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Inhalable Microparticles as Carriers for Pulmonary Delivery of Thymopentin-Loaded Solid Lipid Nanoparticles

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ABSTRACT

Purpose

Microparticles containing solid lipid nanoparticles (SLNs) are receiving increased attention as carriers for the lung delivery of the SLNs. Thus, we aim to prepare the hybrid microparticles and thoroughly evaluate their feasibility for the pulmonary drug delivery.

Methods

The microparticles were prepared by co-spray-drying the thymopentin (TP5)-loaded SLNs with bulking agents. Thereafter, we systematically estimated the potential of the microparticles as the carriers for the pulmonary delivery of the SLNs, including the investigations of their characteristics, aerodynamic properties, pharmacokinetics and pharmacodynamics.

Results

The spherical and hollow microparticles presented a size of 4.1 ± 0.1 μm and a low tap density of 0.175 ± 0.02 g/cm3. In addition, the microparticles showed a high aerosolization efficiency (emitted dose of 98.0% ± 1.23% and respirable fraction of 51.07% ± 1.21%). Furthermore, the SLNs could be easily recovered from the microparticles without essential changes on their characteristics and the drug release behavior. The pharmacokinetic and pharmacodynamic studies suggested that, compared to i.v. TP5 solution, the bioavailability and therapeutic efficacy of TP5 were remarkably strengthened after the pulmonary administration of the microparticles.

Conclusions

Taken together, we believe the microparticles were suitable for inhalation and possesed an ample potential for the pulmonary delivery of the SLNs.

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Abbreviations

AUC:

area under the curve

CLSM:

confocal laser scanning microscope

ED:

emitted dose

EE%:

encapsulation efficacy

DPI:

dry powder inhaler

FITC:

fluorescein isothiocyanate

HPLC:

high performance liquid chromatography

i.v.:

intravenous injection

mAb:

monoclonal Antibodies

MRT:

mean residence time

PBS:

phosphate buffer

PDI:

polydispersity index

RD:

respirable dose

RF:

respirable fraction

SD:

standard deviation

SEM:

scanning electron microscopy

SLNs:

solid lipid nanoparticles

SOD:

superoxide dismutase

TP5:

thymopentin

TSI:

twin stage impinger

W/O:

water in oil

W/O/W:

water in oil in water

REFERENCES

  1. Goldstein G, Scheid M, Boyse E, Schlesinger D, Wauwe JV. A synthetic pentapeptide with biological activity characteristic of the thymic hormone thymopoietin. Science. 1979;204:1309–10.

    Article  CAS  PubMed  Google Scholar 

  2. Clumeck N, Cran S, Van de Perre P, Lemone FM, Duchateau J, Bolla K. Thymopentin treatment in AIDS and pre-AIDS patients. Immunol Res. 1985;4:58–62.

    Google Scholar 

  3. Singh VK, Biswas S, Mathur KB, Haq W, Garg SK, Agarwal SS. Thymopentin and splenopentin as immunomodulators. Immunol Res. 1998;17:345–68.

    Article  CAS  PubMed  Google Scholar 

  4. Tischio JP, Patrick JE, Weintraub HS, Chasin M, Goldstein G. Short in vitro half-life of thymopoietin32–36 pentapeptide in human plasma. Int J Pept Protein Res. 1979;14:479–84.

    CAS  PubMed  Google Scholar 

  5. Jalalipour M, Gilani K, Tajerzadeh H, Najafabadi AR, Barghi M. Characterization and aerodynamic evaluation of spray dried recombinant human growth hormone using protein stabilizing agents. Int J Pharm. 2008;352:209–16.

    CAS  PubMed  Google Scholar 

  6. Ungaro F, Rosa GD, Miro A, Quaglia F, Rotonda MIL. Cyclodextrins in the production of large porous particles: development of dry powders for the sustained release of insulin to the lungs. Eur J Pharm Sci. 2006;28:423–32.

    Article  CAS  PubMed  Google Scholar 

  7. Salama RO, Traini D, Chan H-K, Sung A, Ammit AJ, Young PM. Preparation and evaluation of controlled release microparticles for respiratory protein therapy. J Pharm Sci. 2009;98:2709–17.

    Article  CAS  PubMed  Google Scholar 

  8. EXUBERA official site. http://www.exubera.com/content/con_index.jsp?setShowOn=../content/con_indx.jsp&setShowHighlightOn=../content/con_index.jsp.ed.

  9. Yang Y, Bajaj N, Xu P, Ohn K, Tsifansky MD, Yeo Y. Development of highly porous large PLGA microparticles for pulmonary drug delivery. Biomaterials. 2009;30:1947–53.

    Article  CAS  PubMed  Google Scholar 

  10. Seville PC, Learoyd TP, Li H-Y, Williamson IJ, Birchall JC. Amino acid-modified spray-dried powders with enhanced aerosolisation properties for pulmonary drug delivery. Powder Technol. 2007;178:40–50.

    Article  CAS  Google Scholar 

  11. Sivadasa N, O’Rourkea D, Tobina A, Buckley V, Ramtoolaa Z, Kellya JG, et al. A comparative study of a range of polymeric microspheres as potential carriers for the inhalation of proteins. Int J Pharm. 2008;358:159–67.

    Article  Google Scholar 

  12. Tsapis N, Bennett D, Jackson B, Weitz DA, Edwards DA. Trojan particles: large porous carriers of nanoparticles for drug delivery. Proc Natl Acad Sci. 2002;99:12001–5.

    Article  CAS  PubMed  Google Scholar 

  13. Hadinoto K, Phanapavudhikul P, Kewu Z, Tan RBH. Novel formulation of large hollow nanoparticles aggregates as potential carriers in inhaled delivery of nanoparticulate drugs. Ind Eng Chem Res. 2006;45:3697–706.

    Article  CAS  Google Scholar 

  14. Hadinoto K, Zhu K, Tan RBH. Drug release study of large hollow nanoparticulate aggregates carrier particles for pulmonary delivery. Int J Pharm. 2007;341:195–206.

    Article  CAS  PubMed  Google Scholar 

  15. Shama JO-H, Zhang Y, Finlay WH, Roaa WH, Löbenberg R. Formulation and characterization of spray-dried powders containing nanoparticles for aerosol delivery to the lung. Int J Pharm. 2004;269:457–67.

    Article  Google Scholar 

  16. Makino K, Yamamoto N, Higuchi K, Harada N, Ohshima H, Terada H. Phagocytic uptake of polystyrene microspheres by alveolar macrophages: effects of the size and surface properties of the microspheres. Colloids Surf B Biointerfaces. 2003;27:33–9.

    Article  CAS  Google Scholar 

  17. García-Fuentes M, Torres D, Alonso MJ. Design of lipid nanoparticles for the oral delivery of hydrophilic macromolecules. Colloids Surf B Biointerfaces. 2002;27:159–68.

    Article  Google Scholar 

  18. Kho K, Hadinoto K. Aqueous re-dispersibility characterization of spray-dried hollow spherical silica nano-aggregates. Powder Technol. 2010;198:354–63.

    Article  CAS  Google Scholar 

  19. Freitas C, Müller RH. Spray-drying of solid lipid nanoparticles (SLN™). Eur J Pharm Biopharm. 1998;46:145–51.

    Article  CAS  PubMed  Google Scholar 

  20. Grenha A, Seijo B, Serra C, Remuñán-López C. Chitosan nanoparticle-loaded mannitol microspheres: structure and surface characterization. Biomacromolecules. 2007;8:2072–9.

    Article  CAS  PubMed  Google Scholar 

  21. Grenha A, Remuñán-López C, Carvalho ELS, Seijo B. Microspheres containing lipid/chitosan nanoparticles complexes for pulmonary delivery of therapeutic proteins. Eur J Pharm Biopharm. 2008;69:83–93.

    Article  CAS  PubMed  Google Scholar 

  22. Gómez-Gaete C, Fattal E, Silva L, Besnard M, Tsapis N. Dexamethasone acetate encapsulation into Trojan particles. J Control Release. 2008;128:41–9.

    Article  PubMed  Google Scholar 

  23. Liu J, Gong T, Wang CG, Zhong ZR, Zhang ZR. Solid lipid nanoparticles loaded with insulin by sodium cholate-phosphatidylcholine-based mixed micelles: preparation and characterization. Int J Pharm. 2007;340:153–62.

    Article  CAS  PubMed  Google Scholar 

  24. Bosquillon C, Préat V, Vanbever R. Pulmonary delivery of growth hormone using dry powders and visualization of its local fate in rats. J Control Release. 2004;96:233–44.

    Article  CAS  PubMed  Google Scholar 

  25. Wang J, Lu WL, Liang GW, Wu KC, Zhang C-G, Zhang X, et al. Pharmacokinetics, toxicity of nasal cilia and immunomodulating effects in sprague-dawley rats following intranasal delivery of thymopentin with or without enhancers. Peptides. 2006;27:826–35.

    Article  CAS  PubMed  Google Scholar 

  26. Treitinger A, Spada C, Verdi JC, Miranda AFB, Oliveira OV, Silveira MVS, et al. Decreased antioxidant defence in individuals infected by the human immunodeficiency virus. Eur J Clin Investig. 2001;30:454–9.

    Article  Google Scholar 

  27. Yin YS, Chen DW, Qiao MX, Lu Z, Hu HY. Preparation and evaluation of lectin-conjugated PLGA nanoparticles for oral delivery of thymopentin. J Control Release. 2006;116:337–45.

    Article  CAS  PubMed  Google Scholar 

  28. French DL, Edwards DA, Niven RW. The influence of formulation on emission, deaggregation and deposition of dry powders for inhalation. J Aerosol Sci. 1996;27:769–83.

    Article  CAS  Google Scholar 

  29. Maury M, Murphy K, Kumar S, Mauerer A, Lee G. Spray-drying of proteins: effects of sorbitol and trehalose on aggregation and FT-IR amide I spectrum of an immunoglobulin G. Eur J Pharm Biopharm. 2005;59:251–61.

    Article  CAS  PubMed  Google Scholar 

  30. Bosquillon C, Lombry C, Préat V, Vanbever R. Influence of formulation excipients and physical characteristics of inhalation dry powders on their aerosolization performance. J Control Release. 2001;70:329–39.

    Article  CAS  PubMed  Google Scholar 

  31. Kibbe AH. Handbook of pharmaceutical excipients, London; 2000.

  32. Souilliac PO, Middaugh CR, Rytting JH. Investigation of protein/carbohydrate interactions in the dried state. 2. Diffuse reflectance FTIR studies. Int J Pharm. 2002;235:207–18.

    Article  Google Scholar 

  33. Tzannis ST, Prestrelski SJ. Activity-stability consideration of trypsinogen during spray drying: effect of sucrose. J Pharm Sci. 1999;88:351–9.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

This work was funded by the National S & T Major Project of China (Grant No: 2009ZX09310–002) and the National Science Foundation of PR China (No.30873165).

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Authors and Affiliations

  1. Key Laboratory of Drug Targeting and Novel Drug Delivery Systems West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, 610041, People’s Republic of China

    Yan-Zhen Li, Xun Sun, Tao Gong, Jie Liu, Jiao Zuo & Zhi-Rong Zhang

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  1. Yan-Zhen Li
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  2. Xun Sun
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  3. Tao Gong
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  4. Jie Liu
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  5. Jiao Zuo
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  6. Zhi-Rong Zhang
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Correspondence to Tao Gong or Zhi-Rong Zhang.

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Li, YZ., Sun, X., Gong, T. et al. Inhalable Microparticles as Carriers for Pulmonary Delivery of Thymopentin-Loaded Solid Lipid Nanoparticles. Pharm Res 27, 1977–1986 (2010). https://doi.org/10.1007/s11095-010-0201-z

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  • DOI: https://doi.org/10.1007/s11095-010-0201-z

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