Nasal delivery of high molecular weight drugs

Yildiz Ozsoy, Sevgi Gungor, Erdal Cevher, Yildiz Ozsoy, Sevgi Gungor, Erdal Cevher

Abstract

Nasal drug delivery may be used for either local or systemic effects. Low molecular weight drugs with are rapidly absorbed through nasal mucosa. The main reasons for this are the high permeability, fairly wide absorption area, porous and thin endothelial basement membrane of the nasal epithelium. Despite the many advantages of the nasal route, limitations such as the high molecular weight (HMW) of drugs may impede drug absorption through the nasal mucosa. Recent studies have focused particularly on the nasal application of HMW therapeutic agents such as peptide-protein drugs and vaccines intended for systemic effects. Due to their hydrophilic structure, the nasal bioavailability of peptide and protein drugs is normally less than 1%. Besides their weak mucosal membrane permeability and enzymatic degradation in nasal mucosa, these drugs are rapidly cleared from the nasal cavity after administration because of mucociliary clearance. There are many approaches for increasing the residence time of drug formulations in the nasal cavity resulting in enhanced drug absorption. In this review article, nasal route and transport mechanisms across the nasal mucosa will be briefly presented. In the second part, current studies regarding the nasal application of macromolecular drugs and vaccines with nano- and micro-particulate carrier systems will be summarised.

Figures

Figure 1
Figure 1
(1) Paracellular route (1a) intercellular spaces, (1b) tight junctions, (2) transcellular route (2a) passive diffusion, (2b) active transport, (3) transcytosis (modified from Ref. [9]).
Figure 2
Figure 2
Changes of plasma glucose levels after intravenous administration of insulin solution and intranasal administration of insulin-incorporated gelatin (GMS) and aminated gelatin microspheres (AGMS) in dry powder forms. The dose of insulin was 0.5 IU/kg for intravenous route and 5 IU/kg for intranasal route (PBS-phosphate buffer saline). Each point represents mean ± SD (n = 4–5) [reprinted with permission from Ref. [64], copyright Elsevier (2006)].
Figure 3
Figure 3
Comparative hypoglycemic effects of EE–NPs (crosslinked with epichlorohydin/prepared emulsion method nanoparticles) in the presence of Na glycocholate and lysophosphatidylcholine after nasal administration to STZ (streotozotocin) induced diabetic rats (mean ± SE, n = 5) [reprinted with permission from Ref. [52], copyright Elsevier (2008)].
Figure 4
Figure 4
Plasma insulin (a) and blood glucose (b) concentration vs. time profiles following nasal administration of insulin (10 IU/kg) with different CPPs (0.5 mM). Each data point represents the mean ± SEM (n = 3). Key: (▲) insulin; (○) L-R8 (specific L-penetratin); (□) D-R8 (specific D-penetratin); (●) l-penetratin; (■) d-penetratin [reprinted with permission from Ref. [64], copyright Elsevier (2009)].
Figure 5
Figure 5
Comparison of plasma concentration–time profiles following nasal administration of liquid and powder formulations, and subcutaneous administration (○) of 0.3 mg of sCT in dogs. ▲; Formulation-L (sCT in saline), ●; Formulation-PN (powder formulation with NAC and ethylcellulose). Data represent mean plasma concentrations of sCT ± S.D. (n = 4) [reprinted with permission from Ref. [74], copyright Elsevier (2006)].
Figure 6
Figure 6
Changes in anti-factor Xa activity after nasal administration of enoxaparin formulated in saline or in the presence of different concentrations of (A) PEI-25 kDa, (B) PEI-750 kDa, or (C) PEI-1000 kDa. Data represent mean ± S.E.M., n = 3–5 [reprinted with permission from Ref. [91], copyright Elsevier (2006)].
Figure 6
Figure 6
Changes in anti-factor Xa activity after nasal administration of enoxaparin formulated in saline or in the presence of different concentrations of (A) PEI-25 kDa, (B) PEI-750 kDa, or (C) PEI-1000 kDa. Data represent mean ± S.E.M., n = 3–5 [reprinted with permission from Ref. [91], copyright Elsevier (2006)].
Figure 7
Figure 7
IgG antibody levels after i.n. administration of two doses of antigen (10 and 30 μg), encapsulated in chitosan nanoparticles (70 kDa) or in solution in mice (geometric mean ± SEM) [reprinted with permission from Ref. [109], copyright Elsevier (2004)].

References

    1. Ugwoke M.I., Verbeke N., Kinget R. The biopharmaceutical aspects of nasal mucoadhesive drug delivery. J. Pharm. Pharmacol. 2001;53:3–21. doi: 10.1211/0022357011775145.
    1. Behl C.R., Pimplaskar H.K., Sileno A.P., deMeireles J., Romeo V.D. Effects of physicochemical properties and other factors on systemic nasal drug delivery. Adv. Drug Deliv. Rev. 1998;29:89–116. doi: 10.1016/S0169-409X(97)00063-X.
    1. Arora P., Sharma S., Garg S. Permeability issues in nasal drug delivery. Drug Discov. Today. 2002;7:967–975. doi: 10.1016/S1359-6446(02)02452-2.
    1. Cornaz A.L., Buri P. Nasal Mucosa as an Absorption Barrier. Eur. J. Pharm. Biopharm. 1994;40:261–270.
    1. Jones N. The Nose and paranasal sinuses physiology and anatomy. Adv. Drug Deliv. Rev. 2001;51:5–19. doi: 10.1016/S0169-409X(01)00172-7.
    1. Sciarra J.J. In: Remington: The Science and Practice of Pharmacy. Gennaro A.R., editor. Mack Publishing Company; Easton, PA, USA: 1995. p. 1676. Chapter 95.
    1. Sanders P., Washington N., Frier M., Wilson C.G., Feely L.C., Washington C. The deposition of solution-based and suspension-based aerosols from metered dose inhalers in healthy subjects and asthmatic patients. S.T.P. Pharm. Sci. 1997;7:300–306.
    1. Schipper N.G., Verhoef J.C., Merkus F.W. The nasal mucociliary clearance: Relevance to nasal drug delivery. Pharm. Res. 1991;8:807–814. doi: 10.1023/A:1015830907632.
    1. Ingemann M., Frokjaer S., Hovgaard L., Brøndsted H. Peptide and Protein Drug Delivery Systems for Non-Parenteral Routes of Administration. In: Frokjaer S., Hovgaard L., editors. Pharmaceutical Formulation Development of Peptides and Proteins. Taylor & Francis; Philadelphia, PA, USA: 2000. p. 189. Chapter 10.
    1. Wermeling D.P., Miller J.L. Intranasal Drug Delivery. In: Rathbone M.J., Hadgraft J., Roberts M.S., editors. Modified Release Drug Delivery Technology. Marcel Dekker, Inc.; New York, NY, USA: 2002. p. 727. Chapter 61.
    1. Ungell A.L., Andreasson A., Lundin K., Utter L. Effects of enzymatic inhibition and increased paracellular shunting on transport of vasopressin analogues in the rat. J. Pharm. Sci. 1992;81:640–645. doi: 10.1002/jps.2600810710.
    1. Corbo D.C., Liu J.C., Chien Y.W. Drug absorption through mucosal membranes: Effect of mucosal route and penetrant hydrophilicity. Pharm. Res. 1989;6:848–852. doi: 10.1023/A:1015952320372.
    1. McMartin C., Hutchinson L.E., Hyde R., Peters G.E. Analysis of structural requirements for the absorption of drugs and macromolecules from the nasal cavity. J. Pharm. Sci. 1987;76:535–540. doi: 10.1002/jps.2600760709.
    1. Tuma P.L., Hubbard L. Transcytosis: Crossing cellular barriers. Physiol. Rev. 2003;83:871–932. doi: 10.1152/physrev.00001.2003.
    1. Illum L. Nasal Drug delivery-possibilities, problems and solutions. J. Control. Release. 2003;87:187–198. doi: 10.1016/S0168-3659(02)00363-2.
    1. Hussain A.A. Intranasal drug delivery. Adv. Drug Deliv. Rev. 1998;29:39–49. doi: 10.1016/S0169-409X(97)00060-4.
    1. O’Hagan D.T., Illum L. Absorption of peptides and proteins from the respiratory tract and the potential for development of locally administered vaccine. Crit. Rev. Ther. Drug Carrier Syst. 1990;7:35–97.
    1. Irwin W.J., Dwivedi A.K., Holbrook P.A., Dey M.J. The Effect of cyclodextrins on the stability of peptides in nasal enzymic systems. Pharm. Res. 1994;11:1698–1703. doi: 10.1023/A:1018946829225.
    1. Morita T., Yamahara H. In: Encyclopedia of Pharmaceutical Technology. 3rd ed. Swarbrick J., editor. Vol. 4. Informa Healthcare; London, UK: 2007. p. 2678.
    1. Stolnic S., Shakesheff K. Formulation for delivery the therapeutics proteins. Biotechnol. Lett. 2009;31:1–11. doi: 10.1007/s10529-008-9834-y.
    1. Romeo V.D., deMeireles J.C., Gries W.J., Xia W.J., Sileno A.P., Pimplaskar H.K., Behl C.R. Optimization of systemic nasal drug delivery with pharmaceutical excipients. Adv. Drug Deliv. Rev. 1998;29:117–133.
    1. Sarkar M.A. Drug Metabolism in the nasal mucosa. Pharm. Res. 1992;9:1–9. doi: 10.1023/A:1018911206646.
    1. Ozsoy Y., Tunçel T., Can A., Akev N., Birteksöz S., Gerçeker A. In vivo studies on nasal preparations of ciprofloxacin hydrochloride. Pharmazie. 2000;55:607–609.
    1. Davis S.S., Illum L. Absorption enhancers for nasal drug delivery. Clin. Pharmacokinet. 2003;42:1107–1128. doi: 10.2165/00003088-200342130-00003.
    1. Law S.L., Huang K.J., Chou H.Y. Preparation of desmopressin-containing liposomes for intranasal delivery. J. Control. Release. 2001;70:375–382. doi: 10.1016/S0168-3659(00)00369-2.
    1. Mitra R., Pezron I., Chu W.A., Mitra A.K. Lipid emulsions as vehicles for enhanced nasal delivery of insulin. Int. J. Pharm. 2000;205:127–134. doi: 10.1016/S0378-5173(00)00506-8.
    1. Kumar M., Pathak K., Misra A. Formulation and characterization of nanoemulsion-based drug delivery system of risperidone. Drug Dev. Ind. Pharm. 2009;35:387–395. doi: 10.1080/03639040802363704.
    1. Gungor S., Okyar A., Erturk-Toker S., Baktir G., Ozsoy Y. Ondansetron-loaded biodegradable microspheres as a nasal sustained delivery system: In vitro/in vivo studies. Pharm. Dev. Tech. 2009 doi: 10.1080/10837450903148257.
    1. Gungor S., Okyar A., Erturk-Toker S., Baktir G., Ozsoy Y. In Vitro and in Vivo Studies on Ondansetron HCl-Loaded Chitosan Microspheres for Nasal Drug Delivery; 6th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology; Barcelona, Spain. 7–10 April 2008.
    1. Brooking J., Davis S.S., Illum L. Transport of nanoparticles accross the rat nasal mucosa. J. Drug Target. 2001;9:267–279. doi: 10.3109/10611860108997935.
    1. McGinity J.W., O’Donnell P.B. Preparation of microspheres by the solvent evaporation technique. Adv. Drug Deliv. Rev. 1997;28:25–42.
    1. Rajaonarivony M., Vauthier C., Couarraze G., Puisieux F., Couvreur P. Development of a new drug carrier made from alginate. J. Pharm. Sci. 1993;82:912–917. doi: 10.1002/jps.2600820909.
    1. Chowdary K.P., Rao Y.S. Mucoadhesive microspheres for controlled drug delivery. Biol. Pharm. Bull. 2004;27:1717–1724. doi: 10.1248/bpb.27.1717.
    1. Agnihotri S.A., Mallikarjuna N.N., Aminabhavi T.M. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J. Control. Release. 2004;100:5–28. doi: 10.1016/j.jconrel.2004.08.010.
    1. Ozsoy Y. In: Handbook of Particulate Drug Delivery. Kumar M.N.V.R., editor. Vol. 2. American Scientific Publisher; Stevenson Ranch, CA, USA: 2008. p. 143. Chapter 8.
    1. van der Lubben I.M., Verhoef J.C., Borchard G., Junginger H.E. Chitosan and its derivatives in mucosal drug and vaccine delivery. Eur. J. Pharm. Sci. 2001;14:201–207. doi: 10.1016/S0928-0987(01)00172-5.
    1. Wong T.W. Chitosan and its use in design of insulin delivery system. Recent Pat. Drug Deliv. Formul. 2009;3:8–25. doi: 10.2174/187221109787158346.
    1. Henriksen I., Green K.L., Smart J.D., Smistad G., Karlsen J. Bioadhesion of hydrated chitosan: An in vitro and in vivo study. Int. J. Pharm. 1996;145:231–240. doi: 10.1016/S0378-5173(96)04776-X.
    1. Schipper N.G., Olsson S., Hoogstraate J.A., deBoer A.G., Varum K.M., Artursson P. Chitosans as absorption enhancers for poorly absorbable drugs 2: Mechanism of absorption enhancement. Pharm. Res. 1997;14:923–929. doi: 10.1023/A:1012160102740.
    1. Lehr C.M., Bouwstra J.A., Schacht E.H., Junginger H.E. In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int. J. Pharm. 1992;78:43–48. doi: 10.1016/0378-5173(92)90353-4.
    1. Artursson P., Lindmark T., Davis S.S., Illum L. Effect of chitosan on the permeability of monolayers of intestinal epithelial cells (Caco-2) Pharm. Res. 1994;11:1358–1361. doi: 10.1023/A:1018967116988.
    1. Alpar H.O., Eyles J.E., Williamson E.D., Somavarapu S. Intranasal vaccination against plague, tetanus and diphtheria. Adv. Drug Deliv. Rev. 2001;51:173–201. doi: 10.1016/S0169-409X(01)00166-1.
    1. Vila A., Sánchez A., Tobío M., Calvo P., Alonso M.J. Design of biodegradable particles for protein delivery. J. Control. Release. 2002;78:15–24. doi: 10.1016/S0168-3659(01)00486-2.
    1. Vila A., Sánchez A., Evora C., Soriano I., Vila Jato J.L., Alonso M.J. PEG-PLA nanoparticles as carriers for nasal vaccine delivery. J. Aerosol. Med. 2004;17:174–185. doi: 10.1089/0894268041457183.
    1. Farraj N.F., Johansen B.R., Davis SS., Illum L. Nasal administration of insulin using bioadhesive microspheres as a delivery system. J. Control. Release. 1990;13:253–261. doi: 10.1016/0168-3659(90)90016-M.
    1. Björk E., Edman P. Characterization of degradable starch microspheres as a nasal delivery system for drugs. Int. J. Pharm. 1990;62:187–192. doi: 10.1016/0378-5173(90)90232-S.
    1. Edman P., Björk E., Ryden L. Microspheres as a nasal delivery system for peptide drugs. J. Control. Release. 1992;21:165–172. doi: 10.1016/0168-3659(92)90018-M.
    1. Callens C., Remon J.P. Evaluation of starch-maltodextrin-carbopol 974 P mixtures for the nasal delivery of insulin in rabbits. J. Control. Release. 2000;66:215–220. doi: 10.1016/S0168-3659(99)00271-0.
    1. Illum L., Fisher A.N., Jabbal-Gill I., Davis S.S. Bioadhesive starch microspheres and absorption enhancing agents act synergistically to enhance the nasal absorption of polypeptides. Int. J. Pharm. 2001;222:109–119. doi: 10.1016/S0378-5173(01)00708-6.
    1. Callens C., Pringels E., Remon J.P. Influence of multiple nasal administrations of bioadhesive powders on the insulin bioavailability. Int. J. Pharm. 2003;250:415–422. doi: 10.1016/S0378-5173(02)00555-0.
    1. Pringels E., Vervaet C., Verbeeck R., Foreman P., Remon J.P. The addition of calcium ions to starch/carbopol mixtures enhances the nasal bioavailability of insulin. Eur. J. Pharm. Biopharm. 2008;68:201–206. doi: 10.1016/j.ejpb.2007.05.008.
    1. Jain A.K., Khar R. K., Ahmed F. J., Diwan P.V. Effective insulin delivery using starch nanoparticles as a potential trans-nasal mucoadhesive carrier. Eur. J. Pharm. Biopharm. 2008;69:426–435. doi: 10.1016/j.ejpb.2007.12.001.
    1. Pereswetoff-Morath L., Edman P. Dextran microspheres as a potential nasal drug delivery system for insulin-in vitro and in vivo properties. Int. J. Pharm. 1995;124:37–44. doi: 10.1016/0378-5173(95)00070-Y.
    1. Takenaga M., Serizawa Y., Azechi Y., Ochiai A., Kosaka Y., Igarashi R., Mizushima Y. Microparticle resins as a potential nasal drug delivery system for insulin. J. Control. Release. 1998;52:81–87. doi: 10.1016/S0168-3659(97)00193-4.
    1. Illum L., Farraj N.F., Fisher A.N., Gill I., Miglietta M., Benedetti L.M. Hyaluronic acid ester microspheres as a nasal delivery system for insulin. J. Control. Release. 1994;29:133–141. doi: 10.1016/0168-3659(94)90129-5.
    1. Fernandez-Urrusuno R., Romani D., Calvo P., Vila-Jato J.L., Alonso M.J. Development of a freeze-dried formulation of insulin-loaded chitosan nanoparticles intended for nasal administration. S.T.P. Pharma. Sci. 1999;9:429–436.
    1. Varshosaz J., Sadrai H., Alinagari R. Nasal delivery of insulin using chitosan microspheres. J. Microencapsul. 2004;21:761–774. doi: 10.1080/02652040400015403.
    1. Krauland A.H., Leitner V.M., Grabovac V., Bernkop-Schnürch A. In vivo evealuation of a nasal insulin delivery system based on thiolated chitosan. J. Pharm. Sci. 2006;95:2463–2472. doi: 10.1002/jps.20700.
    1. Krauland A.H., Alonso M.J. Chitosan/cyclodextrin nanoparticles as macromolecular drug delivery system. Int. J. Pharm. 2007;340:134–142. doi: 10.1016/j.ijpharm.2007.03.005.
    1. Bhumkar D.R., Joshi H.M., Sastry M., Pokharkar V.B. Chitosan reduced gold nanoparticles as novel carriers for transmucosal delivery of insulin. Pharm. Res. 2007;24:1415–1426. doi: 10.1007/s11095-007-9257-9.
    1. Wang X., Zheng C., Wu Z., Teng D., Zhang X., Wang Z., Li C. Chitosan-NAC nanoparticles as a Vehicle for nasal absorption enhancement of insulin. J. Biomed. Mater. Res. 2009;88:150–161. doi: 10.1002/jbm.b.31161.
    1. Teijeiro-Osorio D., Remunán-López C., Alonso M.J. New generation of hybrid poly/oligosaccharide nanoparticles as carriers for the nasal delivery of macromolecules. Biomacromolecules. 2009;10:243–249. doi: 10.1021/bm800975j.
    1. Wang J., Tabata Y., Morimoto K. Aminated gelatin microspheres as a nasal delivery system for peptide drugs: Evaluation of in vitro release and in vivo absorption in rats. J. Control. Release. 2006;113:31–37. doi: 10.1016/j.jconrel.2006.03.011.
    1. Khafagy E.S., Morishita M., Isowa K., Imai J., Takayama K. Effect of cell-penetrating peptides on the nasal absorption of insulin. J. Control. Release. 2009;133:103–108. doi: 10.1016/j.jconrel.2008.09.076.
    1. Moeller E.M., Jorgensen L. Alternative routes of administration for systemic delivery of protein pharmaceuticals. Drug Discov. Today Technol. 2008 doi: 10.1016/j.ddtec.2008.11.005.
    1. Critchley H., Davis S.S., Farraj N.F., Illum L. Nasal absorption of desmopressin in rats and sheep. Effect of a bioadhesive microsphere delivery system. J. Pharm. Pharmacol. 1994;46:651–656. doi: 10.1111/j.2042-7158.1994.tb03876.x.
    1. Fransén N., Bredenberg S., Björk E. Clinical study shows improved absorption of desmopressin with novel formulation. Pharm. Res. 2009;26:1618–1625. doi: 10.1007/s11095-009-9871-9.
    1. Morimoto K., Katsumata H., Yabuta T., Iwanaga K., Kakemi M., Tabata Y., Ikada Y. Evaluation of gelatin microspheres for nasal and intramuscular administrations of salmon calcitonin. Eur. J. Pharm. Sci. 2001;13:179–185. doi: 10.1016/S0928-0987(01)00094-X.
    1. Hinchcliffe M., Jabbal-Gill I., Smith A. Effect of chitosan on the intranasal absorption of salmon calcitonin in sheep. J. Pharm. Pharmacol. 2005;57:681–687. doi: 10.1211/0022357056073.
    1. Lee K.C., Park M.O., Na D.H., Youn Y.S., Lee S.D., Yoo S.D., Lee H.S., DeLuca P.P. Intranasal delivery of pegylated salmon calcitonins: Hypocalcemic effects in rats. Calcif. Tissue Int. 2003;73:545–549. doi: 10.1007/s00223-002-0034-9.
    1. Ishikawa F., Katsura M., Tamai I., Tsuji A. Improved nasal bioavailability of elcatonin by insoluble powder formulation. Int. J. Pharm. 2001;224:105–114. doi: 10.1016/S0378-5173(01)00736-0.
    1. Lee W.A., Ennis R.D., Longenecker J.P., Bengtsson P. The bioavailability of intranasal salmon calcitonin in healthy volunteers with and without a permeation enhancer. Pharm. Res. 1994;11:747–750. doi: 10.1023/A:1018992716621.
    1. Pontiroli A.E., Pajetta E, Calderara A., Alberetto M., Pozza G., Manganelli V., Resmini G., Tessari L., Maresca V. Intranasal and intramuscular human calcitonin in female osteoporosis and in paget’s disease of bones: A pilot study. J. Endocrinol. Invest. 1991;14:47–51. doi: 10.1007/BF03350260.
    1. Matsuyama T., Morita T., Horikiri Y., Yamahara H., Yoshino H. Improved nasal absorption of salmon calcitonin by powdery formulation with N-acetyl-L-cysteine as a mucolytic agent. J. Control. Release. 2006;115:183–188. doi: 10.1016/j.jconrel.2006.08.004.
    1. Matsuyama T., Morita T., Horikiri Y., Yamahara H., Yoshino H. Enhancement of nasal absorption of large molecular weight compounds by combination of mucolytic agent and nonionic surfactant. J. Control. Release. 2006;110:347–352. doi: 10.1016/j.jconrel.2005.09.047.
    1. Adjei A., Sundberg D., Miller J., Chun A. Bioavailability of leuprolide acetate following nasal and inhalation delivery to rats and healthy humans. Pharm. Res. 1992;9:244–249. doi: 10.1023/A:1018997625726.
    1. Abe K., Irie T., Uekama K. Enhanced nasal delivery of luteinizing hormone releasing hormone agonist buserelin by oleic acid solubilized and stabilized in hydroxypropyl-beta–cyclodextrin. Chem. Pharm. Bull. 1995;43:2232–2237. doi: 10.1248/cpb.43.2232.
    1. Illum L., Watts P., Fisher A.N., Jabbal Gill I., Davis S.S. Novel chitosan-based delivery systems for the nasal administration of a LHRH-analogue. S.T.P. Pharma Sci. 2000;10:89–94.
    1. Illum L., Farraj N.F., Davis S.S., Johansen B.R., O’Hagan D.T. Investigation of the nasal absorption of biosynthetic human growth hormone in sheep – use of a bioadhesive microsphere delivery system. Int. J. Pharm. 1990;63:207–211. doi: 10.1016/0378-5173(90)90126-O.
    1. Laursen T., Grandjean B., Jorgensen J.O., Christiansen J.S. Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deficient patients: Comparison with intravenous and subcutaneous administration. Eur. J. Endocrinol. 1996;135:309–315. doi: 10.1530/eje.0.1350309.
    1. Agerholm C., Bastholm L., Johansen P.B., Nielsen M.H., Elling F. Epithelial transport and bioavailability of intranasally administered human growth hormone formulated with the absorption enhancers Didecanoyl-L-alpha-phosphatidylcholine and Alpha-cyclodextrin in rabbits. J. Pharm. Sci. 1994;83:1706–1711. doi: 10.1002/jps.2600831212.
    1. Hedin L., Olsson B., Diczfalusy M., Flyg C., Petersson A.S., Rosberg S., Albertsson-Wikland K. Intranasal administration of human growth hormone (hGH) in combination with a membrane permeation enhancer in patients with GH deficiency: A pharmacokinetic study. J. Clinical Endocrinol. Metab. 1993;76:962–967.
    1. Leitner V.M., Guggi D., Krauland A.H., Bernkop-Schnürch A. Nasal Delivery of human growth hormone: In vitro and in vivo evaluation of a thiomer/glutathione microparticulate delivery system. J. Control. Release. 2004;100:87–95. doi: 10.1016/j.jconrel.2004.08.001.
    1. Vancheri C., Mastruzzo C., Armato F., Tomaselli V., Magrì S., Pistorio M.P., LaMicela M., D’Amico L., Crimi N. Intranasal heparin reduces eosinophil recruitment after nasal allergen challenge in patients with allergic rhinitis. J. Allergy Clin. Immunol. 2001;108:703–708. doi: 10.1067/mai.2001.118785.
    1. Zeng D., Prosperini G., Russo C., Spicuzza L., Cacciola R.R., Di Maria G.U., Polosa R. Heparin attenuates symptoms and mast cell degranulation induced by AMP nasal provocation. J. Allergy Clin. Immunol. 2004;114:316–320. doi: 10.1016/j.jaci.2004.05.026.
    1. Yıldız A., Okyar A., Baktır G., Araman A., Ozsoy Y. Nasal administration of heparin-loaded microspheres based on poly(lactic acid) Il Farmaco. 2005;60:919–924. doi: 10.1016/j.farmac.2005.08.004.
    1. Arnold J., Ahsan F., Meezan E., Pillion D.J. Nasal administration of low molecular weight heparin. J. Pharm. Sci. 2002;91:1707–1714. doi: 10.1002/jps.10171.
    1. Yang T., Hussain A., Paulson J., Abbruscato T.J., Ahsan F. Cyclodextrins in nasal delivery of low-molecular-weight heparins in vivo and in vitro studies. Pharm. Res. 2004;21:1127–1136. doi: 10.1023/B:PHAM.0000032998.84488.7a.
    1. Mustafa F., Yang T., Khan M.A., Ahsan F. Chain length-dependent effects of alkylmaltosides on nasal absorption of enoxaparin. J. Pharm. Sci. 2004;93:675–683. doi: 10.1002/jps.10579.
    1. Yang T., Mustafa F., Ahsan F. Alkanoylsucroses in nasal delivery of low molecular weight heparins: In vivo absorption and reversibility studies in rats. J. Pharm. Pharmacol. 2004;56:53–60. doi: 10.1211/0022357022377.
    1. Yang T., Hussain A., Bai S., Khalil I.A., Harashima H., Ahsan F. Positively charged polyethylenimines enhance nasal absorption of the negatively charged drug, low molecular weight heparin. J. Control. Release. 2006;115:289–297. doi: 10.1016/j.jconrel.2006.08.015.
    1. Li Y., Jiang H.L., Zhu K.J., Liu J.H., Hao Y.L. Preparation, characterization and nasal delivery of α-cobrotoxin-loaded poly(lactide-co-glycolide)/polyanhydride microspheres. J. Control. Release. 2005;108:10–20. doi: 10.1016/j.jconrel.2005.07.007.
    1. Gedulin B.R., Smith P.A., Jodka C.M., Chen K., Bhavsar S., Nielsen L.L., Parkes D.G., Young A.A. Pharmacokinetics and pharmacodynamics of exenatide following alternate routes of administration. Int. J. Pharm. 2008;356:231–238. doi: 10.1016/j.ijpharm.2008.01.015.
    1. Teshima D., Yamauchi A., Makino K., Kataoka Y., Arita Y., Nawata H., Oishi R. Nasal glucagon delivery using microcrystalline cellulose in healthy volunteers. Int. J. Pharm. 2002;233:61–66. doi: 10.1016/S0378-5173(01)00930-9.
    1. Zhang Y., Zhang Q., Sun Y., Sun J., Wang X., Chen M. Nasal recombinant hirudin-2 delivery: absorption and its mechanism in vivo and in vitro studies. Biol. Pharm. Bull. 2005;28:2263–2267. doi: 10.1248/bpb.28.2263.
    1. Kissel T., Drewe J., Bantle S., Rummelt A., Beglinger C. Tolerability and absorption enhancement of intranasally administered octreotide by sodium taurodihydrofusidate in healthy subjects. Pharm. Res. 1992;9:52–57. doi: 10.1023/A:1018927710280.
    1. Oechslein C.R., Fricker G., Kissel T. Nasal delivery of octreotide: absorption enhancement by particulate carrier systems. Int. J. Pharm. 1996;139:25–32. doi: 10.1016/0378-5173(96)04569-3.
    1. Davis S.S. Nasal vaccines. Adv. Drug. Deliv. Rev. 2001;51:21–42. doi: 10.1016/S0169-409X(01)00162-4.
    1. Gutierro I.G., Hernandez R.M., Igartua M., Gascon A. R., Pedraz J. L. Influence of dose and immunization route on the serum IgG antibody response to BSA loaded PLGA microspheres. Vaccine. 2002;20:2181–2190. doi: 10.1016/S0264-410X(02)00146-9.
    1. Olszewska W., Steward M.W. Nasal delivery of epitope based vaccines. Adv. Drug Deliv. Rev. 2001;51:161–171. doi: 10.1016/S0169-409X(01)00164-8.
    1. Vyas S.P., Gupta P.N. Implication of nanoparticles/microparticles in mucosal vaccine delivery. Expert Rev. Vaccines. 2007;6:401–418. doi: 10.1586/14760584.6.3.401.
    1. Sharma S., Mukkur T.K.S., Benson H.A.E., Chen Y. Pharmaceutical aspects of intranasal delivery of vaccines using particulate systems. J. Pharm. Sci. 2009;98:812–843. doi: 10.1002/jps.21493.
    1. Singh M., Chakrapani A., O’Hagan D. Nanoparticles and microparticles as vaccine-delivery systems. Expert Rev. Vaccines. 2007;6:797–808. doi: 10.1586/14760584.6.5.797.
    1. Csaba N., Gargia-Fuentes M., Alonso M.R. Nanoparticles for nasal vaccination. Adv. Drug. Del. Rev. 2009;61:140–157. doi: 10.1016/j.addr.2008.09.005.
    1. Alpar H.O., Özsoy Y., Bowen J., Eyles J.E., Conway B.R., Williamson E.D. Potential of Particulate carriers for the mucosal delivery of dna vaccines. Biochem. Soc. Trans. 1997;25:337S. doi: 10.1042/bst025337s.
    1. Salomon S.K., Cevher E., Somavarapu S., Li X.W., Brocchini S., Sesardic T., Alpar H.O. Novel N-Trimethyl Chitosan- Poly(γ-Glutamic Acid) Nanoparticles for Mucosal Delivery of Vaccines; 34th Annual Meeting & Exposition of the Controlled Release Society; Long Beach, CA, USA. 7–11 July 2007.
    1. Singh J., Pandit S., Bramwell V.W., Alpar H.O. Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal vaccine delivery systems. Methods. 2006;38:96–105. doi: 10.1016/j.ymeth.2005.11.003.
    1. Illum L., Jabbal-Gill I., Hincgcliffe M., Fisher A.N., Davis S.S. Chitosan as a novel delivery system for vaccines. Adv. Drug. Del. Rev. 2001;51:81–96. doi: 10.1016/S0169-409X(01)00171-5.
    1. Vila A., Sánchez A., Janes K., Behrens I., Kissel T., Vila Jato J.L., Alonso M.J. Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice. Eur. J. Pharm. Biopharm. 2004;57:123–131. doi: 10.1016/j.ejpb.2003.09.006.
    1. Jung T., Kamm W., Breitenbach A., Hungerer K.D., Hundt E., Kissel T. Tetanus toxoid loaded nanoparticles from sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide): Evaluation of antibody response after oral and nasal application in mice. Pharm. Res. 2001;18:352–360. doi: 10.1023/A:1011063232257.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir