Intranasal Surface-Modified Mosapride Citrate-Loaded Nanostructured Lipid Carriers (MOS-SMNLCs) for Treatment of Reflux Diseases: In vitro Optimization, Pharmacodynamics, and Pharmacokinetic Studies

Abstract

Gastroesophageal reflux disease (GERD) is an esophageal injury occurred when the stomach contents reflux abnormally into the esophagus. GERD complications include esophageal adenocarcinoma. Mosapride (MOS) is a safe prokinetic agent potentially used to treat GERD. Yet, its low solubility and bioavailability due to extensive first-pass metabolism limits its applications. This study aimed to formulate MOS nanostructured lipid carriers (MOS-NLCs) via the intranasal route to improve its bioavailability. Melt–emulsification low temperature–solidification technique using 23 full factorial design was adopted to formulate MOS-NLCs. Eight formulae were prepared and assessed in terms of entrapment efficiency (%EE), particle size, and in vitro release. Glycerol addition significantly reduced the particle sizes and improved %EE and %drug released. Surface modification using chitosan was applied. The optimized MOS surface-modified nanostructured lipid carriers (MOS-SMNLCs-F7)(stearic acid, 4% glycerol, 0.5% LuterolF127, 0.5% chitosan) showed low particle size 413.8 nm ± 11.46 nm and high %EE 90.19% ± 0.06% and a threefold increase in permeation of MOS with respect to the drug suspension. MOS-SMNLCs (F7) was also evaluated for its bioavailability compared with drug suspension and commercial product. Statistical analysis revealed a significant increase in gastric emptying rate to be 21.54 ± 1.88 contractions/min compared with10.02 ± 0.62 contractions/min and 8.9 ± 0.72 contractions/min for drug suspension and oral marketed product respectively. Pharmacokinetic studies showed 2.44-fold rise in bioavailability as compared to MOS suspension and 4.54-fold as compared to the oral marketed product. In vitro/in vivo studies proven to level A correlation between in vitro permeation through sheep nasal mucosa and in vivo absorption. Therefore, MOS-SMNLCs could be considered a step forward towards enhancing the clinical efficacy of Mosapride.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

References

  1. 1.

    Tack J, Camilleri M, Chang L, Chey WD, Galligan JJ, Lacy BE, et al. Systematic review: cardiovascular safety profile of 5-HT 4 agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35(7):745–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Ali AA, Sayed OM. Preparation and characterization of mosapride citrate inclusion complexes with natural and synthetic cyclodextrins. Pharm Dev Technol. 2013;18(5):1–9.

    Google Scholar 

  3. 3.

    Fry LC, Mönkemüller K, Malfertheiner P. Functional heartburn, nonerosive reflux disease, and reflux esophagitis are all distinct conditions—a debate: Con. Curr Treat Options Gastroenterol Curr Med Gr LLC ISSN [Internet]. 2007 [cited 2018 Feb 24];10:305–11. Available from: https://link.springer.com/content/pdf/10.1007%2Fs11938-007-0073-4.pdf

  4. 4.

    Ren L-H, Chen W-X, Qian L-J, Li S, Gu M, Shi R-H. Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis. World J Gastroenterol [Internet]. 2014 [cited 2018 Feb 24];20(9):2412–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24605040.

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    ElMeshad AN, El Hagrasy AS. Characterization and optimization of orodispersible mosapride film formulations. AAPS PharmSciTech [Internet]. 2011;12(4):1384–92. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3225544&tool=pmcentrez&rendertype=abstract

    CAS  Google Scholar 

  6. 6.

    Quigley EMM. JNM Journal of Neurogastroenterology and Motility Prokinetics in the Management of Functional Gastrointestinal Disorders. J Neurogastroenterol Motil [Internet]. 2015 [cited 2018 Feb 24];21(3):2093–879. Available from: www.jnmjournal.org

  7. 7.

    Sakashita M, Yamaguchi T, Miyazaki H, Sekine Y, Nomiyama T, Tanaka S, et al. Pharmacokinetics of the gastrokinetic agent mosapride citrate after single and multiple oral administrations in healthy subjects. Arzneimittelforschung. 1993;43(8):867–72.

    CAS  PubMed  Google Scholar 

  8. 8.

    Sayed OM, Ali AA, El-Nabarawi MA, Bary AA. Bioequivalence study of buccal formulations of two prokinetic agents versus the conventional oral tablets. Int J Drug Deliv. 2013;5(3):257–63.

    CAS  Google Scholar 

  9. 9.

    Emmanuel AV, Roy AJ, Nicholls TJ, Kamm MA. Prucalopride, a systemic enterokinetic, for the treatment of constipation. Aliment Pharmacol Ther. 2002;16(7):1347–56.

    CAS  PubMed  Google Scholar 

  10. 10.

    Kumar A, Pandey AN, Jain SK. Nasal-nanotechnology: revolution for efficient therapeutics delivery. Drug Deliv [Internet]. 2014;7544(October):1–13. Available from. https://doi.org/10.3109/10717544.2014.920431.

    CAS  Article  Google Scholar 

  11. 11.

    Ibrahim WM, AlOmrani AH, Yassin AEB. Novel sulpiride-loaded solid lipid nanoparticles with enhanced intestinal permeability. Int J Nanomedicine [Internet]. 2014;9:129–44. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3872145&tool=pmcentrez&rendertype=abstract

    Google Scholar 

  12. 12.

    Bitter C, Suter-Zimmermann K, Surber C. Nasal drug delivery in humans. Top Appl Mucosa. 2011;40(c):20–35.

    CAS  Google Scholar 

  13. 13.

    Attama A A, Momoh MA, Builders PF. Lipid nanoparticulate drug delivery systems: a revolution in dosage form design and development. Recent Adv Nov Drug Carr Syst [Internet]. 2012;107–40. Available from: doi: https://doi.org/10.5772/50486

    Google Scholar 

  14. 14.

    Eskandari S, Varshosaz J, Minaiyan M, Tabbakhian M. Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: in vivo pharmacodynamic studies using rat electroshock model. Int J Nanomedicine. 2011;6:363–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Liu D, Liu Z, Wang L, Zhang C, Zhang N. Nanostructured lipid carriers as novel carrier for parenteral delivery of docetaxel. Colloids Surfaces B Biointerfaces [Internet]. 2011;85(2):262–9. Available from. https://doi.org/10.1016/j.colsurfb.2011.02.038.

    CAS  Article  Google Scholar 

  16. 16.

    Gaba B, Fazil M, Khan S, Ali A, Baboota S, Ali J. Nanostructured lipid carrier system for topical delivery of terbinafine hydrochloride. Bull Fac Pharm Cairo Univ [Internet]. 2015;53(2):147–59. Available from. https://doi.org/10.1016/j.bfopcu.2015.10.001.

    Article  Google Scholar 

  17. 17.

    Li B, Ge Z-Q. Nanostructured lipid carriers improve skin permeation and chemical stability of idebenone. AAPS PharmSciTech [Internet]. 2012 [cited 2018 mar 16];13(1):276–83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22234598.

  18. 18.

    Ugwoke MI, Agu RU, Verbeke N, Kinget R. Nasal mucoadhesive drug delivery: background, applications, trends and future perspectives. Adv Drug Deliv Rev. 2005;57(11):1640–65.

    CAS  PubMed  Google Scholar 

  19. 19.

    Hao J, Fang X, Zhou Y, Wang J, Guo F, Li F, et al. Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design. Int J Nanomedicine. 2011;6:683–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Luo Q, Zhao J, Zhang X, Pan W. Nanostructured lipid carrier (NLC) coated with Chitosan Oligosaccharides and its potential use in ocular drug delivery system. Int J Pharm [Internet]. 2011;403(1–2):185–91. Available from: https://doi.org/10.1016/j.ijpharm.2010.10.013

    CAS  PubMed  Google Scholar 

  21. 21.

    Gartziandia O, Herran E, Pedraz JL, Carro E, Igartua M, Hernandez RM. Chitosan coated nanostructured lipid carriers for brain delivery of proteins by intranasal administration. Colloids Surfaces B Biointerfaces [Internet]. 2015;134:304–13. Available from. https://doi.org/10.1016/j.colsurfb.2015.06.054.

    CAS  Article  Google Scholar 

  22. 22.

    Cui F, Qian F, Yin C. Preparation and characterization of mucoadhesive polymer-coated nanoparticles. Int J Pharm. 2006;316(1–2):154–61.

    CAS  PubMed  Google Scholar 

  23. 23.

    Shinde RL, Bharkad GP, Devarajan PV. Intranasal microemulsion for targeted nose to brain delivery in neurocysticercosis: role of docosahexaenoic acid. Eur J Pharm Biopharm [Internet]. 2015;96:363–79. Available from. https://doi.org/10.1016/j.ejpb.2015.08.008.

    CAS  Article  Google Scholar 

  24. 24.

    Joshi AS, Patel HS, Belgamwar VS, Agrawal A, Tekade AR. Solid lipid nanoparticles of ondansetron HCl for intranasal delivery: development, optimization and evaluation. J Mater Sci Mater Med. 2012;23(9):2163–75.

    CAS  PubMed  Google Scholar 

  25. 25.

    Morsi NM, Ghada A, Abdelbary MAA. Article|Preparation and physicochemical characterization of mosapride citrate pharmacosomes|Inventi Journals Pvt.Ltd. Inven Impact NDDS, 2014(4)233–237 [Internet]. 2014;4:233–7. Available from: http://inventi.in/journal/article/impact/2/11197/ndds/pi

  26. 26.

    Wang Y, Zhang H, Hao J, Li B, Li M, Xiuwen W. Lung cancer combination therapy: co-delivery of paclitaxel and doxorubicin by nanostructured lipid carriers for synergistic effect. Drug Deliv [Internet]. 2016;23(4):1398–403. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26079530

    CAS  Google Scholar 

  27. 27.

    Sharma D, Maheshwari D, Philip G, Rana R, Bhatia S, Singh M, et al. Formulation and optimization of polymeric nanoparticles for intranasal delivery of lorazepam using Box-Behnken design:in vitro and in vivo evaluation. Biomed Res Int. 2014;2014:1–14.

    Google Scholar 

  28. 28.

    Hosny KM, Hassan AH. Intranasal in situ gel loaded with saquinavir mesylate nanosized microemulsion: preparation, characterization, and in vivo evaluation. Int J Pharm [Internet]. 2014;475(1–2):191–7. Available from. https://doi.org/10.1016/j.ijpharm.2014.08.064.

    CAS  Article  Google Scholar 

  29. 29.

    Higuchi T. Mechanism of sustained-action medication. theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci [Internet]. 1963 [cited 2017 Jul 27];52:1145–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14088963.

    CAS  PubMed  Google Scholar 

  30. 30.

    Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm [Internet]. 1983 May [cited 2017 Jul 27];15(1):25–35. Available from: http://linkinghub.elsevier.com/retrieve/pii/0378517383900649

    CAS  Google Scholar 

  31. 31.

    Hassan EE, Gallo JM. A simple rheological method for the in vitro assessment of mucin-polymer bioadhesive bond strength. Vol. 7, Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists. 1990. p. 491–5.

  32. 32.

    Oechsner M, Keipert S. Polyacrylic acid/polyvinylpyrrolidone bipolymeric systems. I. Rheological and mucoadhesive properties of formulations potentially useful for the treatment of dry-eye-syndrome. Eur J Pharm Biopharm. 1999;47(2):113–8.

    CAS  PubMed  Google Scholar 

  33. 33.

    Mahajan HS, Gattani SG. Gellan gum based microparticles of metoclopromide hydrochloride for intranasal delivery: development and evaluation. Chem Pharm Bull (Tokyo). 2009;57(4):388–92.

    CAS  Google Scholar 

  34. 34.

    Tung IC. Rheological behavior of poloxamer 407 aqueous solutions during sol-gel and dehydration processes. Int J Pharm. 1994;107(2):85–90.

    CAS  Google Scholar 

  35. 35.

    Zaki NM, Awad GA, Mortada ND, Abd ElHady SS. Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. Eur J Pharm Sci. 2007;32(4–5):296–307.

    CAS  PubMed  Google Scholar 

  36. 36.

    Soliman SM, NS Abdel Malak, ON El-Gazayerly Nabaweya A. Novel non-ionic surfactant proniosomes for transdermal delivery of lacidipine: Optimization using 23 factorial design and in vivo evaluation in rabbits. 2015.

  37. 37.

    Malak NSA. Formulation of coated polymer reinforced gellan gum beads of Tizanidine HCL using fractional factorial design. Int J Pharm Pharm Sci. 2012;4(SUPPL. 5):369–79.

    Google Scholar 

  38. 38.

    Yassin AEB, Khalid Anwer MD, Mowafy HA, El-Bagory IM, Bayomi MA, Alsarra IA. Optimization of 5-fluorouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer. Int J Med Sci. 2010;7(6):398–408.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Gavini E, Rassu G, Sanna V, Cossu M, Giunchedi P. Mucoadhesive microspheres for nasal administration of an antiemetic drug, metoclopramide: in-vitro/ex-vivo studies. J Pharm Pharmacol [Internet]. 2005;57(3):287–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15807983

    CAS  Google Scholar 

  40. 40.

    Üstündağ Okur N, Apaydın Ş, Karabay Yavaşoğlu NÜ, Yavaşoğlu A, Karasulu HY. Evaluation of skin permeation and anti-inflammatory and analgesic effects of new naproxen microemulsion formulations. Int J Pharm [Internet]. 2011 [cited 2018 Mar 7];416(1):136–44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21723930.

  41. 41.

    Center for Drug Evaluation and Research. Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. US Dep Heal Hum Serv [Internet]. 2005 [cited 2018 Jun 9];(July):1–27. Available from: http://www.fda.gov/cder/guidance/index.htm

  42. 42.

    Alsarra IA, Hamed AY, Alanazi FK. Acyclovir liposomes for intranasal systemic delivery: development and pharmacokinetics evaluation. Drug Deliv. 2008;15(5):313–21.

    CAS  PubMed  Google Scholar 

  43. 43.

    Gomaa NA, Ibrahim HMM, Ishii M, Nassif MN, El-khodery SA. Dose-dependent effects of mosapride citrate on duodenal and cecal motility in donkeys (Equus asinus). Int J Vet Sci Med [Internet]. 2013;1(2):51–6. Available from. https://doi.org/10.1016/j.ijvsm.2013.09.001.

    Article  Google Scholar 

  44. 44.

    Mitchell CF, Malone ED, Sage AM, Niksich K. Evaluation of gastrointestinal activity patterns in healthy horses using B mode and Doppler ultrasonography. Can Vet J = La Rev Vet Can [Internet]. 2005 [cited 2018 mar 17];46(2):134–40. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15825515.

  45. 45.

    Zhou D, Qiu Y. Dissolution and in vitro - in vivo correlation. J Valid Technol. 2010;Winter:57–70.

  46. 46.

    Tiwari R, Pathak K. Nanostructured lipid carrier versus solid lipid nanoparticles of simvastatin: comparative analysis of characteristics, pharmacokinetics and tissue uptake. Int J Pharm [Internet]. 2011;415(1–2):232–43. Available from. https://doi.org/10.1016/j.ijpharm.2011.05.044.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Hedaya MA. Basic pharmacokinetics, Second Edition. Pharm Press www.pharmpress.com. 2012;105–26.

  48. 48.

    Shah B, Khunt D, Bhatt H, Misra M, Padh H. Intranasal delivery of venlafaxine loaded nanostructured lipid carrier: risk assessment and QbD based optimization. J Drug Deliv Sci Technol. 2016;33(March 2016):37–50.

    CAS  Google Scholar 

  49. 49.

    Elmowafy M, Ibrahim HM, Ahmed MA, Shalaby K, Salama A, Hefesha H. Atorvastatin-loaded nanostructured lipid carriers (NLCs): strategy to overcome oral delivery drawbacks. Drug Deliv [Internet]. 2017;24(1):932–41. Available from. https://doi.org/10.1080/10717544.2017.1337823.

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Sanad RA, Malak NSA, El-Bayoomy TS, Badawi AA. Preparation and characterization of oxybenzone-loaded solid lipid nanoparticles (SLNs) with enhanced safety and sunscreening efficacy: SPF and UVA-PF. Drug Discov Ther. 2010;4(6):472–83.

    CAS  PubMed  Google Scholar 

  51. 51.

    RC Rowe, Paul J, Sheskey, SCO. Handbook of pharmaceutical excipients 5th edition.pdf. Raymond C Rowe, Paul J Sheskey SCO, editor. London. Chicago: Pharmaceutical Press and American Pharmacists Association 2006; 2006.

  52. 52.

    Morsi NM, Ghorab DM, Badie HA. Brain targeted solid lipid nanoparticles for brain ischemia: preparation and in vitro characterization. Pharm Dev Technol. 2013;18(3):736–44.

    CAS  PubMed  Google Scholar 

  53. 53.

    Martins S, Tho I, Ferreira DC, Souto EB, Brandl M. Physicochemical properties of lipid nanoparticles: effect of lipid and surfactant composition. Drug Dev Ind Pharm. 2011;37(7):815–24.

    CAS  PubMed  Google Scholar 

  54. 54.

    Khalil RM, El-bary AA, Kassem MA, Ghorab MM, Basha M. Influence of formulation parameters on the physicochemical properties of meloxicam-loaded solid lipid nanoparticles. Egyptian Pharm J 2013;63–72.

  55. 55.

    Paliwal R, Rai S, Vaidya B, Khatri K, Goyal AK, Mishra N, et al. Effect of lipid core material on characteristics of solid lipid nanoparticles designed for oral lymphatic delivery. Nanomedicine Nanotechnology Biol Med [Internet]. 2009;5(2):184–91. Available from. https://doi.org/10.1016/j.nano.2008.08.003.

    CAS  Article  Google Scholar 

  56. 56.

    Vivek K, Reddy H, Murthy RSR. Investigations of the effect of the lipid matrix on drug entrapment, in vitro release, and physical stability of olanzapine-loaded solid lipid nanoparticles. AAPS PharmSciTech. 2007;8(4):E83.

    CAS  PubMed  Google Scholar 

  57. 57.

    Mitrea E, Lacatusu I, Badea N, Ott C, Oprea O, Meghea A. New approach to prepare willow bark extract–lipid based nanosystems with enhanced antioxidant activity. J Nanosci Nanotechnol [Internet]. 2015;15(6):4080–9. Available from: http://openurl.ingenta.com/content/xref?genre=article&issn=1533-4880&volume=15&issue=6&spage=4080

    CAS  Google Scholar 

  58. 58.

    Kumar VV, Chandrasekar D, Ramakrishna S, Kishan V, Rao YM, Diwan PV. Development and evaluation of nitrendipine loaded solid lipid nanoparticles: influence of wax and glyceride lipids on plasma pharmacokinetics. Int J Pharm. 2007;335(1–2):167–75.

    CAS  PubMed  Google Scholar 

  59. 59.

    López-Garcia R, Ganem-Rondero A. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): occlusive effect and penetration enhancement ability. J Cosmet Dermatological Sci Appl. 2015;(June):62–72.

    Google Scholar 

  60. 60.

    Randhawa JK, Sacheen K. RSC Advances Solid lipid nanoparticles of stearic acid for the drug delivery of paliperidone. RSC Adv. 2015;5:68743–50.

    Google Scholar 

  61. 61.

    Tiyaboonchai W, Tungpradit W, Plianbangchang P. Formulation and characterization of curcuminoids loaded solid lipid nanoparticles. Int J Pharm. 2007;337(1–2):299–306.

    CAS  PubMed  Google Scholar 

  62. 62.

    Zhao Y, Brown MB, Jones SA. The effects of particle properties on nanoparticle drug retention and release in dynamic minoxidil foams. Int J Pharm. 2010;383(1–2):277–84.

    CAS  PubMed  Google Scholar 

  63. 63.

    Ghosh I, Bose S, Vippagunta R, Harmon F. Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth. Int J Pharm [Internet]. 2011 May [cited 2017 Sep 11];409(1–2):260–8. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0378517311001864

    CAS  PubMed  Google Scholar 

  64. 64.

    Mohammadi M, Pezeshki A, Mesgari Abbasi M, Ghanbarzadeh B, Hamishehkar H. Vitamin D3-loaded nanostructured lipid carriers as a potential approach for fortifying food beverages; in vitro and in vivo evaluation. Adv Pharm Bull [Internet]. 2017 [cited 2017 Sep 11];7(1):61–71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28507938.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Pardeshi CV, Belgamwar VS, Tekade AR, Surana SJ. Novel surface modified polymer-lipid hybrid nanoparticles as intranasal carriers for ropinirole hydrochloride: in vitro, ex vivo and in vivo pharmacodynamic evaluation. J Mater Sci Mater Med. 2013;24(9):2101–15.

    CAS  PubMed  Google Scholar 

  66. 66.

    Li Q, Cai T, Huang Y, Xia X, Cole S, Cai Y. A review of the structure, preparation, and application of NLCs, PNPs, and PLNs. Nanomaterials [Internet]. 2017;7(6):122. Available from: http://www.mdpi.com/2079-4991/7/6/122

    Google Scholar 

  67. 67.

    Patel NR, Patel DA, Bharadia PD, Pandya V, Modi D. Microsphere as a novel drug delivery. Int J Pharm Life Sci. 2011;2(8):992–7.

    CAS  Google Scholar 

  68. 68.

    Chronopoulou L, Massimi M, Giardi MF, Cametti C, Devirgiliis LC, Dentini M, et al. Chitosan-coated PLGA nanoparticles: a sustained drug release strategy for cell cultures. Colloids Surfaces B Biointerfaces [Internet]. 2013;103:310–7. Available from. https://doi.org/10.1016/j.colsurfb.2012.10.063.

    CAS  Article  Google Scholar 

  69. 69.

    Savale S, Mahajan H. www.ajbr.in Nose to brain: a versatile mode of drug delivery system. Asian J Biomater Res [Internet]. 2017 [cited 2017 Jul 9];3(16):16–38. Available from: http://ajbr.in/uploaded/p70.pdf

  70. 70.

    Shete AS, Yadav A V, Murthy SM. Chitosan and chitosan chlorhydrate based various approaches for enhancement of dissolution rate of carvedilol. Daru [Internet]. 2012 [cited 2018 May 25];20(1):93. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23351907.

  71. 71.

    Portero A,Remuñán-López C, JL Vila-Jato. Effect of chitosan and chitosan glutamate enhancing the dissolution properties of the poorly water soluble drug nifedipine. Int J Pharm. 1998;175.

    CAS  Google Scholar 

  72. 72.

    Abdelbary G. Ocular ciprofloxacin hydrochloride mucoadhesive chitosan-coated liposomes. Pharm Dev Technol. 2011;16(1):44–56.

    CAS  PubMed  Google Scholar 

  73. 73.

    Seyfoddin A., Sherwin T., Patel D., McGhee C., Rupenthal TJ and Taylor JA, Al-Kassas R. Ex vivo and in vivo evaluation of chitosan coated nanostructured lipid carriers for ocular delivery of acyclovir. 2016. p. 13.

  74. 74.

    Gulati N, Nagaich U, Saraf SA. Intranasal delivery of chitosan nanoparticles for migraine therapy. Sci Pharm. 2013;81(3):843–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Choi K-O, Choe J, Suh S, Ko S. Positively charged nanostructured lipid carriers and their effect on the dissolution of poorly soluble drugs. Molecules [Internet]. 2016;21(5):672. Available from: http://www.mdpi.com/1420-3049/21/5/672

    Google Scholar 

  76. 76.

    Chen J, Huang GD, Tan SR, Guo J, Su ZQ. The preparation of Capsaicin-Chitosan Microspheres (CCMS) enteric coated tablets. Int J Mol Sci. 2013;14(12):24305–19.

    PubMed  PubMed Central  Google Scholar 

  77. 77.

    Nokhodchi A, Raja S, Patel P, Asare-Addo K. The role of oral controlled release matrix tablets in drug delivery systems. BioImpacts. 2012;2(4):175–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Eshel-Green T, Bianco-Peled H. Mucoadhesive acrylated block copolymers micelles for the delivery of hydrophobic drugs. Colloids Surfaces B Biointerfaces [Internet]. 2016;139:42–51. Available from. https://doi.org/10.1016/j.colsurfb.2015.11.044.

    CAS  Article  Google Scholar 

  79. 79.

    Illing A, Unruh T. Investigation on the flow behavior of dispersions of solid triglyceride nanoparticles. Int J Pharm. 2004;284(1–2):123–31.

    CAS  PubMed  Google Scholar 

  80. 80.

    Sharma M, Gupta N, Gupta S. Implications of designing clarithromycin loaded solid lipid nanoparticles on their pharmacokinetics, antibacterial activity and safety. RSC Adv [Internet]. 2016;6:76621–31. Available from. https://doi.org/10.1039/C6RA12841F.

    CAS  Article  Google Scholar 

  81. 81.

    Fang C-L, Al-Suwayeh SA, Fang J-Y. Nanostructured lipid carriers (NLCs) for drug delivery and targeting. Recent Pat Nanotechnol [Internet]. 2013;7(1):41–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22946628

    CAS  Google Scholar 

  82. 82.

    Ebrahimi HA, Javadzadeh Y, Hamidi M, Jalali MB. Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles. Daru [Internet]. 2015;23(1):46. Available from. https://doi.org/10.1186/s40199-015-0128-3.

    CAS  Article  Google Scholar 

  83. 83.

    Müller RH, Runge SA, Ravelli V, Thünemann AF, Mehnert W, Souto EB. Cyclosporine-loaded solid lipid nanoparticles (SLN??): drug-lipid physicochemical interactions and characterization of drug incorporation. Eur J Pharm Biopharm. 2008;68(3):535–44.

    PubMed  Google Scholar 

  84. 84.

    General Chapters_ _401_ Fats and fixed oils.pdf [Internet]. [cited 2018 Jul 30]. Available from: http://www.pharmacopeia.cn/v29240/usp29nf24s0_c401.html

  85. 85.

    Araújo F, Shrestha N, Shahbazi MA, Fonte P, Mäkilä EM, Salonen JJ, et al. The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium. Biomaterials. 2014;35(33):9199–207.

    PubMed  Google Scholar 

  86. 86.

    Jambhekar SS, Breen PJ. Basic pharmacokinetics. Taylor & Francis/CRC Press; 2009.p. 425

  87. 87.

    Hernandez RM, Gascon AR, Calvo MB, Caramella C, Conte U, Dominguez-Gil A, et al. Influence of route of administration and dosage form in the pharmacokinetics and bioavailability of salbutamol. Eur J Drug Metab Pharmacokinet [Internet]. 1997;22(2):145–50. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9248783

    CAS  Google Scholar 

  88. 88.

    Cheng C, Wu PC, Lee HY, Hsu KY. Development and validation of an in vitroein vivo correlation (IVIVC) model for propranolol hydrochloride extended-release matrix formulations. J Food Drug Anal [Internet]. 2014;22(2):257–63. Available from. https://doi.org/10.1016/j.jfda.2013.09.016.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported by National Organization for Drug Control and Research, Egypt, and Faculty of Pharmacy, Cairo University, Egypt. The ultrasonography examination was conducted with the help of Dr. Mohamed El-said Associate lecturer, Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Reham Waheed Hammad.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Disclaimer

The authors only are responsible for the content and writing of the article.

Electronic Supplementary Material

ESM 1

(AVI 8447 kb)

ESM 2

(AVI 3320 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hammad, R.W., Sanad, R.A.B., Abdelmalk, N.S. et al. Intranasal Surface-Modified Mosapride Citrate-Loaded Nanostructured Lipid Carriers (MOS-SMNLCs) for Treatment of Reflux Diseases: In vitro Optimization, Pharmacodynamics, and Pharmacokinetic Studies. AAPS PharmSciTech 19, 3791–3808 (2018). https://doi.org/10.1208/s12249-018-1142-9

Download citation

KEY WORDS

  • Mosapride citrate
  • surface-modified nanostructured lipid carriers
  • intranasal administration
  • in vitro permeation
  • gastric emptying rate