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A novel biocompatible and biodegradable hydrophilic lipid nanoparticle (LLNP) was formulated for enhanced antitumor activity and tumor penetration. The lipid nanoparticles consisted of linoleic acid-derivatized glycyrrhetinic acid (LA-GA) conjugated with the poly(ethylene glycol) (PEG) derivatives of two different sizes, i.e., PEG20k and PEG5k. The amphiphilic PEG derivatives formed a lipid nanoparticle core and the hydrophobic linoleic acid-derived GA was conjugated to the PEG chain at the end of the nanoparticle for a dual targeting approach. Aqueous solubility, cellular uptake and in vitro release of the nanoparticles were evaluated. The biodistribution of the PEG5k nanoparticles (LA-GA-PEG5k-NPs) in vivo was evaluated. The results showed that the LA-GA-PEG5k-NPs possessed unique properties in terms of their water solubility and cellular uptake. Moreover, the PEG5k-NPs had significantly improved the aqueous solubility of the hydrophobic drug. In vitro, LA-GA-PEG5k-NPs had a sustained drug release with a slow release rate as indicated by the release over 96 h. PEG5k-NPs showed an enhanced tumor uptake that was faster than LA-GA-PEG5k-NPs. In vivo, the LA-GA-PEG5k-NPs significantly inhibited the growth of murine TC-1 cells compared to the LA-GA-PEG20k-NPs.Q:
How to calculate the derivative of this vector function?
Take $F(x,y)$ such that
$$F(x,y)=\left(\begin{matrix}
e^x(x-y-1)-1 \\
-(x-y)^2e^x(x-y-1)+e^x(x
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