Spray-dried cyclophosphamide-loaded polyhydroxyalkanoate microparticles: design and characterization
Original scientific article
DOI:
https://doi.org/10.5599/admet.2434Keywords:
Microencapsulation, drug loading, drug release
Abstract
Background and purpose: Cyclophosphamide (CP) is a widely used antitumor and immunosuppressive drug, but it is highly cytotoxic and has carcinogenic and teratogenic potential. To reduce adverse effects of CP therapy and the frequency of its administration, the microencapsulation of CP into biodegradable polymeric matrices can be performed. However, according to the literature, only a few polymers were found suitable to encapsulate CP and achieve its’ sustained release. Experimental approach: In this research, spray-dried cyclophosphamide-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microparticles were prepared and characterized in terms of their average hydrodynamic diameter, polydispersity index, surface morphology, zeta potential, encapsulation efficiency, drug loading, thermal properties and cytotoxicity against 3T3 cells. Key results: The obtained CP-loaded microparticles had a regular spherical shape, uniform size distribution with an average diameter of 4.21±0.04 μm and zeta potential of -34.2±0.2 mV. The encapsulation of cyclophosphamide into the PHBV matrix led to a decrease in melting and degradation temperatures and an increase in diameter, glass transition and cold crystallization temperatures compared to blank microparticles. Moreover, microencapsulation of cyclophosphamide lowered its cytotoxicity compared to the pure drug: the number of dead cells in the culture decreased by 28 %, while their metabolic activity increased by 20 %. The cumulative in vitro drug release studies showed a gradual release of CP up to 18 days, so the obtained microparticle formulation can be used as a sustained-release cyclophosphamide delivery system. Conclusion: In this research, a novel cyclophosphamide-loaded platform based on PHBV microparticles was established and characterized. Overall, this study offers promising prospects for cancer therapy in the future.
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References
H. Arnold, F. Bourseaux, N. Brock. Chemotherapeutic Action of a Cyclic Nitrogen Mustard Phosphamide Ester (B 518-ASTA) in Experimental Tumours of the Rat. Nature 181 (1958) 931-931. https://doi.org/10.1038/181931a0.
N. Helsby, M. Yong, K. Burns, M. Findlay, D. Porter. Cyclophosphamide bioactivation pharmacogenetics in breast cancer patients. Cancer Chemotherapy and Pharmacology 88 (2021) 533-542. https://doi.org/10.1007/s00280-021-04307-0.
I. El-Serafi, S. Steele. Cyclophosphamide Pharmacogenomic Variation in Cancer Treatment and Its Effect on Bioactivation and Pharmacokinetics. Advances in Pharmacological and Pharmaceutical Sciences 2024 (2024) 862706. https://doi.org/10.1155/2024/4862706.
E. Dabbish, S. Scoditti, M.N.I. Shehata, I. Ritacco, M.A.A. Ibrahim, T. Shoeib, E. Sicilia. Insights on cyclophosphamide metabolism and anticancer mechanism of action: A computational study. Journal of Computational Chemistry 45 (2024) 663-670. https://doi.org/10.1002/jcc.27280.
J.J. Lokich, A. Bothe. Phase-I Study of Continuous Infusion Cyclophosphamide for Protracted Durations: A Preliminary Report. Cancer Drug Delivery 1 (1984) 329-332. https://doi.org/10.1089/cdd.1984.1.329.
M.J. Moore. Clinical Pharmacokinetics of Cyclophosphamide. Clinical Pharmacokinetics 20 (1991) 194-208. https://doi.org/10.2165/00003088-199120030-00002.
R. Samaritani, G. Corrado, E. Vizza, C. Sbiroli. Cyclophosphamide “metronomic” chemotherapy for palliative treatment of a young patient with advanced epithelial ovarian cancer. BMC Cancer 7 (2007) 65. https://doi.org/10.1186/1471-2407-7-65.
M. Petri, R.A. Brodsky, R.J. Jones, D. Gladstone, M. Fillius, L.S. Magder. High‐dose cyclophosphamide versus monthly intravenous cyclophosphamide for systemic lupus erythematosus: A prospective randomized trial. Arthritis & Rheumatism 62 (2010) 1487-1493. https://doi.org/10.1002/art.27371.
Z. Cai, L. Gao, K. Hu, Q.-M. Wang. Parthenolide enhances the metronomic chemotherapy effect of cyclophosphamide in lung cancer by inhibiting the NF-kB signaling pathway. World Journal of Clinical Oncology 15 (2024) 895-907. https://doi.org/10.5306/wjco.v15.i7.895.
S. Cetik Yildiz, C. Demir, M. Cengiz, H. Irmak, B.P. Cengiz, A. Ayhanci. In Vitro Antitumor and Antioxidant Capacity as well as Ameliorative Effects of Fermented Kefir on Cyclophosphamide-Induced Toxicity on Cardiac and Hepatic Tissues in Rats. Biomedicines 12 (2024) 1199. https://doi.org/10.3390/biomedicines12061199.
T. Drie, M.I. Alsamman, R. Tarcha, G. Haidar, M. Kudsi. Successful pregnancy after cyclophosphamide therapy for systemic lupus erythematosus: a case report. Annals of Medicine & Surgery 86 (2024) 1156-1160. https://doi.org/10.1097/MS9.0000000000001641.
S. Saracchini, L. Foltran, F. Tuccia, A. Bassini, S. Sulfaro, E. Micheli, A. Del Conte, M. Bertola, M. Gion, M. Lorenzon, S. Tumolo. Phase II study of liposome-encapsulated doxorubicin plus cyclophosphamide, followed by sequential trastuzumab plus docetaxel as primary systemic therapy for breast cancer patients with HER2 overexpression or amplification. The Breast 22 (2013) 1101-1107. https://doi.org/10.1016/j.breast.2013.09.001.
K. Żółtowska, U. Piotrowska, E. Oledzka, U. Luchowska, M. Sobczak, A. Bocho-Janiszewska. Development of biodegradable polyesters with various microstructures for highly controlled release of epirubicin and cyclophosphamide. European Journal of Pharmaceutical Sciences 96 (2017) 440-448. https://doi.org/10.1016/j.ejps.2016.10.014.
F. Abedin, M.R. Anwar, R. Asmatulu, S.-Y. Yang. Albumin-based micro-composite drug carriers with dual chemo-agents for targeted breast cancer treatment. Journal of Biomaterials Applications 30 (2015) 38-49. https://doi.org/10.1177/0885328215569614.
A.A.Majeed, The assessment of Cyclophosphamide chemotherapy effect loading-PLGA nanoparticles against ovarian cancer cells line (OVCAR-4 & PEO1). Journal of Pharmaceutical Negative Results 13 (2022) 39-43. https://www.pnrjournal.com/index.php/home/article/view/180.
Y.L. Ding, S.S. Ding, G.F. Ding. Preparation and Characterization of Cyclophosphamide-Loaded Chitosan Microspheres. Advanced Materials Research 621 (2012) 130-133. https://doi.org/10.4028/www.scientific.net/AMR.621.130.
N.O. Zhila, K.Yu. Sapozhnikova, E.G. Kiselev, E.I. Shishatskaya, T.G. Volova. Biosynthesis of Polyhydroxyalkanoates in Cupriavidus necator B-10646 on Saturated Fatty Acids. Polymers 16 (2024) 1294. https://doi.org/10.3390/polym16091294.
A. V. Murueva, A.E. Dudaev, E.I. Shishatskaya, F.D.E. Ghorabe, I. V. Nemtsev, A. V. Lukyanenko, T.G. Volova. Biodegradable polymer casting films for drug delivery and cell culture. Giant 19 (2024) 100314. https://doi.org/10.1016/j.giant.2024.100314.
N.O. Zhila, E.G. Kiselev, V. V. Volkov, O.Ya. Mezenova, K.Yu. Sapozhnikova, E.I. Shishatskaya, T.G. Volova. Properties of Degradable Polyhydroxyalkanoates Synthesized from New Waste Fish Oils (WFOs). International Journal of Molecular Sciences 24 (2023) 14919. https://doi.org/10.3390/ijms241914919.
L.Q. Fook, H.T. Tan, M. Lakshmanan, I. Zainab-L, A. Ahmad, S.L. Ang, K. Sudesh. Polyhydroxyalkanoate Biosynthesis from Waste Cooking Oils by Cupriavidus necator Strains Harbouring phaCBP-M-CPF4. Journal of Polymers and the Environment 32 (2024) 3490-3502. https://doi.org/10.1007/s10924-023-03166-5.
S. Bano, A.A. Aslam, A. Khan, A. Shabbir, F. Qayyum, N. Wahab, A. Jabar, I. Ul Islam, S.L. Ng. A mini-review on polyhydroxyalkanoates: Synthesis, extraction, characterization, and applications. Process Biochemistry 146 (2024) 250-261. https://doi.org/10.1016/j.procbio.2024.07.033.
R. Ma, J. Li, R. Tyagi, X. Zhang. Carbon dioxide and methane as carbon source for the production of polyhydroxyalkanoates and concomitant carbon fixation. Bioresource Technology 391 (2024) 129977. https://doi.org/10.1016/j.biortech.2023.129977.
A.B. Kharissova, O. V. Kharissova, B.I. Kharisov, Y.P. Méndez. Carbon negative footprint materials: A review. Nano-Structures & Nano-Objects 37 (2024) 101100. https://doi.org/10.1016/j.nanoso.2024.101100.
T.G. Volova, E.I. Shishatskaya, Cupriavidus eutrophus VKPM B-10646 Bacteria Strain — Producer of Polyhydroxyalkanoates and Production Method Thereof, RU2439143C1, 2012. https://patents.google.com/patent/RU2439143C1/en.
Z.H. Mohamed, S.M. Amer, A.M. El-Kousasy. Colorimetric determination of cyclophosphamide and ifosphamide. Journal of Pharmaceutical and Biomedical Analysis 12 (1994) 1131-1136. https://doi.org/10.1016/0731-7085(94)E0020-2.
A.P. Li, A. Uzgare, Y.S. LaForge. Definition of metabolism-dependent xenobiotic toxicity with co-cultures of human hepatocytes and mouse 3T3 fibroblasts in the novel integrated discrete multiple organ co-culture (IdMOC) experimental system: Results with model toxicants aflatoxin B1, cyclophosphamide and tamoxifen. Chemico-Biological Interactions 199 (2012) 1-8. https://doi.org/10.1016/j.cbi.2012.05.003.
C.A. Schneider, W.S. Rasband, K.W. Eliceiri. NIH Image to ImageJ: 25 years of image analysis. Nature Methods 9 (2012) 671-675. https://doi.org/10.1038/nmeth.2089.
S. Rodrigues, A. da Costa, N. Flórez-Fernández, M. Torres, M. Faleiro, F. Buttini, A. Grenha. Inhalable Spray-Dried Chondroitin Sulphate Microparticles: Effect of Different Solvents on Particle Properties and Drug Activity. Polymers 12 (2020) 425. https://doi.org/10.3390/polym12020425.
G. Troiano, M. Figa, Abhimanyu Sabnis, Drug loaded polymeric nanoparticles and methods of making and using same, US 8.420,123 B2, 2013. https://patentimages.storage.googleapis.com/61/6c/13/c52dc4a0d5e5b2/US8420123.pdf
J.K. Staas, T.R. Tice, B.W. Hudson, A. J. Tipton, Methods for manufacturing delivery devices and devices thereof, US 8,541,028 B2, 2013. https://patentimages.storage.googleapis.com/cd/73/7d/f88544b7ed22c4/US8541028.pdf
A. Dorokhin, S. Lipaikin, G. Ryltseva, E. Shishatskaya, S.Kachin. Preparation and Characterization of Rifampicin-Loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Microparticles. Journal of Siberian Federal University. Chemistry 16(2) (2023) 159-167. https://elib.sfu-kras.ru/bitstream/handle/2311/150144/01_Dorokhin.pdf
F. Masood, P. Chen, T. Yasin, N. Fatima, F. Hasan, A. Hameed. Encapsulation of Ellipticine in poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) based nanoparticles and its in vitro application. Materials Science and Engineering: C 33 (2013) 1054-1060. https://doi.org/10.1016/j.msec.2012.11.025.
S. Lightfoot Vidal, C. Rojas, R. Bouza Padín, M. Pérez Rivera, A. Haensgen, M. González, S. Rodríguez-Llamazares. Synthesis and characterization of polyhydroxybutyrate- co -hydroxyvalerate nanoparticles for encapsulation of quercetin. Journal of Bioactive and Compatible Polymers 31 (2016) 439-452. https://doi.org/10.1177/0883911516635839.
A. Shershneva, A. Murueva, E. Nikolaeva, E. Shishatskaya, T. Volova. Novel spray-dried PHA microparticles for antitumor drug release. Drying Technology 36 (2018) 1387-1398. https://doi.org/10.1080/07373937.2017.1407940.
G.A. Senhorini, S.F. Zawadzki, P. V. Farago, S.M.W. Zanin, F.A. Marques. Microparticles of poly(hydroxybutyrate-co-hydroxyvalerate) loaded with andiroba oil: Preparation and characterization. Materials Science and Engineering: C 32 (2012) 1121-1126. https://doi.org/10.1016/j.msec.2012.02.027.
A.V. Vladimirova, A. V. Murueva, A. M. Shershneva, S.V. Prudnikova, A.V. Shabanov, E.I. Shishatskaya. Biocompatible Systems for Controlled Delivery of Antiseptics for Topical Application. Journal of Siberian Federal University. Biology 17 (2024) 19-32. https://elib.sfu-kras.ru/bitstream/handle/2311/152806/02_Vladimirova.pdf?sequence=1
M.E. de Jonge, A.D.R. Huitema, S. Rodenhuis, J.H. Beijnen. Clinical Pharmacokinetics of Cyclophosphamide. Clinical Pharmacokinetics 44 (2005) 1135-1164. https://doi.org/10.2165/00003088-200544110-00003.
Y. Zhang, S. Fei, M. Yu, Y. Guo, H. He, Y. Zhang, T. Yin, H. Xu, X. Tang. Injectable sustained release PLA microparticles prepared by solvent evaporation-media milling technology. Drug Development and Industrial Pharmacy 44 (2018) 1591-1597. https://doi.org/10.1080/03639045.2018.1483382.
E. Yapar, Ö. İnal, Y. Özkan, T. Baykara. Injectable In Situ Forming Microparticles: A Novel Drug Delivery System. Tropical Journal of Pharmaceutical Research 11 (2012) 307-318. https://doi.org/10.4314/tjpr.v11i2.19.
A. Cambronero-Rojas, P. Torres-Vergara, R. Godoy, C. von Plessing, J. Sepúlveda, C. Gómez-Gaete. Capreomycin oleate microparticles for intramuscular administration: Preparation, in vitro release and preliminary in vivo evaluation. Journal of Controlled Release 209 (2015) 229-237. https://doi.org/10.1016/j.jconrel.2015.05.001.
E.I. Shishatskaya, O.N. Voinova, A. V. Goreva, O.A. Mogilnaya, T.G. Volova. Tissue reaction to intramuscular injection of resorbable polymer microparticles. Bulletin of Experimental Biology and Medicine 144 (2007) 786-790. https://doi.org/10.1007/s10517-007-0432-0.
S.P. Schwendeman, R.B. Shah, B.A. Bailey, A.S. Schwendeman. Injectable controlled release depots for large molecules. Journal of Controlled Release 190 (2014) 240-253. https://doi.org/10.1016/j.jconrel.2014.05.057.
R.L. Juliano. Factors affecting the clearance kinetics and tissue distribution of liposomes, microspheres and emulsions. Advanced Drug Delivery Reviews 2 (1988) 31-54. https://doi.org/10.1016/0169-409X(88)90004-X.
D. Liu, D.T. Auguste. Cancer targeted therapeutics: From molecules to drug delivery vehicles. Journal of Controlled Release 219 (2015) 632-643. https://doi.org/10.1016/j.jconrel.2015.08.041.
A. Kumar, C.K. Dixit. Methods for characterization of nanoparticles. in: Advances in Nanomedicine for the Delivery of Therapeutic Nucleic Acids, Elsevier, 2017: p. 43-58. https://doi.org/10.1016/B978-0-08-100557-6.00003-1.
A.M. Shershneva, A. V. Murueva, E.I. Shishatskaya, T.G. Volova. Study of electrokinetic potential of drug micro-carriers prepared from resorbable polymers bioplastotan. Biophysics 59 (2014) 561-567. https://doi.org/10.1134/S000635091404023X.
R. Singh, J.W. Lillard. Nanoparticle-based targeted drug delivery. Experimental and Molecular Pathology 86 (2009) 215-223. https://doi.org/10.1016/j.yexmp.2008.12.004.
I. Corrado, R. Di Girolamo, C. Regalado-González, C. Pezzella. Polyhydroxyalkanoates-Based Nanoparticles as Essential Oil Carriers. Polymers 14 (2022) 166. https://doi.org/10.3390/polym14010166.
A. V. Murueva, A.M. Shershneva, I. V. Nemtsev, E.I. Shishatskaya, T.G. Volova. Collagen conjugation to carboxyl-modified poly(3-hydroxybutyrate) microparticles: preparation, characterization and evaluation in vitro. Journal of Polymer Research 29 (2022). https://doi.org/10.1007/s10965-022-03181-5.
S.Y. Lipaikin, I.A. Yaremenko, A.O. Terent’ev, T.G. Volova, E.I. Shishatskaya. Development of Biodegradable Delivery Systems Containing Novel 1,2,4-Trioxolane Based on Bacterial Polyhydroxyalkanoates. Advances in Polymer Technology 2022 (2022) 6353909. https://doi.org/10.1155/2022/6353909.
Q. Xu, A. Crossley, J. Czernuszka. Preparation and characterization of negatively charged poly(lactic-co-glycolic acid) microspheres. Journal of Pharmaceutical Sciences 98 (2009) 2377-2389. https://doi.org/10.1002/jps.21612.
G. Ruan, S.-S. Feng. Preparation and characterization of poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) microspheres for controlled release of paclitaxel. Biomaterials 24 (2003) 5037-5044. https://doi.org/10.1016/S0142-9612(03)00419-8.
A.M. Shershneva, A. V. Murueva, N.O. Zhila, T.G. Volova. Antifungal activity of P3HB microparticles containing tebuconazole. Journal of Environmental Science and Health, Part B 54 (2019) 196-204. https://doi.org/10.1080/03601234.2018.1550299.
E. Campos, J. Branquinho, A.S. Carreira, A. Carvalho, P. Coimbra, P. Ferreira, M.H. Gil. Designing polymeric microparticles for biomedical and industrial applications. European Polymer Journal 49 (2013) 2005-2021. https://doi.org/10.1016/j.eurpolymj.2013.04.033.
D. Sendil, I. Gürsel, D. L. Wise, V. Hasırcı. Antibiotic release from biodegradable PHBV microparticles. Journal of Controlled Release 59 (1999) 207-217. https://doi.org/10.1016/S0168-3659(98)00195-3.
W. Huang, Y. Wang, L. Ren, C. Du, X. Shi. A novel PHBV/HA microsphere releasing system loaded with alendronate. Materials Science and Engineering: C 29 (2009) 2221-2225. https://doi.org/10.1016/j.msec.2009.05.015.
N. Pettinelli, S. Rodríguez-Llamazares, Y. Farrag, R. Bouza, L. Barral, S. Feijoo-Bandín, F. Lago. Poly(hydroxybutyrate-co-hydroxyvalerate) microparticles embedded in κ-carrageenan/locust bean gum hydrogel as a dual drug delivery carrier. International Journal of Biological Macromolecules 146 (2020) 110-118. https://doi.org/10.1016/j.ijbiomac.2019.12.193.
C. Zhang, Y. Dong, L. Zhao. Preparation and characterization of novel microparticles based on poly(3-hydroxybutyrate-co-3-hydroxyoctanoate). Journal of Microencapsulation 31 (2014) 9-15. https://doi.org/10.3109/02652048.2013.799241.
B. Remila, I. Zembouai, L. Zaidi, A. Alane, M. Kaci, A. Kervoelen, S. Bruzaud. Investigations on structure and properties of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) reinforced by diss fibers: Effect of various surface treatments. Industrial Crops and Products 221 (2024) 119302. https://doi.org/10.1016/j.indcrop.2024.119302.
Z. Keshtmand, S.N. Naimi, Z. Koureshi Piran, P. Poorjafari Jafroodi, M. Tavakkoli Yaraki. Enhanced anticancer effect of Artemisia turcomanica extract in niosomal formulation on breast cancer cells: In-vitro study. Nano-Structures & Nano-Objects 35 (2023) 101030. https://doi.org/10.1016/j.nanoso.2023.101030.
L. Li, L. Jing, Z. Tang, J. Du, Y. Zhong, X. Liu, M. Yuan. Dual-targeting liposomes modified with BTP-7 and pHA for combined delivery of TCPP and TMZ to enhance the anti-tumour effect in glioblastoma cells. Journal of Microencapsulation 41 (2024) 419-433. https://doi.org/10.1080/02652048.2024.2376114.
Z. Salmasi, H. Kamali, H. Rezaee, F. Nazeran, Z. Jafari, F. Eisvand, M. Teymouri, E. Khordad, J. Mosafer. Simultaneous therapeutic and diagnostic applications of magnetic PLGA nanoparticles loaded with doxorubicin in rabbit. Drug Delivery and Translational Research (2024). https://doi.org/10.1007/s13346-024-01693-9.
S. Sur, A. Rathore, V. Dave, K.R. Reddy, R.S. Chouhan, V. Sadhu. Recent developments in functionalized polymer nanoparticles for efficient drug delivery system. Nano-Structures & Nano-Objects 20 (2019) 100397. https://doi.org/10.1016/j.nanoso.2019.100397.
A. Estrada-Monje, M.A. Silva-Goujon, I. Rodríguez-Sánchez, A.S. Conejo-Dávila, C.I. Piñón-Balderrama, A. Zaragoza-Estrada, L.A. Baldenegro-Pérez, E.A. Zaragoza-Contreras. Effect of the Addition of PLA on the Thermal and Mechanical Properties of Reprocessed HDPE. Polymers 16 (2024) 2387. https://doi.org/10.3390/polym16162387.
N. Zafar, A. Mahmood, R.M. Sarfraz, H. Ijaz, M.U. Ashraf, S. Mehr. Facile synthesis of β-cyclodextrin-cyclophosphamide complex-loaded hydrogel for controlled release drug delivery. Polymer Bulletin 80 (2023) 10939-10971. https://doi.org/10.1007/s00289-022-04567-7.
P. Kommavarapu, A. Maruthapillai, A. Ravikiran, P. Kamaraj. Sorption-Desorption Behavior and Characterization of Cyclophosphamide. Chemical Science Transactions 2 (2013). http://www.e-journals.in/pdf/v2ns1/s135-s140.pdf.
N.O. Zhila, K.Yu. Sapozhnikova, E.G. Kiselev, E.I. Shishatskaya, T.G. Volova. Synthesis and Properties of Polyhydroxyalkanoates on Waste Fish Oil from the Production of Canned Sprats. Processes 11 (2023) 2113. https://doi.org/10.3390/pr11072113.
C.C. Nwazojie, J.D. Obayemi, A.A. Salifu, S.M. Borbor-Sawyer, V.O. Uzonwanne, C.E. Onyekanne, U.M. Akpan, K.C. Onwudiwe, J.C. Oparah, O.S. Odusanya, W.O. Soboyejo. Targeted drug-loaded PLGA-PCL microspheres for specific and localized treatment of triple negative breast cancer. Journal of Materials Science: Materials in Medicine 34 (2023) 41. https://doi.org/10.1007/s10856-023-06738-y.
S.M. Jusu, J.D. Obayemi, A.A. Salifu, C.C. Nwazojie, V. Uzonwanne, O.S. Odusanya, W.O. Soboyejo. Drug-encapsulated blend of PLGA-PEG microspheres: in vitro and in vivo study of the effects of localized/targeted drug delivery on the treatment of triple-negative breast cancer. Scientific Reports 10 (2020) 14188 . https://doi.org/10.1038/s41598-020-71129-0.
P. V. Farago, R.P. Raffin, A.R. Pohlmann, S.S. Guterres, S.F. Zawadzki. Physicochemical characterization of a hydrophilic model drug-loaded PHBV microparticles obtained by the double emulsion/solvent evaporation technique. Journal of the Brazilian Chemical Society 19 (2008) 1298-1305. https://doi.org/10.1590/S0103-50532008000700011.
M.K. Sahu, N. Dubey, R. Pandey, S.S. Shukla, B. Gidwani. Formulation, Evaluation, and Validation of Microspheres of Cyclophosphamide for Topical Delivery. Pharmacophore 14 (2023) 1-8. https://doi.org/10.51847/e4GvuoN96z.
A. V. Murueva, A.M. Shershneva, K. V. Abanina, S. V. Prudnikova, E.I. Shishatskaya. Development and characterization of ceftriaxone-loaded P3HB-based microparticles for drug delivery. Drying Technology 37 (2019) 1131-1142. https://doi.org/10.1080/07373937.2018.1487451.
E.G. Kiselev, S. V. Baranovskiy. The Kinetics of Fungicide and Herbicide Release from Slow-Release Formulations Prepared from Degradable Poly-3- Hydroxybutyrate. Journal of Siberian Federal University. Biology 9 (2016) 233-240. https://doi.org/10.17516/1997-1389-2016-9-2-233-240.
T.G. Volova, A. V. Demidenko, A. V. Murueva, A.E. Dudaev, I. Nemtsev, E.I. Shishatskaya. Biodegradable Polyhydroxyalkanoates Formed by 3- and 4-Hydroxybutyrate Monomers to Produce Nanomembranes Suitable for Drug Delivery and Cell Culture. Technologies 11 (2023) 106. https://doi.org/10.3390/technologies11040106.
A. V. Murueva, A.M. Shershneva, E.I. Shishatskaya, T.G. Volova. Characteristics of Microparticles Based on Resorbable Polyhydroxyalkanoates Loaded with Antibacterial and Cytostatic Drugs. International Journal of Molecular Sciences 24 (2023) 14983. https://doi.org/10.3390/ijms241914983.
K. Ghosal, A. Das, S.K. Das, S. Mahmood, M.A.M. Ramadan, S. Thomas. Synthesis and characterization of interpenetrating polymeric networks based bio-composite alginate film: A well-designed drug delivery platform. International Journal of Biological Macromolecules 130 (2019) 645-654. https://doi.org/10.1016/j.ijbiomac.2019.02.117.
K.S. Joshy, M.A. Susan, S. Snigdha, K. Nandakumar, A.P. Laly, T. Sabu. Encapsulation of zidovudine in PF-68 coated alginate conjugate nanoparticles for anti-HIV drug delivery. International Journal of Biological Macromolecules 107 (2018) 929-937. https://doi.org/10.1016/j.ijbiomac.2017.09.078.
K.S. Joshy, A. George, J. Jose, N. Kalarikkal, L.A. Pothen, S. Thomas. Novel dendritic structure of alginate hybrid nanoparticles for effective anti-viral drug delivery. International Journal of Biological Macromolecules 103 (2017) 1265-1275. https://doi.org/10.1016/j.ijbiomac.2017.05.094.
N. Durán, M.A. Alvarenga, E.C. Da Silva, P.S. Melo, P.D. Marcato. Microencapsulation of antibiotic rifampicin in poly(3-hydroxybutyrate-co-3-hydroxyvalerate). Archives of Pharmacal Research 31 (2008) 1509-1516. https://doi.org/10.1007/s12272-001-2137-7.
L. Nair, J. Sankar, S.A. Nair, G.V. Kumar. Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA. International Journal of Nanomedicine (2011) 1685-1697. https://doi.org/10.2147/IJN.S20165
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Ministry of Science and Higher Education of the Russian Federation
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