Oxytocin Sustained Release Using Natural Rubber Latex Membranes

  • Natan Roberto de Barros
  • Matheus Carlos Romeiro Miranda
  • Felipe Azevedo Borges
  • Ricardo José de Mendonça
  • Eduardo Maffud Cilli
  • Rondinelli Donizetti Herculano


The demand for biomaterials with properties that provide sustained release of substances with pharmacological interest is constant. One candidate for applications in this area is the Natural Rubber Latex (NRL) extracted from the rubber tree Hevea brasiliensis. Recent studies indicate the NRL as a matrix for sustained release, showing promising results for biomedical applications such as: can stimulate natural angiogenesis and is capable of adhering cells on its surface, promoting the replacement and regeneration of tissue. So, the NRL is an excellent candidate to propitiate the sustained release of peptides of pharmacological interest such as oxytocin, a hormonal peptide which has the function to promote uterine muscle contractions and reduce bleeding during childbirth, and stimulate the release of breast milk. Results demonstrated that 90 μg mL−1 (45 %) of the incorporated peptide in Natural Rubber Latex Biomedical (NRLb) functionalized membranes was released at 10 h in phosphate-buffered saline (PBS) solution. Swelling kinetics assay showed that the NRLb membranes are able to absorb over a period of 16 h up to 1.08 grams of water per grams of membrane. Scanning electron microscopy showed that the peptide was adsorbed on the surface and within NRLb membrane. Fourier transform infrared and Derivative Thermogravimetric analysis indicated that oxytocin did not interacted chemically with the membrane. Furthermore, hemolysis of erythrocytes, quantified spectrophotometrically using materials (Oxytocin, NRLb, and NRLb + Oxytocin) showed no hemolytic effects up to 100 μg mL−1 (compounds and mixtures), indicating no detectable disturbance of the red blood cell membranes. Based on these results it was possible to conclude that the NRLb has shown effectiveness as a model in the release of peptides with pharmacological interest.


Oxytocin Natural rubber latex Peptide Sustained release Biomaterial 



This work was supported by CAPES, CNPq and FAPESP (Processes 2014/17526-8, 2015/02343-8).

Compliance with Ethical Standards

Conflicts of Interest

Author Natan Roberto de Barros declares that he has no conflict of interest. Author Matheus Carlos Romeiro Miranda declares that he has no conflict of interest. Author Felipe Azevedo Borges declares that he has no conflict of interest. Author Ricardo José de Mendonça declares that he has no conflict of interest. Author Eduardo Maffud Cilli declares that he has no conflict of interest. Author Rondinelli Donizetti Herculano declares that he has no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Aielo PB, Borges FA, Romeira KM, Miranda MCR, Arruda LB, Lisboa-Filho PN, Drago BC, Herculano RD (2014) Evaluation of sodium diclofenac release using natural rubber latex as carrier. Mat Res. doi: 10.1590/S1516-14392014005000010 Google Scholar
  2. Allarcon JB, Malito M, Linde H, Brito MEM (2003) Alergia ao látex. Rev Bras Anestesiol. doi: 10.1590/S0034-70942003000100012 PubMedGoogle Scholar
  3. Alves COM (2003) Teste da angiogênese estimulada por membranas de látex natural. University of São PauloGoogle Scholar
  4. Barros NR, Chagas PAM, Borges FA, Gemeinder JLP, Miranda MCR, Garms BC, Herculano RD (2015) Diclofenac potassium transdermal patches using natural rubber latex biomembranes as carrier. J Mater. doi: 10.1155/2015/807948 Google Scholar
  5. Barth A (2007) Infrared spectroscopy of proteins. Biochim Biophys Acta. doi: 10.1016/j.bbabio.2007.06.004 Google Scholar
  6. Blaabjerg MSB, Andersen KE, Bindslev-Jensen C, Mortz CG (2015) Decrease in the rate of sensitization and clinical allergy to natural rubber latex. Contact Dermat. doi: 10.1111/cod.12386 Google Scholar
  7. Borges FA, Bolognesi LFC, Treco A, Drago BC, Arruda LB, Lisboa-Filho PN, Perri EG, Graeff CFO, Santos AG, Miranda MCR, Herculano RD (2014) Natural rubber latex: study of a novel carrier for Casearia sylvestris Swartz delivery. ISRN Polym Sci. doi: 10.1155/2014/241297 Google Scholar
  8. Borges FA, Almeida-Filho E, Miranda MCR, dos Santos ML, Herculano RD, Guastaldi AC (2015) Natural rubber latex coated with calcium phosphate for biomedical application. J Biomater Sci Polym Ed. doi: 10.1080/09205063.2015.1086945 PubMedGoogle Scholar
  9. Bozkurt O, Bayari SH, Severcan M, Krafft C, Popp J, Severcan F (2012) Structural alterations in rat liver proteins due to streptozotocin-induced diabetes and the recovery effect of selenium: Fourier transform infrared microspectroscopy and neural network study. J Biomed Opt. doi: 10.1117/1.JBO.17.7.076023 PubMedGoogle Scholar
  10. Costa PJC (2002) Avaliação in vitro da lioequivalência de formulações farmacêuticas. Bras Cienc Farm, Rev. doi: 10.1590/S1516-93322002000200003 Google Scholar
  11. D’Auzac J, Jacob JL, Chrestin H (1989) Physiology of rubber tree: the composition of latex from Hevea brasiliensis as a laticiferous cytoplasm. CRC Press, Boca RatonGoogle Scholar
  12. De Dreu CK, Greer LL, Van-Kleef GA, Shalvi S, Handgraaf MJJ (2011) Oxytocin promotes human ethnocentrism. Proc Natl Acad Sci USA. doi: 10.1073/pnas.1015316108 PubMedGoogle Scholar
  13. Ereno C, Guimarães SAC, Pasetto S, Herculano RD, Silva CP, Graeff CFO, Tavano O, Baffa O, Kinoshita A (2010) Latex use as an occlusive membrane for guided bone regeneration. J Biomed Mater Res A. doi: 10.1002/jbm.a.32919 PubMedGoogle Scholar
  14. Ferreira M, Mendonça RJ, Coutinho-Netto J, Mulato M (2009) Angiogenic properties of natural rubber latex biomembranes and the serum fraction of Hevea brasiliensis. Braz J Phys. doi: 10.1590/S0103-97332009000500010 Google Scholar
  15. Fischer D, Li Y, Ahlemeyer B, Krieglstein J, Kissel T (2003) In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials. doi: 10.1016/S0142-9612(02)00445-3 Google Scholar
  16. Frade MAC, Cursi IB, Andrade FF, Coutinho-Netto J, Barbetta FM, Foss NT (2004) Management of diabetic skin wounds with a natural latex biomembrane. Med Cutan Ibero Lat Am 32(4):157–162Google Scholar
  17. Guidelli EJ, Kinoshita A, Ramos AP, Baffa O (2003) Silver nanoparticles delivery based on natural rubber membranes. J Nanopart Res. doi: 10.1007/s11051-013-1536-2 Google Scholar
  18. Hasma H, Subramauian A (1986) Composition of lipids in latex of Hevea brasiliensis clone RRIM 501. J Nat Rubb Res. 1(1):30–40Google Scholar
  19. Herculano RD, Pereira CP, Ereno C, Catanzaro-Guimarães SA, Kinoshita A, Graeff CFO (2009) Natural rubber latex used as drug delivery system in guided bone regeneration (GBR). Mat Res. doi: 10.1590/S1516-14392009000200023 Google Scholar
  20. Herculano RD, Guimarães SAC, Belmonte GC, Duarte MAH, Oliveira ONJ, Kinoshita A, Graeff CFO (2010) Metronidazole release using natural rubber latex as matrix. Mat Res. doi: 10.1590/S1516-14392010000100013 Google Scholar
  21. Herculano RD, de Queiroz AAA, Kinoshita A, Oliveira ON Jr, Graeff CFO, Herculano RD (2011) On the release of metronidazole from natural rubber latex membranes. Mat Sci Eng C-Biomim. doi: 10.1016/j.msec.2010.09.007 Google Scholar
  22. Huang X, Brazel CS (2001) On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release. doi: 10.1016/S0168-3659(01)00248-6 Google Scholar
  23. Lee H-J, Macbeth AH, Pagani JH, Young WS (2009) Oxytocin: the great facilitator of life. Prog Neurobiol. doi: 10.1016/j.pneurobio.2009.04.001 PubMedPubMedCentralGoogle Scholar
  24. McMahan C, Kostya D, Lhamo DL, Cornish K (2015) Protein influences on guayule and Hevea natural rubber sol and gel. J Appl Polym Sci. doi: 10.1002/app.42051 Google Scholar
  25. Mendonça RJ, Maurício VB, Teixeira LB, Lachat JJ, Coutinho-Netto J (2009) Increased vascular permeability, angiogenesis and wound healing induced by the serum of natural latex of the rubber tree Hevea brasiliensis. Phytother Res. doi: 10.1002/ptr.3043 Google Scholar
  26. Miranda MCR (2014) Obtenção e estudos físico-químicos de biomembranas conjugadas de látex e peptídeos bioativos. Dissertation, UNESP - Univ Estadual PaulistaGoogle Scholar
  27. Mrué F, Coutinho-Netto J, Ceneviva R, Lachat JJ, Thomazine JA, Tambelini H (2004) Evaluation of the biocompatibility of a new biomembrane. Mat Res. doi: 10.1590/S1516-14392004000200010 Google Scholar
  28. Murbach HD, Ogawa GJ, Borges FA, Miranda MCR, Lopes R, Barros NR, Mazalli AVG, Silvia RG, Cinman JLF, Drago BC, Herculano RD (2014) Ciprofloxacin release using natural rubber latex membranes as carrier. Int J Biomater. doi: 10.1155/2014/157952 Google Scholar
  29. Neda I, Vlazan P, Pop RO, Sfarloaga P, Grozescu I, Segneanu A-E (2012) Peptide and amino acids separation and identification from natural products. InTech. doi: 10.5772/51619 Google Scholar
  30. Onuma Y, Satake M, Ukena T, Roux J, Chanteau S, Rasolofonirina N, Ratsimaloto M, Naoki H, Yasumoto T (1999) Identification of putative palytoxin as the cause of clupeotoxism. Toxicon. doi: 10.1016/S0041-0101(98)00133-0 PubMedGoogle Scholar
  31. Pichayakorn W, Suksaeree J, Boonme P, Amnuaikit T, Taweepreda W, Ritthidej G (2012) Nicotine transdermal patches using polymeric natural rubber as the matrix controlling system: effect of polymer and plasticizer blends. J MembrSci. doi: 10.1016/j.memsci.2012.04.017 Google Scholar
  32. Pinho ECCM, Sousa SJF, Schaud F, Lachat JJ (2004) Experimental use of latex biomembrane in conjunctival reconstruction. Arq Bras Oftalmol. doi: 10.1590/S0004-27492004000100005 Google Scholar
  33. Romeira KM, Drago BC, Murbach HD, Aielo PB, Silva RMG, Brunello CA, Herculano RD (2012) Evaluation of Stryphnodendron sp. release using natural rubber latex membrane as carrier. J Appl Sci. doi: 10.3923/jas.2012.693.697 Google Scholar
  34. Salamon BF (2011) Controle de qualidade de cápsulas de cloridrato de venlafaxina manipuladas em farmácias magistrais de Porto Alegre – RS. Dissertation. UFRGS - Univ Fed Rio Grande do SulGoogle Scholar
  35. Steingräber T, Schtoltz T, Rodrigues PO (2008) Avaliação da influência de adjuvantes não-poliméricos solúveis na liberação do nimodipino a partir de formulações matriciais de liberação prolongada. Rev Colomb Ciencias Quim Farm 37(2):122–132Google Scholar
  36. Thote AJ, Chappell JT Jr, Kumar R, Gupta RB (2008) Reduction in the initial-burst release by surface crosslinking of PLGA microparticles containing hydrophilic or hydrophobic drugs. Drug Dev Ind Pharm. doi: 10.1081/DDC-43985 Google Scholar
  37. Turjanmaa K, Alenius H, Makinen-Kiljunen S, Reunala T, Palosuo T (1996) Natural rubber latex allergy. Allergy. doi: 10.1111/j.1398-9995.1996.tb04678.x PubMedGoogle Scholar
  38. World Health Organization (2015) WHO model list of essential medicines. Accessed 12 January 2015

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Natan Roberto de Barros
    • 1
  • Matheus Carlos Romeiro Miranda
    • 1
  • Felipe Azevedo Borges
    • 1
  • Ricardo José de Mendonça
    • 2
  • Eduardo Maffud Cilli
    • 1
  • Rondinelli Donizetti Herculano
    • 3
  1. 1.Chemistry InstituteSão Paulo State UniversityAraraquaraBrazil
  2. 2.UFTM – ICBNUberabaBrazil
  3. 3.Pharmaceutical Sciences FacultySão Paulo State UniversityAraraquaraBrazil

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