Characteristics of Microparticles Based on Resorbable Polyhydroxyalkanoates Loaded with Antibacterial and Cytostatic Drugs
Abstract
:1. Introduction
2. Results
2.1. Influence of Manufacturing Methods on the Properties of P(3HB) Microparticles
2.2. Influence of the Chemical Composition of PHAs on the Properties of Microparticles
2.3. Drug-Loaded PHA-Microparticle and Drug Release In Vitro
2.4. Antibacterial and Antitumor Efficacy of Drug-Loaded PHA Microparticles
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Methods of Preparation of PHAs Microparticles
4.3. Characterization of Microparticles
4.3.1. Particle Size, Size Distribution and ζ Potential
4.3.2. Microscopic Analysis
4.3.3. Loading of Drugs and Encapsulation Efficiency
4.3.4. In Vitro Release Studies
4.4. Antimicrobial and Antitumor Efficacy of Drug-Loaded PHA Microparticles
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Concentration of P(3HB), % | Dispersion Technique | Average Diameter, μm | ζ Potential, mV | Yield of Microparticles, % |
Emulsion method | ||||
1.0 | Hh * | 1.2 ± 0.09 | −16.2 ± 0.49 | 73.8 ± 4.6 |
2.0 | Hh * | 1.58 ± 0.15 | −15 ± 0.28 | 78.5 ± 3.8 |
4.0 | Hh * | 2.32 ± 0.3 | −21.6 ± 0.7 | 78.7 ± 4.3 |
2.0 | Us 12 * | 2.5 ± 0.14 | −23 ± 0.31 | 56 ± 4.2 |
2.0 | Us 20 * | 1.2 ± 0.08 | −19 ± 0.25 | 61.5 ± 3.5 |
Spray drying | ||||
Temperature, °C | Solution Feed Rate, mL/min | Average Diameter, μm | ζ Potential, mV | Yield Microparticles, % |
75 | 1.5 | 3.4 ± 0.6 | −45 ± 0.5 | 83.5 |
75 | 3.2 | 3.8 ± 0.5 | −44.5 ± 1.1 | 71 |
75 | 5.0 | 5.5± 0.5 | −43.2± 1.2 | 85 |
85 | 1.5 | 5.7 ± 0.5 | −47.1 ± 0.4 | 78 |
85 | 3.2 | 5.6 ± 0.6 | −42.3 ± 0.6 | 90 |
85 | 5.0 | 5.2 ± 0.3 | −49 ± 3.4 | 45 |
95 | 1.5 | 4.2 ± 0.3 | −41.6 ± 0.8 | 75 |
95 | 3.2 | 7.0 ± 0.48 | −47.4 ± 0.4 | 71 |
95 | 5.0 | 6.2 ± 0.5 | −50.8 ± 0.5 | 75 |
PHA Composition, mol.% | Structural Formula | Mw, kDa | Mn, kDa | D | Cx, % | Tmelt, °C | Tdegr, °C |
---|---|---|---|---|---|---|---|
P(3HB) | |||||||
100.0 | 1200 | 710 | 1.69 | 76 | 169 | 272 | |
P(3HB/3HV) | |||||||
93.2/6.8 | 890 | 466 | 1.91 | 60 | 162 | 264 | |
67.2/32.8 | 398 | 115 | 3.46 | 54 | 160 | 259 | |
P(3HB/4HHx) | |||||||
93.0/7.0 | 410 | 140 | 2.93 | 56 | 162 | 258 | |
86.4/13.6 | 390 | 130 | 3.00 | 49 | 160 | 264 | |
P(3HB/4HB) | |||||||
93.9/6.1 | 416 | 142 | 2.93 | 52 | 160 | 254 | |
84.0/16.0 | 520 | 168 | 3.10 | 41 | 154 | 260 |
Drug | Structural Formula | Mechanism of Action |
---|---|---|
Ceftriaxone | Inhibition of bacterial cell wall synthesis through acetylation of membrane-bound transpeptidases with further disruption of cell wall peptidoglycan synthesis. | |
Rifampicin | Violates RNA synthesis in a bacterial cell: binds to the beta subunit of DNA-dependent RNA polymerase, preventing its attachment to DNA, and inhibits RNA transcription. | |
Doxorubicin | Suppression of the synthesis of nucleic acids, followed by the formation of free radicals and effect on cell membranes. | |
5-Fluorourocil | Inhibits the process of cell division by blocking DNA synthesis (due to inhibition of thymidylate synthetase enzyme activity) and the formation of structurally imperfect RNA (due to the introduction of fluorouracil into its structure). |
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Murueva, A.V.; Shershneva, A.M.; Shishatskaya, E.I.; Volova, T.G. Characteristics of Microparticles Based on Resorbable Polyhydroxyalkanoates Loaded with Antibacterial and Cytostatic Drugs. Int. J. Mol. Sci. 2023, 24, 14983. https://doi.org/10.3390/ijms241914983
Murueva AV, Shershneva AM, Shishatskaya EI, Volova TG. Characteristics of Microparticles Based on Resorbable Polyhydroxyalkanoates Loaded with Antibacterial and Cytostatic Drugs. International Journal of Molecular Sciences. 2023; 24(19):14983. https://doi.org/10.3390/ijms241914983
Chicago/Turabian StyleMurueva, Anastasiya V., Anna M. Shershneva, Ekaterina I. Shishatskaya, and Tatiana G. Volova. 2023. "Characteristics of Microparticles Based on Resorbable Polyhydroxyalkanoates Loaded with Antibacterial and Cytostatic Drugs" International Journal of Molecular Sciences 24, no. 19: 14983. https://doi.org/10.3390/ijms241914983