Abstract:
Objective
To explore the improvement effect of HCPT/PEG-PBLG nanoparticles on the treatment of oral squamous cell carcinoma.
Methods
PEG-PBLG nanoparticles loaded closed ring form HCPT were synthesized and measured.Intervention was performed in Golden Hamster cheek pouch squamous cell carcinoma model： normal saline， PEG-PBLG were used as blank control and HCPT & HCPT/PEG-PBLG was given through intraperitoneal injection once a day for 5 days at a dosage of 3 mg/kg.The gross volume of the tumor， the tumor's doubling time （DT）， repression rate and pharmacokinetics index were calculated.
Results
HCPT/PEGPBLG nanoparticles had been successfully synthesized， with 56.8% in encapsulation efficiency and 7.5% in loading level.Gross volume of tumor treated by HCPT decreased since 4th day reached its minimum， tumor doubling time delayed and the tumor repression rate was 63.58%.In HCPT/PEG-PBLG group， the tumor gross volume decreased on 4th day， reached their minimum on 8th day， tumor doubling time was obviously longer than HCPT group （P=0.01） and tumor repression rate was 76.50%.The pharmacokinetics of HCPT carboxylic sodium salt dosage form showed two- compartment model， that of HCPT/PEG-PBLG showed a burst-and-delayed release model in vivo： Tmax and t1/2β were longer， Cmax lower， AUC and Vd increased than HCPT.
Conclusions
HCPT fairly restrained tumor growth of OSCC in vivo.But in clinical， HCPT is usually converted to carboxylic sodium salt dosage form with E-lactone ring opened to make the agent solvable， which has weakened its activity of tumor-depressing， and given the agent a fast rate of metabolism as well as lower affinity to tissue in vivo， leading to the limitation of application.HCPT/PEG-PBLG nanoparticles， which has preserved the key structure of tumordepressing， E-lactone ring， increase the solubility and stabilized the lactone ring， slow down the drug release， prolong the metabolic elimination， scale up the drug affinity to tissue and make tumor-targetting possible.Compared with open ring form HCPT， it showed better therapeutic effects.
Key words:
Hydroxycamptothecine (HCPT),
Pharmaceutical dosage form,
Poly[ethylene glycol](PEG),
Poly[γ-benzyl-L-glutamate](PBLG),
Oral Squamous Cell Carcinoma(OSCC),
Nanoparticles
Dan CHEN, Xue-qiang DING, Li-ping CHAI, Anxun WANG, Su LI, Yu CHEN, Ji WANG, Wang-xiang YAN. Studies of Hydroxycamptothecine Nanoparticles therapautics to Golden Hamster cheek pouch squamous cell carcinoma[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2009, 3(01): 42-49.