SITE SPECIFIC DRUG DELIVERY THROUGH NASAL ROUTE USING BIOADHESIVE POLYMERS
Abstract
This review explains some aspects of mucoadhesion related to the nasal drug delivery system. On the first count, the theories of the adhesion of mucoadhesive polymers to the mucosa epithelium are described. Secondly, the characteristics and application of several widely used mucoadhesive polymers in nasal drug delivery are presented. The nasal mucosa provides a potentially good route for systemic drug delivery. One of the most important features of the nasal route is that it avoids first-pass hepatic metabolism, thereby reducing metabolism. The application of mucoadhesive polymers in nasal drug delivery systems has gained to promote dosage form residence time in the nasal cavity as well as improving intimacy of contact with absorptive membranes of the biological system. The aspiration of any drug delivery system is to endow with a therapeutic amount of drug to the proper site in the body to achieve promptly & then uphold the desired drug concentration. That is why the drug delivery system should deliver drug at a state dictated by the needs of the body over a specified period of treatment. This idealized objective points to the two aspects most important to drug delivery, namely, spatial placement relates to targeting a drug to a specific organ or tissue while temporal delivery refers to the control of rate of drug delivery to the target tissue. Over the last few decades, the relevance of mucoadhesive polymers in nasal drug delivery systems has gained significance among pharmaceutical scientists as a means of promoting dosage form residence time in the nasal cavity as well as for improving intimacy of contact with absorptive membranes of the biological system. In addition, the improved paracellular absorption subsequent the swelling of the mucoadhesive polymers on the nasal membranes provides an important way for the absorption of the macromolecules through the nasal cavity.
Keywords: Nasal route, Mucoadhesive polymers, Paracellular absorption,
DOI
https://doi.org/10.22270/jddt.v5i1.873References
Asane GS, Nirmal SA, Rasal KB, Naik AA, Mahadik MS, Madhusudan Rao YM. Polymers for mucoadhesive drug delivery system: A current status. Drug Dev Ind Pharm. 2008; 34:1246 66.
KR Kamath, K Park. Mucosal Adhesive Preparations. In Encyclopedia of Pharmaceutical Technology: Swarbrick J, Boylon J.C. 1st Eds. Vol-10, Marcel Dekker, New York, 1994, 133.
Gavini E, Hegge AB, Rassu G, Sanna V, Testa C, Pirisino G, Karlsen J, Giunchedi P. Nasal
administration of Carbamazepine using chitosan microspheres: In vitro/in vivo studies Int J Pharm. 2006;307(1): 9–15
Mainardes RM, Urban MC, Cinto PO, Chaud MV, Evangelista RC, Gremiao MP. Liposomes and micro / nanoparticles as colloidal carriers for nasal drug delivery. Curr Drug Deliv. 2006; 3(3): 275-85.
Ugwoke MI, Verbeke N, Kinget R. The biopharmaceutical aspects of nasal mucoadhesive drug delivery. J Pharm Pharmacol. 2001; 53(1):3–21.
Song K, Fasano A, Eddington ND. Enhanced nasal absorption of hydrophilic markers after dosing with AT1002, a tight junction modulator. Eur J Pharm Biopharm. 2008; 69(1):231–7.
Khafagy E, Morishita M, Isowa K, Imai J, Takayama K. Effect of cell-penetrating peptides on the nasal absorption of insulin. J Control Release. 2009; 133(2):103–8.
Li L, Nandi I, Kim KH. Development of an ethyl laurate based microemulsion for rapid-onset intranasal delivery of diazepam. Int J Pharm. 2002; 237(1-2):77–85.
Zaki NM, Awad GAS, Mortada ND, Abdelhady SS. Rapid-onset intranasal delivery of metoclopramide hydrochloride: Part I: Influence of formulation variables on drug absorption in anesthetized rats. Int J Pharm. 2006; 327(1-2):89–96.
Illum L, Fisher AN, Jabbal-Gill I, Davis SS. Bioadhesive starch microspheres and absorption enhancing agents act synergistically to enhance the nasal absorption of polypeptides. Int J Pharm. 2001; 222(1):109–19.
Romeo VD, DeMeireles JC, Gries WJ, Xia WJ, Sileno AP, Pimplaskar HK, Behl CR. Optimization of systemic nasal drug delivery with pharmaceutical excipients. Adv Drug Deliv Rev. 1998; 29: 117–33.
Farraj NF, Johansen BR, Davis SS, Illum L. Nasal administration of insulin using bioadhesive microspheres as a delivery system. J Control Release. 1990; 13(2-3):253–61.
Hascicek C, Gonul N, Erk N. Mucoadhesive microspheres containing gentamicin sulfate for nasal administration:Preparation and in vitro characterization. IL Farmaco. 2003; 58(1):11–6.
Harris AS. Review: Clinical opportunities provided by the nasal administration of peptides. J Drug Targeting. 1993;1:101–16.
Longer MA, Robinson JR. Fundamental aspects of bioadhesion. Pharm Int. 1986; 7:114–7.
Gu JM, Robinson JR, Leung SH. Binding of acrylic polymers to mucin/epithelial surfaces: Structure-property relationships. Crit Rev Ther Drug Carrier Syst. 1988; 5(1):21–67.
Jimenez-Castellanos MR, Zia H, Rhodes CT. Mucoadhesive drug delivery systems. Drug Dev Ind Pharm.1993; 19(1-2):143–94.
Sriamornsak P, Wattanakorn N, Nunthanid J, Puttipipatkhachorn S. Mucoadhesion of pectin as evidence by wettability and chain interpenetration. Carbohydr Polymers. 2008; 74(3):458–67.
Smart JD. The basics and underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev.2005;57(11):1556–68.
Jabbari E, Wisniewski N, Peppas NA. Evidence of mucoadhesion by chain interpenetration at a poly (acrylicacid)/mucin interface using ATRFTIR spectroscopy. J Control Release.1993; 26(2):99–108.
Grabovac V, Guggi D, Bernkop-Schnurch A. Comparison of the mucoadhesive properties of various polymers. Adv Drug Deliv Rev.2005; 57:1713–23.
Accili D, Menghi G, Bonacucina G, Martino PD, Palmieri GF. Mucoadhesion dependence of pharmaceutical polymers on mucosa characteristics. Eur J Pharm Sci. 2004; 22(4):225–34.
Nakamura K, Maitani Y, Lowman AM, Takayama K, Peppas NA, Nagai T. Uptake and release of budesonide from mucoadhesive, pH-sensitive copolymers and their application to nasal delivery. J Control Release 1999, 61,329– 335.
Park JS, Oh YK, Yoon H, Kim JM, Kim CK. In situ gelling and mucoadhesive polymer vehicles for controlled intranasal delivery of plasmid DNA. J Biomed Mater Res 2002, 59,144–151.
Joshi M, Misra A. Dry powder inhalation of liposomal Ketotifen fumarate; formulation and characterization. Int J Pharm. 2001; 223:15–27.
Kublik H, Vidgren MT. Nasal delivery systems and their effect on deposition and absorption. Adv Drug Deliv Rev. 1998; 29:157–77.
Castellanos J, Zia H, Rhodes CT. Mucoadhesive drug delivery systems. Drug Dev Ind Pharm. 1993; 19:143–94.
Lee WA, Narog BA, Patapoff TW, Wang YJ. Intranasal bioavailability of insulin powder formulations: Effect of permeation enhancer-to-protein ratio. J Pharm Sci. 1991; 80:725–9.
Sankar C, Rani M, Srivastava AK, Mishra B., Chitosan based pentazocine microspheres for intranasal systemic delivery: Development and biopharmaceutical evaluation. Pharmazie. 2001; 56:223–6.
Lim ST, Forbes B, Martin GP, Brown MB., In vivo and in vitro characterization of novel microparticulates based on hyaluronan and chitosan hydroglutamate. AAPS PharmSci Tech. 2001; 2(4):20.
Mao S, Chen J, Wei Z, Liu H, Bi D., Intranasal administration of melatonin starch microspheres. Int J Pharm. 2004; 272:37–43.
Pringels E, Vervaet C, Verbeeck R, Foreman P, Remon JP., The addition of calcium ions to starch/carbopol mixtures enhances the nasal bioavailability of insulin. Eur J Pharm Biopharm. 2008; 68:201–6.
Illum L, Fisher AN, Jabbal-Gill I, Davis SS. Bioadhesive starch microspheres and absorption enhancing agents act synergistically to enhance the nasal absorption of polypeptides. Int J Pharm. 2001; 222(1):109–19.
Sinswat P, Tengamnuay P., Enhancing effect of chitosan on nasal absorption of salmon calcitonin in rats: Comparison with hydroxypropyl-beta and dimethyl-betacyclodextrins. Int J Pharm, 2003; 257:15–22.
Yu S, Zhao Y, Wu F, Zhang X, Lu W, Zhang H, Zhang Q. Nasal insulin delivery in the chitosan solution: In vitro and in vivo studies. Int J Pharm. 2004; 281:11–23.
Lim ST, Forbes B, Berry DJ, Martin GP, Brown MB., In vivo evaluation of novel hyaluronan/chitosan microparticulate delivery systems for the nasal delivery of gentamicin in rabbits. Int J Pharm. 2002; 231:73–82.
Vivien N, Buri P, Balant L, Lacroix S., Nasal absorption of metoclopramide administered to man. Eur J Pharm Biopharm. 1994; 40:228–31.
Shahiwala A, Misra A. Nasal delivery of levonorgestrel for contraception: An experimental study in rats. Fertil Steril. 2004;81:893–8.
Paul W, Sharma CP. Chitosan, a drug carrier for the 21st century: A review. STP Pharm Sci. 2000; 10(1):5–22.
Zaki NM, Mortada ND, Awad GAS, Abd Elhady SS. Rapid-onset intranasal delivery of metoclopramide hydrochloride Part II: Safety of various absorption enhancers and pharmacokinetic evaluation. Int J Pharm. 2006; 327:97–103.
Dondeti P, Zia H, Needham TE., In vivo evaluation of spray formulations of human insulin for nasal delivery. Int J Pharm. 1995; 122: 91–105.
Loftsson T, Gudmundsdottir H, Sigurjonsdottir JF, Sigurdsson HH, Sigfusson SD, Masson M, Stefansson E. Cyclodextrin solubilization of benzodiazepines: Formulation of midazolam nasal spray. Int J Pharm. 2001;212:29–40.
Zaki NM, Awada GA, Mortadaa ND, Abd Elhadyb 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.
Ozsoy Y, Tuncel T, Can A, Akev N, Birteksoz S, Gerceker A. In vivo studies on nasal preparations of ciprofloxacin hydrochloride. Pharmazie. 2000; 55(8):607–9.
Issa MM, Koping-Hoggard M, Artursson P. Chitosan and the mucosal delivery of biotechnology drugs. Drug Discov Today. 2005; 2(1):1–6.
Paul W, Sharma CP. Chitosan, a drug carrier for the 21st century: A review. STP Pharm Sci. 2000; 10(1):5–22.
Illum L. Nasal drug delivery: New developments and strategies. Drug Discov Today. 2002; 7:1184–9.
Soane RJ, Hinchcliffe M, Davis SS, Illum L. Clearance characteristics of chitosan based formulations in the sheep nasal cavity. Int J Pharm. 2001; 217(1-2):183–91.
Kotze AF, Luesen HL, De Boer AG, Verhoef JC, Junginger HE. Chitosan for enhanced intestinal permeability: Prospects for derivatives soluble in neutral and basic environments. Eur J Pharm Sci.1999;7:145–51.
Thanou M, Verhoef JC, Verheijden JH, Junginger HE. Intestinal absorption of octeriotide: N-trimethyl chitosan chloride (TMC) ameliorates the permeability and absorption properties of the somatostatin analogue in vitro and in vivo. J Pharm Sci. 2000; 89:951–7.
Lai WF, Lin MC. Nucleic acid delivery with chitosan and its derivatives. J Control Release. 2009;134:158–68.
Mei D, Mao S, Sun W, Wang Y, Kissel T. Effect of chitosan structure properties and molecular weight on the intranasal absorption of tetramethylpyrazine phosphate in rats. Eur J Pharm Biopharm.2008;70:874–81.
Tengamnuay P, Sahamethapat A, Sailasuta A, Mitra AK. Chitosans as nasal absorption enhancers of peptides: Comparison between free amine chitosans and soluble salts. Int J Pharm. 2000; 197:53–67.
Quadir M, Zia H, Needham TE. Toxicological implications of nasal formulations. Drug Del. 1999;6:227–42.
Callens C, Pringels E, Remon JP. Influence of multiple nasal administrations of bioadhesive powders on the insulin bioavailability. Int J Pharm. 2003; 250:415–22.
Bjork E, Bjurstrom S, Edman P. Morphologic examination of rabbit nasal mucosa after nasal administration of degradable starch microspheres. Int J Pharm.1991; 75:73–79.
Holmberg K, Bjork E, Bake B, Edman P. Influence of degradable starch microspheres on human nasal mucosa. Rhinology. 1994; 32(2):74–7.
Bjork E, Edman P. Characterization of degradable starch microspheres as a nasal delivery system for drugs. Int J Pharm. 1990; 62(2-3):187–92.
Illum L, Jorgensen H, Bisgaard H, Krogsgaard O, Rossing N. Bioadhesive microspheres as a potential nasal drug delivery system. Int J Pharm. 1987; 39(3):189–99.
Zaki NM, Awada GA, Mortadaa ND, Abd ElHadyb SS. Enhanced bioavailability of metoclopramide HCl by intranasal administration of mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. Eur J Pharm Sci. 2007; 32:296–307.
Wang X, Chi N, Tang X. Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting. Eur J Pharm Biopharm. 2008;70:735–40.
Ikeda K, Murata K, Kobayashi M, Noda K. Enhancement of bioavailability of dopamine via nasal route in beagle dogs. Chem Pharm Bull. 1992; 40(8):2155–8.
Bommareddy GS, Paker-Leggs S, Saripella KK, Neau SH. Extruded and spheronized beads containing Carbopol 974P to deliver non electrolytes and salts of weakly basic drugs. Int J Pharm. 2006; 321(1-2):62–71.
Qi H, Chen W, Huang C, Li L, Chen C, Li W, Wu C. Development of a poloxamer analogs/carbopol-based in situ gelling and mucoadhesive ophthalmic delivery system for puerarin. Int J Pharm. 2007; 337(1-2):178–87.
Funke AP, Gunther C, Muller RH, Lipp R. In-vitro release and transdermal fluxes of a highly lipophilic drug and of enhancers from matrix TDS. J Control Release 2002; 82(1):63–70.
Liu W, Hu M, Liu W, Xue C, Xu H, Yang X. Investigation of the carbopol gel of solid lipid nanoparticles for the transdermal iontophoretic delivery of triamcinolone acetonide acetate. Int J Pharm. 2008; 364(1):135–41.
Callens C, Remon JP. Evaluation of starch maltodextrin-Carbopol 974P mixtures for the nasal delivery of insulin in rabbits. J Control Release. 2000; 66(2-3):215–20.
Callens C, Adriaens E, Dierckens K, Remon JP. Toxicological evaluation of a bioadhesive nasal powder containing a starch and Carbopol 974 P on rabbit nasal mucosa and slug mucosa. J Control Release. 2001; 76(1-2):81–91
Ugwoke MI, Sam E, Van Den Mooter G, Verbeke N, Kinget R. Nasal mucoadhesive delivery systems of the anti-Parkinsonian drug, apomorphine: Influence of drugloading on in vitro and in vivo release in rabbits. Int J Pharm. 1999; 181:125–38.
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