Penetration Enhancers for the Development of Intranasal Formulations for Use in Equines
Keywords:
Horses, cyclodextrins, chitosan, surfactants, bile acids, sodium taurodihidrydrofusidate, phospholipidsAbstract
The aim of this review is to assess penetration enhancers, such as cyclodextrins, chitosan and their derivatives, surfactants, bile acids, their salts and derivatives, sodium taurodihidrydrofusidate, and phospholipids used in the development of intranasal formulations with a potential application in horses. In the last few years, the interest in the intranasal administration route in humans has grown because it is bloodless, noninvasive, and painless and represents a direct path toward the central nervous system. However, in equine medicine, the use of this administration route is scarce. Since equines have a nasal cavity with large surface area and blood irrigation, a high bioavailability of intranasal administered drugs is expected. Nowadays, the development of formulations for intranasal administration in equines is a challenge. The present review proposes the assessment of the characteristics and potential effects of the most important penetration enhancers in the development of intranasal formulations for use in equines.
References
Kim D-D. In Vitro Cellular Models for Nasal Drug Absorption Studies. 1st ed., California, USA: 2008, p. 216–34. https://doi.org/10.1007/978-0-387-74901-3_9.
Bhise SB, Yadav AV, Avachat AM, Malayandi R. Bioavailability of intranasal drug delivery system. Asian Journal of Pharmaceutics (AJP): Free Full Text Articles from Asian J Pharm 2014;2. https://doi.org/10.22377/ajp.v2i4.203.
Muñoz-Cernada A, Fernández-Cervera M, García-Rodríguez JC. Factors involved in the design of nasal delivery systems for peptides and proteins. Biotecnología Aplicada 2013;30:88–96.
Ferreira V, Velloso MI, Vita M, Landoni MF. Vía intranasal: una alternativa para la administración de fármacos de acción central en equinos. Intranasal drug delivery: an alternative for the administration of central acting drugs in horses 2019;39, no. 1. https://doi.org/10.24215/15142590e033.
Singh AK, Singh A, Madhv NVS. Nasal Cavity, a Promising Transmucosal Platform for Drug Delivery and Research Approaches from Nasal to Brain Targetting. Journal of Drug Delivery and Therapeutics 2012;2. https://doi.org/10.22270/jddt.v2i3.163.
Tortora GJ, Derrickson B, Tzal K, Gutierrez M de los A, Klajn D. Principios de Anatomía y Fisiología. Mexico: México Editorial Médica Panamericana; 2013.
Lochhead JJ, Thorne RG. Intranasal Drug Delivery to the Brain. In: Hammarlund-Udenaes M, de Lange ECM, Thorne RG, editors. Drug Delivery to the Brain: Physiological Concepts, Methodologies and Approaches, New York, NY: Springer; 2014, p. 401–31. https://doi.org/10.1007/978-1-4614-9105-7_14.
Ross MH, Wojciech P, Alday A, Giacomucci M. Histología: texto y atlas : correlación con biología celular y molecular. 7th ed. Barcelona, España: Wolters Kluwer; 2016.
Alnasser S. A Review on Nasal Drug Delivery System and Its Contribution in Therapeutic Management. Asian Journal of Pharmaceutical and Clinical Research 2019:40–5. https://doi.org/10.22159/ajpcr.2019.v12i1.29443.
Dufes C, Olivier J-C, Gaillard F, Gaillard A, Couet W, Muller J-M. Brain delivery of vasoactive intestinal peptide (VIP) following nasal administration to rats. International Journal of Pharmaceutics 2003;255:87–97. https://doi.org/10.1016/S0378-5173(03)00039-5.
Keller L-A, Merkel O, Popp A. Intranasal drug delivery: opportunities and toxicologic challenges during drug development. Drug Deliv and Transl Res 2021. https://doi.org/10.1007/s13346-020-00891-5.
Mujawar N, Ghatage S, Navale S, Sankpal B, Patil S, Patil S. Nasal Drug Delivery: Problem Solution and Its Application. Journal of Current Pharma Research 2014;4:1231–45. https://doi.org/10.33786/JCPR.2014. V04I03.008.
Ozsoy Y, Güngör S. Nasal route: an alternative approach for antiemetic drug delivery. Expert Opin Drug Deliv 2011;8:1439–53. https://doi.org/10.1517/17425247.2011.607437.
Geneser F, Bruel A, Christensen EI, Tranum-Jensen J, Qvortrup K. Geneser Histología. 4th ed. Buenos Aires, Argentina: Editorial médica panamericana; 2015.
Maher S, Casettari L, Illum L. Transmucosal Absorption Enhancers in the Drug Delivery Field. Pharmaceutics 2019;11:339. https://doi.org/10.3390/pharmaceutics11070339.
Williams OW, Sharafkhaneh A, Kim V, Dickey BF, Evans CM. Airway Mucus. Am J Respir Cell Mol Biol 2006;34:527–36. https://doi.org/10.1165/rcmb.2005-0436SF.
Gänger S, Schindowski K. Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa. Pharmaceutics 2018;10:116. https://doi.org/10.3390/pharmaceutics10030116.
Erdő F, Bors LA, Farkas D, Bajza Á, Gizurarson S. Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Research Bulletin 2018;143:155–70. https://doi.org/10.1016/j.brainresbull.2018.10.009.
Dhuria SV, Hanson LR, Frey WH. Intranasal delivery to the central nervous system: Mechanisms and experimental considerations. JPharmSci 2010;99:1654–73. https://doi.org/10.1002/jps.21924.
Agrawal M, Saraf S, Saraf S, Antimisiaris SG, Chougule MB, Shoyele SA, et al. Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs. Journal of Controlled Release 2018;281:139–77. https://doi.org/10.1016/j.jconrel.2018.05.011.
Mittal D, Ali A, Md S, Baboota S, Sahni JK, Ali J. Insights into direct nose to brain delivery: current status and future perspective. Drug Delivery 2014;21:75–86. https://doi.org/10.3109/10717544.2013.838713.
Balin BJ, Broadwell RD, Salcman M, El-Kalliny M. Avenues for entry of peripherally administered protein to the central nervous system in mouse, rat, and squirrel monkey. Journal of Comparative Neurology 1986;251:260–80. https://doi.org/10.1002/cne.902510209.
Baker H, Spencer RF. Transneuronal transport of peroxidase-conjugated wheat germ agglutinin (WGA-HRP) from the olfactory epithelium to the brain of the adult rat. Exp Brain Res 1986;63:461–73. https://doi.org/10.1007/BF00237470.
Kristensson K, Olsson Y. Uptake of exogenous proteins in mouse olfactory cells. Acta Neuropathol 1971;19:145–54. https://doi.org/10.1007/BF00688493.
Perl D, Good P. Uptake of Aluminium into Central Nervous System along Nasal-Olfactory Pathways. The Lancet 1987;329:1028. https://doi.org/10.1016/S0140-6736(87)92288-4.
Westin UE, Boström E, Gråsjö J, Hammarlund-Udenaes M, Björk E. Direct Nose-to-Brain Transfer of Morphine After Nasal Administration to Rats. Pharm Res 2006;23:565–72. https://doi.org/10.1007/s11095-006-9534-z.
Gizurarson S. Anatomical and Histological Factors Affecting Intranasal Drug and Vaccine Delivery. Current Drug Delivery n.d.;9:566–82.
Monti-Bloch L, Jennings-White C, Dolberg DS, Berliner DL. The human vomeronasal system. Psychoneuroendocrinology 1994;19:673–86. https://doi.org/10.1016/0306-4530(94)90049-3.
Ying W. The nose may help the brain: intranasal drug delivery for treating neurological diseases. Future Neurology 2008;3:1–4. https://doi.org/10.2217/14796708.3.1.1.
Behl CR, Pimplaskar HK, Sileno AP, Xia WJ, Gries WJ, deMeireles JC, et al. Optimization of systemic nasal drug delivery with pharmaceutical excipients. Advanced Drug Delivery Reviews 1998;29:117–33. https://doi.org/10.1016/S0169-409X(97)00064-1.
Aulton ME. Farmacia: La Ciencia y Diseño de Las Formas Farmacéuticas. 2nd ed. Elsevier España; 2004.
Aungst BJ. Absorption Enhancers: Applications and Advances. AAPS J 2012;14:10–8. https://doi.org/10.1208/s12248-011-9307-4.
Villafuerte Robles L. Los excipientes y su funcionalidad en productos farmacéuticos sólidos. Revista mexicana de ciencias farmacéuticas 2011;42:18–36.
Ghadiri M, Young PM, Traini D. Strategies to Enhance Drug Absorption via Nasal and Pulmonary Routes. Pharmaceutics 2019;11:113. https://doi.org/10.3390/pharmaceutics11030113.
Na L, Mao S, Wang J, Sun W. Comparison of different absorption enhancers on the intranasal absorption of isosorbide dinitrate in rats. International Journal of Pharmaceutics 2010;397:59–66. https://doi.org/10.1016/j.ijpharm.2010.06.048.
Leyva E, Moctezuma E, Leyva R, Oros S. Estudio de los complejos de inclusión de ácido nalidíxico y ácido oxolínico con ciclodextrinas. Revista de la Sociedad Química de México 2004;48:189–95.
Merkus FWHM, Verhoef JC, Marttin E, Romeijn SG, van der Kuy PHM, Hermens WAJJ, et al. Cyclodextrins in nasal drug delivery. Advanced Drug Delivery Reviews 1999;36:41–57. https://doi.org/10.1016/S0169-409X(98)00054-4.
Davis SS, Illum L. Absorption Enhancers for Nasal Drug Delivery. Clin Pharmacokinet 2003;42:1107–28. https://doi.org/10.2165/00003088-200342130-00003.
Connors KA. The Stability of Cyclodextrin Complexes in Solution. Chem Rev 1997;97:1325–58. https://doi.org/10.1021/cr960371r.
Brewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Advanced Drug Delivery Reviews 2007;59:645–66. https://doi.org/10.1016/j.addr.2007.05.012.
Villiers A. [On the fermentation of starch by the action of butyric ferment]. Comptes rendus de l’Académie des sciences Sci 1891;112:536–8.
Loftsson T, Duchêne D. Cyclodextrins and their pharmaceutical applications. Int J Pharm 2007;329:1–11. https://doi.org/10.1016/j.ijpharm.2006.10.044.
Muankaew C, Loftsson T. Cyclodextrin-Based Formulations: A Non-Invasive Platform for Targeted Drug Delivery. Basic & Clinical Pharmacology & Toxicology 2018;122:46–55. https://doi.org/10.1111/bcpt.12917.
Popr M. Synthesis of cyclodextrin derivates for practical applications. PhD Thesis. Charles University in Prague, 2016.
Balte AS, Goyal PK, Gejjia SP. Theoretical studies on the encapsulation of Paracetamol in the a, b and g Cyclodextrins. Journal of Chemical and Pharmaceutical Research 2012;4:2391–9.
Szejtli J. Past, present, and future of cyclodextrin research. Pure and Applied Chemistry 2004;76:1825–46.
Cheung RCF, Ng TB, Wong JH, Chan WY. Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications. Marine Drugs 2015;13:5156–86. https://doi.org/10.3390/md13085156.
Schipper NGM, Vårum KM, Stenberg P, Ocklind G, Lennernäs H, Artursson P. Chitosans as absorption enhancers of poorly absorbable drugs: 3: Influence of mucus on absorption enhancement. European Journal of Pharmaceutical Sciences 1999;8:335–43. https://doi.org/10.1016/S0928-0987(99)00032-9.
Dodane V, Vilivalam VD. Pharmaceutical applications of chitosan. Pharmaceutical Science & Technology Today 1998;1:246–53. https://doi.org/10.1016/S1461-5347(98)00059-5.
Illum L, Jabbal-Gill I, Hinchcliffe M, Fisher AN, Davis SS. Chitosan as a novel nasal delivery system for vaccines. Advanced Drug Delivery Reviews 2001;51:81–96. https://doi.org/10.1016/S0169-409X(01)00171-5.
Wikimedia Commons contributors. File:Chitosan chemical structural formula.svg. Wikimedia Commons, the Free Media Repository 2014. https://commons.wikimedia.org/wiki/File:Chitosan_chemical_structural_formula.svg (accessed March 14, 2022).
Bansal V, Sharma P, Sharma N, Pal O, Malviya R. Applications of Chitosan and Chitosan Derivatives in Drug Delivery. Advances in Biological Research 2011;5:28–37.
Shariatinia Z. Pharmaceutical applications of chitosan. Advances in Colloid and Interface Science 2019;263:131–94. https://doi.org/10.1016/j.cis.2018.11.008.
Aspden TJ, Mason JDT, Jones NS, Lowe J, Skaugrud Ø, Illum L. Chitosan as a Nasal Delivery System: The Effect of Chitosan Solutions on in Vitro and in Vivo Mucociliary Transport Rates in Human Turbinates and Volunteers. Journal of Pharmaceutical Sciences 1997;86:509–13. https://doi.org/10.1021/js960182o.
Suhail M, Janakiraman AK, Khan A, Naeem A, Badshah SF. Surfactants and their role in Pharmaceutical Product Development: An Overview. Journal of Pharmacy and Pharmaceutics 2019;6:72–82.
Sekhon BS. Surfactants: Pharmaceutical and Medicinal Aspects. Journal of Pharmaceutical Technology, Research and Management 2013;1:43–68. https://doi.org/10.15415/jptrm.2013.11004.
Kulkarni VS, Shaw C. Essential Chemistry for Formulators of Semisolid and Liquid Dosages. 1st ed. London, United Kingdom: Academic Press; 1999.
De S, Malik S, Ghosh A, Saha R, Saha B. A review on natural surfactants. RSC Adv 2015;5:65757–67. https://doi.org/10.1039/C5RA11101C.
Schreier S, Malheiros SVP, de Paula E. Surface active drugs: self-association and interaction with membranes and surfactants. Physicochemical and biological aspects. Biochimica et Biophysica Acta (BBA) - Biomembranes 2000;1508:210–34. https://doi.org/10.1016/S0304-4157(00)00012-5.
Tadros T. Chemical Technology of Cosmetics. 1st ed. New Jersey, USA: John Wiley & Sons, Inc; 2013.
National Center for Biotechnology Information. PubChem Compound Summary for CID 14250, Cetrimide 2022. https://pubchem.ncbi.nlm.nih.gov/compound/Cetrimide (accessed March 14, 2022).
National Center for Biotechnology Information. PubChem Compound Summary for CID 16700, Ammonium dodecyl sulfate 2022. https://pubchem.ncbi.nlm.nih.gov/compound/Ammonium-dodecyl-sulfate. (accessed March 14, 2022).
National Center for Biotechnology Information. PubChem Compound Summary for CID 443314, Polysorbate 20 2022. https://pubchem.ncbi.nlm.nih.gov/compound/Tween-20 (accessed March 14, 2022).
National Center for Biotechnology Information. PubChem Compound Summary for CID 10425705, Phospholipids egg n.d. https://pubchem.ncbi.nlm.nih.gov/compound/Phospholipids-egg (accessed March 15, 2022).
Rosen MJ. Characteristic Features of Surfactants. Surfactants and Interfacial Phenomena. 3rd ed., New Jersey, USA: John Wiley & Sons, Ltd; 2004, p. 1–15. https://doi.org/10.1002/9781118228920.ch1.
Inactive Ingredient Search for Approved Drug Products n.d. https://www.accessdata.fda.gov/scripts/cder/iig/index.cfm (accessed August 25, 2022).
Chhajed S, Sangale S, Barhate SD. Advantageous Nasal Drug Delivery System: A Review. International Journal of Pharmaceutical Sciences and Research 2011;2:1322–30.
Li Y, Li J, Zhang X, Ding J, Mao S. Non-ionic surfactants as novel intranasal absorption enhancers: in vitro and in vivo characterization. Drug Delivery 2016;23:2272–9. https://doi.org/10.3109/10717544.2014.971196.
Velloso MI, Andreeta HA, Landoni MF. Effect of two surfactants on in vitro permeation of butorphanol through horse nasal mucosa. Uniciencia 2021;35:1–9. https://doi.org/10.15359/ru.35-2.1.
Vijayakuma S, Varatharajan S. Biosurfactants-Types, Sources and Applications. Research Journal of Microbiology 2015;10:181–92. https://doi.org/10.3923/jm.2015.181.192.
Pavlović N, Goločorbin-Kon S, Ðanić M, Stanimirov B, Al-Salami H, Stankov K, et al. Bile Acids and Their Derivatives as Potential Modifiers of Drug Release and Pharmacokinetic Profiles. Frontiers in Pharmacology 2018;9.
Moghimipour E, Ameri A, Handali S. Absorption-Enhancing Effects of Bile Salts. Molecules 2015;20:14451–73. https://doi.org/10.3390/molecules200814451.
Moiseev RV, Morrison PWJ, Steele F, Khutoryanskiy VV. Penetration Enhancers in Ocular Drug Delivery. Pharmaceutics 2019;11:321. https://doi.org/10.3390/pharmaceutics11070321.
Faustino C, Serafim C, Rijo P, Reis CP. Bile acids and bile acid derivatives: use in drug delivery systems and as therapeutic agents. Expert Opinion on Drug Delivery 2016;13:1133–48. https://doi.org/10.1080/17425247.2016.1178233.
Stojančević M, Pavlović N, Goločorbin-Kon S, Mikov M. Application of bile acids in drug formulation and delivery. Frontiers in Life Science 2013;7:112–22. https://doi.org/10.1080/21553769.2013.879925.
Wikimedia Commons contributors. File:Lithocholic acid acsv.svg. Wikimedia Commons, the Free Media Repository n.d. https://commons.wikimedia.org/w/index.php?title=File:Lithocholic_acid_acsv.svg&oldid=637160850 (accessed March 15, 2022).
Bhattacharjee J, Verma G, Aswal VK, Date AA, Nagarsenker MS, Hassan PA. Tween 80−Sodium Deoxycholate Mixed Micelles: Structural Characterization and Application in Doxorubicin Delivery. J Phys Chem B 2010;114:16414–21. https://doi.org/10.1021/jp108225r.
Maestrelli F, Cirri M, Mennini N, Zerrouk N, Mura P. Improvement of oxaprozin solubility and permeability by the combined use of cyclodextrin, chitosan, and bile components. European Journal of Pharmaceutics and Biopharmaceutics 2011;78:385–93. https://doi.org/10.1016/j.ejpb.2011.03.012.
Mukaizawa F, Taniguchi K, Miyake M, Ogawara K, Odomi M, Higaki K, et al. Novel oral absorption system containing polyamines and bile salts enhances drug transport via both transcellular and paracellular pathways across Caco-2 cell monolayers. International Journal of Pharmaceutics 2009;367:103–8. https://doi.org/10.1016/j.ijpharm.2008.09.027.
Duchateau GSMJE, Zuidema J, Merkus FWHM. Bile salts and intranasal drug absorption. International Journal of Pharmaceutics 1986;31:193–9. https://doi.org/10.1016/0378-5173(86)90153-5.
Park G-B, Shao Z, Mitra AK. Acyclovir Permeation Enhancement Across Intestinal and Nasal Mucosae by Bile Salt-Acylcarnitine Mixed Micelles. Pharm Res 1992;9:1262–7. https://doi.org/10.1023/A:1015845031488.
Lee WA, Lu HF-L, Maffuid PW, Botet MT, Baldwin PA, Benkert TA, et al. The synthesis, characterization and biological testing of a novel class of mucosal permeation enhancers. Journal of Controlled Release 1992;22:223–37. https://doi.org/10.1016/0168-3659(92)90097-B.
Beaudoin M, Carey MC, Small DM. Effects of taurodihydrofusidate, a bile salt analogue, on bile formation and biliary lipid secretion in the rhesus monkey. J Clin Invest 1975;56:1431–41. https://doi.org/10.1172/JCI108224.
Longenecker JP, Moses AC, Flier JS, Silver RD, Carey MC, Dubovi EJ. Effects of Sodium Taurodihydrofusidate on Nasal Absorption of Insulin in Sheep. Journal of Pharmaceutical Sciences 1987;76:351–5. https://doi.org/10.1002/jps.2600760502.
National Center for Biotechnology Information. PubChem Compound Summary for CID 44144474, Sodium taurodihydrofusidate. n.d. https://pubchem.ncbi.nlm.nih.gov/compound/Sodium-taurodihydrofusidate. (accessed March 15, 2022).
Deurloo MJM, Hermens WAJJ, Romeyn SG, Verhoef JC, Merkus FWHM. Absorption Enhancement of Intranasally Administered Insulin by Sodium Taurodihydrofusidate (STDHF) in Rabbits and Rats. Pharm Res 1989;6:853–6. https://doi.org/10.1023/A:1015904404442.
Baldwin PA, Klingbeil CK, Grimm CJ, Longenecker JP. The Effect of Sodium Tauro-24,25-Dihydrofusidate on the Nasal Absorption of Human Growth Hormone in Three Animal Models. Pharm Res 1990;7:547–52. https://doi.org/10.1023/A:1015885204249.
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;9:52–7. https://doi.org/10.1023/A:1018927710280.
Dondeti P. Development of a New Non-surgical Perfusion Technique to Evaluate Nasal Drug Delivery. Master’s Thesis. University of Rhode Island, 1991.
Drescher S, van Hoogevest P. The Phospholipid Research Center: Current Research in Phospholipids and Their Use in Drug Delivery. Pharmaceutics 2020;12:1235. https://doi.org/10.3390/pharmaceutics12121235.
Li J, Wang X, Zhang T, Wang C, Huang Z, Luo X, et al. A review on phospholipids and their main applications in drug delivery systems. Asian Journal of Pharmaceutical Sciences 2015;10:81–98. https://doi.org/10.1016/j.ajps.2014.09.004.
Ishii F, Nii T. Properties of various phospholipid mixtures as emulsifiers or dispersing agents in nanoparticle drug carrier preparations. Colloids and Surfaces B: Biointerfaces 2005;41:257–62. https://doi.org/10.1016/j.colsurfb.2004.12.018.
Lee M-K. Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence and Recent Approaches. Pharmaceutics 2020;12:264. https://doi.org/10.3390/pharmaceutics12030264.
Drejer K, Vaag A, Bech K, Hansen P, Sørensen A r., Mygind N. Intranasal Administration of Insulin With Phospholipid as Absorption Enhancer: Pharmacokinetics in Normal Subjects. Diabetic Medicine 1992;9:335–40. https://doi.org/10.1111/j.1464-5491.1992.tb01792.x.
Alsarra IA, Hamed AY, Alanazi FK. Acyclovir Liposomes for Intranasal Systemic Delivery: Development and Pharmacokinetics Evaluation. Drug Delivery 2008;15:313–21. https://doi.org/10.1080/10717540802035251.
Natsheh H, Touitou E. Phospholipid Vesicles for Dermal/Transdermal and Nasal Administration of Active Molecules: The Effect of Surfactants and Alcohols on the Fluidity of Their Lipid Bilayers and Penetration Enhancement Properties. Molecules 2020;25:2959. https://doi.org/10.3390/molecules25132959.
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