Polímeros: Ciência e Tecnologia
https://app.periodikos.com.br/journal/polimeros/article/doi/10.1590/0104-1428.20240042
Polímeros: Ciência e Tecnologia
Original Article

NanoSSIEFARL polymeric nanoparticles-based immunotherapeutic for the treatment of genital herpes

Renata Zorzetto; Flávia Pires Peña; Aline Cláudio de Oliveira; Jayme de Castilhos Ferreira Neto; Gabriel Tardin Mota Hilario; Fernanda Teresa Bovi Frozza; Marvin Paulo Lins; Fernanda Poletto; Marcelo Jung Eberhardt; Pedro Roosevelt Torres Romão; Tanira Alessandra Silveira Aguirre; Luiz Carlos Rodrigues Junior

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Abstract

This study aimed to investigate the therapeutic potential of a nanoparticle formulation containing the immunodominant peptide SSIEFARL from Herpes simplex virus 2 glycoprotein B A against genital herpes. A nanoparticle formulation (NanoSSIEFARL) was engineered and characterized for its physicochemical and immunomodulatory properties. NanoSSIEFARL displayed mean particle size of 212 ± 5 nm, polydispersity index of 0.12 ± 0.01 and zeta potential of -7.4 ± 2.5 mV, exhibiting spherical morphology. pH stability remained consistent over 30 days (day 0: 4.5 ± 0.5; day 30: 5.0 ± 0.5). A novel high-performance liquid chromatography method was validated for SSIEFARL quantification. Peptide association efficiency reached 98.3% ± 2.1, with 41.6% ± 4.4 peptide release from nanoparticles after 4 hours. Cytotoxicity assessment revealed cellular viability exceeding 90%, with macrophage uptake observed after 4 hours. Altogether, these results suggest that NanoSSIEFARL is a promising candidate for effective immunotherapy against genital herpes.

 

Keywords

babassu oil, genital herpes, HPLC, polymeric nanoparticle

References

1 Gupta, R., Warren, T., & Wald, A. (2007). Genital herpes. Lancet, 370(9605), 2127-2137. http://doi.org/10.1016/S0140-6736(07)61908-4. PMid:18156035.

2 Looker, K. J., & Garnett, G. P. (2005). A systematic review of the epidemiology and interaction of herpes simplex virus types 1 and 2. Sexually Transmitted Infections, 81(2), 103-107. http://doi.org/10.1136/sti.2004.012039. PMid:15800084.

3 Looker, K. J., Magaret, A. S., May, M. T., Turner, K. M. E., Vickerman, P., Gottlieb, S. L., & Newman, L. M. (2015). Global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 2012. PLoS One, 10(10), e0140765. http://doi.org/10.1371/journal.pone.0140765. PMid:26510007.

4 Perng, G. C., & Jones, C. (2010). Towards an understanding of the herpes simplex virus type 1 latency-reactivation cycle. Interdisciplinary Perspectives on Infectious Diseases, 2010, 262415. http://doi.org/10.1155/2010/262415. PMid:20169002.

5 Garner, J. A. (2003). Herpes simplex virion entry into and intracellular transport within mammalian cells. Advanced Drug Delivery Reviews, 55(11), 1497-1513. http://doi.org/10.1016/j.addr.2003.07.006. PMid:14597143.

6 Frank, G. M., Lepisto, A. J., Freeman, M. L., Sheridan, B. S., Cherpes, T. L., & Hendricks, R. L. (2010). Early CD4 + T cell help prevents partial CD8 + T cell exhaustion and promotes maintenance of herpes simplex virus 1 latency. Journal of Immunology, 184(1), 277-286. http://doi.org/10.4049/jimmunol.0902373. PMid:19949087.

7 St. Leger, A. J., Peters, B., Sidney, J., Sette, A., & Hendricks, R. L. (2011). Defining the herpes simplex virus-specific CD8 + T cell repertoire in C57BL/6 mice. Journal of Immunology, 186(7), 3927-3933. http://doi.org/10.4049/jimmunol.1003735. PMid:21357536.

8 Treat, B. R., Bidula, S. M., Ramachandran, S., St Leger, A. J., Hendricks, R. L., & Kinchington, P. R. (2017). Influence of an immunodominant herpes simplex virus type 1 CD8+ T cell epitope on the target hierarchy and function of subdominant CD8+ T cells. PLoS Pathogens, 13(12), e1006732. http://doi.org/10.1371/journal.ppat.1006732. PMid:29206240.

9 Treat, B. R., Bidula, S. M., St. Leger, A. J., Hendricks, R. L., & Kinchington, P. R. (2020). Herpes simplex virus 1-specific CD8+ T cell priming and latent ganglionic retention are shaped by viral epitope promoter kinetics. Journal of Virology, 94(5), e01193-19. http://doi.org/10.1128/JVI.01193-19. PMid:31826989.

10 Koelle, D. M., Dong, L., Jing, L., Laing, K. J., Zhu, J., Jin, L., Selke, S., Wald, A., Varon, D., Huang, M.-L., Johnston, C., Corey, L., & Posavad, C. (2022). HSV-2-specific human female reproductive tract tissue resident memory t cells recognize diverse HSV antigens. Frontiers in Immunology, 13, 867962. http://doi.org/10.3389/fimmu.2022.867962. PMid:35432373.

11 Reardon, J. E., & Spector, T. (1989). Herpes simplex virus type 1 DNA polymerase: mechanism of inhibition by acyclovir triphosphate. The Journal of Biological Chemistry, 264(13), 7405-7411. http://doi.org/10.1016/S0021-9258(18)83248-3. PMid:2540193.

12 Kost, R. G., Hill, E. L., Tigges, M., & Straus, S. E. (1993). Recurrent acyclovir-resistant genital herpes in an immunocompetent patient. The New England Journal of Medicine, 329(24), 1777-1782. http://doi.org/10.1056/NEJM199312093292405. PMid:8232486.

13 Kimberlin, D. W., Crumpacker, C. S., Straus, S. E., Biron, K. K., Drew, W. L., Hayden, F. G., McKinlay, M., Richman, D. D., & Whitley, R. J. (1995). Antiviral resistance in clinical practice. Antiviral Research, 26(4), 423-438. http://doi.org/10.1016/0166-3542(95)00031-G. PMid:7574544.

14 Hanke, T., Graham, F. L., Rosenthal, K. L., & Johnson, D. C. (1991). Identification of an immunodominant cytotoxic T-lymphocyte recognition site gB of herpes simplex virus by using recombnant adenovirus vectors. Journal of Virology, 65(3), 1177-1186. http://doi.org/10.1128/jvi.65.3.1177-1186.1991. PMid:1847447.

15 Çuburu, N., Kim, R., Guittard, G. C., Thompson, C. D., Day, P. M., Hamm, D. E., Pang, Y.-Y. S., Graham, B. S., Lowy, D. R., & Schiller, J. T. (2019). A prime-pull-amplify vaccination strategy to maximize induction of circulating and genital-resident intraepithelial CD8 + memory T cells. Journal of Immunology, 202(4), 1250-1264. http://doi.org/10.4049/jimmunol.1800219. PMid:30635393.

16 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. Química Nova, 26(5), 726-737. http://doi.org/10.1590/S0100-40422003000500017.

17 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://doi.org/10.1016/j.colsurfb.2009.09.001. PMid:19782542.

18 Woodruff, M. A., & Hutmacher, D. W. (2010). The return of a forgotten polymer: polycaprolactone in the 21st century. Progress in Polymer Science, 35(10), 1217-1256. http://doi.org/10.1016/j.progpolymsci.2010.04.002.

19 Limayem Blouza, I., Charcosset, C., Sfar, S., & Fessi, H. (2006). Preparation and characterization of spironolactone-loaded nanocapsules for paediatric use. International Journal of Pharmaceutics, 325(1-2), 124-131. http://doi.org/10.1016/j.ijpharm.2006.06.022. PMid:16872764.

20 Fiel, L. A., Contri, R. V., Bica, J. F., Figueiró, F., Battastini, A. M. O., Guterres, S. S., & Pohlmann, A. R. (2014). Labeling the oily core of nanocapsules and lipid-core nanocapsules with a triglyceride conjugated to a fluorescent dye as a strategy to particle tracking in biological studies. Nanoscale Research Letters, 9(1), 233. http://doi.org/10.1186/1556-276X-9-233. PMid:24936156.

21 Oliveira, J. V. R., Silveira, P. L., Spingolon, G., Alves, G. A. L., Peña, F. P., & Aguirre, T. A. S. (2023). Polymeric nanoparticles containing babassu oil: a proposed drug delivery system for controlled release of hydrophilic compounds. Chemistry and Physics of Lipids, 253, 105304. http://doi.org/10.1016/j.chemphyslip.2023.105304. PMid:37080377.

22 Reis, M. Y. F. A., Santos, S. M., Silva, D. R., Silva, M. V., Correia, M. T. S., Ferraz Navarro, D. M. A., Santos, G. K. N., Hallwass, F., Bianchi, O., Silva, A. G., Melo, J. V., Mattos, A. B., Ximenes, R. M., Machado, G., & Saraiva, K. L. A. (2017). Anti-inflammatory activity of babassu oil and development of a microemulsion system for topical delivery. Evidence-Based Complementary and Alternative Medicine, 2017(1), 3647801. http://doi.org/10.1155/2017/3647801. PMid:29430254.

23 Intahphuak, S., Khonsung, P., & Panthong, A. (2010). Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil. Pharmaceutical Biology, 48(2), 151-157. http://doi.org/10.3109/13880200903062614. PMid:20645831.

24 Campos, J. L. A., Silva, T. L. L., Albuquerque, U. P., Peroni, N., & Araújo, E. L. (2015). Knowledge, use, and management of the Babassu Palm (Attalea speciosa Mart. ex Spreng) in the Araripe Region (Northeastern Brazil). Economic Botany, 69(3), 240-250. http://doi.org/10.1007/s12231-015-9315-x.

25 Santos, L., & Loschi, M. (2019). Quebradeiras de coco babaçu preservam tradição no interior do Maranhão. Revista Retratos, 15, 1-28. Retrieved in 2024, April 21, from https://agenciadenoticias.ibge.gov.br/agencia-noticias/2012-agencia-de-noticias/noticias/23624-quebradeiras-de-coco-babacu-preservam-tradicao-no-interior-do-maranhao

26 Rodrigues, E. C. R., Ferreira, A. M., Vilhena, J. C. E., Almeida, F. B., Cruz, R. A. S., Amado, J. R. R., Florentino, A. C., Carvalho, J. C. T., & Fernandes, C. P. (2014). Development of babassu oil based nanoemulsions. Latin American Journal of Pharmacy, 34(2), 338-343. Retrieved in 2024, April 21, from http://www.latamjpharm.org/resumenes/34/2/LAJOP_34_2_1_20.pdf

27 Plaza-Oliver, M., Santander-Ortega, M. J., & Lozano, M. V. (2021). Current approaches in lipid-based nanocarriers for oral drug delivery. Drug Delivery and Translational Research, 11(2), 471-497. http://doi.org/10.1007/s13346-021-00908-7. PMid:33528830.

28 Leyva-Gómez, G., Piñón-Segundo, E., Mendoza-Muñoz, N., Zambrano-Zaragoza, M. L., Mendoza-Elvira, S., & Quintanar-Guerrero, D. (2018). Approaches in polymeric nanoparticles for vaginal drug delivery: A review of the state of the art. International Journal of Molecular Sciences, 19(6), 1549. http://doi.org/10.3390/ijms19061549. PMid:29882846.

29 Poletto, F. S., Fiel, L. A., Lopes, M. V., Schaab, G., Gomes, A., Guterres, S. S., Rossi-Bergmann, B., & Pohlmann, A. R. (2012). Fluorescent-labeled poly(ε-caprolactone) lipid-core nanocapsules: synthesis, physicochemical properties and macrophage uptake. Journal of Colloid Science and Biotechnology, 1(1), 89-98. http://doi.org/10.1166/jcsb.2012.1015.

30 Hilario, G. M., Sulczewski, F. B., Liszbinski, R., Mello, L. D., Hagen, G., Fazolo, T., Neto, J., Dallegrave, E., Romão, P., Aguirre, T., & Rodrigues, L. C., Jr. (2021). Development and immunobiological evaluation of nanoparticles containing an immunodominant epitope of herpes simplex virus. IET Nanobiotechnology/IET, 15(6), 532-544. http://doi.org/10.1049/nbt2.12043. PMid:34694744.

31 International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. (2005). ICH harmonised tripartite guideline: validation of analytical procedures: text and methodology Q2(R1). Geneva: ICH.

32 Brasil. Ministério da Saúde. Agência Nacional de Vigilância Sanitária. Diretoria Colegiada. (2017, 25 de julho). Resolução RDC nº 166, de 24 de julho de 2017. Dispõe sobre a validação de métodos analíticos e dá outras providências. Diário Oficial da República Federativa do Brasil, Brasília.

33 Justus, B., Kanunfre, C. C., Budel, J. M., Faria, M. F., Raman, V., Paula, J. P., & Farago, P. V. (2019). New insights into the mechanisms of French lavender essential oil on non-small-cell lung cancer cell growth. Industrial Crops and Products, 136, 28-36. http://doi.org/10.1016/j.indcrop.2019.04.051.

34 Lopes, C. E., Langoski, G., Klein, T., Ferrari, P. C., & Farago, P. V. (2017). A simple hplc method for the determination of halcinonide in lipid nanoparticles: development, validation, encapsulation efficiency, and in vitro drug permeation. Brazilian Journal of Pharmaceutical Sciences, 53(2), e15250. http://doi.org/10.1590/s2175-97902017000215250.

35 Sutariya, V., Wehrung, D., & Geldenhuys, W. J. (2012). Development and validation of a novel RP-HPLC method for the analysis of reduced glutathione. Journal of Chromatographic Science, 50(3), 271-276. http://doi.org/10.1093/chromsci/bmr055. PMid:22337804.

36 Chaudhari, S. P., & Dugar, R. P. (2017). Application of surfactants in solid dispersion technology for improving solubility of poorly water soluble drugs. Journal of Drug Delivery Science and Technology, 41, 68-77. http://doi.org/10.1016/j.jddst.2017.06.010.

37 Patel, A., Patel, M., Yang, X., & Mitra, A. (2014). Recent advances in protein and peptide drug delivery: a special emphasis on polymeric nanoparticles. Protein and Peptide Letters, 21(11), 1102-1120. http://doi.org/10.2174/0929866521666140807114240. PMid:25106908.

38 Kim, M. R., Feng, T., Zhang, Q., Chan, H. Y. E., & Chau, Y. (2019). Co-encapsulation and co-delivery of peptide drugs via polymeric nanoparticles. Polymers, 11(2), 288. http://doi.org/10.3390/polym11020288. PMid:30960272.

39 McClements, D. J. (2018). Encapsulation, protection, and delivery of bioactive proteins and peptides using nanoparticle and microparticle systems: a review. Advances in Colloid and Interface Science, 253, 1-22. http://doi.org/10.1016/j.cis.2018.02.002. PMid:29478671.

40 Falciani, C., Zevolini, F., Brunetti, J., Riolo, G., Gracia, R., Marradi, M., Loinaz, I., Ziemann, C., Cossío, U., Llop, J., Bracci, L., & Pini, A. (2020). Antimicrobial peptide-loaded nanoparticles as inhalation therapy for Pseudomonas aeruginosa infections. International Journal of Nanomedicine, 15, 1117-1128. http://doi.org/10.2147/IJN.S218966. PMid:32110011.

41 Casciaro, B., d’Angelo, I., Zhang, X., Loffredo, M. R., Conte, G., Cappiello, F., Quaglia, F., Di, Y.-P. P., Ungaro, F., & Mangoni, M. L. (2019). Poly(lactide- co-glycolide) nanoparticles for prolonged therapeutic efficacy of esculentin-1a-derived antimicrobial peptides against Pseudomonas aeruginosa lung infection: in vitro and in vivo studies. Biomacromolecules, 20(5), 1876-1888. http://doi.org/10.1021/acs.biomac.8b01829. PMid:31013061.

42 Frank, L. A., Contri, R. V., Beck, R. C. R., Pohlmann, A. R., & Guterres, S. S. (2015). Improving drug biological effects by encapsulation into polymeric nanocapsules. Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology, 7(5), 623-639. http://doi.org/10.1002/wnan.1334. PMid:25641603.

43 Frank, L. A., Sandri, G., D’Autilia, F., Contri, R. V., Bonferoni, M. C., Caramella, C., Frank, A. G., Pohlmann, A. R., & Guterres, S. S. (2014). Chitosan gel containing polymeric nanocapsules: a new formulation for vaginal drug delivery. International Journal of Nanomedicine, 9(1), 3151-3161. http://doi.org/10.2147/IJN.S62599. PMid:25061292.

44 Frank, L. A., Chaves, P. S., D’Amore, C. M., Contri, R. V., Frank, A. G., Beck, R. C. R., Pohlmann, A. R., Buffon, A., & Guterres, S. S. (2017). The use of chitosan as cationic coating or gel vehicle for polymeric nanocapsules: increasing penetration and adhesion of imiquimod in vaginal tissue. European Journal of Pharmaceutics and Biopharmaceutics, 114, 202-212. http://doi.org/10.1016/j.ejpb.2017.01.021. PMid:28161547.

45 Harshyne, L. A., Watkins, S. C., Gambotto, A., & Barratt-Boyes, S. M. (2001). Dendritic cells acquire antigens from live cells for cross-presentation to CTL. Journal of Immunology, 166(6), 3717-3723. http://doi.org/10.4049/jimmunol.166.6.3717. PMid:11238612.

46 Nayak, J. V., Hokey, D. A., Larregina, A., He, Y., Salter, R. D., Watkins, S. C., & Falo, L. D., Jr. (2006). Phagocytosis induces lysosome remodeling and regulated presentation of particulate antigens by activated dendritic cells. Journal of Immunology, 177(12), 8493-8503. http://doi.org/10.4049/jimmunol.177.12.8493. PMid:17142747.

47 Kong, B., Seog, J. H., Graham, L. M., & Lee, S. B. (2011). Experimental considerations on the cytotoxicity of nanoparticles. Nanomedicine, 6(5), 929-941. http://doi.org/10.2217/nnm.11.77. PMid:21793681.
 

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