. The coarse emulsions were first prepared by low-speed stator homogenization and then poured into the premix reservoir. Nanodroplets were achieved by extruding the coarse emulsions through the SPG (Shirasu porous glass) membrane with a high pressure. The nanodroplets were further cross-linked to obtain chitosan nanospheres. In this process, several factors played key roles in obtaining chitosan nanoparticles with narrow size distribution, including the amounts of emulsifier in oil phase, the composition of oil phase, the concentration of chitosan, the ratio of water to oil phase, the transmembrane pressure and number of passes, and so on. The results showed that the chitosan nanospheres from 300 nm to 1.85 µm were successfully prepared by premix membrane emulsification by changing the pore size of the membrane and the polydispersity index could be as low as 0.027 under optimized conditions, and it is a potential technique to prepare size-controllable uniform chitosan nanospheres with fast production.

Preparation strategies of thermo-sensitive P(NIPAM-co-AA) microspheres with narrow size distribution

“…Considering the simplicity of operation, 3 times trans-membrane passes were employed in the next preparation process. The result is in accordance with the results of the other research [23,24].…”

“…Therefore, 250 kPa was used in the following study when using 5.2 μm. The optimized trans-membrane pressures for membrane pores of 2.8 μm and 1.4 μm were 300 kpa and 950 kpa respectively [23,24]. These results showed that membrane pore size will have great effect on the trans-membrane pressure, that is, the optimal trans-membrane pressure will decrease with the increase of membrane pore size.…”

“…Here we would optimize the emulsification conditions by premix membrane emulsification method. Previous study showed that transmembrane pressure had great effect on the uniformity of the prepared microspheres or nanospheres [23]. The optimum trans-membrane pressure is largely dependent on the size of membrane pores and viscosity of the emulsion system [24].…”

“…Premix membrane emulsification technique is another valuable technique because it can obtain uniform droplets efficiently under higher nitrogen pressure. Although narrow-sized polylactide (PLA), polylactic-polyglycolic acid (PLGA) and chitosan microspheres have been prepared by using direct or premix membrane emulsification technique in our previous reports [23,24], it is still a big challenge to prepare thermo-sensitive microspheres. First, the viscosity of the NIPAM aqueous phase is largely different from that of macromolecules such as PLA, PLGA and chitosan, which further changed the transmembrane pressure and other key factors for preparing uniform microspheres.…”

Micro and nano polycaprolactone particles preparation by pulsed back-and-forward cross-flow batch membrane emulsification for parenteral administration

“…Particulate systems such as spheres, beads, capsules have been prepared in a micron range (Vladisavljevi c and Williams, 2005) by using membrane emulsification (ME) technology, whereas few works are reported for the preparation of particles in submicron range Lv et al, 2009;Wei et al, 2008;Sheibat-Othman et al, 2008).…”