Advertisement

Colloid and Polymer Science

, Volume 297, Issue 11–12, pp 1465–1475 | Cite as

Preparation and characterization of dithiocarbazate Schiff base–loaded poly(lactic acid) nanoparticles and analytical validation for drug quantification

  • Thacilla Ingrid de Menezes
  • Rebeca de Oliveira Costa
  • Rute Nazaré Fernandes Sanches
  • Denise de Oliveira Silva
  • Rodrigo Luis Silva Ribeiro SantosEmail author
Original Contribution
  • 82 Downloads

Abstract

Dithiocarbazate Schiff bases have been reported as a class of compounds that exhibit a wide range of pharmacological activities against neglected diseases such as malaria, trypanosomiasis, and tuberculosis. This work reports the encapsulation of the 1-(S-benzyldithiocarbazate)-3-methyl-5-phenyl-pyrazole (DTC) into biodegradable polymeric nanoparticles (NPs) of poly(lactic acid) (PLA) aiming potential drug delivery application. The DTC-loaded PLA-NPs were prepared by the single-nanoemulsification method using the poly(vinyl alcohol) (PVA) as a surfactant. The nanostructured system was characterized mainly by dynamic light scattering (DLS), electrophoretic light scattering (ELS), and transmission electron microscopy (TEM). The NPs show good colloidal stability exhibiting mean hydrodynamic diameter 157 ± 5 nm and zeta potential − 36 ± 3 mV. The encapsulation efficiency and drug loading were 52 ± 14% and 4.8 ± 1.5%, respectively. The quantifications of DTC and residual PVA in the NPs were performed by UV-Vis absorption spectroscopy. The analytical methods were validated according to regulatory agencies. Both quantification analytical curves showed good precision, in repeatability (intra-day) and intermediate (inter-day), and also good accuracy with low values of detection and quantification. The new nanostructured system, DTC-loaded PLA-NPs, shows advantages to improve stability and to overcome water solubility problems of the dithiocarbazate Schiff bases aiming potential drug delivery applications.

Graphical abstract

.

Keywords

Azomethine Pyrazole Emulsion polymerization Nanostructured system Colloidal system 

Notes

Acknowledgments

T. I. Menezes and R. O. Costa acknowledge the FAPESB (Fundação de Amparo à Pesquisa do Estado da Bahia) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for the Master degree scholarships. The authors are also sincerely thankful to Prof. Dr. André Gustavo A. Fernandes (UESC) for donating the DTC compound. We also thank Prof. Dr. Luiz Carlos Salay (UESC) for providing laboratory facilities to perform the experiments, and Prof. Dra. Luana Novaes (UESC) for careful reading and suggestions on the validation methods. We are also grateful to the Electron Microscopy Center (UESC) and Alfredo Duarte (IQ-USP) for the technical assistance on the MET analyses.

Funding information

Author D. de Oliveira Silva received financial support from from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) [2018/00297-4] and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) [303103/2018-3].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

396_2019_4572_MOESM1_ESM.pdf (234 kb)
ESM 1 (PDF 233 kb)

References

  1. 1.
    Pridgen EM, Langer R, Farokhzad OC (2007) Biodegradable, polymeric nanoparticle delivery systems for cancer therapy. Nanomedicine 2:669–680PubMedGoogle Scholar
  2. 2.
    Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70:1–20PubMedGoogle Scholar
  3. 3.
    Stark WJ (2011) Nanoparticles in biological systems. Angew Chem Int Ed 50:1242–1258Google Scholar
  4. 4.
    Singh R, Lillard JW (2009) Nanoparticle-based targeted drug delivery. Exp Mol Pathol 86:215–223PubMedPubMedCentralGoogle Scholar
  5. 5.
    Letchford K, Burt H (2007) A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes. Eur J Pharm Biopharm 65:259–269PubMedGoogle Scholar
  6. 6.
    Mora-Huertas CE, Fessi H, Elaissari a. (2010) Polymer-based nanocapsules for drug delivery. Int J Pharm 385:113–142PubMedGoogle Scholar
  7. 7.
    Pinto Reis C, Neufeld RJ, Ribeiro AJ, Veiga F (2006) Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomed Nanotechnol Biol Med 2:8–21Google Scholar
  8. 8.
    Martínez Rivas CJ, Tarhini M, Badri W, Miladi K, Greige-Gerges H, Nazari QA, Galindo Rodríguez SA, Román RÁ, Fessi H, Elaissari A (2017) Nanoprecipitation process: from encapsulation to drug delivery. Int J Pharm 532:66–81PubMedGoogle Scholar
  9. 9.
    Zhang Y, Chan HF, Leong KW (2013) Advanced materials and processing for drug delivery: the past and the future. Adv Drug Deliv Rev 65:104–120PubMedGoogle Scholar
  10. 10.
    Rao JP, Geckeler KE (2011) Polymer nanoparticles: preparation techniques and size-control parameters. Prog Polym Sci 36:887–913Google Scholar
  11. 11.
    Tyler B, Gullotti D, Mangraviti A, Utsuki T, Brem H (2016) Polylactic acid (PLA) controlled delivery carriers for biomedical applications. Adv Drug Deliv Rev 107:163–175PubMedGoogle Scholar
  12. 12.
    James R, Manoukian OS, Kumbar SG (2016) Poly(lactic acid) for delivery of bioactive macromolecules. Adv Drug Deliv Rev 107:277–288PubMedGoogle Scholar
  13. 13.
    Muppalaneni SA, Omidian H (2013) Polyvinyl alcohol in medicine and pharmacy: a perspective. J Dev Drugs 02:1000112Google Scholar
  14. 14.
    Wang T, Turhan M, Gunasekaran S (2004) Selected properties of pH-sensitive, biodegradable chitosan–poly(vinyl alcohol) hydrogel. Polym Int 53:911–918Google Scholar
  15. 15.
    Hua S, Ma H, Li X, Yang H, Wang A (2010) pH-sensitive sodium alginate/poly(vinyl alcohol) hydrogel beads prepared by combined Ca2+ crosslinking and freeze-thawing cycles for controlled release of diclofenac sodium. Int J Biol Macromol 46:517–523PubMedGoogle Scholar
  16. 16.
    Takasu A, Aoi K, Tsuchiya M, Okada M (1999) New chitin-based polymer hybrids, 4: soil burial degradation behavior of poly(vinyl alcohol)/chitin derivative miscible blends. J Appl Polym Sci 73:1171–1179Google Scholar
  17. 17.
    Akbar Ali M, Livingstone SE (1974) Metal complexes of sulphur-nitrogen chelating agents. Coord Chem Rev 13:101–132Google Scholar
  18. 18.
    Pavan FR, da S Maia PI, Leite SRA, Deflon VM, Batista AA, Sato DN, Franzblau SG, Leite CQF (2010) Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: anti - mycobacterium tuberculosis activity and cytotoxicity. Eur J Med Chem 45:1898–1905PubMedGoogle Scholar
  19. 19.
    Akbar Ali M, Mirza AH, Butcher RJ, Tarafder MT, Keat TB, Ali AM (2002) Biological activity of palladium(II) and platinum(II) complexes of the acetone Schiff bases of S-methyl- and S-benzyldithiocarbazate and the X-ray crystal structure of the [Pd(asme)2] (asme=anionic form of the acetone Schiff base of S-methyldithiocarbazate) complex. J Inorg Biochem 92:141–148PubMedGoogle Scholar
  20. 20.
    Ali MA, Mirza AH, Butcher RJ, Crouse KA (2006) The preparation, characterization and biological activity of palladium(II) and platinum(II) complexes of tridentate NNS ligands derived from S-methyl- and S-benzyldithiocarbazates and the X-ray crystal structure of the [Pd(mpasme)Cl] complex. Transit Met Chem 31:79–87Google Scholar
  21. 21.
    Nanjundan N, Narayanasamy R, Butcher RJ, Jasinski JP, Velmurugan K, Nandhakumar R, Balakumaran MD, Kalaichelvan PT, Gnanasoundari VG (2017) Synthesis, crystal structure, biomolecular interactions and anticancer properties of Ni(II), Cu(II) and Zn(II) complexes bearing S-allyldithiocarbazate. Inorg Chim Acta 455:283–297Google Scholar
  22. 22.
    Maia PIS, Fernandes AGAF, Silva JJN, Andricopulo AD, Lemos SS, Lang ES, Abram U, Deflon VM (2010) Dithiocarbazate complexes with the [M(PPh3)]2+ (M=Pd or Pt) moiety Synthesis, characterization and anti- Tripanosoma cruzi activity. J Inorg Biochem 104:1276–1282PubMedGoogle Scholar
  23. 23.
    Abu-Dief AM, Mohamed IMA (2015) A review on versatile applications of transition metal complexes incorporating Schiff bases. Beni-Suef Univ J Basic Appl Sci 4:119–133Google Scholar
  24. 24.
    da Silva CM, da Silva DL, Modolo LV, Alves RB, de Resende MA, Martins CVB, de Fátima A (2011) Schiff bases: a short review of their antimicrobial activities. J Adv Res 2:1–8Google Scholar
  25. 25.
    Ansari A, Ali A, Asif M, Shamsuzzaman S (2017) Review: biologically active pyrazole derivatives. New J Chem 41:16–41Google Scholar
  26. 26.
    Islan GA, Durán M, Cacicedo ML, Nakazato G, Kobayashi RKT, Martinez DST, Castro GR, Durán N (2017) Nanopharmaceuticals as a solution to neglected diseases: is it possible? Acta Trop 170:16–42PubMedGoogle Scholar
  27. 27.
    Carneiro ZA, Pedro PI, Sesti-Costa R, Lopes CD, Pereira TA, Milanezi CM, da Silva MAP, Lopez RFV, Silva JS, Deflon VM (2014) In vitro and in vivo trypanocidal activity of H2bdtc-loaded solid lipid nanoparticles. PLoS Negl Trop Dis 8:e2847PubMedPubMedCentralGoogle Scholar
  28. 28.
    de Sousa GF, Gatto CC, Resck IS, Deflon VM (2011) Synthesis, spectroscopic studies and X-ray crystal structures of new pyrazoline and pyrazole derivatives. J Chem Crystallogr 41:401–408Google Scholar
  29. 29.
    Santos RLSR, Costa AR, Menezes TI, Fernades AG (2017) Synthesis and characterization of novel potential trypanocidal metallodrug of ruthenium(II)-dithiocarbazate. J Biol Inorg Chem 22:S106.  https://doi.org/10.1007/s00775-017-1475-y
  30. 30.
    Costa AR, de Menezes TI, Nascimento RR, dos Anjos PNM, Viana RB, Fernandes AGA, Santos RLSR (2019) Ruthenium(II) dimethylsulfoxide complex with pyrazole/dithiocarbazate ligand. J Therm Anal Calorim 138:1683–1696.  https://doi.org/10.1007/s10973-019-08185-w Google Scholar
  31. 31.
    Silva JTDP, Silva ACD, Geiss JMT, de Araújo PHH, Becker D, Bracht L, Leimann FV, Bona E, Guerra GP, Gonçalves OH (2017) Analytical validation of an ultraviolet–visible procedure for determining lutein concentration and application to lutein-loaded nanoparticles. Food Chem 230:336–342PubMedGoogle Scholar
  32. 32.
    World Health Organization (1992) Validation of analytical procedures used in the examination of pharmaceutical materials (Annex 5), GenevaGoogle Scholar
  33. 33.
    do Rego ECP, Sakuma A, Avila AK, Bizarri CHB, de Oliveira EC, del Castillo F, Lemos IMG, Oliveras LY, Rodrigues LCV, Aguiar PF, da Silva PALopes, Martins PR, Araujo TO, de Azevedo MWD, de Oliveira AGHR, de Oliveira EFR, Hubner MTW, Camargo PW (2016) Orientação sobre validação de métodos analíticos, INMETRO (DOQ-CGCRE-008). Rio de JaneiroGoogle Scholar
  34. 34.
    Ankrum JA, Miranda OR, Ng KS, Sarkar D, Xu C, Karp JM (2014) Engineering cells with intracellular agent-loaded microparticles to control cell phenotype. Nat Protoc 9:233–245PubMedPubMedCentralGoogle Scholar
  35. 35.
    Finley JH (1961) Spectrophotometric determination of polyvinyl alcohol in paper coatings. Anal Chem 33:1925–1927Google Scholar
  36. 36.
    Joshi DP, Lan-Chun-Fung YL, Pritchard JG (1979) Determination of poly(vinyl alcohol) via its complex with boric acid and iodine. Anal Chim Acta 104:153–160Google Scholar
  37. 37.
    Ribani M, Botoli CBG, Collins CH, Jardim ICSF, Melo LFC (2004) Validation for chromatographic and electrophoretic methdos. Quim Nova 27:771–780Google Scholar
  38. 38.
    Thompson M, Ellison SLR, Fajgelj A, Willetts P, Wood R (1999) Harmonized guidelines for the use of recovery information in analytical measurement. Pure Appl Chem 71:337–348Google Scholar
  39. 39.
    Andrade JM, Estévez-Pérez MG (2014) Statistical comparison of the slopes of two regression lines: a tutorial. Anal Chim Acta 838:1–12PubMedGoogle Scholar
  40. 40.
    Maharana T, Mohanty B, Negi YS (2010) Preparation of poly(lactic acid) nanoparticles and optimization of the particle size. Int J Green Nanotechnol Phys Chem 2:P100–P109Google Scholar
  41. 41.
    Hong JS, Srivastava D, Lee I (2018) Fabrication of poly(lactic acid) nano- and microparticles using a nanomixer via nanoprecipitation or emulsion diffusion. J Appl Polym Sci 135:46199Google Scholar
  42. 42.
    Blanco E, Shen H, Ferrari M (2015) Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol 33:941–951PubMedPubMedCentralGoogle Scholar
  43. 43.
    Kumar B, Jalodia K, Kumar P, Gautam HK (2017) Recent advances in nanoparticle-mediated drug delivery. J Drug Deliv Sci Technol 41:260–268Google Scholar
  44. 44.
    Bhattacharjee S (2016) DLS and zeta potential – what they are and what they are not? J Control Release 235:337–351PubMedGoogle Scholar
  45. 45.
    Zhu D, Tao W, Zhang H, Liu G, Wang T, Zhang L, Zeng X, Mei L (2016) Docetaxel (DTX)-loaded polydopamine-modified TPGS-PLA nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Acta Biomater 30:144–154PubMedGoogle Scholar
  46. 46.
    Szwed M, Santos-Oliveira R (2016) Nanoparticles with therapeutic properties generate various response of human peripheral blood mononuclear cells. J Nanosci Nanotechnol 16:6545–6550PubMedGoogle Scholar
  47. 47.
    Thauvin C, Schwarz B, Delie F, Allémann E (2018) Functionalized PLA polymers to control loading and/or release properties of drug-loaded nanoparticles. Int J Pharm 548:771–777PubMedGoogle Scholar
  48. 48.
    Derjaguin B, Landau L (1993) Theory of the stability of strongly charged lyophobic sols and of the adhesion of strongly charged particles in solutions of electrolytes. Prog Surf Sci 43:30–59Google Scholar
  49. 49.
    Verwey EJW, Overbeek JTG (1948) Theory of the stability of lyophobic colloids. Elsevier Publishing Company, AmsterdamGoogle Scholar
  50. 50.
    Sharma S, Shukla P, Misra A, Mishra PR (2014) Interfacial and colloidal properties of emulsified systems: pharmaceutical and biological perspective. In: Colloid and Interface Science in Pharmaceutical Research and Development. Elsevier, pp 149–172Google Scholar
  51. 51.
    Moore TL, Rodriguez-Lorenzo L, Hirsch V, Balog S, Urban D, Jud C, Rothen-Rutishauser B, Lattuada M, Petri-Fink A (2015) Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chem Soc Rev 44:6287–6305PubMedGoogle Scholar
  52. 52.
    Ge C, Tian J, Zhao Y, Chen C, Zhou R, Chai Z (2015) Towards understanding of nanoparticle–protein corona. Arch Toxicol 89:519–539PubMedGoogle Scholar
  53. 53.
    Li F, Zhu A, Song X, Ji L (2014) Novel surfactant for preparation of poly(l-lactic acid) nanoparticles with controllable release profile and cytocompatibility for drug delivery. Colloids Surf B: Biointerfaces 115:377–383PubMedGoogle Scholar
  54. 54.
    Musyanovych A, Dausend J, Dass M, Walther P, Mailänder V, Landfester K (2011) Criteria impacting the cellular uptake of nanoparticles: a study emphasizing polymer type and surfactant effects. Acta Biomater 7:4160–4168PubMedGoogle Scholar
  55. 55.
    Altmeyer C, Karam TK, Khalil NM, Mainardes RM (2016) Tamoxifen-loaded poly(L-lactide) nanoparticles: development, characterization and in vitro evaluation of cytotoxicity. Mater Sci Eng C 60:135–142Google Scholar
  56. 56.
    Roussaki M, Gaitanarou A, Diamanti PC, Vouyiouka S, Papaspyrides C, Kefalas P, Detsi A (2014) Encapsulation of the natural antioxidant aureusidin in biodegradable PLA nanoparticles. Polym Degrad Stab 108:182–187Google Scholar
  57. 57.
    Chu KS, Schorzman AN, Finniss MC, Bowerman CJ, Peng L, Luft JC, Madden AJ, Wang AZ, Zamboni WC, DeSimone J (2013) Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy. Biomaterials 34:8424–8429PubMedGoogle Scholar
  58. 58.
    Essa S, Rabanel JM, Hildgen P (2010) Effect of polyethylene glycol (PEG) chain organization on the physicochemical properties of poly(d, l-lactide) (PLA) based nanoparticles. Eur J Pharm Biopharm 75:96–106PubMedGoogle Scholar
  59. 59.
    Jyothi NVN, Prasanna PM, Sakarkar SN, Prabha KS, Ramaiah PS, Srawan GY (2010) Microencapsulation techniques, factors influencing encapsulation efficiency. J Microencapsul 27:187–197PubMedGoogle Scholar
  60. 60.
    Sahoo SK, Panyam J, Prabha S, Labhasetwar V (2002) Residual polyvinyl alcohol associated with poly (D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. J Control Release 82:105–114PubMedGoogle Scholar
  61. 61.
    Macias CE, Bodugoz-Senturk H, Muratoglu OK (2013) Quantification of PVA hydrogel dissolution in water and bovine serum. Polymer (Guildf) 54:724–729Google Scholar
  62. 62.
    Noguchi H, Jyodai H, Matsuzawa S (1997) Formation of poly (vinyl alcohol)–iodine complexes in solution. J Polym Sci B Polym Phys 35:1701–1709Google Scholar
  63. 63.
    Zhang Z, Feng SS (2006) The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles. Biomaterials 27:4025–4033PubMedGoogle Scholar
  64. 64.
    Zambaux M (1998) Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method. J Control Release 50:31–40PubMedGoogle Scholar
  65. 65.
    Da Silva-Buzanello RA, Ferro AC, Bona E, Cardozo-Filho L, de Araújo PHH, Leimann FV, Gonçalves OH (2015) Validation of an ultraviolet–visible (UV–Vis) technique for the quantitative determination of curcumin in poly(l-lactic acid) nanoparticles. Food Chem 172:99–104PubMedGoogle Scholar
  66. 66.
    Cao Y, Liu F, Chen Y, Yu T, Lou D, Guo Y, Li P, Wang Z, Ran H (2017) Drug release from core-shell PVA/silk fibroin nanoparticles fabricated by one-step electrospraying. Sci Rep 7:11913Google Scholar
  67. 67.
    Lee BK, Yun Y, Park K (2016) PLA micro- and nano-particles. Adv Drug Deliv Rev 107:176–191PubMedPubMedCentralGoogle Scholar
  68. 68.
    Araujo P (2009) Key aspects of analytical method validation and linearity evaluation. J Chromatogr B Anal Technol Biomed Life Sci 877:2224–2234Google Scholar
  69. 69.
    AOAC International (2012) Official methods of analysis of AOAC International. In: AOAC Official Methods of Analysis, in Guidelines for Standard Method Performance Requirements (Appendix F). Gaithersburg, pp 1–17Google Scholar
  70. 70.
    Procházková L, Rodríguez-Muñoz Y, Procházka J, Wanner J (2014) Simple spectrophotometric method for determination of polyvinylalcohol in different types of wastewater. Int J Environ Anal Chem 94:399–410Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Departamento de Ciências Exatas e TecnológicasUniversidade Estadual de Santa CruzIlhéusBrazil
  2. 2.Departamento de Química Fundamental, Instituto de QuímicaUniversidade de São PauloSão PauloBrazil

Personalised recommendations