Novel spray-dried PHA microparticles for antitumor drug release

ABSTRACT

The production of poly-3-hydroxybutyrate (P3HB) and poly-3-hydroxybutyrate/polyethylene glycol (PEG)-based microparticles, loaded with antitumor drugs paclitaxel (PTX) and 5-Fluorouracil (5-FU) by spray-drying technique, was investigated. The average diameter of microparticles was found to be 3.4 ± 0.5 µm and zeta potential was about −44 mV. The addition of surfactant PEG did not show any effect on the morphological characteristics of the particles. But the chemical structure of drug influenced on the properties. Microparticles had heterogeneous pores on the surface when the hydrophobic PTX was encapsulated. It was established that the addition of surfactant positively influenced on the properties of particles and led to the loading of 5-FU directly into the matrix. This is confirmed by the results of electron microscopy and dynamics of drug release in vitro. As a whole, the release profiles of PTX and 5-FU from composite P3HB/PEG microparticles were less than from P3HB microparticles. The results of the morphological evaluation of Hela cells demonstrated that the use of cytostatic drugs loaded in P3HB microparticles induces morphological changes associated with apoptosis (chromatin condensation, core fragmentation, margination of nucleus). Thus, the obtained results can serve as the basis for the development of new antitumor drugs of prolonged action, intended for various modes of administration.

KEYWORDS:

• 5-Fluorouracil
• efficiency
• microparticles
• paclitaxel
• polyhydroxyalkanoates
• spray-drying

Acknowledgments

The authors would like to thank Aleksandr Shabanov and Ivan Nemtsev (Federal Research Center Krasnoyarsk Scientific Center of the Siberian Branch of the RAS) for their support with SEM.

Additional information

Funding

This work was supported by the state budget allocated to the fundamental research at the Russian Academy of Sciences: [Project no. AAAA-A17- 117013050028-8].