Enhancement of Paclitaxel Therapeutic Effect by Aptamer Targeted Delivery in PLGA Nanoparticles

Abstract

Objectives: Paclitaxel is a drug molecule used in the therapy of various cancer types, including breast cancer. It is one of the preferred chemotherapy agent due to its high efficacy. However, many side effects have been observed associ- ated with paclitaxel use such as allergy, hair loss, diarrhea and pain. Methods: We evaluated therapeutic efficacy of paclitaxel when it is actively targeted to breast cancer tumours inside a polymeric nanoparticle. Targeted delivery of paclitaxel to tumour sites has been reported as an improved cytotoxicity strategy with a variety of nanoparticles. In this study, poly Lactic-co-Glycolic Acid (PLGA) nanoparticles were used as drug carrier and nucleolin aptamers as affinity targeting agents. Results: Paclitaxel molecules were entrapped during the synthesis of PLGA nanoparticles of 238 nm in diameter. The encapsulation and loading efficiencies of paclitaxel was 97% and 21% respectively. The paclitaxel loaded PLGA nanoparticles were functionalized with nucleolin aptamers and their targeting ability to cultured mouse cancer cells was determined for two cell lines (E0771 and 4T1). E0771 cell line was chosen for the preparation of allograph breast cancer mouse models. Evaluations of the targeted paclitaxel in PLGA nanoparticles showed 38% better performance in inhibiting tumour growth compared to free paclitaxel treatment groups of mouse models. Conclusion: The chemotherapeutic effect of cancer drugs like paclitaxel can be increased by loading inside tumour targeted polymeric nanoparticles