Polímeros: Ciência e Tecnologia
https://revistapolimeros.org.br/article/doi/10.1590/0104-1428.20220016
Polímeros: Ciência e Tecnologia
Original Article

Development and optimization by factorial design of polymeric nanoparticles for simvastatin delivery

Dalila Pinto Malaquias; Lays Fernanda Nunes Dourado; Ângela Maria Quintão Lana; Fernando Souza; José Vilela; Margareth Andrade; Juan Pedro Bretas Roa; Álvaro Dutra de Carvalho-Junior; Elaine Amaral Leite

Downloads: 0
Views: 727

Abstract

Controlled release systems can modify the release rate of drugs and direct them to specific sites of action, making them more effective and/or reducing the adverse effects. The objective of this study was investigated, poly(β-hydroxybutyrate) (PHB) and poly(ε-caprolactone) (PCL) nanospheres to improve the delivery of Simvastatin (SIM). Nanospheres were prepared by the emulsion/evaporation technique of the solvent, varying the amount of SIM added. The SIM quantification was performed using a validated high-performance liquid chromatography method. The average diameter and PDI of formulations without SIM were lower 250 nm and 0.3, respectively. Nanospheres containing 30% of SIM showed values of 265 nm and 0.09, respectively. The average zeta potential was -31.8 mV, suggesting the predominance of repulsive forces that prevent aggregation. In vitro release suggest transport occurs by diffusion. Morphological analysis demonstrated spherical particles and rough surfaces. In conclusion, data suggest that PHB/PCL nanospheres are promising delivery systems to SIM.

 

 

Keywords

drug delivery, nanoparticles, PHB, PHB/PCL blend, simvastatin

References

1 Endo, A. (2010). A historical perspective on the discovery of statins. Proceedings of the Japan Academy. Series B, Physical and Biological Sciences, 86(5), 484-493. http://dx.doi.org/10.2183/pjab.86.484. PMid:20467214.

2 Liu, Y. S., Ou, M. E., Liu, H., Gu, M., Lv, L. W., Fan, C., Chen, T., Zhao, X. H., Jin, C. Y., Zhang, X., Ding, Y., & Zhou, Y. S. (2014). The effect of simvastatin on chemotactic capability of SDF-1α and the promotion of bone regeneration. Biomaterials, 35(15), 4489-4498. http://dx.doi.org/10.1016/j.biomaterials.2014.02.025. PMid:24589359.

3 Yue, X., Niu, M., Zhang, T., Wang, C., Wang, Z., Wu, W., Zhang, Q., Lai, C., & Zhou, L. (2016). In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration. Nanotechnology, 27(11), 115708. http://dx.doi.org/10.1088/0957-4484/27/11/115708. PMid:26881419.

4 Liu, X., Li, X., Zhou, L., Li, S., Sun, J., Wang, Z., Gao, Y., Jiang, Y., Lu, H., Wang, Q., & Dai, J. (2013). Effects of simvastatin-loaded polymeric micelles on human osteoblast-like MG-63 cells. Colloids and Surfaces. B, Biointerfaces, 102, 420-427. http://dx.doi.org/10.1016/j.colsurfb.2012.06.037. PMid:23006576.

5 Basniwal, P. K., & Jain, D. (2012). Simvastatin: review of updates on recent trends in pharmacokinetics, pharmacodynamics, drug-drug interaction, impurities and analytical methods. Current Pharmaceutical Analysis, 8(2), 135-156. http://dx.doi.org/10.2174/1573412911208020135.

6 Yin, H., Shi, Z.-G., Yu, Y.-S., Hu, J., Wang, R., Luan, Z.-P., & Guo, D.-H. (2012). Protection against osteoporosis by statins is linked to a reduction of oxidative stress and restoration of nitric oxide formation in aged and ovariectomized rats. European Journal of Pharmacology, 674(2-3), 200-206. http://dx.doi.org/10.1016/j.ejphar.2011.11.024. PMid:22130356.

7 Lindenberg, M., Kopp, S., & Dressman, J. B. (2004). Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines according to the biopharmaceutics classification system. European Journal of Pharmaceutics and Biopharmaceutics, 58(2), 265-278. http://dx.doi.org/10.1016/j.ejpb.2004.03.001. PMid:15296954.

8 Jiang, T., Han, N., Zhao, B., Xie, Y., & Wang, S. (2012). Enhanced dissolution rate and oral bioavailability of simvastatin nanocrystal prepared by sonoprecipitation. Drug Development and Industrial Pharmacy, 38(10), 1230-1239. http://dx.doi.org/10.3109/03639045.2011.645830. PMid:22229827.

9 García, M. J., Reinoso, R. F., Sánchez Navarro, A., & Prous, J. R. (2003). Clinical pharmacokinetics of statins. Methods and Findings in Experimental and Clinical Pharmacology, 25(6), 457-481. http://dx.doi.org/10.1358/mf.2003.25.6.769652. PMid:12949632.

10 Paulraj, P., Vnootheni, N., Chandramohan, M., & Thevarkattil, M. J. P. (2018). Exploration of Global Trend on Biomedical Application of Polyhydroxyalkanoate (PHA): a patent survey. Recent Patents on Biotechnology, 12(3), 186-199. http://dx.doi.org/10.2174/1872208312666180131114125. PMid:29384069.

11 Bokrova, J., Marova, I., Matouskova, P., & Pavelkova, R. (2019). Fabrication of novel PHB-liposome nanoparticles and study of their toxicity in vitro. Journal of Nanoparticle Research, 21(3), 49. http://dx.doi.org/10.1007/s11051-019-4484-7.

12 Bidone, J., Melo, A. P. P., Bazzo, G. C., Carmignan, F., Soldi, M. S., Pires, A. T. N., & Lemos-Senna, E. (2009). Preparation and characterization of ibuprofen-loaded microspheres consisting of poly(3-hydroxybutyrate) and methoxy poly (ethylene glycol)-b-poly (D,L-lactide) blends or poly(3-hydroxybutyrate) and gelatin composites for controlled drug release. Materials Science and Engineering C, 29(2), 588-593. http://dx.doi.org/10.1016/j.msec.2008.10.016.

13 Bugnicourt, E., Cinelli, P., Lazzeri, A., & Alvarez, V. (2014). Polyhydroxyalkanoate (PHA): review of synthesis, characteristics, processing and potential applications in packaging. Express Polymer Letters, 8(11), 791-808. http://dx.doi.org/10.3144/expresspolymlett.2014.82.

14 Roa, J. P. B., Mano, V., Faustino, P. B., Felix, E. B., Silva, M. E. S. R., & Souza Filho, J. D. (2010). Síntese e Caracterização do Copolímero Poli(3 Hidroxibutirato co ε Caprolactona) a Partir de Poli(3 Hidroxibutirato) e Poli(ε Caprolactona). Polímeros: Ciência e Tecnologia, 20(3), 221-226. http://dx.doi.org/10.1590/S0104-14282010005000038.

15 Gassner, F., & Owen, A. J. (1994). Physical properties of poly(β-hydroxybutyrate)-poly(ε-caprolactone) blends. Polymer, 35(10), 2233-2236. http://dx.doi.org/10.1016/0032-3861(94)90258-5.

16 Huang, M.-H., Li, S., Hutmacher, D. W., Coudane, J., & Vert, M. (2006). Degradation characteristics of poly(ε-caprolactone)-based copolymers and blends. Journal of Applied Polymer Science, 102(2), 1681-1687. http://dx.doi.org/10.1002/app.24196.

17 Lovera, D., Márquez, L., Balsamo, V., Taddei, A., Castelli, C., & Müller, A. J. (2007). Crystallization, morphology, and enzymatic degradation of polyhydroxybutyrate/ polycaprolactone (PHB/PCL) blends. Macromolecular Chemistry and Physics, 208(9), 924-937. http://dx.doi.org/10.1002/macp.200700011.

18 Chee, M. J. K., Ismail, J., Kummerlöwe, C., & Kammer, H. W. (2002). Study on miscibility of PEO and PCL in blends with PHB by solution viscometry. Polymer, 43(4), 1235-1239. http://dx.doi.org/10.1016/S0032-3861(01)00725-X.

19 Suave, J., Dall’Agnol, E. C., Pezzin, A. P. T., Meier, M. M., & Silva, D. A. K. (2010). Biodegradable microspheres of poly(3-hydroxybutyrate)/poly(ε-caprolactone) loaded with malathion pesticide: Preparation, characterization, and in vitro controlled release testing. Journal of Applied Polymer Science, 117(6), 3419-3427. http://dx.doi.org/10.1002/app.32082.

20 Huang, J., Wigent, R. J., & Schwartz, J. B. (2006). Nifedipine molecular dispersion in microparticles of ammonio methacrylate copolymer and ethylcellulose binary blends for controlled drug delivery: effect of matrix composition. Drug Development and Industrial Pharmacy, 32(10), 1185-1197. http://dx.doi.org/10.1080/03639040600832827. PMid:17090441.

21 Oliveira, M. A., Yoshida, M. I., Gomes, E. C. L., Mussel, W. N., Vianna-Soares, C. D., & Pianetti, G. A. (2010). Análise térmica aplicada à caracterização da sinvastatina em formulações farmacêuticas. Quimica Nova, 33(8), 1653-1657. http://dx.doi.org/10.1590/S0100-40422010000800007.

22 Zhang, Y., Zhang, J., Jiang, T., & Wang, S. (2011). Inclusion of the poorly water-soluble drug simvastatin in mesocellular foam nanoparticles: drug loading and release properties. International Journal of Pharmaceutics, 410(1-2), 118-124. http://dx.doi.org/10.1016/j.ijpharm.2010.07.040. PMid:20674729.

23 Kouhi, M., Morshed, M., Varshosaz, J., & Fathi, M. H. (2013). Poly (ε-caprolactone) incorporated bioactive glass nanoparticles and simvastatin nanocomposite nanofibers: Preparation, characterization and in vitro drug release for bone regeneration applications. Chemical Engineering Journal, 228, 1057-1068. http://dx.doi.org/10.1016/j.cej.2013.05.091.

24 Liechty, W. B., Kryscio, D. R., Slaughter, B. V., & Peppas, N. A. (2010). Polymers for drug delivery systems. Annual Review of Chemical and Biomolecular Engineering, 1(1), 149-173. http://dx.doi.org/10.1146/annurev-chembioeng-073009-100847. PMid:22432577.

25 Farrag, Y., Montero, B., Rico, M., Barral, L., & Bouza, R. (2018). Preparation and characterization of nano and micro particles of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) via emulsification/solvent evaporation and nanoprecipitation techniques. Journal of Nanoparticle Research, 20(3), 71. http://dx.doi.org/10.1007/s11051-018-4177-7.

26 Makadia, H. K., & Siegel, S. J. (2011). Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers, 3(3), 1377-1397. http://dx.doi.org/10.3390/polym3031377. PMid:22577513.

27 Deng, C., Jiang, Y., Cheng, R., Meng, F., & Zhong, Z. (2012). Biodegradable polymeric micelles for targeted and controlled anticancer drug delivery: promises, progress and prospects. Nano Today, 7(5), 467-480. http://dx.doi.org/10.1016/j.nantod.2012.08.005.

28 Kumari, A., Yadav, S. K., & Yadav, S. C. (2010). Biodegradable polymeric nanoparticles based drug delivery systems. Colloids and Surfaces. B, Biointerfaces, 75(1), 1-18. http://dx.doi.org/10.1016/j.colsurfb.2009.09.001. PMid:19782542.

29 Yu, L., Dean, K., & Li, L. (2006). Polymer blends and composites from renewable resources. Progress in Polymer Science, 31(6), 576-602. http://dx.doi.org/10.1016/j.progpolymsci.2006.03.002.

30 Enrrico, C., Bartoli, C., Chiellini, F., & Chiellini, E. (2009). Poly(hydroxyalkanoates)-based polymeric nanoparticles for drug delivery. Journal of Biomedicine & Biotechnology, 2009, 571702. http://dx.doi.org/10.1155/2009/571702. PMid:19789653.

31 Shakeri, F., Shakeri, S., & Hojjatoleslami, M. (2014). Preparation and characterization of carvacrol loaded polyhydroxybutyrate nanoparticles by nanoprecipitation and dialysis methods. Journal of Food Science, 79(4), N697-N705. http://dx.doi.org/10.1111/1750-3841.12406. PMid:24621231.

32 Kim, B. O., & Woo, S. I. (1998). Compatibilizing capability of poly(β-hydroxybutyrate-co-ε-caprolactone) in the blend of poly(β-hydroxybutyrate) and poly(ε-caprolactone). Polymer Bulletin, 41(6), 707-712. http://dx.doi.org/10.1007/s002890050422.

33 Leimann, F. V., Cardozo Filho, L., Sayer, C., & Araújo, P. H. H. (2013). Poly(3-hydroxybutyrate-co-3- hydroxyvalerate) nanoparticles prepared by a miniemulsion/solvent evaporation technique: effect of phbv molar mass and concentration. Brazilian Journal of Chemical Engineering, 30(2), 369-377. http://dx.doi.org/10.1590/S0104-66322013000200014.

34 Musyanovych, A., Schmitz-Wienke, J., Mailänder, V., Walther, P., & Landfester, K. (2008). Preparation of Biodegradable Polymer Nanoparticles by Miniemulsion Technique and Their Cell Interactions. Macromolecular Bioscience, 8(2), 127-139. http://dx.doi.org/10.1002/mabi.200700241. PMid:18213594.

35 Dourado, L. F. N., Pierucci, A., Roa, J. P. B., & Carvalho Júnior, Á. D. (2021). Assessment of implantable drug delivery technology: poly (3-hydroxybutyrate) / polypropylene glycol films containing simvastatin. Matéria (Rio de Janeiro), 26(04), 1-14. http://dx.doi.org/10.1590/s1517-707620210004.1389.

36 Terukina, T., Naito, Y., Tagami, T., Morikawa, Y., Henmi, Y., Prananingrum, W., Ichikawa, T., & Ozeki, T. (2016). The effect of the release behavior of simvastatin from different PLGA particles on bone regeneration in vitro and in vivo: comparison of simvastatin-loaded PLGA microspheres and nanospheres. Journal of Drug Delivery Science and Technology, 33, 136-142. http://dx.doi.org/10.1016/j.jddst.2016.03.005.

37 Sinha, V. R., Bansal, K., Kaushik, R., Kumria, R., & Trehan, A. (2004). Poly-ε-caprolactone microspheres and nanospheres: an overview. International Journal of Pharmaceutics, 278(1), 1-23. http://dx.doi.org/10.1016/j.ijpharm.2004.01.044. PMid:15158945.

38 Souto, E. B., Severino, P., & Santana, M. H. A. (2012). Preparação de nanopartículas poliméricas a partir de polímeros pré-formados: parte II. Polimeros: Ciência e Tecnologia, 22(1), 101-106. http://dx.doi.org/10.1590/S0104-14282012005000005.

39 Montasser, I., Fessi, H., & Coleman, A. W. (2002). Atomic force microscopy imaging of novel type of polymeric colloidal nanostructures. European Journal of Pharmaceutics and Biopharmaceutics, 54(3), 281-284. http://dx.doi.org/10.1016/S0939-6411(02)00087-5. PMid:12445557.

40 Auras, R. A., Harte, B., Selke, S., & Hernandez, R. (2003). Mechanical, physical, and barrier properties of poly(lactide) films. Journal of Plastic Film & Sheeting, 19(2), 123-135. http://dx.doi.org/10.1177/8756087903039702.

41 Ding, Y., Roether, J. A., Boccaccini, A. R., & Schubert, D. W. (2014). Fabrication of electrospun poly (3-hydroxybutyrate)/poly (ε-caprolactone)/silica hybrid fibermats with and without calcium addition. European Polymer Journal, 55, 222-234. http://dx.doi.org/10.1016/j.eurpolymj.2014.03.020.

42 Calvo, P., Vila-Jato, J. L., & Alonso, M. J. (1996). Comparative in vitro evaluation of several colloidal systems, nanoparticles, nanocapsules, and nanoemulsions, as ocular drug carriers. Journal of Pharmaceutical Sciences, 85(5), 530-536. http://dx.doi.org/10.1021/js950474+. PMid:8742946.

43 D’Souza, S. S., & DeLuca, P. P. (2005). Development of a dialysis in vitro release method for biodegradable microspheres. AAPS PharmSciTech, 6(2), E323-E328. http://dx.doi.org/10.1208/pt060242. PMid:16353991.

44 Schaffazick, S. R., Guterres, S. S., Freitas, L. L., & Pohlmann, A. R. (2003). Caracterização e estabilidade físico-química de sistemas poliméricos nanoparticulados para administração de fármacos. Quimica Nova, 26(5), 726-737. http://dx.doi.org/10.1590/S0100-40422003000500017.

45 Dash, T. K., & Konkimalla, V. B. (2012). Poly-ε-caprolactone based formulations for drug delivery and tissue engineering: a review. Journal of Controlled Release, 158(1), 15-33. http://dx.doi.org/10.1016/j.jconrel.2011.09.064. PMid:21963774.

46 Schaefer, M. J., & Singh, J. (2002). Effect of tricaprin on the physical characteristics and in vitro release of etoposide from PLGA microspheres. Biomaterials, 23(16), 3465-3471. http://dx.doi.org/10.1016/S0142-9612(02)00053-4. PMid:12099290.

47 Wischke, C., & Schwendeman, S. P. (2008). Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles. International Journal of Pharmaceutics, 364(2), 298-327. http://dx.doi.org/10.1016/j.ijpharm.2008.04.042. PMid:18621492.

48 Schaffazick, S. R., Pohlmann, A. R., Freitas, L. L., & Guterres, S. S. (2002). Caracterização e estudo de estabilidade de suspensões de nanocápsulas e de nanoesferas poliméricas contendo diclofenaco. Latin American Journal of Pharmacy, 21(2), 99-106. Retrieved in 2022, February 21, from http://www.latamjpharm.org/trabajos/21/2/LAJOP_21_2_1_4_740TAXZEY7.pdf
 

6356f799a95395367f3c1b62 polimeros Articles
Links & Downloads

Polímeros: Ciência e Tecnologia

Share this page
Page Sections