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Paliperidone-Loaded Nanolipomer System for Sustained Delivery and Enhanced Intestinal Permeation: Superiority to Polymeric and Solid Lipid Nanoparticles

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Abstract

Paliperidone (PPD) is the most recent second-generation atypical antipsychotic approved for the treatment of schizophrenia. An immediate release dose causes extrapyramidal side effects. In this work, a novel nanolipomer carrier system for PPD with enhanced intestinal permeability and sustained release properties has been developed and optimized. PPD was successfully encapsulated into a lipomer consisting of a specific combination of biocompatible materials including poly-ε-caprolactone as a polymeric core, Lipoid S75, and Gelucire® 50/13 as a lipid shell and polyvinyl alcohol as a stabilizing agent. The lipomer system was characterized by dynamic light scattering, TEM, DSC, and FTIR. An optimized lipomer formulation possessed a particle size of 168 nm, PDI of 0.2, zeta potential of −23 mV and an encapsulation efficiency of 87.27% ± 0.098. Stability in simulated gastrointestinal fluids investigated in terms of particle size, zeta potential, and encapsulation efficiency measurements ensured the integrity of the nanoparticles upon oral administration. PPD-loaded nanolipomers demonstrated a superior sustained release behavior up to 24 h and better ex vivo intestinal permeation for PPD compared to the corresponding polymeric and solid lipid nanoparticles and drug suspension. The in vitro hemocompatibility test on red blood cells revealed no hemolytic effect of PPD-loaded lipomers which reflects its safety. The elaborated nanohybrid carrier system represents a promising candidate for enhancing the absorption of PPD providing a 2.6-fold increase in the intestinal permeation flux compared to the drug suspension while maintaining a sustained release behavior. It is a convenient alternative to the commercially available dosage form of PPD.

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REFERENCES

  1. Yang LP. Oral paliperidone. CNS Drugs. 2011;25(6):523–38.

    Article  CAS  PubMed  Google Scholar 

  2. Kumar S, Randhawa JK. Preparation and characterization of paliperidone loaded solid lipid nanoparticles. Colloids Surf, B. 2013;102:562–8.

    Article  CAS  Google Scholar 

  3. Canuso CM, Youssef EA, Bossie CA, Turkoz I, Schreiner A, Simpson GM. Paliperidone extended-release tablets in schizophrenia patients previously treated with risperidone. Int Clin Psychopharmacol. 2008;23(4):209–15.

    Article  PubMed  Google Scholar 

  4. Wang D, Zhao J, Liu X, Sun F, Zhou Y, Teng L, et al. Parenteral thermo-sensitive organogel for schizophrenia therapy, in vitro and in vivo evaluation. Eur J Pharm Sci. 2014;60:40–8.

    Article  CAS  PubMed  Google Scholar 

  5. Patel RB, Patel MR, Bhatt KK, Patel BG. Paliperidone-loaded mucoadhesive microemulsion in treatment of schizophrenia: formulation consideration. J Pharm Innov. 2013;8(3):195–204.

    Article  Google Scholar 

  6. Kanuganti S, Jukanti R, Veerareddy PR, Bandari S. Paliperidone-loaded self-emulsifying drug delivery systems (SEDDS) for improved oral delivery. J Dispersion Sci Technol. 2012;33(4):506–15.

    Article  CAS  Google Scholar 

  7. Medina C, Santos‐Martinez M, Radomski A, Corrigan O, Radomski M. Nanoparticles: pharmacological and toxicological significance. Br J Pharmacol. 2007;150(5):552–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hadinoto K, Sundaresan A, Cheow WS. Lipid-polymer hybrid nanoparticles as a new generation therapeutic delivery platform: a review. Eur J Pharm Biopharm. 2013;85(3):427–43.

    Article  CAS  PubMed  Google Scholar 

  9. Raemdonck K, Braeckmans K, Demeester J, De Smedt SC. Merging the best of both worlds: hybrid lipid-enveloped matrix nanocomposites in drug delivery. Chem Soc Rev. 2014;43(1):444–72.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang LI, Zhang L. Lipid-polymer hybrid nanoparticles: synthesis, characterization and applications. Nano LIFE. 2010;01(01n02):163–73.

    Article  CAS  Google Scholar 

  11. Rao S, Prestidge CA. Polymer-lipid hybrid systems: merging the benefits of polymeric and lipid-based nanocarriers to improve oral drug delivery. Expert Opin Drug Deliv. 2016;13(5):691–707.

    Article  CAS  PubMed  Google Scholar 

  12. Hallan SS, Kaur P, Kaur V, Mishra N, Vaidya B. Lipid polymer hybrid as emerging tool in nanocarriers for oral drug delivery. Artificial Cells, Nanomedicine, and Biotechnology. 2015:1–16.

  13. Belletti D, Riva G, Tosi G, Forni F, Barozzi P, Luppi M, et al. Novel polymeric/lipidic hybrid systems (PLHs) for effective cidofovir delivery: preparation, characterization and comparative in vitro study with polymeric particles and liposomes. Int J Pharm. 2011;413(1–2):220–8.

    Article  CAS  PubMed  Google Scholar 

  14. Benival DM, Devarajan PV. Lipomer of doxorubicin hydrochloride for enhanced oral bioavailability. Int J Pharm. 2012;423(2):554–61.

    Article  CAS  PubMed  Google Scholar 

  15. Cheow WS, Hadinoto K. Factors affecting drug encapsulation and stability of lipid-polymer hybrid nanoparticles. Colloids Surf, B. 2011;85(2):214–20.

    Article  CAS  Google Scholar 

  16. Cheow WS, Chang MW, Hadinoto K. The roles of lipid in anti-biofilm efficacy of lipid-polymer hybrid nanoparticles encapsulating antibiotics. Colloids Surf A:Physicochem Eng Asp. 2011;389(1–3):158–65.

    Article  CAS  Google Scholar 

  17. Jain S, Valvi PU, Swarnakar NK, Thanki K. Gelatin coated hybrid lipid nanoparticles for oral delivery of amphotericin B. Mol Pharmaceutics. 2012;9(9):2542–53.

    Article  CAS  Google Scholar 

  18. Peter Christoper GV, Vijaya Raghavan C, Siddharth K, Siva Selva Kumar M, Hari Prasad R. Formulation and optimization of coated PLGA - zidovudine nanoparticles using factorial design and in vitro in vivo evaluations to determine brain targeting efficiency. Saudi Pharm J. 2014;22(2):133–40.

    Article  CAS  PubMed  Google Scholar 

  19. Prego C, Torres D, Fernandez-Megia E, Novoa-Carballal R, Quiñoá E, Alonso M. Chitosan-PEG nanocapsules as new carriers for oral peptide delivery: effect of chitosan pegylation degree. J Controlled Release. 2006;111(3):299–308.

    Article  CAS  Google Scholar 

  20. Freag MS, Elnaggar YSR, Abdallah OY. Development of novel polymer-stabilized diosmin nanosuspensions: in vitro appraisal and ex vivo permeation. Int J Pharm. 2013;454(1):462–71.

    Article  CAS  PubMed  Google Scholar 

  21. Cattani VB, Fiel LA, Jäger A, Jäger E, Colomé LM, Uchoa F, et al. Lipid-core nanocapsules restrained the indomethacin ethyl ester hydrolysis in the gastrointestinal lumen and wall acting as mucoadhesive reservoirs. Eur J Pharm Sci. 2010;39(1):116–24.

    Article  PubMed  Google Scholar 

  22. Khurana S, Jain N, Bedi P. Development and characterization of a novel controlled release drug delivery system based on nanostructured lipid carriers gel for meloxicam. Life Sci. 2013;93(21):763–72.

    Article  CAS  PubMed  Google Scholar 

  23. Fang RH, Aryal S, Hu C-MJ, Zhang L. Quick synthesis of lipid−polymer hybrid nanoparticles with low polydispersity using a single-step sonication method. Langmuir. 2010;26(22):16958–62.

    Article  CAS  PubMed  Google Scholar 

  24. Sinha V, Bansal K, Kaushik R, Kumria R, Trehan A. Poly-ϵ-caprolactone microspheres and nanospheres: an overview. Int J Pharm. 2004;278(1):1–23.

    Article  CAS  PubMed  Google Scholar 

  25. Jürgens K, Müller B. A new formulation concept for drugs with poor water solubility for parenteral application. Die Pharmazie-An Int J Pharm Sci. 2005;60(9):665–70.

    Google Scholar 

  26. Valencia PM, Basto PA, Zhang L, Rhee M, Langer R, Farokhzad OC, et al. Single-step assembly of homogenous lipid−polymeric and lipid−quantum dot nanoparticles enabled by microfluidic rapid mixing. ACS Nano. 2010;4(3):1671–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharmaceutics. 2008;5(4):505–15.

    Article  CAS  Google Scholar 

  28. Polymeric nanomaterials. In: Kumar CSSR, editor. Nanomaterials for the Life Sciences: WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim; 2011.

  29. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm. 2010;67:217–23.

    CAS  PubMed  Google Scholar 

  30. Abdelwahed W, Degobert G, Fessi H. A pilot study of freeze drying of poly (epsilon-caprolactone) nanocapsules stabilized by poly (vinyl alcohol): formulation and process optimization. Int J Pharm. 2006;309(1):178–88.

    Article  CAS  PubMed  Google Scholar 

  31. Leimann FV, Biz MH, Kaufmann KC, Maia WJ, Honçalves OH, Cardozo Filho L, et al. Characterization of progesterone loaded biodegradable blend polymeric nanoparticles. Ciência Rural. 2015;45(11):2082–8.

    Article  Google Scholar 

  32. Reis EFD, Campos FS, Lage AP, Leite RC, Heneine LG, Vasconcelos WL, et al. Synthesis and characterization of poly (vinyl alcohol) hydrogels and hybrids for rMPB70 protein adsorption. Mater Res. 2006;9(2):185–91.

    Article  Google Scholar 

  33. Passerini N, Perissutti B, Moneghini M, Voinovich D, Albertini B, Cavallari C, et al. Characterization of carbamazepine-Gelucire 50/13 microparticles prepared by a spray‐congealing process using ultrasounds. J Pharm Sci. 2002;91(3):699–707.

    Article  CAS  PubMed  Google Scholar 

  34. Desai PP, Date AA, Patravale VB. Overcoming poor oral bioavailability using nanoparticle formulations—opportunities and limitations. Drug Discov Today: Technol. 2012;9(2):e87–95.

    Article  CAS  Google Scholar 

  35. Balimane PV, Chong S, Morrison RA. Current methodologies used for evaluation of intestinal permeability and absorption. J Pharmacol Toxicol Methods. 2000;44(1):301–12.

    Article  CAS  PubMed  Google Scholar 

  36. Mathiowitz E, Jacob JS, Jong YS, Carino GP, Chickering DE, Chaturvedi P, et al. Biologically erodable microspheres as potential oral drug delivery systems. Nature. 1997;386(6623):410–4.

    Article  CAS  PubMed  Google Scholar 

  37. Aji Alex MR, Chacko AJ, Jose S, Souto EB. Lopinavir loaded solid lipid nanoparticles (SLN) for intestinal lymphatic targeting. Eur J Pharm Sci. 2011;42(1–2):11–8.

    Article  CAS  PubMed  Google Scholar 

  38. Chen C, Cheng YC, Yu CH, Chan SW, Cheung MK, Yu PH. In vitro cytotoxicity, hemolysis assay, and biodegradation behavior of biodegradable poly (3‐hydroxybutyrate)-poly (ethylene glycol)-poly (3‐hydroxybutyrate) nanoparticles as potential drug carriers. J Biomed Mater Res, Part A. 2008;87(2):290–8.

    Article  Google Scholar 

  39. Nafee N, Schneider M, Schaefer UF, Lehr C-M. Relevance of the colloidal stability of chitosan/PLGA nanoparticles on their cytotoxicity profile. Int J Pharm. 2009;381(2):130–9.

    Article  CAS  PubMed  Google Scholar 

  40. Bender EA, Adorne MD, Colomé LM, Abdalla DS, Guterres SS, Pohlmann AR. Hemocompatibility of poly (ɛ-caprolactone) lipid-core nanocapsules stabilized with polysorbate 80-lecithin and uncoated or coated with chitosan. Int J Pharm. 2012;426(1):271–9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Gattefossé Company for providing the lipid used in this study and Lipoid Company for providing Lipoid S75.

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Authors and Affiliations

  1. Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, 1 Midan Alkhartoom square, Alazarita, Alexandria, Egypt

    Hala Mahmoud Helal, Sana Mohamed Mortada & Marwa Ahmed Sallam

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  1. Hala Mahmoud Helal
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  2. Sana Mohamed Mortada
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  3. Marwa Ahmed Sallam
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Correspondence to Marwa Ahmed Sallam.

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Helal, H.M., Mortada, S.M. & Sallam, M.A. Paliperidone-Loaded Nanolipomer System for Sustained Delivery and Enhanced Intestinal Permeation: Superiority to Polymeric and Solid Lipid Nanoparticles. AAPS PharmSciTech 18, 1946–1959 (2017). https://doi.org/10.1208/s12249-016-0657-1

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