| Summary: | 碩士 === 國立臺灣大學 === 醫學工程學研究所 === 103 === Background: Curcumin (Cur) is a hydrophobic molecule, it has the characteristics of anti-oxidation, anti-inflammation, but low bioavailability. Solid Lipid Nanoparticle (SLNP) has good biocompatibility and long term physicochemical stability, and hence it can be an efficient drug carrier.
Purpose: The research used SLNP to encapsulate Cur to form Cur SLNP and then combined with antitumor nanodrug Pegylated Liposomal Doxorubicin (PLD) to inhibit tumor growth and reduce the side effects of drug.
Materials and Methods: GEC-Cholesterol and Cholesterol were used to compose SLNP to encapsulate Cur. Dynamic light scattering was used to analyze the particle size and zeta potential, and fluorescence spectrophotometer was used to measure the absorbance of Cur to calculate the encapsulation efficiency. The stability of Cur SLNP in different temperatures and the release rate of Cur in different pH solution were measured. 4T1 mouse breast cancer cells were used to perform cell toxicity testing for Cur SLNP and Free Cur. Pharmacokinetics and biodistribution of Cur SLNP in mice were studied. 4T1 mouse breast tumors were implanted in the backs of BALB/c female mice and the treatment started when the tumors grew up to 50 mm3. The experimental groups were divided into Control, Cur SLNP, PLD (4 mg/kg, 10 mg/kg), PLD (4 mg/kg) + Cur SLNP. 28 days later, the mice were sacrificed and the tumors were harvested, weighted, sectioned and paraffined for H&E staining.
Result: The molar ratio of 3:4 for SLNP and Cur had the highest encapsulation efficiency, approximately 57.8 %. Cur SLNP at low temperature was more stable and Cur released faster in an acidic environment. Cell toxicity testing showed that Cur SLNP at alow concentration still had the ability to inhibit cancer cell growth. Pharmacokinetics study revealed that SLNP could prolong Cur circulation time in the blood. PLD (4 mg/kg) + Cur SLNP had the same performance for tumor growth inhibition as PLD (10 mg/kg), and H&E staining confirmed the result.
Conclusion: Cur SLNP was stable at low temperatures. Cur SLNP remained the inhibition ability for cancer cellsat low concentrations. SLNP could prolong Cur circulation time in the blood. PLD (4 mg/kg) + Cur SLNP and PLD (10 mg/kg) had similar effectiveness for tumor growth inhibition. The results indicated that Cur SLNP could be used to assist antitumor nanodrug to inhibit tumor growth.
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