| Solid lipid nanoparticles(SLN) are nanotechnology-based drug delivery systems composed of biodegradable solid lipophilic matrix and encapsulated drugs in the lipid core.However, SLN still exhibit a series of disadvantageous properties including particles aggregate, low loading capacity, poor stability and even burst release. Due to the crystallization of solid lipid carriers, the drugs entrapped into SLN are subjected to be excluded from the lipid crystal matrix during the solidification and storage of SLN.Polyethylene glycol(PEG) as biodegradable, non-toxic and biocompatible materials are approved by Food and Drug Administration(FDA), can be used as materials for modification of lipids based drug delivery system to solve the problems mentioned above, and improve the bioeffect of nanocarriers.In the present work, resveratrol(RES) loaded SLN modified by Polyethylene glycol2000(PEG2000) and Polyethylene glycol-2000-1, 2-distearoyl-sn-glycero-3-phosphoethanolamine(PEG2000-DSPE) were prepared using the method of emulsion evaporation and low temperature solidification. The loading capacity, particles size and polydispersity index of RES-SLN were discussed, the micromorphology, thermal properties, phase characteristics,crystalline structure and lipid-drug-modifier interaction were characterized. The modification mechanism of modifier to SLN were disclosed based on the relationship between physicochemical properties and microsturcture of surface and lipids matrix. The in vitro release behavior and release mechanism of nanoparticles were studied, and the antioxidant properties of resveratrol were evaluated.The entrapment efficiency of RES-PEG-SLN and RES-PEG-DSPE-SLN are enhanced to(86.38±0.65)% and(88.24±0.59)%, loading capacity are(7.84±0.04)% and(7.87±0.04)%,respectively. The particle size were about 100 nm, suggesting a uniform and narrow size distribution. The surface microtopography of RES-PEG-SLN and RES-PEG-DSPE-SLN revealing their compact structure and regular spherical shape, well distributed and non-adherent nature, could avoid the drug leakage. According to phase characteristics and crystalline structure information, PEG modifiers are dispersed in the lipid matrix crystal anddisrupts the crystalline arrangement of the lipids to some extent, RES incorporated into the lipid matrix in amorphous or disordered structure. In this way, PEG/lipid eutectic dopant containing lattice defects with α metastable are formed and inhibits transformation of the lipid matrix from α metastable to the more stable β-form during the process of drying and solidification. The lattice defects structure provide more flexible spacing, which makes it available for incorporation of more drugs and preventing drug exclusion from the lipid matrices. The release behavior of RES-PEG-SLN and RES-PEG-DSPE-SLN follow a two-stage exponential kinetic equation, demonstrating a sustained release pattern. The p H-sensitive release of RES-PEG-DSPE-SLN made it possible for a targeted and effective release in the tumor cell or tissue, which drug accumulated release contents were above 90%.The antioxidant activity of RES are improved distinctly by SLN modified by PEG, this study could provide scientific guidance for expanded applications of RES.These results confirm that both surface steric hindrance and matrix doping effects produced by the presence of PEG polymers play important roles in improving drug loading,avoid burst release and maintaining sustained release, prevent particles aggregate, and enhanced the bioeffect of lipid nanocarrier ultimately. This present research established a evaluation system for drug delivery system via the design of lipid nanocarrier, which would providing scientific basis and guidance for the complexes lipid carrier with high bioavailability. |
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