Mucoadhesive and muco-penetrating delivery systems for eradication of Helicobacter pylori
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Abstract
complete eradication has major limitations like low residence time of delivery system in stomach, poor penetration of drug in gastric mucosa, acidic degradation of antibiotics, and development of antibiotics resistance. The poor penetration
of antibiotics through thick viscoelastic mucosal gel results in incomplete eradication of H. pylori. Various investigators have formulated novel gastro-retentive drug delivery systems such as floating systems, mucoadhesive systems, pH-sensitive gel systems, and muco-penetrating delivery systems for increasing the concentration of antibiotic in close proximity to the site of H. pylori infection. This review summarizes the novel drug delivery approaches investigated during the last few years and suggests that a high eradication rate can be achieved by therapy comprising of muco-penetrating delivery systems of
antibiotics against H. pylori.
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References
Warren JR, Marshall BJ. Unidentified curved bacilli on gastric epithelium
in active chronic gastritis. Lancet 1983;342:1273-75.
Malfertheiner P, Selgrad M. Helicobacter pylori infection and current
clinical areas of contention. Curr Opin Gastroenterol 2010;26:618-23.
Cover TL, Blaser MJ. Helicobacter pylori in health and disease.
Gastroenterology 2009;136:1863-73.
Blaser MJ, Atherton JC. Helicobacter pylori persistence: Biology and
disease. J Clin Invest 2004;113:321-33.
Graham DY. Campylobacter pylori and peptic ulcer disease.
Gastroenterology 1989;96:615-25.
Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH,
Orentreich N. Helicobacter pylori infection and the risk of gastric
carcinoma. N Engl J Med 1991;325:1127-31.
Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, De Boni M,
et al. Regression of primary low grade B-cell gastric lymphoma of
mucosa-associated lymphoid tissue type after eradication of Helicobacter
pylori. Lancet 1993;342:575-7.
Targa AC, Cesar AC, Cury PM, Silva, AE. Apoptosis in different gastric
lesions and gastric cancer: Relationship with Helicobacter pylori,
overexpression of p53 and aneuploidy. Genet Mol Res 2007;6:554-65.
Mishra S, Singh V, Rao GRK, Dixit VK, Gulati AK, Nath G. Prevalence
of Helicobacter pylori in asymptomatic subjects—A nested PCR based
study. Infect Genet Evol 2008;8:815-9.
Singh V, Mishra S, Maurya P, Rao G, Jain AK, Dixit VK, et al. Drug
resistance pattern and clonality in H. pylori strains. J Infect Develop
Count 2009;3:130-6.
Endo H, Yoshida H, Ohmi N, Ohta K, Higuchi S. Localization of [14C]
amoxicillin in rat gastric tissue when administered with lansoprazole
and clarithromycin. J Antimicrob Chemother 2001;48:923-6.
Endo H, Yoshida H, Ohmi N, Ohta K, Higuchi S, Suga T. Localization
of [14C] clarithromycin in rat gastric tissue when administered with
lansaprazole and amoxicillin. J Antimicrob Chemother 2002;50:285-8.
Schreiber S, Scheid P. Gastric mucus of the guinea pig: Proton carrier
and diffusion barrier. Am J Physiol 1997;272:G63-70.
Worku ML, Sidebotham RL, Walker MM, Keshavarz T, Karim QN. The
relationship between Helicobacter pylori motility, morphology and
phaseof growth: Implications for gastric colonization and pathology.
Microbiology 1999;145:2803-11.
Celli JP, Turner BS, Afdhal NH, Keates S, Ghiran I, Kelly CP, et al. Helicobacter pylori moves through mucus by reducing mucin viscoelasticity. Proc Natl Acad Sci U S A 2009;106:1421-6.
Ho SB, Shekels LL, Toribara NW, Kim YS, Lyftogt C, Cherwitz DL, et al.
Mucin gene expression in normal, preneoplastic, andneoplastic human
gastric epithelium. Cancer 1995;55:2681-90.
Ozbek A, Ozbek E, Dursun H, Kalkan Y, Demirci T. Can Helicobacter
pylori invade human gastric mucosa? An in vivo study using electron
microscopy, immunohistochemical methods, and real-time polymerase
chain reaction. J Clin Gastroenterol 2010;44:416-22.
Eaton KA, Morgan DR, Krakowka S. Motility as a factor in the
colonization of gnotobiotic piglets by Helicobacter pylori. J Med
Microbiol 1992;37:123-7.
Eaton KA, Krakowka S. Effect of gastric pH on urease-dependent
colonization of gnotobiotic piglets by Helicobacter pylori. InfectImmun
;62:3604-7.
Moran AP. Relevance of fucosylation and Lewis antigen expression
in the bacterial gastroduodenal pathogen H. pylori. Carbonhydr Res
;343:1952-65.
Ilver D, Arnqvist A, Ogren J, Frick IM, Kersulyte D, Incecik ET, et al.
Helicobacter pylori adhesion binding fucosylatedhisto-blood group
antigens revealed by retagging. Science 1998;279:373-7.
Mahdavi J, Sonden B, Hurtig M, Olfat FO, Forsberg L, Roche N, et al.
Helicobacter pylori Sab Aadhesin in persistent infection and chronic
inflammation. Science 2002;297:573-8.
Yamaoka Y. Roles of Helicobacter pylori BabA in gastroduodenal
pathogenesis. World J Gastroenterol 2008;14:4265-72.
Sheu BS, Sheu SM, Yang HB, Huang AH, Wu JJ. Host gastric Lewis
expressions determine the bacterial density of babA2-genopositve H.
pyloriinfection. Gut 2003;52:927-32.
Papini E, Zorrati M, Cover TL. In search of Helicobacter pylori Vac A
mechanism of action. Toxin 2001;39:1757-67.
Iijima K, Sekin H, Kokie T, Imatani A, Ohara S, Shimosegawa T.
Long term effect of H. pylori eradication on the reversibility of acid
secretion in profound hydrochlorhydria. Aliment Pharmacol Ther
;19:1181-8.
Ghiara P. Therapeutic intragastric vaccination against Helicobacter
pylori in mice eradicates an otherwise chronic infection and confers
protection against reinfection. Infect Immun 1997;65:4996-5002.
Rad R, Gerhard R, Lang M. The Helicobacter pylori blood group antigen-
binding adhesin facilitates bacterial colonization and augments a
nonspecific immune response. J Immunol 2002;168:3033-41.
Tannaes T, Bukholm IK, Bukholm G. High relative content of
lysophospholipids of Helicobacter pylori mediates increased risk for
ulcer disease. Immunol Med Microbiol 2005;44:17-23.
Jonge D, Durrani RZ, Rijpkema SG. Role of the Helicobacter pylori outer-
membrane proteins AlpA and AlpB in colonization of the guinea pig
stomach. J Med Microbiol 2004;53:375-9.
Figueiredo C, Quint WG, Sanna R. Genetic organization and heterogeneity
of the iceA locus of Helicobacter pylori. Gene 2000;246:59-68.
Lu H, Hsu PI, Graham DY, Yamaoka Y. Duodenal ulcer promoting gene
of Helicobacter pylori. Gastroenterology 2005;128:833-48.
Kudo T, Nurgalieva ZZ, Conner ME, Crawford S, Odenbreit S, Haas R.
Correlation between Helicobacter pyloriOipA protein expression and
oipAgene switch status. J Clin Microbiol 2004;42:2279-81.
Pedrazzoli J Jr, Calafatti SA, Ortiz RA, Dias FE, Deguer M, Mendes FD,
et al. Transfer of clarithromycin to gastric juice is enhanced by
omeprazole in Helicobacter pylori-infected individuals. Scand J
Gastroenterol 2001;36:1248-53.
Uygun A, Kadayifci A, Yesilova Z, Ates Y, Safali M, Ilgan S, et al. Poor
efficacy of ranitidine bismuth citrate – based triple therapies for
eradication. Indian J Gastroenterol 2007;26:174-7.
Bhatia SJ, Kulkarni SG. Cost effectiveness of Helicobactor pylori
Eradication in India: To live and let live... expensively?. Indian J
Gastroenterol 1997;16:S25.
Kato M, Yamaoka Y, Kim JJ, Reddy R, Asaka M, Kashina K, et al. Regional
differences in metronidazole resistance and increasing clarithromycin
resistance among H. pylori isolates from Japan. Antimicrob Agent
Chemother 2000;44:2214-6.
Ramteke S, Ganesh N, Bhattacharya A, Jain NK. Amoxicillin,
clarithromycin, and omeprazole based targeted nanoparticles for the
treatment of H. pylori. J Drug Targeting 2009;17:225-34.
Achtman M, Azuma T, Berg DE, Ito Y, Morelli G, Pan ZJ, et al.
Recombination and clonal groupings within Helicobacter pylori from
different geographical regions. Mol Microbiol 1999;32:459-70.
Suerbaum S, Smith JM, Bapumia K, Morelli G, Smith NH, Dyrek EKI,et al.
Free recombination within Helicobacter pylori. Proc Nat Acad Scien
;95:12619-24.
Mégraud F. H. pylori antibiotic resistance: Prevalence, importance, and
advances in testing. Gut 2004;53:1374.
Cooreman MP, Krausgrill P, Hengels KJ. Local gastric and serum
amoxicillin concentration after different oral application forms.
Antimicrob Agents Chemother 1993;37:1506-9.
Moes AJ. Gastric retention systems for oral drug delivery. Business
Briefing: Pharmatech; 2003. p. 157-9.
Krogel I, Bodmeier R. Development of a multifunctional matrix drug
delivery system surrounded by an impermeable cylinder. J Control
Release 1999;61:43-50.
Sriamornsak P, Thirawong N, Puttipipatkhachorn S. Emulsion gel beads
of calcium pectinate capable of floating on the gastric fluid: Effect of
some additives, hardening agent or coating on release behavior of
metronidazole. Eur J Pharm Sci 2005;24:363-73.
Streubel A, Siepmann J, Bodmeier R. Floating microparticles based on
low density foam powder. Int J Pharm 2002;241:279-92.
Lai SK, Wang YY, Hanes J. Mucus-penetrating nanoparticles for drug and
gene delivery to mucosal tissues. Adv Drug Del Rev 2009;61:158-71.
Wilding IR, Davis SS, O’Hagan DT. Targeting of drugs and vaccines to
the gut. Pharmacol Ther 1994;62:97-124.
Caldwell LJ, Gardner CR, Cargill RC. Drug delivery device which can
be retained in the stomach for a controlled period of time. US Patent
, April 5,1988.
Kagan L, Hoffman A. Systems for region selective drug delivery in the
gastrointestinal tract: Biopharmaceutical considerations. Expert Opin
Drug Del 2008;5:681-92.
Nama M, Gonugunta CSR, Veerareddy PR. Formulation and evaluation
of gastroretentive dosage forms of Clarithromycin. AAPS PharmSciTech
;9:231-37.
Thakkar VT, Shah PA, Soni TG, Parmar MY, Gohel MC, Gandhi TR.
Fabrication and evaluation of levofloxacin hemihydrate floating tablet.
Research in Pharmaceutical Sciences 2008;3:65-72.
Barhate SD, Patel MM, Patil AB, Pawar SR, Rathi SR.Formulation and
optimization of controlled released floating tablets of Clarithromycin.
J Pharm Res 2009;2:445-8.
Gnanaprakash K, Chandhrashekhar KB, Chetty CM. Floating tablets of
Famotidine with natural polymer: An approach for gastric treatment.
J Pharm Sci Res 2010;2:657-62.
Timmermans J, Andre JM. Factors controlling the buoyancy and
gastric retention capabilities of floating matrix capsules: New data for
reconsidering the controversy. J Pharm Sci 1994;83:18-24.
Vyas SP, Khar RK. Gastroretentive systems in: Controlled drug delivery:
Concepts and advances. 1sted. New Delhi: Vallabh Prakashan; 2002.
p.196-217.
Chitnis VS, Malshe VS, Lalla JK. Bioadhesive polymers-synthesis,
evaluation and application in controlled release tablets. Drug Dev Ind
Pharm 1991;17:879-92.
Asane GS, Nirmal SA, Rasal KB, Naik AA, Mahadik MS, Rao YM. Polymers
for mucoadhesive drug delivery system: A current status. Drug Dev Ind
Pharm 2008;34:1246-66.
Cone RA. Mucus. In: Mucosal Immunology. In: Ogra PL, Mestecky J,
Lamm ME, Strober W, Bienenstock J, McGhee JR, editors. 2nd ed. San
Diego: Academic Press; 1999. p. 43-64
Lehr CM, Bodde HE, Bouwstra JA, Junginger HE. A surface energy
analysis of mucoadhesion. II. Prediction of mucoadhesive performance
by spreading coefficients. Eur J Pharm Sci 1993;1:19-30.
Wang J, Yoshihiko T, Yoshiharu D, Kazuhiro M, Yasuhiko T, Yashito I.
Positively charged gelatin microspheres as gastric mucoadhesive drug
delivery system for eradication of H. pylori. Drug Deliv 2000;7:237-43.
Mascher HJ, Kikuta C. Determination of amoxicillin in human serum
and plasma by high-performance liquid chromatography and on-line
post column derivatisation. J Chromatogr A 1998;812:221-6.
Erah PO, Goddard AF, Barrett DA, Shaw PN, Spiller RC. The stability
of amoxicillin, clarithromycin and metronidazole in gastric juice:
Relevance to the treatment of Helicobacter pylori infection. J Antimicrob
Chemother 1997;39:5-12.
Chadha R, Kashid N, Jain DV. Kinetic studies of the degradation of
an amino penicillin antibiotic (amoxicillin trihydrate) in aqueous
solution using heat conduction microcalorimetry. J Pharm Pharmacol
;55:1495-503.
Liu Z, Lu W, Qian L, Zhang X, Zeng P, Pan J. In vitro and in vivo studies on
mucoadhesive microspheres of amoxicillin. J ContRel 2007;102:135-44.
PatelJK, PatelMM. Stomach specific anti-Helicobacter pylori therapy:
Preparation and evaluation of amoxicillin-loaded chitosan mucoadhesive
microspheres. Curr Drug Del 2007;4:41-50.
Patel JK, Chavda JR. Formulation and evaluation of stomach-specific
amoxicillin-loaded carbopol-934P mucoadhesive microspheres for
anti-Helicobacter pylori therapy. J Microencapsul 2009;26:365-76.
Narkar M, Sher P, Pawar A. Stomach-specific controlled release gellan
beads of acid-soluble drug prepared by ionotropic gelation method.
AAPS PharmSciTech 2010;11:267-77.
Umamaheshwari RB, Jain S, Tripathi PK, Agrawal GP, Jain NK. Floating-
bioadhesive microspheres containing acetohydroxamic acid for the
clearance of Helicobacter pylori. Drug Deliv 2002;9:221-33.
Umamaheshwari RB, Jain S, Bhadra D, Jain NK. Floating microspheres
bearing acetohydroxamic acid for the treatment of Helicobacter pylori.
J Pharm Phamacol 2003;55:1607-13.
Ishak AHI, Gehanne ASA, Mortada ND. Preparation, in vitro and in vivo
evaluation of stomach-specific metronidazole-loaded alginate beads
as local anti-Helicobacter pylori therapy. J Cont Rel 2007;119:207-14.
Rajnikanth PS, Mishra B. Preparation and in vitro characterization of
Gellan based floating beads of acetohydroxamic acid for eradication
of H. pylori. Acta Pharm 2007;57:413-27.
El. Nujumi AM, Dorrian CA, Chittajallu RS, Neithercut WD,
McColl KE. Effect of inhibition of Helicobacter pylori urease activity of
acetohydroxamic acid on serum gastrin in duodenal ulcer subjects. Gut
;32:866-70.
Rajnikanth PS, Balasubramaniam J, Mishra B. Development and
evaluation of a novel floating in situ gelling system of amoxicillin for
eradication of Helicobacter pylori. Int J Pharm 2007;335:114-22.
Ramteke S, Jain NK. Clarithromycin and omeprazole-containing gliadin
nanoparticles for the treatment of Helicobacter pylori. J Drug Targeting
;16:65-72.
Chang CH, Lin YH, Yeh CL, Chen YC, Chiou SF, Hsu YM, et al. Nanoparticles
incorporated in pH-sensitive hydrogels asamoxicillin delivery for
eradication of Helicobacter pylori. Biomacromolecules 2010;11:133-42.
Moogooee M, Ramezanzadeh H, Jasoori S, Omidi Y, Davaran S. Synthesis
and in vitro studies of cross- linked hydrogel nanoparticlescontaining
amoxicillin. J Pharm Sci 2011;100:1057-66.
Umamaheshwari RB, Jain NK. Receptor-mediated targeting of lipobeads
bearing acetohydroxamic acid for eradication of Helicobacter pylori. J
ContRel 2004;99:27-40.
Bardonnet PL, Faivre V, Boullanger P, Ollivon M, Falson F. Glycosylated
liposomes against Helicobacter pylori: Behavior in acidic conditions.
Biochem Biophys Res Commun 2009;383:48-53.
Jain P, Jain S, Prasad KN, Jain SK, Vyas SP. Polyelectrolyte coated
multilayered liposomes (nanocapsules) for the treatment of Helicobacter
pylori infection. Mol Pharm 2009;6:593-603.
Wong KH, Skelton SK, Feeley JC. Strain characterization and grouping of
Campylobacter jejuna and Campylobacter coli by interaction with lectins.
J Clin Microbiol 1986;23:407-10.
Ascencio F, Guruge JL, Ljungh A, Megraud F, Wei S, Wadstrm T. Lectin
typing of Helicobacter pylori. In: Malfertheiner P, Ditschuneit H, editors.
Helicobacter pylori, gastritis and peptic ulcer. Berlin: Springer Verlag;
p.105-9.
Kellens JIC, Jacobs JA, Peumans WJ, Strobbersingh EE. The
agglutination of a haemolytic streptococcus by lectins. J Med Microbiol
;39:440-8.
Khin MM, Hua JS, Ng HC, Wadstrom T, Bow H. Agglutination of Helicobacter
pylori coccoids by lectins. World J Gastroenterol 2000;6:202-9.
Umamaheshwari RB, Jain NK. Receptor mediated targeting of lectin
conjugated gliadin nanoparticles in the treatment of Helicobacter pylori.
J Drug Target 2003;11:415-24.
Ramteke S, Ganesh N, Bhattacharya S, Jain NK. Triple therapy-based
targeted nanoparticles for the treatment of Helicobacter pylori. J Drug
Target 2008;16:694-705.
Unge P, Gad A, Gnarpe H, Olsson J. Does omeprazole improve
antimicrobial therapy directed towards gastric Campylobacter pylori
in patients with antral gastritis–a pilot study. Scand J Gastroenterol
;24:49-54.
Sjostrom JE, Fryklund J, Kuhler T, Larsson H. In vitro antibacterial
activity of omeprazole and its selectivity for Helicobacter spp.
are dependent on incubation conditions. J Med Microbiol
;441:425-33.
Dawson M,Krauland E, Wirtz D, Hanes J. Transport of polymeric
nanoparticle gene carriers in gastric mucus. Biotechnol Prog
;20:851-7.
Lin YH, Chang CH, Wu YS, Hsu YM, Chiou SF, Chen YJ. Development
of pH-responsive chitosan/heparin nanoparticles for stomach- specific
anti-Helicobacter pylori therapy. Biomaterials 2009;30:3332-42.
Suk JS, Lai SK, Wang YY, Ensign LM, Zeitlin PL, Boyle MP, et al. The
penetration of fresh undiluted sputum expectorated by cystic fibrosis
patients by non-adhesive polymer nanoparticles. Biomaterials
;30:2591-7.
Tang BC, Dawson M, Lai SK, Wang YY, Suk JS, Yang M, et al. Biodegradable
polymer nanoparticles that rapidly penetrate the human mucus barrier.
Proc Natl Acad Sci U S A 2009;106:19268-73.
Zhang X, Zhang H, Wu Z, Wang Z, Niu H, Li C. Nasal absorption
enhancement of insulin using PEG-grafted chitosan nanoparticles. Eur
J Pharm Biopharm 2007;68:526-34.
van der Lubben IM, Verhoef JC, Borchard G, Junginger HE. Chitosan
and its derivatives in mucosal drug and vaccine delivery. Eur J Pharm
Sci 2001;14:201-7.
Fernandez-Urrusuno R, Romani D, Calvo P, Vila-Jato JR, Alonso MJ.
Development of a freeze-dried formulation of insulin-loaded chitosan
nanoparticles intended for nasal administration. STP Pharma Sci
;9:429-36.
van der Lubben IM, Verhoef JC, van Aelst A, Borchard G, Junginger HE. Chitosan
microparticles for oral vaccination: Preparation, Characterization and
preliminary in vivo uptake studies in murine Peyer’s patches. Biomaterials
;22:687-94.
Arora S, Gupta S, Narang RK, Budhiraja RD. Amoxicillin loaded chitosan–
alginate polyelectrolyte complex nanoparticles as muco-penetrating
delivery system for H. pylori. Sci Pharm 2011;79:673-94.