To improve the physicochemical and pharmacokinetic properties, solid lipid nanoparticles (SLNs) modified with (Polyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG2000-DSPE) were prepared using glyceryl monostearate as a lipid carrier and resveratrol as a model
drug. Compared to ordinary SLNs, SLNs doped with low amount of PEG2000-DSPE [m(PEG2000-DSPE):m(lipids) = 1:5, w/w] exhibited improved physicochemical and pharmacokinetic properties, including higher entrapment efficiency (above 80%), smaller particle size (approximately 100 nm), more
distinguished drug release at low pH values (pH < 6.0), and longer drug circulation in vivo. According to the characterizations performed, the DSPE moiety was doped into lipid matrix to form a PEG2000-DSPE/lipid eutectic dopant, inhibiting lipid polymorphism transformation
from α-form to β-form, thereby preventing drug expulsion from the lipid. The dopant contained lattice defects, allowing for the incorporation of more resveratrol. Resveratrol was released in a sustained and pH-sensitive pattern due to nanoparticles destabilization
induced by partial protonation of PEG2000-DSPE. PEG chains distributed on the nanoparticle surface caused steric hindrance and “stealth” properties, thus maintaining dispersion stability and extending circulation time of nanoparticles. These results confirm that PEG2000-DSPE modification
effects are attributable to the matrix and surface structures of nanoparticles, which consist of a core containing DSPEinduced lattice defects and a shell coated with PEG chains.
The objective of this study was to develop an injectable hydrogel based on furfuryl amine-conjugated hyaluronic acid (FA- conj -HA) and evaluate the in vivo anti-4 T1 tumor activity of doxorubicin-loaded hydrogel (DOX@FA- conj -HA gel ). The cargo-free hydrogel (FA- conj -HA gel ) was fabricated through a Diels-Alder reaction at 37 °C with FA- conj -HA as a gel material and four armed poly(ethylene glycol)2000-maleimide (4-arm-PEG2000-Mal) as a cross-linker. The bio-safety of FA- conj -HA gel were assessed, and the in vivo antitumor activity of DOX@FA- conj -HA gel was also investigated. Many 3D network structures were observed from scanning electron microscope (SEM) photograph, confirming the successful preparation of FA- conj -HA gel . The absence of cytotoxicity from FA- conj -HA gel was proved by the high viability of 4 T1 cells. In vivo bio-safety studies suggested that the obtained FA- conj -HA gel did not induce acute toxicity or other lesions in treated mice, confirming its high bio-safety. The reduced tumor volumes, hematoxylin-eosin staining (H&E), and TdT-mediated dUTP-biotin nick end labeling (TUNEL) analysis indicated the potent in vivo anti-4 T1 tumor effects of DOX@FA- conj -HA gel . In conclusion, the favorable bio-safety and potent antitumor activity of DOX@FA- conj -HA gel highlighted its potential application in oncological therapy.
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