Abstract
Biocompatible and biodegradable polymer microparticles are contemporary medicines able to eliminate the side effects and unsatisfactory pharmacokinetics of already existing preparations. In this work we have developed a high-tech scalable method for the synthesis of paclitaxel-loaded poly(3-hydroxybutyrate) (PHB)-based microparticles. These particles were synthesized on a B-90 Buchi nano spray dryer by piezoelectric spray drying in an inert atmosphere. A regular spherical shape, narrow size distribution, and satisfactory results for the release of paclitaxel from the polymeric matric of microparticles in vitro make this polymeric medicinal form promising for its further application in pharmaceutics. Nanoparticles with a similar composition synthesized via the laboratory one-stage emulsification method were used for comparison. This study is the first stage in the creation of a sustained-action anticancer paclitaxel preparation.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
References
H. Gelderblom et al., “Cremophor EL: The drawbacks and advantages of vehicle selection for drug formulation,” Eur. J. Cancer 37, 1590–1598 (2001).
J. Whelan et al., “Targeted taxane therapy for cancer,” Drug Discov. Today 7, 90–92 (2002).
A. J. M. Nieuweboer et al., “Predicting paclitaxelinduced neutropenia using the DMET platform,” Pharmacogenomics 16, 1231–1241 (2015).
J. Park, M. Ye, and K. Park, “Biodegradable polymers for microencapsulation of drugs,” Molecules 10, 146–161 (2005).
H. J. Chung et al., “Heparin immobilized porous PLGA microspheres for angiogenic growth factor delivery,” Pharm. Res. 23, 1835–1841 (2006).
M. Jenkins, Biomedical Polymers (Univ. Birmingham Press, UK, 2007).
M. I. Shtilman, Polymeric Biomaterials. Part 1: Polymer Implants (VSP, Utrecht, Boston, 2003).
A. P. Bonartsev et al., “Poly (3-hydroxybutyrate) and poly (3-hydroxybutyrate)-based biopolymer systems,” Biochemistry (Moscow) Suppl. Ser. B: Biomed. Chem. 5, 10–21 (2011).
G. Q. Chen and Q. Wu, “The application of polyhydroxyalkanoates as tissue engineering materials,” Biomaterials 26, 6565–6578 (2005).
A. P. Boskhomdzhiev et al., “Biodegradation kinetics of poly (3-hydroxybutyrate)-based biopolymer systems,” Biochemistry (Moscow) Suppl. Ser. B: Biomed. Chem. 4, 177–183 (2010).
A. P. Bonartsev, et al., “Hydrolytic degradation of poly (3-hydroxybutyrate), polylactide and their derivatives: Kinetics, crystallinity, and surface morphology,” Mol. Cryst. Liq. Cryst. 556, 288–300 (2012).
V. L. Myshkina, et al., “Biosynthesis of poly (3-hydroxybutyrate- Co-3-hydroxyvalerate) copolymer by azotobacter chroococcum strain 7B,” Appl. Biochem. Microbiol. 46, 289–296 (2010).
A. P. Bonartsev et al., “Cell attachment on poly (3- hydroxybutyrate)-poly (ethylene glycol) copolymer produced by azotobacter chroococcum 7B,” BMC Biochem. 14, 1 (2013).
A. P. Bonartsev et al., “Controlled release profiles of dipyridamole from biodegradable microspheres on the base of poly (3-hydroxybutyrate),” Express Polym. Lett. 1, 797–803 (2007).
M. Beck-Broichsitter et al., “Characterization of novel spray-dried polymeric particles for controlled pulmonary drug delivery,” J. Controlled Release 158, 329–335 (2012).
V. L. Myshkina et al., “Effect of growth conditions on the molecular weight of poly-3-hydroxybutyrate produced by azotobacter chroococcum 7B,” Appl. Biochem. Microbiol. 44, 482–486 (2008).
G. A. Bonartseva, E. D. Zagreba, V. L. Myshkina, and E. K. Furina, “Azotobacter chroococcum strain as poly-ß-hydroxybutyrate producer,” RF Patent No. 2194759, Byull. Izobret., No. 33 (2002).
G. Yu and R. H. Marcheßsault, “Characterization of low molecular weight poly (ß-hydroxybutyrate) s from alkaline and acid hydrolysis,” Polymer 41, 1087–1098 (2000).
“Nano spray dryer B-90 application booklet,” Application Note for PLA (polylactic acid) No. R 202 H, Order No. 092243 (2009).
A. P. Bonartsev et al., “Sustained release of the antitumor drug paclitaxel from poly-3-hydroxybutyrate based microspheres,” Biomed. Khim. 57, 232–240 (2011).
Z. Zheng et al., “Effects of crystallization of polyhydroxyalkanoate blend on surface physicochemical properties and interactions with rabbit articular cartilage chondrocytes,” Biomaterials 26, 3537–3548 (2005).
P. J. Barham et al., “Crystallization and morphology of a bacterial thermoplastic: Poly-3-hydroxybutyrate,” J. Mater. Sci. 19, 2781–2794 (1984).
J. Asrar et al., “Biosynthesis and properties of poly (3-hydroxybutyrate-Co-3-hydroxyhexanoate) polymers,” Biomacromolecules 3, 1006–1012 (2002).
A. P. Bonartsev et al., “Poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate)-based biopolymer systems,” Biochemistry (Moscow) Suppl. Ser. B: Biomed. Chem. 57, 10 (2011).
D. V. Bagrov et al., “Amorphous and semicrystalline phases in ultrathin films of poly (3-hydroxybutirate),” in Proceedings of the Conference on TechConnect World NTSI-Nanotech 2012 (2012), pp. 602–605.
Nano Spray Dryer B-90, Technical Data Sheet.
X. Li et al., “Nanoparticles by spray drying using innovative new technology: the buchi nano spray dryer B-90,” J. Controlled Release 147, 304–310 (2010).
G. T. Vladisavljevic and R. A. Williams, “Recent developments in manufacturing emulsions and particulate products using membranes,” Adv. Colloid Interface Sci. 113, 1–20 (2005).
P. Kolhar and S. Mitragotri, “Polymer microparticles exhibit size and shape dependent accumulation around the nucleus after endocytosis,” Adv. Funct. Mater. 22, 3759–3764 (2012).
A. P. Bonartsev et al., “Sustained release of the antitumor drug paclitaxel from poly (3-hydroxybutyrate)- based microspheres,” Biochemistry (Moscow) Suppl. Ser. B: Biomed. Chem. 6, 42–47 (2012).
S. G. Yakovlev, “Drug systmes based on micro and nanoparticles from polyhydroxybutyrate, its co-polymers and composites,” Cand. Sci. (Biol.) Dissertation (Moscow, 2013), pp. 113–123, 133–137.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © A.L. Zernov, A.P. Bonartsev, S.G. Yakovlev, V.L. Myshkina, T.K. Makhina, E.S. Parshina, E.P. Kharitonova, G.A. Bonartseva, K.V. Shaitan, 2017, published in Rossiiskie Nanotekhnologii, 2017, Vol. 12, Nos. 3–4.
Rights and permissions
About this article
Cite this article
Zernov, A.L., Bonartsev, A.P., Yakovlev, S.G. et al. Low molecular weight poly(3-hydroxybutyrate) microparticles synthesized by piezoelectric spray drying for the sustained release of paclitaxel. Nanotechnol Russia 12, 218–225 (2017). https://doi.org/10.1134/S1995078017020136
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1995078017020136