Amoxicillin-loaded Nanotechnological Carriers for the Effective
Treatment of Helicobacter pylori Infection

Darsh      Gautam; Poonam      Talwan; Sahil      Dhiman; Rahul      Gill; Aparna      Thakur; Simran      Dhiman; Deexa      Sharma; Akhil      Kumar; Saksham      Sharma
Abstract

Background: The bacterium Helicobacter pylori (H. pylori) is known to cause gastroduodenal disorders associated with the stomach lining that grows in the gastrointestinal tract, and can cause gastritis, peptic ulcer, gastric lymphoma, and stomach cancer. Nearly 50% of people worldwide suffer from H. pylori infection. This infection is more prominent in poor nations and undeveloped countries, and is caused by multiple factors, such as consumption of unhygienic food, crowded living style, etc. In the eradication treatment of gastric H. pylori infection, conventional dosage forms have various adverse effects on patients.
Methods: In this study, we have explored current developments in the utilization of nanotechnological carriers for the successful management of H. pylori infection. In order to combat rising amoxicillin resistance, this review has focused on therapeutic strategies that use cyclodextrins, niosomes, liposomes, microspheres, nanoparticles, solid lipid nanoparticles, and nanostructure nanoparticles to improve therapy against H. pylori.
Results: The entrapment of amoxicillin in various nanotechnological carriers enhances its effectiveness and reduces adverse effects. These carriers lead to targeted drug release and improve drug penetration to the gastroduodenal disease site that locally controls and adjusts the drug release.
Conclusion: For the effective treatment of H. pylori infection, nanotechnological carriers have provided a new avenue for the development of innovative, high-impact, and low-dose systems. The main objective of this review was to outline the present limitations of H. pylori therapy and new potential alternatives, as well as to report how nanotechnological carriers may be used to overcome treatment shortcomings.
Graphical Abstract

[1]
Sharara, A.I. Rabeprazole: The role of proton pump inhibitors in Helicobacter pylori eradication. Expert Rev. Anti Infect. Ther.,  2005, 3(6), 863-870.
 [http://dx.doi.org/10.1586/14787210.3.6.863] [PMID: 16307499]

[2]
Rothenbacher, D.; Brenner, H. Burden of Helicobacter pylori and H. pylori-related diseases in developed countries: Recent developments and future implications. Microbes Infect.,  2003, 5(8), 693-703.
 [http://dx.doi.org/10.1016/S1286-4579(03)00111-4] [PMID: 12814770]

[3]
Miwa, H.; Go, M.F.; Sato, N.H. pylori and gastric cancer: The Asian enigma. Am. J. Gastroenterol.,  2002, 97(5), 1106-1112.
 [http://dx.doi.org/10.1111/j.1572-0241.2002.05663.x] [PMID: 12014714]

[4]
Atherton, J.C.; Blaser, M.J. Coadaptation of Helicobacter pylori and humans: Ancient history, modern implications. J. Clin. Invest.,  2009, 119(9), 2475-2487.
 [http://dx.doi.org/10.1172/JCI38605] [PMID: 19729845]

[5]
Sugimoto, M.; Yamaoka, Y. Review of Helicobacter pylori infection and chronic renal failure. Ther. Apher. Dial.,  2011, 15(1), 1-9.
 [http://dx.doi.org/10.1111/j.1744-9987.2010.00851.x] [PMID: 21272246]

[6]
Graham, D.Y. History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer. World J. Gastroenterol.,  2014, 20(18), 5191-5204.
 [http://dx.doi.org/10.3748/wjg.v20.i18.5191] [PMID: 24833849]

[7]
Rothenbacher, D.; Bode, G.; Brenner, H. History of breastfeeding and Helicobacter pylori infection in pre-school children: Results of a population-based study from Germany. Int. J. Epidemiol.,  2002, 31(3), 632-637.
 [http://dx.doi.org/10.1093/ije/31.3.632] [PMID: 12055166]

[8]
Kato, M.; Toda, A.; Yamamoto-Honda, R.; Arase, Y.; Sone, H. Association between Helicobacter pylori infection, eradication and diabetes mellitus. J. Diabetes Investig.,  2019, 10(5), 1341-1346.
 [http://dx.doi.org/10.1111/jdi.13011] [PMID: 30663265]

[9]
Cadamuro, A.C.T.; Rossi, A.F.; Maniezzo, N.M.; Silva, A.E. Helicobacter pylori infection: Host immune response, implications on gene expression and microRNAs. World J. Gastroenterol.,  2014, 20(6), 1424-1437.
 [http://dx.doi.org/10.3748/wjg.v20.i6.1424] [PMID: 24587619]

[10]
Shokrzadeh, L.; Baghaei, K.; Yamaoka, Y.; Shiota, S.; Mirsattari, D.; Porhoseingholi, A.; Zali, M.R. Prevalence of Helicobacter pylori in-fection in dyspeptic patients in Iran. Gastroenterol. Insights,  2012, 4(1), 8.
 [http://dx.doi.org/10.4081/gi.2012.e8]

[11]
Razavi, A.; Bagheri, N.; Azadegan-Dehkordi, F.; Shirzad, M.; Rahimian, G.; Rafieian-Kopaei, M.; Shirzad, H. Comparative immune re-sponse in children and adults with H. pylori Infection. J. Immunol. Res.,  2015, 2015, 1-6.
 [http://dx.doi.org/10.1155/2015/315957] [PMID: 26495322]

[12]
Huttner, A.; Bielicki, J.; Clements, M.N.; Frimodt-Møller, N.; Muller, A.E.; Paccaud, J.P.; Mouton, J.W. Oral amoxicillin and amoxicillin-clavulanate: Properties, indications, and usage. Clin. Microbiol. Infect.,  2020, 26(7), 871-879.
 [http://dx.doi.org/10.1016/j.cmi.2019.11.028] [PMID: 31811919]

[13]
Lopes-de-Campos, D.; Pinto, R.M.; Lima, S.A.C.; Santos, T.; Sarmento, B.; Nunes, C.; Reis, S. Delivering amoxicillin at the infection site - A rational design through lipid nanoparticles. Int. J. Nanomedicine,  2019, 14, 2781-2795.
 [http://dx.doi.org/10.2147/IJN.S193992] [PMID: 31114195]

[14]
Leung, W.K.; Graham, D.Y. Clarithromycin for Helicobacter pylori infection. Expert Opin. Pharmacother.,  2000, 1(3), 507-514.
 [http://dx.doi.org/10.1517/14656566.1.3.507] [PMID: 11249534]

[15]
de Marco, B.A.; Natori, J.S.H.; Fanelli, S.; Tótoli, E.G.; Salgado, H.R.N. Characteristics, properties and analytical methods of amoxicillin: A review with green approach. Crit. Rev. Anal. Chem.,  2017, 47(3), 267-277.
 [http://dx.doi.org/10.1080/10408347.2017.1281097] [PMID: 28080135]

[16]
Zeller, V.; Puyraimond-Zemmour, D.; Sené, T.; Lidove, O.; Meyssonnier, V.; Ziza, J.M. Amoxicillin crystalluria, an emerging complica-tion with an old and well-known antibiotic. Antimicrob. Agents Chemother.,  2016, 60(5), 3248.
 [http://dx.doi.org/10.1128/AAC.00359-16] [PMID: 26926627]

[17]
Kao, C.Y.; Sheu, B.S.; Wu, J.J. Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis. Biomed. J.,  2016, 39(1), 14-23.
 [http://dx.doi.org/10.1016/j.bj.2015.06.002] [PMID: 27105595]

[18]
Camilo, V.; Sugiyama, T.; Touati, E. Pathogenesis of Helicobacter pylori infection. Helicobacter,  2017, 22(S1), e12405.
 [http://dx.doi.org/10.1111/hel.12405] [PMID: 28891130]

[19]
Gu, H. Role of flagella in the pathogenesis of helicobacter pylori. Curr. Microbiol.,  2017, 74(7), 863-869.
 [http://dx.doi.org/10.1007/s00284-017-1256-4] [PMID: 28444418]

[20]
Sharndama, H.C.; Mba, I.E. Helicobacter pylori: An up-to-date overview on the virulence and pathogenesis mechanisms. Braz. J. Microbiol.,  2022, 53(1), 33-50.
 [http://dx.doi.org/10.1007/s42770-021-00675-0] [PMID: 34988937]

[21]
Yamaoka, Y. Pathogenesis of Helicobacter pylori -related gastroduodenal diseases from molecular epidemiological studies. Gastroenterol. Res. Pract.,  2012, 2012, 1-9.
 [http://dx.doi.org/10.1155/2012/371503] [PMID: 22829807]

[22]
Miller, M.A.; Kuemmerle, N.B.; Gentile, G. Amoxycillin and ampicillin. A comparative study of in vitro sensitivity and induced morpho-logical alterations in Serratiamarcescens. Jpn. J. Microbiol.,  1975, 19(3), 219-224.

[23]
Huttner, A.; Bielicki, J.; Clements, M.N.; Frimodt-Møller, N.; Muller, A.E.; Paccaud, J.P.; Mouton, J.W. Oral amoxicillin and amoxicillin–clavulanic acid: Properties, indications and usage. Clin. Microbiol. Infect.,  2020, 26(7), 871-879.
 [http://dx.doi.org/10.1016/j.cmi.2019.11.028] [PMID: 31811919]

[24]
Weber, D.J.; Tolkoff-Rubin, N.E.; Rubin, R.H. Amoxicillin and potassium clavulanate: An antibiotic combination. Mechanism of action, pharmacokinetics, antimicrobial spectrum, clinical efficacy and adverse effects. Pharmacotherapy,  1984, 4(3), 122-133.
 [http://dx.doi.org/10.1002/j.1875-9114.1984.tb03333.x] [PMID: 6739312]

[25]
Zarowny, D.; Ogilvie, R.; Tamblyn, D.; Macleod, C.; Ruedy, J. Pharmacokinetics of amoxicillin. Clin. Pharmacol. Ther.,  1974, 16(6), 1045-1051.
 [http://dx.doi.org/10.1002/cpt19741661045] [PMID: 4433471]

[26]
Gottberg, B.; Berné, J.; Quiñónez, B.; Solórzano, E. Prenatal effects by exposing to amoxicillin on dental enamel in Wistar rats. Med. Oral Patol. Oral Cir. Bucal,  2014, 19(1), e38-e43.
 [http://dx.doi.org/10.4317/medoral.18807] [PMID: 24121904]

[27]
Tandan, M.; Vellinga, A.; Bruyndonckx, R.; Little, P.; Verheij, T.; Butler, C.; Goossens, H.; Coenen, S. Adverse effects of amoxicillin for acute lower respiratory tract infection in primary care: Secondary and subgroup analysis of a randomised clinical trial. Antibiotics,  2017, 6(4), 36.
 [http://dx.doi.org/10.3390/antibiotics6040036] [PMID: 29236038]

[28]
Salvo, F.; Polimeni, G.; Moretti, U.; Conforti, A.; Leone, R.; Leoni, O.; Motola, D.; Dusi, G.; Caputi, A.P. Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: Data from spontaneous reporting in Italy. J. Antimicrob. Chemother.,  2007, 60(1), 121-126.
 [http://dx.doi.org/10.1093/jac/dkm111] [PMID: 17449881]

[29]
Davydov, L.; Yermolnik, M.; Cuni, L.J. Warfarin and amoxicillin/clavulanate drug interaction. Ann. Pharmacother.,  2003, 37(3), 367-370.
 [http://dx.doi.org/10.1345/aph.1C243] [PMID: 12639164]

[30]
Delavenne, X.; Laporte, S.; Demasles, S.; Mallouk, N.; Basset, T.; Tod, M.; Girard, P.; Mismetti, P. Investigation of PK-PD drug-drug interaction between acenocoumarol and amoxicillin plus clavulanic acid. Fundam. Clin. Pharmacol.,  2009, 23(1), 127-135.
 [http://dx.doi.org/10.1111/j.1472-8206.2008.00642.x]

[31]
Uddin, M.N.; Das, M.; Khan, S.H.; Shill, S.K.; Bhuiyan, H.R.; Karim, R. Simultaneous determination of amoxicillin and chloramphenicol and their drug interaction study by the validated UPLC method. J. Taibah Univ. Sci.,  2016, 10(5), 755-765.
 [http://dx.doi.org/10.1016/j.jtusci.2015.11.005]

[32]
Roszczenko-Jasińska, P.; Wojtyś, M.I.; Jagusztyn-Krynicka, E.K. Helicobacter pylori treatment in the post-antibiotics era—searching for new drug targets. Appl. Microbiol. Biotechnol.,  2020, 104(23), 9891-9905.
 [http://dx.doi.org/10.1007/s00253-020-10945-w] [PMID: 33052519]

[33]
Fischbach, W.; Malfertheiner, P. Helicobacter Pylori Infection. Dtsch. Arztebl. Int.,  2018, 115(25), 429-436.
 [http://dx.doi.org/10.3238/arztebl.2018.0429] [PMID: 29999489]

[34]
Yang, J.C.; Lu, C.W.; Lin, C.J. Treatment of Helicobacter pylori infection: Current status and future concepts. World J. Gastroenterol.,  2014, 20(18), 5283-5293.
 [http://dx.doi.org/10.3748/wjg.v20.i18.5283] [PMID: 24833858]

[35]
Georgopoulos, S.; Papastergiou, V. An update on current and advancing pharmacotherapy options for the treatment of H. pylori infection. Expert Opin. Pharmacother.,  2021, 22(6), 729-741.
 [http://dx.doi.org/10.1080/14656566.2020.1845649] [PMID: 33131337]

[36]
Yun, J.; Wu, Z.; Qi, G.; Han, T.; Zhang, D. The high-dose amoxicillin-proton pump inhibitor dual therapy in eradication of Helicobacter pylori infection. Expert Rev. Gastroenterol. Hepatol.,  2021, 15(2), 149-157.
 [http://dx.doi.org/10.1080/17474124.2021.1826306] [PMID: 32960107]

[37]
Matsumoto, H.; Shiotani, A.; Graham, D.Y. Current and future treatment of Helicobacter pylori infections. Adv. Exp. Med. Biol.,  2019, 1149, 211-225.
 [http://dx.doi.org/10.1007/5584_2019_367] [PMID: 31016626]

[38]
Graham, D.Y.; Dore, M.P.; Lu, H. Understanding treatment guidelines with bismuth and non-bismuth quadruple Helicobacter pylori eradi-cation therapies. Expert Rev. Anti Infect. Ther.,  2018, 16(9), 679-687.
 [http://dx.doi.org/10.1080/14787210.2018.1511427] [PMID: 30102559]

[39]
Lim, J.H.; Lee, D.H.; Lee, S.T.; Kim, N.; Park, Y.S.; Shin, C.M.; Song, I.S. Moxifloxacin-containing triple therapy after non-bismuth quad-ruple therapy failure for Helicobacter pylori infection. World J. Gastroenterol.,  2015, 21(46), 13124-13131.
 [http://dx.doi.org/10.3748/wjg.v21.i46.13124] [PMID: 26673999]

[40]
Alboraie, M.; Alfadhli, A.; Afifi, M.; Dangi, A. A randomized clinical trial comparing triple therapy versus non-bismuth based quadruple therapy for the eradication of Helicobacter Pylori in Kuwait. J. Glob. Infect. Dis.,  2022, 14(3), 99-105.
 [http://dx.doi.org/10.4103/jgid.jgid_13_22] [PMID: 36237565]

[41]
Vakil, N.H. pylori treatment: New wine in old bottles? Am. J. Gastroenterol.,  2009, 104(1), 26-30.
 [http://dx.doi.org/10.1038/ajg.2008.91] [PMID: 19098845]

[42]
El-Ela, F.I.A.; Farghali, A.A.; Mahmoud, R.K.; Mohamed, N.A.; Moaty, S.A.A. New approach in ulcer prevention and wound healing treatment using doxycycline and amoxicillin/LDH nanocomposites. Sci. Rep.,  2019, 9(1), 6418.
 [http://dx.doi.org/10.1038/s41598-019-42842-2] [PMID: 31015527]

[43]
Wu, Y.; Geng, J.; Cheng, X.; Yang, Y.; Yu, Y.; Wang, L.; Dong, Q.; Chi, Z.; Liu, C. Cosmetic-derived mannosylerythritol lipid-b-phospholipid nanoliposome: An acid-stabilized carrier for efficient gastromucosal delivery of amoxicillin for in vivo treatment of helico-bacter pylori. ACS Omega,  2022, 7(33), 29086-29099.
 [http://dx.doi.org/10.1021/acsomega.2c02953] [PMID: 36033659]

[44]
Kerč, J.; Opara, J. A new amoxicillin/clavulanate therapeutic system: Preparation, in vitro and pharmacokinetic evaluation. Int. J. Pharm.,  2007, 335(1-2), 106-113.
 [http://dx.doi.org/10.1016/j.ijpharm.2006.11.007] [PMID: 17141985]

[45]
Barve, K.; Ruparel, K. Effect of bioenhancers on amoxicillin bioavailability. ADMET DMPK,  2015, 3(1), 45-50.
 [http://dx.doi.org/10.5599/admet.3.1.161]

[46]
Peterson, B.; Weyers, M.; Steenekamp, J.; Steyn, J.; Gouws, C.; Hamman, J. Drug bioavailability enhancing agents of natural origin (bioen-hancers) that modulate drug membrane permeation and pre-systemic metabolism. Pharmaceutics,  2019, 11(1), 33.
 [http://dx.doi.org/10.3390/pharmaceutics11010033] [PMID: 30654429]

[47]
Joshi, K.; Chandra, A.; Jain, K.; Talegaonkar, S. Nanocrystalization: An emerging technology to enhance the bioavailability of poorly solu-ble drugs. Pharm. Nanotechnol.,  2019, 7(4), 259-278.
 [http://dx.doi.org/10.2174/2211738507666190405182524] [PMID: 30961518]

[48]
Patel, J.K.; Bhatia, D.; Pathak, Y.V.; Patel, A. The use of supercritical fluid technologies for nanoparticle production. Emerging Technol. Nanopart. Manufact.,  2021, 109-128.
 [http://dx.doi.org/10.1007/978-3-030-50703-9]

[49]
Sinha, S.; Ali, M.; Baboota, S.; Ahuja, A.; Kumar, A.; Ali, J. Solid dispersion as an approach for bioavailability enhancement of poorly water-soluble drug ritonavir. AAPS PharmSciTech,  2010, 11(2), 518-527.
 [http://dx.doi.org/10.1208/s12249-010-9404-1] [PMID: 20238187]

[50]
Alshehri, S.; Imam, S.S.; Hussain, A.; Altamimi, M.A.; Alruwaili, N.K.; Alotaibi, F.; Alanazi, A.; Shakeel, F. RETRACTED ARTICLE: Potential of solid dispersions to enhance solubility, bioavailability, and therapeutic efficacy of poorly water-soluble drugs: Newer formu-lation techniques, current marketed scenario and patents. Drug Deliv.,  2020, 27(1), 1625-1643.
 [http://dx.doi.org/10.1080/10717544.2020.1846638] [PMID: 33207947]

[51]
Silva, P.T.; Fries, L.L.M.; Menezes, C.R.; Holkem, A.T.; Schwan, C.L.; Wigmann, É.F.; Bastos, J.O.; Silva, C.B. Microencapsulation: Con-cepts, mechanisms, methods and some applications in food technology. Cienc. Rural,  2014, 44(7), 1304-1311.
 [http://dx.doi.org/10.1590/0103-8478cr20130971]

[52]
Choudhury, N.; Meghwal, M.; Das, K. Microencapsulation: An overview on concepts, methods, properties and applications in foods. Food Front.,  2021, 2, 426-442.
 [http://dx.doi.org/10.1002/fft2.94]

[53]
Golovnev, N.N.; Molokeev, M.S.; Lesnikov, M.K.; Sterkhova, I.V.; Atuchin, V.V. Thiobarbiturate and barbiturate salts of pefloxacin drug: Growth, structure, thermal stability and IR-spectra. J. Mol. Struct.,  2017, 1149, 367-372.
 [http://dx.doi.org/10.1016/j.molstruc.2017.08.011]

[54]
Serajuddin, A.T.M. Salt formation to improve drug solubility. Adv. Drug Deliv. Rev.,  2007, 59(7), 603-616.
 [http://dx.doi.org/10.1016/j.addr.2007.05.010] [PMID: 17619064]

[55]
Bae, S.K.; Park, J.B.; Seo, J.H.; Choi, W-K.; Park, S.; Sung, Y.J.; Oh, E. Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate. Drug Des. Devel. Ther.,  2015, 9, 3961-3968.
 [http://dx.doi.org/10.2147/DDDT.S87687] [PMID: 26251575]

[56]
Jornada, D.; dos Santos Fernandes, G.; Chiba, D.; de Melo, T.; dos Santos, J.; Chung, M. The prodrug approach: A successful tool for improving drug solubility. Molecules,  2015, 21(1), 42.
 [http://dx.doi.org/10.3390/molecules21010042] [PMID: 26729077]

[57]
Rawat, S.; Jain, S.K. Solubility enhancement of celecoxib using β-cyclodextrin inclusion complexes. Eur. J. Pharm. Biopharm.,  2004, 57(2), 263-267.
 [http://dx.doi.org/10.1016/j.ejpb.2003.10.020] [PMID: 15018983]

[58]
Semalty, A. Cyclodextrin and phospholipid complexation in solubility and dissolution enhancement: A critical and meta-analysis. Expert Opin. Drug Deliv.,  2014, 11(8), 1255-1272.
 [http://dx.doi.org/10.1517/17425247.2014.916271] [PMID: 24909802]

[59]
Moriwaki, C.; Costa, G.L.; Ferracini, C.N.; Moraes, F.F.; Zanin, G.M.; Pineda, E.A.G.; Matioli, G. Enhancement of solubility of albend-azole by complexation with β-cyclodextrin. Braz. J. Chem. Eng.,  2008, 25(2), 255-267.
 [http://dx.doi.org/10.1590/S0104-66322008000200005]

[60]
Vaishnavi, G.; Sailaja, A.K. Overall review on permeation enhancers in drug delivery systems. J. Arch. Med. Case Reports Case Study,  2021, 4(3), 1-4.
 [http://dx.doi.org/10.31579/2692-9392/051]

[61]
El-Hammadi, M.M.; Arias, J.L. An update on liposomes in drug delivery: A patent review. Expert Opin. Ther. Pat.,  2019, 2911, 891-907.
 [http://dx.doi.org/10.1080/13543776.2019.1679767]

[62]
Yadav, D.; Sandeep, K.; Pandey, D.; Dutta, R.K. Liposomes for drug delivery. J. Biotechnol. Biomater.,  2017, 7(4), 1-8.
 [http://dx.doi.org/10.4172/2155-952X.1000276] [PMID: 28778472]

[63]
Lee, M.K. Liposomes for enhanced bioavailability of water-insoluble drugs: In vivo evidence and recent approaches. Pharmaceutics,  2020, 12(3), 264.
 [http://dx.doi.org/10.3390/pharmaceutics12030264] [PMID: 32183185]

[64]
Jain, P.; Jain, S.; Prasad, K.N.; Jain, S.K.; Vyas, S.P. Polyelectrolyte coated multilayered liposomes (nanocapsules) for the treatment of Helicobacter pylori infection. Mol. Pharm.,  2009, 6(2), 593-603.
 [http://dx.doi.org/10.1021/mp8002539] [PMID: 19718807]

[65]
Trucillo, P.; Ferrari, P.F.; Campardelli, R.; Reverchon, E.; Perego, P. A supercritical assisted process for the production of amoxicillin-loaded liposomes for antimicrobial applications. J. Supercrit. Fluids,  2020, 163, 104842.
 [http://dx.doi.org/10.1016/j.supflu.2020.104842]

[66]
Menikarachchi, M.; Katuwavila, K.; Ekanayake, E.; Thevanesam, V.; Karunaratne, V.; Karunaratne, D.N. Release behaviour of amoxicillin from chitosan coated liposomes derived from eggs. J. Natl. Sci. Found. Sri Lanka,  2016, 442, 167-173.
 [http://dx.doi.org/10.4038/jnsfsr.v44i2.7997]

[67]
Trucillo, P.; Ferrari, P.F.; Campardelli, R.; Reverchon, E. A versatile supercritical assisted process for the one-shot production of liposomes. J.Supercrit. Fluid,  2019, 146, 136-143.
 [http://dx.doi.org/10.1016/j.supflu.2019.01.015]

[68]
Zhang, J.; Ye, C.Z.; Liu, Z.Y.; Yang, Q.; Ye, Y. Preparation and antibacterial effects of carboxymethyl chitosan-modified photo-responsive camellia sapogenin derivative cationic liposomes. Int. J. Nanomedicine,  2019, 14, 8611-8626.
 [http://dx.doi.org/10.2147/IJN.S218101] [PMID: 31802873]

[69]
Kuotsu, K.; Karim, K.M.; Mandal, A.S.; Biswas, N.; Guha, A.; Chatterjee, S.; Behera, M. Niosome: A future of targeted drug delivery sys-tems. J. Adv. Pharm. Technol. Res.,  2010, 1(4), 374-380.
 [http://dx.doi.org/10.4103/0110-5558.76435] [PMID: 22247876]

[70]
Seleci, D.A.; Seleci, M.; Walter, J.; Stahl, F.; Scheper, T. Niosomes as nanoparticular drug carriers: Fundamentals and recent applications. J. Nanomater.,  2016, 1-13.
 [http://dx.doi.org/10.1155/2016/7372306]

[71]
Shadvar, P.; Mirzaie, A.; Yazdani, S. Fabrication and optimization of amoxicillin-loaded niosomes: An appropriate strategy to increase antimicrobial and anti-biofilm effects against multidrug-resistant Staphylococcus aureus strains. Drug Dev. Ind. Pharm.,  2022, 47(10), 1568-1577.
 [http://dx.doi.org/10.1080/03639045.2022.2027958]

[72]
Kumar, B.; Jeyabalan, G. Design and development of dual drug loaded niosomes containing amoxicillin and clavulanic acid. Asian pac. Asian Pacific J. Health Sci.,  2017, 4(2), 206-213.
 [http://dx.doi.org/10.21276/apjhs.2017.4.2.33]

[73]
Onuigibo, E.B.; Eze, J.; Attama, A.A. Functional properties of amoxicillin encapsulated in noisome or liposome. African J. Pharm. Rese. Devel.,  2015, 7(2), 66-71.

[74]
Sharma, N.; Purwar, N.; Gupta, P.C. Microsphere as drug carriers for control drug delivery: A review. Int. J. Pharmaceut Sci. Res.,  2022, 6(11), 4579-4587.

[75]
Das, M.K.; Ahmed, A.B.; Saha, D. Microsphere a drug delivery system: A review. Int. J. Curr. Pharm. Res.,  2019, 11(4), 34-41.
 [http://dx.doi.org/10.22159/ijcpr.2019v11i4.34941]

[76]
Habraken, W.J.E.M.; de Jonge, L.T.; Wolke, J.G.C.; Yubao, L.; Mikos, A.G.; Jansen, J.A. Introduction of gelatin microspheres into an injectable calcium phosphate cement. J. Biomed. Mater. Res. A,  2008, 87A(3), 643-655.
 [http://dx.doi.org/10.1002/jbm.a.31703] [PMID: 18189298]

[77]
Wang, J.; Tauchi, Y.; Deguchi, Y.; Morimoto, K.; Tabata, Y.; Ikada, Y. Positively charged gelatin microspheres as gastric mucoadhesive drug delivery system for eradication of H. pylori. Drug Deliv.,  2000, 7(4), 237-243.
 [http://dx.doi.org/10.1080/107175400455173] [PMID: 11195431]

[78]
Patel, J.K.; Chavda, J.R. Formulation and evaluation of stomach-specific amoxicillin-loaded carbopol-934P mucoadhesive microspheres for anti- Helicobacter pylori therapy. J. Microencapsul.,  2009, 26(4), 365-376.
 [http://dx.doi.org/10.1080/02652040802373012] [PMID: 18720199]

[79]
Liu, Z.; Lu, W.; Qian, L.; Zhang, X.; Zeng, P.; Pan, J. In vitro and in vivo studies on mucoadhesive microspheres of amoxicillin. J. Control. Release,  2005, 102(1), 135-144.
 [http://dx.doi.org/10.1016/j.jconrel.2004.06.022] [PMID: 15653140]

[80]
Farazuddin, M.; Alam, M.; Khan, A.A.; Khan, N.; Parvez, S.; Dutt, G.U.; Mohammad, O. Efficacy of amoxicillin bearing microsphere formulation in treatment of Listeria monocytogenes infection in Swiss albino mice. J. Drug Target.,  2010, 18(1), 45-52.
 [http://dx.doi.org/10.3109/10611860903156401] [PMID: 19624287]

[81]
Nayak, D.; Rajpoot, K.; Jain, S.K. Development and evaluation of cholestyramine-amoxicillin trihydrate-loaded gastro-retentive micro-spheres for attaining extended therapeutic effect against H. pylori infection. Biomed. J. Sci. Technol Res.,  2020, 29(4), 22728-22738.
 [http://dx.doi.org/10.26717/BJSTR.2020.29.004847]

[82]
Earle, R.R.; Bharathi, V.V.; Lakshmi Usha, A.; Ksheera Bhavani, A.V.S. Cross-linked chitosan-based stomach specific mucoadhesive microspheres loaded with amoxicillin: Preparation and ex vivo characterization. Int. J. Pharm. Investig.,  2020, 10(1), 59-63.
 [http://dx.doi.org/10.5530/ijpi.2020.1.11]

[83]
Chen, Y. Nanoparticles-A review. Trop. J. Pharmares.,  2006, 5(1), 561-573.

[84]
Hadizadeh, M.; Toraji, A. Amoxicillin-loaded polymeric nanoparticles of less than 100 nm: Design, preparation and antimicrobial activity against methicillin-resistant Staphylococcus aureus. Iran. J. Sci. Technol. Trans. A Sci.,  2019, 43(2), 379-386.
 [http://dx.doi.org/10.1007/s40995-017-0346-2]

[85]
Güncüm, E.; Işıklan, N.; Anlaş, C.; Ünal, N.; Bulut, E.; Bakırel, T. Development and characterization of polymeric-based nanoparticles	for sustained release of amoxicillin - an antimicrobial drug. Artif. Cells NanomedBiotechnol.,  2018, 46S2, 964-973.
 [http://dx.doi.org/10.1080/21691401.2018.1476371]

[86]
Arora, S.; Gupta, S.; Narang, R.K.; Budhiraja, R.D. Amoxicillin loaded chitosan-alginate polyelectrolyte complex nanoparticles as muco-penetrating delivery system for H. Pylori. Sci. Pharm.,  2011, 79(3), 673-694.
 [http://dx.doi.org/10.3797/scipharm.1011-05] [PMID: 21886911]

[87]
Ramteke, S.; Ganesh, N.; Bhattacharya, S.; Jain, N.K. Amoxicillin, clarithromycin, and omeprazole based targeted nanoparticles for the treatment of H. pylori. J. Drug Target.,  2009, 17(3), 225-234.
 [http://dx.doi.org/10.1080/10611860902718649] [PMID: 19241256]

[88]
Güncüm, E.; Bakırel, T.; Anlaş, C.; Ekici, H.; Işıklan, N. Novel amoxicillin nanoparticles formulated as sustained release delivery system for poultry use. J. Vet. Pharmacol. Ther.,  2018, 41(4), 588-598.
 [http://dx.doi.org/10.1111/jvp.12505] [PMID: 29604071]

[89]
Harsha, S. Pharmaceutical suspension containing both immediate/sustained-release amoxicillin-loaded gelatin nanoparticles: Preparation and in vitro characterization. Drug Des. Devel. Ther.,  2013, 7, 1027-1033.
 [http://dx.doi.org/10.2147/DDDT.S39956] [PMID: 24101859]

[90]
Güncüm, E.; Işıklan, N.; Anlaş, C.; Bulut, E.; Bakırel, T. Preparation, characterization, and evaluation of antibacterial and cytotoxic activity of chitosan-polyethylene glycol nanoparticles loaded with amoxicillin as a novel drug delivery system. J. Biomater. Sci. Polym. Ed.,  2023, 34(12), 1660-1682.
 [http://dx.doi.org/10.1080/09205063.2023.2179269] [PMID: 36756763]

[91]
Mohammadi-Samani, S.; Ghasemiyeh, P. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: Ap-plications, advantages and disadvantages. Res. Pharm. Sci.,  2018, 13(4), 288-303.
 [http://dx.doi.org/10.4103/1735-5362.235156] [PMID: 30065762]

[92]
Sánchez-López, E.; Espina, M.; Doktorovova, S.; Souto, E.B.; García, M.L. Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye – Part II - Ocular drug-loaded lipid nanoparticles. Eur. J. Pharm. Biopharm.,  2017, 110, 58-69.
 [http://dx.doi.org/10.1016/j.ejpb.2016.10.013] [PMID: 27789359]

[93]
Subramaniam, B.; Siddik, Z.H.; Nagoor, N.H. Optimization of nanostructured lipid carriers: Understanding the types, designs, and parame-ters in the process of formulations. J. Nanopart. Res.,  2020, 22(6), 141.
 [http://dx.doi.org/10.1007/s11051-020-04848-0]

[94]
Chen, H.; Wang, Y.; Zhai, Y.; Zhai, G.; Wang, Z.; Liu, J. Development of a ropivacaine-loaded nanostructured lipid carrier formulation for transdermal delivery. Colloids Surf. A Physicochem. Eng. Asp.,  2015, 465, 130-136.
 [http://dx.doi.org/10.1016/j.colsurfa.2014.10.046]

[95]
Bhagurkar, A.M.; Repka, M.A.; Murthy, S.N. A Novel approach for the development of a nanostructured lipid carrier formulation by hot-melt extrusion technology. J. Pharm. Sci.,  2017, 106(4), 1085-1091.
 [http://dx.doi.org/10.1016/j.xphs.2016.12.015] [PMID: 28040458]

[96]
Fan, H.; Liu, G.; Huang, Y.; Li, Y.; Xia, Q. Development of a nanostructured lipid carrier formulation for increasing photo-stability and water solubility of phenylethyl resorcinol. Appl. Surf. Sci.,  2014, 288, 193-200.
 [http://dx.doi.org/10.1016/j.apsusc.2013.10.006]

[97]
Henry, H. Modified release amoxicillin product. U.S. Patent 8,778,924 B2, 2014.

[98]
Rajinder, K. Micronized amoxicillin. U.S. Patent 9,820,943 B2, 2017.

[99]
Alejandro, H. Pediatric oral suspension formulation of Amoxicillin and Clavulanate Potassium and methods for using same. U.S. Patent 2020/0330441 A1, 2020.

[100]
Ma, H. Amoxicillin dispersible tablet and preparation method	thereof. C.N. Patent 109394718 B, 2021.

[101]
Ma, J.; Chen, M. Amoxicillin soluble powder and preparation method thereof. C.N. Patent 113304112A, 2018.

[102]
Xing, F. A kind of preparation method of amoxil capsule. C.N. Patent 109953971A, 2019.

[103]
Xu, H. High water-soluble Amoxicillin and preparation method	thereof. C.N. Patent 109867687B, 2021.

[104]
Huang, G. Preparation method of sterile Amoxicillin. C.N. Patent 113577317A, 2021.

[105]
Xu, D. Amoxicillin capsules preparation method and amoxicillin capsule. C.N. Patent 112156082A, 2021.

[106]
Lu, X. Preparation method and application of high-content amoxicillin soluble powder. C.N. Patent 105726487B, 2020.

[107]
Cui, X. Amoxicillin soluble powder easy to dissolve in water and high in stability and preparation method thereof. C.N. Patent 111529493A, 2020.

[108]
Dai, Y. Compound amoxicillin soluble powder and preparation method thereof. C.N. Patent 110711193A, 2020.

[109]
Lu, C. Alkalescent amoxicillin soluble powder and preparation method thereof. C.N. Patent CN112587481B, 2022.
Cite As
Micro and Nanosystems

Amoxicillin-loaded Nanotechnological Carriers for the Effective Treatment of Helicobacter pylori Infection

Abstract

Graphical Abstract
