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Preclinical evaluation of injectable sirolimus formulated with polymeric nanoparticle for cancer therapy
Ha Na Woo1, Hye Kyung Chung, Eun Jin Ju
1Institute for Innovative Cancer Research, Asan Medical Center, Seoul, Korea.
Abstract:
Nanoparticles are useful delivery vehicles for promising drug candidates that face obstacles for clinical applicability. Sirolimus, an inhibitor of mammalian target of rapamycin has gained attention for targeted anticancer therapy, but its clinical application has been limited by its poor solubility. This study was designed to enhance the feasibility of sirolimus for human cancer treatment. Polymeric nanoparticle (PNP)-sirolimus was developed as an injectable formulation and has been characterized by transmission electron microscopy and dynamic light scattering. Pharmacokinetic analysis revealed that PNP-sirolimus has prolonged circulation in the blood. In addition, PNP-sirolimus preserved the in vitro killing effect of free sirolimus against cancer cells, and intravenous administration displayed its potent in vivo anticancer efficacy in xenograft tumor mice. In addition, PNP-sirolimus enhanced the radiotherapeutic efficacy of sirolimus both in vitro and in vivo. Clinical application of PNP-sirolimus is a promising strategy for human cancer treatment.
Insights
Polymeric nanoparticles (PNP) improve sirolimus delivery for cancer treatment, enhancing its anticancer and radiotherapeutic effects. This injectable formulation shows promise for clinical applications in human oncology.
Area of Science:
- Nanomedicine
- Oncology
- Pharmacology
Background:
- Sirolimus, an mTOR inhibitor, shows anticancer potential but faces clinical limitations due to poor solubility.
- Nanoparticle drug delivery systems offer solutions for challenging drug candidates.
Purpose of the Study:
- To enhance the clinical feasibility of sirolimus for human cancer therapy.
- To develop an injectable polymeric nanoparticle (PNP)-sirolimus formulation.
Main Methods:
- Polymeric nanoparticle (PNP)-sirolimus formulation development.
- Characterization using transmission electron microscopy and dynamic light scattering.
- Pharmacokinetic analysis, in vitro cancer cell killing assays, in vivo xenograft tumor studies, and evaluation of combined radio-chemotherapy.
Main Results:
- PNP-sirolimus demonstrated prolonged blood circulation and maintained in vitro anticancer activity.
- Intravenous administration of PNP-sirolimus showed potent in vivo anticancer efficacy in xenograft models.
- PNP-sirolimus significantly enhanced the radiotherapeutic efficacy of sirolimus both in vitro and in vivo.
Conclusions:
- Injectable PNP-sirolimus is a viable strategy to overcome sirolimus solubility issues for cancer treatment.
- PNP-sirolimus formulation improves sirolimus's pharmacokinetic profile and therapeutic efficacy.
- This nanomedicine approach holds promise for advancing human cancer therapy through enhanced drug delivery and combined treatment modalities.
