Experimental investigation of polymeric nanoparticles for enhanced drug delivery processes in cancer chemotherapy treatments

In 2022, nearly 20 million new cancer cases were reported globally, with cancer-related deaths amounting to 9.7 million, making cancer one of the leading causes of death worldwide. Approximately 25% of cancer patients undergo chemotherapy, with the number of patients requiring chemotherapy expected to increase in the future. Chemotherapy costs account for the largest share in health system budgets and chemo patients experience a vast range of unpleasant side effects and diminished life quality. All these emphasise the requirement for development of novel techniques aiming for the enhanced drug delivery of anticancer drugs on the cancer site with minimal side effects to patients and high treatment efficiency with limited drug waste.
The development of antineoplastic drug delivery systems (DDS) formed by the self-assembly of biodegradable and biocompatible amphiphilic block copolymers was a major research focus in recent years. Although these polymers are intended for pharmaceutical applications, their synthesis is performed in solvents that are highly harmful and toxic. The focus of this work was employing 2-MeTHF as a bio-based polymerisation solvent for the synthesis of amphiphilic block copolymers aimed for chemotherapy DDSs. The results advocate the application of 2-MeTHF as an effective and sustainable multi-polymerisation solvent for the synthesis of various copolymers with varying chemistry, architecture and biodegradability.
The self-assembly mechanism of block copolymer into nanoparticles has been extensively investigated in this work by employing multiple formulation techniques, including the widely used nanoprecipitation process. The development of thermodynamically-driven formulation techniques, which are scarce in the literature, was performed to offer a greater understanding of the nanoparticle formulation. The exact position where the micellisation initiates during the solvent exchange process, is indicated within 20-30vol% of aqueous solvent composition. The formulation of polymeric micelles close to a thermodynamic balance was successful. In addition, nanoprecipitation was proven to be a highly robust, reproducible and easy process for formulation of polymeric nanoparticles with highly desirable size and narrow size distributions.
An improved long-term storage stability of the polymeric DDSs is experienced when the nanoparticle formulations are freeze-dried. However, freeze-drying is a very intensive process requiring the use of cryoprotectants to preserve the materials integrity. In this work, the first ever systematic study of PEGs used for cryopreservation of PEG-PLA nanoparticles was performed with an emphasis on the freezing step of the process. The results show that PEGs are highly successful in preserving the PEG-PLA formulation properties with reconstitution times less than 10 min. Lower molecular weight PEGs appear as more efficient cryoprotectants.
To assess the capabilities of polymeric nanoparticles based on PEG-PLA to form an effective DDSs for cancer chemotherapy, the encapsulation of the hydrophobic Nile Red as a model anticancer drug was performed. The challenges faced with separation of the unencapsulated drug from the drug-loaded nanoparticle suspension were addressed with the employment of diethyl ether as a Nile Red extraction solvent. The encapsulation of Nile Red within the PEG-PLA nanoparticles was highly successful. The final formulation sizes and PDI were in the ideal DDS range and experienced higher encapsulation efficiency compared to data in the literature.