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Self-assembled Thermo-responsive Lipid Nanoparticles Based on Electrospraying:Preparation, Characterizations and in Vitro Release of Drugs

Author: JinChengCheng
Tutor: ZhuLiMin
School: Donghua University
Course: Biochemical Engineering
Keywords: self-assembly liposomes electrospraying drug release
CLC: TQ460.1
Type: Master's thesis
Year: 2014
Downloads: 19
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Abstract


Liposome is a phospholipids bilayer water cavity, which can be processed by a special process and has unique properties, such as long cycle, cell specificity target, pH sensitivity, and the temperature sensitivity. These are by choosing appropriate lipid composition and surface modification of liposomes. In addition, liposomes with good biocompatibility, biodegradable and the advantages of low toxicity, so as a drug carrier, it has potential application value.Thermal-responsive lipid nanoparticles are one liposome in nano size and phase-transition temperature. However such thermal-responsive liposome common deficiencies include:lipid nanoparticles easily gathered into large particles, the location of the gelation tendency, unpredictable polycrystalline model transformation kinetics, and lipid nano crystal structure inherent in the low compatibility. Lipid nanoparticles in stability, particle size distribution, problems existing in the aspects such as large-scale production limit its application and developmentFor instance, considering the size issue, it’s reported that liposomes smaller than70nm are taken up by liver parenchyma cells, but those larger than300nm accumulate in the spleen. An optimum size range of70-200nm has been identified as giving the highest concentration of liposomes in the blood. Another study demonstrated that the biodistribution of liposomes depends both on the mean particle size and on the size distribution. Therefore, the development of new liposome preparation methods for controlling over their properties is required.In this thesis, we describe a facile and convenient strategy for the preparation of self-assembled liposomes from electrospray particles based on the good water-soluble and spinnability of poly (N-isopropyl acrylamide)(PNIPAAm). In this method, amphiphilic particles composed of the hydrophilic PNIPAAm and soybean lecithin were firstly fabricated using an electrospinning process. As a result of the templating of the particles, PC liposomes were spontaneously formed through molecular self-assembly when the particles were added to water. The influence of PC on nanoparticle formation、a possible mechanism of templated liposome formation and phase-transition temperature were discussed. On the basis of work before, we chose ketoprofen (KET) as a model drug, incorporated it into PNIPAAm-based nanoparticles via electrospraying, and subsequently investigated the self-assembly of KET-loaded liposomes, the drug entrapment efficiency and the drug release behavior in vitro. The sustained and controlled drug release from liposome was thus exhibits attractive application in drug delivery.This thesis includes the following contents:We used an electrospraying process to fabricated Amphiphilic PNIPAAm/PC composite particles. Because of the templating of the particles, PC lipid nanoparticles were spontaneously formed from self-assembly when the composite particles were added to water. Through the characterization of composite electrospraying particles and lipid nanoparticles, we discussed the influence of PC content on the properties of spraying solutions, composite particles and lipid nanoparticles. Scanning electron microscopy (SEM) showed that pure PNIPAAm nanoparticles from a10%w/v chloroform and DMAc mixed solution have an average diameter of1208±71nm. As the PC content of the particles was increased (from9.1%to33.3%w/w), the nanoparticle diameter decreased to572±95nm. However, a further increase in PC content to50%w/w led to a sharp increase in diameter (to1844±63nm). In addition, the results from X-ray diffraction (XRD), differential scanning calorimetry (DSC) and flourier transform infrared spectroscopy (FTIR) demonstrate that there are hydrophobic and electrostatic interactions between PNIPAAM and PC, so these secondary interactions must plays a fundamental role in promoting the structural homogeneity of PNIPAAm/PC composite particles. The results of dynamic light scattering (DLS) showed that the size of the vesicles produced is closely linked to the PC content in the nanoparticles. If we increased the PC concentration, it results in a lower polydispersity index (PDI) of the self-assembled liposomes, with the lowest index being0.205at a concentration of33.3%. This suggested that, we can elevat the PC content in the particle composites is beneficial for the production of vesicles with a narrower size distribution. Using the above spraying conditions, we successfully fabricated PNIPAAm/PC/KET composite particles. We also prepared KET-loaded liposomes with these particles templates. The ratio of KET to phospholipids (PC) on the properties of nanoparticles and liposomes has been systematically investigated. Both liposome size and Zeta potential tended to decrease with an increase in the mass ratio of KET to PC.The dialysis technique was used to remove free KET from the KET-loaded liposome suspensions. And methanol was used to break up the KET-loaded liposomes. After that we discussed the release behavior of KET using a model drug liposome in vitro. The entrapment efficiency (E.E.) of KET was determined by UV spectroscopy at λ=260nm. The results showed the highest entrapment efficiency (94.6%) was obtained, when the mass ratio of drug to PC up to3:25, and the release of KET from liposome were closely related to the temperature value of the release medium, with the rate of release rising with a high temperature above the TPP. The liposomes are observed to release the drug over around120h, which is much suitable for use in a sustained release formulation.

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