Novel spray-dried PHA microparticles for antitumor drug release

Abstract

The production of poly-3-hydroxybutyrate and poly-3-hydroxybutyrate/polyethylene glycol-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. For 5-FU loading microparticles, were established that the addition of surfactant positively influenced on the properties of particles and led to the loading of drug 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 P3HBmicroparticles. 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.

Development of Biodegradable Delivery Systems Containing Novel 1,2,4-Trioxolane Based on Bacterial Polyhydroxyalkanoates

“…Zeta potential for ceftriaxone-loaded MP EM and MP SD was −22:3 ± 0:6 mV and −48:0 ± 1:4 mV, respectively (compared to −17:8 ± 0:3 mV and −95:7 ± 0:6 mV for unloaded microspheres). Shershneva et al [52] reported that the average diameter of P3HB-MP SD containing paclitaxel was 3:08 ± 0:7 μm, and zeta potential was − 40:8 ± 0:9 mV, which is slightly lower than the same parameters of blank P3HB-MP SD : the average diameter was 3:36 ± 0:46 μm, and zeta potential was −44:6 ± 0:4 mV.…”

“…These properties make PHBV more suitable in bioengineering, for obtaining particles, films, scaffolds, and surgical suture (maintaining high biocompatibility for different biological systems and complete biodegradation) [47]. Anti-inflammatory [50], antibacterial [51], antitumor [52], herbicidal [53], and other drugs have been successfully encapsulated in the PHA matrix.…”

Recent Biotechnological Applications of Polyhydroxyalkanoates (PHA) in the Biomedical Sector—A Review

“…Microparticles of P3HB and P3HB were combined with polyethylene glycol(PEG) for the paclitaxel(PTX) and 5-Fluorouacil(5-FU) drugs carriage. The method showed improvement in yield and greater incorporation of drugs into microparticles, and extended release of drugs led to inhibition of tumor cell growth [75]. PHA was also utilized as an inhaled drug carrier for the lungs; however, additional research is required to determine the viability of these carriers [76].…”

Development and characterization of ceftriaxone-loaded P3HB-based microparticles for drug delivery

“…29,54 For the first time, the possibility of encapsulating an antitumor drug in a P3HB microparticle was demonstrated using the spray drying method. 55,56 The dependency of microparticle characteristics (yield. average diameter, zeta potential) on the parameters of the production process (inlet temperature, polymer solution feed rate, and polymer solution concentration) has been established.…”