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Alternative Applications for Drug Delivery: Nasal and Pulmonary Routes

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Abstract

For treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins and others. In this chapter, nasal and pulmonary drug delivery mechanisms and some of the relevant drug delivery formulations are evaluated

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References

  1. Wermeling DP, Miller JL. Intranasal Drug Delivery. In: Modified Release Drug Delivery Technology. J Swarbrick (Ex. Ed.), MJ Rathbone, I Hadgraft, MS Roberts (Eds), Marcell Dekker Inc, NewYork-Basel, pp: 727–748 (2003).

    Google Scholar 

  2. Ozer AY. Importance of Intranasal Route for Application of Drugs and Nasal Drug Delivery Systems. Pharmacia-JTPA, 30, 136–147 (1990).

    Google Scholar 

  3. Turker S, Onur E, Ozer AY. Nasal Route and Drug Delivery Systems. Pharm World Sci, 26, 137–142 (2004).

    Article  PubMed  Google Scholar 

  4. Chien YW, Su KSE, Chang SF. Anatomy and Physiology of Nose. In: Nasal Systemic Drug Delivery. YW Chien, KSE Su, SF Chang (Eds), Marcel Dekker Inc., New York, 1–26 (1989).

    Google Scholar 

  5. Celebi N. Nasal and Pulmonary Systems. In: Controlled Drug Delivery Systems. AZ Gursoy (Ed), Elma Bilgisayar Basim, Istanbul, pp: 217–237 (2002).

    Google Scholar 

  6. Sarkar MA. Drug Metabolism in the Nasal Mucosa. Pharm. Res. 9, 1–9 (1992).

    Article  PubMed  CAS  Google Scholar 

  7. Brime B, Ballesteros MP, Frutos P. Preparation and In Vitro Characterization of Gelatin Microspheres Containing Levodopa for Nasal Administration. J. Microencap, 6, 777–784 (2000).

    Article  Google Scholar 

  8. Mygind N, Dahl R. Anatomy, Physiology and Function of the Nasal Cavities in Health and Disease. Adv. Drug Del. Rev. 29, 3–12 (1998).

    Article  CAS  Google Scholar 

  9. Marttin E, Verhoef JC, Cullander C, Romeijn SG, Nagelkerke JF, Merkus FHM. Confocal Laser Scanning Microscopic Visualization of the Transport of Dextran after Nasal Administration to Rats: Effects of Absorption Enhancers. Pharm.Res. 14, 631–637 (1997).

    Article  PubMed  CAS  Google Scholar 

  10. Chien YW, Chang S. Intranasal Drug Delivery for Systemic Medication. Crit. Rev. Ther. Drug Carr. Syst. 4, 67–194 (1987).

    CAS  Google Scholar 

  11. Hehar SS, Mason JDT, Stephen AB, Washington N, Jones NS, Jackson SJ, Bush D. Twenty Four Hour Ambulatory Nasal pH Monitoring. Clin. Otorynolaryngol, 24, 24–25 (1999).

    Article  CAS  Google Scholar 

  12. Schipper NGM, Verhoef JC, Merkus FWHM. The Nasal Mucociliary Clearance of Relevance to Nasal Drug Delivery. Pharm. Res. 8, 807–814 (1991).

    Article  PubMed  CAS  Google Scholar 

  13. Duchateau GSMJE, Graamans K, Zuidema J, Merkus FWHM. Correlation Between Nasal Ciliary Heat Frequency and Mucus Transport Rate in Volunteers. Laryngoscope, 95, 854–859 (1985).

    Article  PubMed  CAS  Google Scholar 

  14. Ugwoke, MI, Verbeke N, Kinget R. The Biopharmaceutical Aspects of Nasal Mucoadhesive Delivery. J. Pharm. Pharmacol. 57, 3–21 (2001).

    Article  Google Scholar 

  15. Chien YW. Nasal Drug Delivery Systems. In: J Swarbrick (Ed), Novel Drug Delivery Systems. New York, Marcel Dekker, pp: 139–196 (1992).

    Google Scholar 

  16. Hussain A. Intranasal Drug Delivery. Adv. Drug Del. Rev. 29, 39–49 (1998).

    Article  CAS  Google Scholar 

  17. Fisher AN, Brown K, Davis SS, Parr GD, Smith DA. The Effect of Molecular Size on the Nasal Absorption of Water-Soluble Compounds in the Albino Rat. J. Pharm. Pharmacol. 39, 357–362 (1987).

    PubMed  CAS  Google Scholar 

  18. Marttin E, Schipper NGM, Verhoef JC, Mercus WHM. Nasal Mucociliary Clearance as a Factor in Nasal Drug Delivery. Adv. Drug. Del. Rev. 29, 13–38 (1998).

    Article  CAS  Google Scholar 

  19. Hasani A, Agnew JE, Pavia D, Vora H, Clarke SW. Effect of Oral Bronchodilators on Lung Mucociliary Clearance During Sleep in Patients with Asthma. Thorax, 48, 287–289 (1993).

    Article  PubMed  CAS  Google Scholar 

  20. Wolff RK, Dolovich MB, Obminski G, Newhouse MT. Effects of Exercise and Eucapric Hyperventilation on Bronchial Clearance in Man. J. Appl. Physiol. 43, 46–50 (1977).

    PubMed  CAS  Google Scholar 

  21. Verra F, Escuider E, Lebargy F, Bernaudin JF, Cremoux HD, Bignon J. Ciliary Abnormalities in Bronchial Ephitelium of Smokers, Ex-Smokers and non-smokers. Am. J. Respir. Crit. Care Med, 151, 630–634 (1995).

    PubMed  CAS  Google Scholar 

  22. Haxel BR, Schafer D, Klimek L. Prostaglandin E2 Activates the Ciliary Beat Frequency of Cultured Human Nasal Mucosa via the Second Messanger Cyclic Adenoside Monophosphate. Eur. Arc. Otorhinolarngology, 258, 230–235 (2001).

    Article  CAS  Google Scholar 

  23. Cho JH, Kurun YS, Jang HS, Kang JM, Won YS, Yoon HR. Long Term Use of Preservatives on Rat Nasal Respiratory Mucosa: Effects of Benzalkonium Chloride and Potassium Sorbate. Laryngoscope, 110, 312–317 (2000).

    Article  PubMed  CAS  Google Scholar 

  24. Behl CR, Pimplaskar HK, Sileno AP Xia WJ, Gries WJ, Emeireles JC, et al. Optimization of Systemic Nasal Drug Delivery with Pharmaceutical Excipients. Adv. Drug Dev. Rev, 29, 117–133 (1998).

    Article  CAS  Google Scholar 

  25. Alpar HO, Bowen JC, Brown MRW. Effectiveness of Liposomes as Adjuvants of Orally and Nasally Administered Tetanus Toxoid. Int. J. Pharm. 88, 335–344 (1992).

    Article  CAS  Google Scholar 

  26. Alpar HO, Eyles JE, Williamson ED, Somava E. Intranasal Vaccination Against Plague, Tetanus Toxoid and Diphteria. Adv. Drug Del. Rev. 51, 173–201 (2001).

    Article  CAS  Google Scholar 

  27. Law SL, Huang KJ, Chou VHY, Cherng JY. Enhancement of Nasal Absorption of Calcitonin Liposomes. J. Liposome Research, 11, 165–174 (2001).

    Article  CAS  Google Scholar 

  28. Hyde SC, Southern KW, Gileadi U, Fitzjohn KA, Waddell BE, Gooi HC, Goddard CA, Hannavy K, Smyth SE, Sorgi FL, Huang L, Cutbert AW, Evans MJ, Colledge WH, Higgins Gill DR. Rpeat Administration of DNA/liposomes to the Ephitelium of Patients with Cystic Fibrosis. Gene Therapy, 7, 1156–1163 (2000).

    Article  PubMed  CAS  Google Scholar 

  29. Maitani Y, Asano S, Takahashi S, Nagagaki M, Nagai T. Permeability of Insulin Entrapped in Liposome Through the Nasal Mucosa of Rabbits. Chem. Pharm. Bull. 40, 1569–1572 (1992).

    PubMed  CAS  Google Scholar 

  30. Gonchorova EP, Ryzhikov AB, Bulychev LE, Lebedev LR, Poryvaev VD, Karpenko LI, Ilichev AA. A Study of Systems for Delivering Antigens for Intranasal Immunization Against Tick-Borne Encephalitis. Weiner Klinische Wochenschrift, 114, 630–635 (2002).

    Google Scholar 

  31. Jung BH, Chung BC, Chung S, Lee M, Shin C. Prolonged Delivery of Nicotine in Rats via Nasal Administration of Proliposomes. J. Control. Rel. 66, 73–79 (2000).

    Article  CAS  Google Scholar 

  32. Bjork E, Erdman P. Degredable Starch Microspheres as a Nasal Delivery System for Insulin. Int. J. Pharm. 47, 233–238 (1988).

    Article  Google Scholar 

  33. Farraj NF, Johanson BR, Davis SS, Illum L. Nasal Administration of Insulin Using Bioadhesive Microspheres as a Delivery System. J. Control. Del, 13, 253–261 (1990).

    Article  CAS  Google Scholar 

  34. Ugwoke MI, Kaufmann G, Verbeke N, Kinget A. Intranasal Bioavailability of Apomorphine from Carboxymethyl Cellulose-based Drug Delivery Systems. Int. J. Pharm. 217, 125–131 (2000).

    Article  Google Scholar 

  35. Illum L, Jorgensen H, Bisgoard H, Krogsgoard Q, Rossing N. Bioadhesive Microspheres as a Potential Nasal Drug Delivery System. Int. J. Pharm. 39, 189–199 (1987).

    Article  CAS  Google Scholar 

  36. Ryden E, Erdman P. Effects of Polymers and Microspheres on the Nasal Absorption of Insulin in Rats. Int. J. Pharm., 83, 1–10 (1992).

    Article  CAS  Google Scholar 

  37. Leitner VM, Guggi D, Krauland AH, Bernkop-Schnurch A. Nasal Delivery of Human Growth Hormone, In Vitro and In Vivo of a Thiomer / Glutathione Microparticulate Delivery System. J. Control. Rel. 100, 87–95 (2004).

    Article  CAS  Google Scholar 

  38. Preda M, Leucuta SE. Oxprenolol-Loaded Bioadhesive Microspheres: Preparation and In Vivo Characterization. J. Microencap. 20, 777–789 (2003).

    Article  CAS  Google Scholar 

  39. Cerchiara T, Luppi B, Bigucci F, Zecchi V. Chitosan Salts as Nasal Sustained Delivery Systems for Peptide Drugs. J. Pharm. Pharmacol. 55, 1623–1627 (2003).

    Article  PubMed  CAS  Google Scholar 

  40. Tengamnuay P, Sahamethapat A, Sailasuta A. Chitosan as Nasal Absorption Enhancers of Peptides: A Comparison Between Free Amine Chitosan and Soluble Salts. Int. J. Pharm, 217, 53–67 (2000).

    Article  Google Scholar 

  41. Vila A, Sanchez A, Janes K, Behrens I, Kiel JLV. Low Molecular Weight Chitosan Nanoparticles and Carriers for Nasal Vaccine Delivery in Mice. Eur. J. Pharm. Biopharm, 57, 123–131 (2004).

    Article  PubMed  CAS  Google Scholar 

  42. Soane RJ, Hinchcliffe M, Davis SS, Illum L. Clearance Characteristics of Chitosan Based Formulatins in the Sheep Nasal Cavity. Int. J. Pharm. 218, 183–191 (2001).

    Article  Google Scholar 

  43. Fernandez-Urrusuno R, Romoni D, Calvo P, Alonso MJ. Development of a Freeze Dried Formulation of Insulin-loaded Chitosan Nanoparticles Intended for Nasal Adiministration. STP Pharma Sci. 9, 4–10 (1999).

    Google Scholar 

  44. Fernandez-Urrusuno R, Calvo P, Remunon-Lopez C, Vila-Jato JL, Alonso MJ. Enhancement of Nasal Absorption of Insulin Using Chitosan Nanoparticles. Pharm. Res, 16, 1576–1581 (1999).

    Article  PubMed  CAS  Google Scholar 

  45. Morimoto K, Tabata H, Morisaka K. Nasal Absorption of Nifedipine from Gel Preparations in Rats. Chem. Pham. Bull. 35, 3041–3044 (1987).

    CAS  Google Scholar 

  46. Morimoto K, Morisaka K, Kamada A. Enhancement of Nasal Absorption of Insulin and Calcitonin Using Polyacrylic Acid Gel. J. Pharm. Pharmacol. 37, 134–136, (1985).

    PubMed  CAS  Google Scholar 

  47. Ugwoke MI, Agu RU, Vanbilloen H, Baetens P, Verbeke N, Mortelmans L, Verbruggen A, Kinget R, Bormans G. Scintigraphic Evaluation in Rabbits of Nasal Drug Delivery Systems Based on Carbopol 971P and Carboxymethylcellulose. J. Control. Rel. 68, 207–214 (2000).

    Article  CAS  Google Scholar 

  48. Illum L, Farraj NF, Critchley H, Johansen BR, Davis SS. Enhanced Nasal Absorption of Insulin in Rats Using Lysophosphatidylcholine. Int. J. Pharm, 57, 49–54 (1989).

    Article  CAS  Google Scholar 

  49. Deponti R, Lardini E, Use of Chemical Enhancers for Nasal Drug Delivery. Drug Dev. Ind. Pharm. 17, 1419–1436 (1991).

    CAS  Google Scholar 

  50. Hermens WAJJ, Hooymans PM, Verhoef JC, Merkus FWHM. Effects of Absorption Enhancers on Human Nasal Tissue Ciliary Movement in Vitro. Pharm. Res. 7, 144–146 (1990).

    Article  PubMed  CAS  Google Scholar 

  51. Hedin L, Olsson B, Diczfalusy M, Flyg C, Petersson AS, Rosberg S, et al. Intranasal Administration of Human Growth Hormone (hGH) in Combination with a Membrane Permeation Enhancer in Patients with GH Deficiency: A Pharmacokinetic, Study. JCE & M, 76, 962–967 (1993).

    CAS  Google Scholar 

  52. Kissel T, Drewe J, Bantle S, Rummelt A, Beglinger C. Tolerability and Absorbtion Enhancement of Intranasally Administered Octreotide by Sodium Taurodihydrofusidate in Healty Subjects. Pharm. Res. 9, 52–57 (1992).

    Article  PubMed  CAS  Google Scholar 

  53. Lee WA, Ennis RD, Longenecker JP, Bengtsson P. The Bioavailability of Intranasal Salmon Calcitonin in Healty Volunteers with and without a Permeation Enhancer. Pharm. Res. 11, 747–750 (1994).

    Article  PubMed  CAS  Google Scholar 

  54. Drejer K, Vaag A, Beck K, Hansen P, Sorensen Ar, Mygind N. Intranasal Administration of Insulin with Phospholipid as Absorption Enhancer. Pharmacokinetics in Nasal Subjects. Diabet. Med. 9, 335–340 (1992).

    Article  PubMed  CAS  Google Scholar 

  55. Mishima M, Okada S, Wakita Y, Nakano M. Promotion of Nasal Absorption of Insulin by Glycyrrhetinic Acid Derivatives. I. J. Pharmacobio-Dyn, 36, 12–31 (1989).

    Google Scholar 

  56. Behl CR, Pimplashar HK, Sileno AP, Xia WJ, Gries WJ, Emeireles JC, et al. Optimization of Systemic Nasal Drug Delivery with Pharmaceutical Excipients. Adv. Drug Del. Rev. 29, 117–133 (1998).

    Article  CAS  Google Scholar 

  57. Marttin E, Verhoef JC, Merkus FWHM. Efficacy, Safety and Mechanism of Cyclodextrins as Absorption Enhancer in Nasal Delivery of Peptide and Protein Drugs. J. Drug Target, 6, 17–36 (1998).

    PubMed  CAS  Google Scholar 

  58. Sinswat P, Temgamnuay P. Enhancing effect of Chitosan on Nasal Absorption of Calcitonin in Rats: Comparison with Hydroxypropyl-Alfa and Dimethyl Beta Cyclodextrins. Int. J. Pharm, 21, 220, 15–22 (2003).

    Article  CAS  Google Scholar 

  59. Shao Z, Krishnamoorthy R, Mitra A. Cyclodextrins as Nasal Absorption Promoters of Insulin: Mechanistic Evaluations. Chem. Pharm. Bull. 40, 3100–3104 (1992).

    Google Scholar 

  60. Merkus FWHM, Verhoef JC, Romeijn SG, Schipper NGM. Absorption Enhancing Effect of Cyclodextrins on Intranasally Administrated Insulin in Rats. Pharm. Res. 8, 588–592 (1991).

    Article  PubMed  CAS  Google Scholar 

  61. Agerholm C, Bastholm L, Johanson PB, Nielsen MH, Elling F. Ephitelial Transport and Bioavailability of Intranasally Administered Human Growth Hormone Formulated with the Absorption Enhancers Didecanoyl-L-α-phosphatidylcholine and α-cyclodextrins in Rabbits. J. Pharm. Sci. 83, 1706–1711 (1994).

    Article  PubMed  CAS  Google Scholar 

  62. Al-Ghananeem AM, Traboulsi AA, Dittert LW, Hussain AA. Targeted Brain Delivery of 17-Beta-Estradiol via Nasally Administered Water Soluble Prodrugs. AAPS Pharm Sci Tech. 3, E5 (2002).

    Article  Google Scholar 

  63. Green GM. Alveolobronchiolar Transport Mechanisms. Arch. Int. Med. 131, 109 (1973).

    Article  CAS  Google Scholar 

  64. Taylor KMG, Farr SJ. Liposomes for Pulmonary Drug Delivery. In: Liposomes in Drug Delivery, G Gregoriadis, AT Florence, M Patel (Eds), Harwood Academic Publishers, Switzerland, 95–109 (1993).

    Google Scholar 

  65. Yu I, Chien YW. Pulmonary Drug Delivery: Physiologic and Mechanistic Aspects, Critical Review. In: Therapeutic Drug Carrier Systems, 14, 395–453 (1997).

    CAS  Google Scholar 

  66. Taylor KMG, Farr SJ. Liposoemes for Pulmonary Drug Delivery. In: Liposomes in Drug Delivery. G Gregoriadis, AT Florence, M Patel (Eds), Harwood Academic Publishers, Switzerland, 111–133 (1993).

    Google Scholar 

  67. Gonda I, Schuster J. Pulmonary Delivery of Drugs by Inhalation. In: Modified Release Drug Delivery Technology. J Surarbrich (Ed), Marcel Dekker Inc., New York-Basel, pp: 807–815 (2003).

    Google Scholar 

  68. Fielding RM. The Use of Inhaled Liposome Formulations for Drug Delivery to the Lung and Systemic Circulation. Proc. West. Pharmacol. 32, 103–106 (1989).

    CAS  Google Scholar 

  69. Kitson C, Angel B, Judd D, Rothery S, Seville A, Huang L, Wadsworth SC, Cheng SH, Geddes DM, Alton EWFW. The Extra and Intracellular Barriers to Lipid Adenovirus Mediated Pulmonary Gene Transfer in Native Airway Epithelium. Gene Therapy, 6, 534–546 (1999).

    Article  PubMed  CAS  Google Scholar 

  70. Cockett MI. Technology Evaluation: Cystic Fibrosis Therapy. Current Opinion in the Molecular Therapeutics, 19, 279–283 (1998).

    Google Scholar 

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Ozer, A.Y. (2007). Alternative Applications for Drug Delivery: Nasal and Pulmonary Routes. In: Mozafari, M.R. (eds) Nanomaterials and Nanosystems for Biomedical Applications. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6289-6_6

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