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Erschienen in: Journal of Nanoparticle Research 1/2020

01.01.2020 | Research Paper

Design of enzyme decorated mucopermeating nanocarriers for eradication of H. pylori infection

verfasst von: Hajra Zafar, Maria Hassan Kiani, Faisal Raza, Aisha Rauf, Iqra Chaudhery, Nasir Mahmood Ahmad, Sohail Akhtar, Gul Shahnaz

Erschienen in: Journal of Nanoparticle Research | Ausgabe 1/2020

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Abstract

The study was aimed to develop amoxicillin (AM) loaded thiomer based mucopermeating and mucoadhesive nanocarrier system that allows it to reach the bacterium, hiding in deeper mucus layers and extends its availability at infection site. Amoxicillin loaded nanocargoes were prepared using unmodified polycarbophil (PCP), thiolated polycarbophil (PCP-Cys), and papain modified thiolated polycarbophil (PCP-Cys-PAP) by ionic gelation method and processed for in vitro and ex vivo and in vivo characterization. All the nanocargoes were in size range of 111–288 nm. Drug loaded papain modified thiolated polycarbophil (AM-PCP-Cys-PAP) based nanocargoes showed an entrapment efficiency of 78 ± 7.2%, a zeta potential of − 13.4 mV and spherical shape. Both AM-PCP-Cys and AM-PCP-Cys-PAP exhibited a sustained release of drug up to 48 h and AM-PCP-Cys-PAP nanocargoes showed significant stability in acidic pH as compared to pure drug. Rheological investigation demonstrated a twofold higher mucoadhesion for thiolated polycarbophil nanocargoes. Ex vivo muco-penetration studies demonstrated deepest permeation of papain modified nanocargoes into the mucus. Cytotoxicity analysis showed that nanocarrier formulations were non-toxic to Caco-2 cells and maintained cell viability after 48 h. In vitro growth inhibition assay for H. pylori exhibited better efficacy for AM-PCP-Cys-PAP nanocargoes in terms of improved stability along with complete eradication of bacteria over prolonged period of time. In vivo acute toxicity studies on vital organs of mice exhibited no significant change in cell morphology. In vivo clearance study showed that AM-PCP-Cys-PAP nanoformulation was successful in complete eradication of bacteria. Based on above findings, amoxicillin loaded papain modified thiolated polycarbophil nanocarrier system was able to completely eradicate H. pylori infection that was attributed to its enhanced mucopermeating and mucoadhesive nature. The functionalized nanocarriers showed an interesting future potential for infectious therapy.

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Literatur
Zurück zum Zitat Arora S, Gupta S, Narang RK, Budhiraja RD (2011) Amoxicillin loaded chitosan–alginate polyelectrolyte complex nanoparticles as mucopenetrating delivery system for H. pylori. Sci Pharm 79(3):673–694 Arora S, Gupta S, Narang RK, Budhiraja RD (2011) Amoxicillin loaded chitosan–alginate polyelectrolyte complex nanoparticles as mucopenetrating delivery system for H. pylori. Sci Pharm 79(3):673–694
Zurück zum Zitat Arora, S., Bisen, G., & Budhiraja, R. (2014). Mucoadhesive and muco-penetrating delivery systems for eradication of Helicobacter pylori. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm, 6(1) Arora, S., Bisen, G., & Budhiraja, R. (2014). Mucoadhesive and muco-penetrating delivery systems for eradication of Helicobacter pylori. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm, 6(1)
Zurück zum Zitat Asija R (2014) Gastrointestinal mucoadhesive drug delivery system: an overview. J Drug Discov Ther 2(20):213–219 Asija R (2014) Gastrointestinal mucoadhesive drug delivery system: an overview. J Drug Discov Ther 2(20):213–219
Zurück zum Zitat Balzus B, Colombo M, Sahle FF, Zoubari G, Staufenbiel S, Bodmeier R (2016) Comparison of different in vitro release methods used to investigate nanocarriers intended for dermal application. Int J Pharm 513(1–2):247–254 Balzus B, Colombo M, Sahle FF, Zoubari G, Staufenbiel S, Bodmeier R (2016) Comparison of different in vitro release methods used to investigate nanocarriers intended for dermal application. Int J Pharm 513(1–2):247–254
Zurück zum Zitat Barthelmes J, Dünnhaupt S, Unterhofer S, Perera G, Schlocker W, Bernkop-Schnürch A (2013) Thiolated particles as effective intravesical drug delivery systems for treatment of bladder-related diseases. Nanomedicine 8(1):65–75 Barthelmes J, Dünnhaupt S, Unterhofer S, Perera G, Schlocker W, Bernkop-Schnürch A (2013) Thiolated particles as effective intravesical drug delivery systems for treatment of bladder-related diseases. Nanomedicine 8(1):65–75
Zurück zum Zitat Bergin IL, Witzmann FA (2013) Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps. Int J Biomed Nanosci Nanotechnol 3(1–2):49–58 Bergin IL, Witzmann FA (2013) Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps. Int J Biomed Nanosci Nanotechnol 3(1–2):49–58
Zurück zum Zitat Bernkop-Schnürch A (2005) Thiomers: a new generation of mucoadhesive polymers. Adv Drug Deliv Rev 57(11):1569–1582 Bernkop-Schnürch A (2005) Thiomers: a new generation of mucoadhesive polymers. Adv Drug Deliv Rev 57(11):1569–1582
Zurück zum Zitat Bernkop-Schnürch A, Gilge B (2000) Anionic mucoadhesive polymers as auxiliary agents for the peroral administration of (poly) peptide drugs: influence of the gastric juice. Drug Dev Ind Pharm 26(2):107–113 Bernkop-Schnürch A, Gilge B (2000) Anionic mucoadhesive polymers as auxiliary agents for the peroral administration of (poly) peptide drugs: influence of the gastric juice. Drug Dev Ind Pharm 26(2):107–113
Zurück zum Zitat Bernkop-Schnürch A, Scholler S, Biebel RG (2000) Development of controlled drug release systems based on thiolated polymers. J Control Release 66(1):39–48 Bernkop-Schnürch A, Scholler S, Biebel RG (2000) Development of controlled drug release systems based on thiolated polymers. J Control Release 66(1):39–48
Zurück zum Zitat Bernkop-Schnürch A, Weithaler A, Albrecht K, Greimel A (2006) Thiomers: preparation and in vitro evaluation of a mucoadhesive nanoparticulate drug delivery system. Int J Pharm 317(1):76–81 Bernkop-Schnürch A, Weithaler A, Albrecht K, Greimel A (2006) Thiomers: preparation and in vitro evaluation of a mucoadhesive nanoparticulate drug delivery system. Int J Pharm 317(1):76–81
Zurück zum Zitat Cevher E, Sensoy D, Taha MA, Araman A (2008) Effect of thiolated polymers to textural and mucoadhesive properties of vaginal gel formulations prepared with polycarbophil and chitosan. AAPS PharmSciTech 9(3):953–965 Cevher E, Sensoy D, Taha MA, Araman A (2008) Effect of thiolated polymers to textural and mucoadhesive properties of vaginal gel formulations prepared with polycarbophil and chitosan. AAPS PharmSciTech 9(3):953–965
Zurück zum Zitat Clausen AE, Bernkop-Schnürch A (2000) In vitro evaluation of the permeation-enhancing effect of thiolated polycarbophil. J Pharm Sci 89(10):1253–1261 Clausen AE, Bernkop-Schnürch A (2000) In vitro evaluation of the permeation-enhancing effect of thiolated polycarbophil. J Pharm Sci 89(10):1253–1261
Zurück zum Zitat Cone RA (2009) Barrier properties of mucus. Adv Drug Deliv Rev 61(2):75–85 Cone RA (2009) Barrier properties of mucus. Adv Drug Deliv Rev 61(2):75–85
Zurück zum Zitat Crater JS, Carrier RL (2010) Barrier properties of gastrointestinal mucus to nanoparticle transport. Macromol Biosci 10(12):1473–1483 Crater JS, Carrier RL (2010) Barrier properties of gastrointestinal mucus to nanoparticle transport. Macromol Biosci 10(12):1473–1483
Zurück zum Zitat da Silva CR, Oliveira MB, Motta ES, de Almeida GS, Varanda LL, de Pádula M, Leitão AC, Caldeira-de-Araújo A (2010) Genotoxic and cytotoxic safety evaluation of papain (Carica papaya L.) using in vitro assays. Biomed Res Int 2010:75–88 da Silva CR, Oliveira MB, Motta ES, de Almeida GS, Varanda LL, de Pádula M, Leitão AC, Caldeira-de-Araújo A (2010) Genotoxic and cytotoxic safety evaluation of papain (Carica papaya L.) using in vitro assays. Biomed Res Int 2010:75–88
Zurück zum Zitat Dünnhaupt S, Barthelmes J, Hombach J, Sakloetsakun D, Arkhipova V, Bernkop-Schnürch A (2011) Distribution of thiolated mucoadhesive nanoparticles on intestinal mucosa. Int J Pharm 408(1):191–199 Dünnhaupt S, Barthelmes J, Hombach J, Sakloetsakun D, Arkhipova V, Bernkop-Schnürch A (2011) Distribution of thiolated mucoadhesive nanoparticles on intestinal mucosa. Int J Pharm 408(1):191–199
Zurück zum Zitat Dünnhaupt S, Barthelmes J, Köllner S, Sakloetsakun D, Shahnaz G, Düregger A, Bernkop-Schnürch A (2015) Thiolated nanocarriers for oral delivery of hydrophilic macromolecular drugs. Carbohydr Polym 117:577–584 Dünnhaupt S, Barthelmes J, Köllner S, Sakloetsakun D, Shahnaz G, Düregger A, Bernkop-Schnürch A (2015) Thiolated nanocarriers for oral delivery of hydrophilic macromolecular drugs. Carbohydr Polym 117:577–584
Zurück zum Zitat Greindl M, Bernkop-Schnürch A (2006) Development of a novel method for the preparation of thiolated polyacrylic acid nanoparticles. Pharm Res 23(9):2183–2189 Greindl M, Bernkop-Schnürch A (2006) Development of a novel method for the preparation of thiolated polyacrylic acid nanoparticles. Pharm Res 23(9):2183–2189
Zurück zum Zitat Hanefeld U, Gardossi L, Magner E (2009) Understanding enzyme immobilisation. Chem Soc Rev 38(2):453–468 Hanefeld U, Gardossi L, Magner E (2009) Understanding enzyme immobilisation. Chem Soc Rev 38(2):453–468
Zurück zum Zitat Homaei AA, Sajedi RH, Sariri R, Seyfzadeh S, Stevanato R (2010) Cysteine enhances activity and stability of immobilized papain. Amino Acids 38(3):937–942 Homaei AA, Sajedi RH, Sariri R, Seyfzadeh S, Stevanato R (2010) Cysteine enhances activity and stability of immobilized papain. Amino Acids 38(3):937–942
Zurück zum Zitat Iqbal J, Shahnaz G, Perera G, Hintzen F, Sarti F, Bernkop-Schnürch A (2012) Thiolated chitosan: development and in vivo evaluation of an oral delivery system for leuprolide. Eur J Pharm Biopharm 80(1):95–102 Iqbal J, Shahnaz G, Perera G, Hintzen F, Sarti F, Bernkop-Schnürch A (2012) Thiolated chitosan: development and in vivo evaluation of an oral delivery system for leuprolide. Eur J Pharm Biopharm 80(1):95–102
Zurück zum Zitat Kaul P, Sathish H, Prakash V (2002) Effect of metal ions on structure and activity of papain from Carica papaya. Mol Nutr Food Res 46(1):2–6 Kaul P, Sathish H, Prakash V (2002) Effect of metal ions on structure and activity of papain from Carica papaya. Mol Nutr Food Res 46(1):2–6
Zurück zum Zitat Köllner S, Dünnhaupt S, Waldner C, Hauptstein S, de Sousa IP, Bernkop-Schnürch A (2015) Mucus permeating thiomer nanoparticles. Eur J Pharm Biopharm 97:265–272 Köllner S, Dünnhaupt S, Waldner C, Hauptstein S, de Sousa IP, Bernkop-Schnürch A (2015) Mucus permeating thiomer nanoparticles. Eur J Pharm Biopharm 97:265–272
Zurück zum Zitat Kumar D, Dharmendra S, Jhansee M, Shrikant N, Pandey S (2011) Development and characterization of chitosan nanoparticles loaded with amoxicillin. Int Res J Phar 2:145–511 Kumar D, Dharmendra S, Jhansee M, Shrikant N, Pandey S (2011) Development and characterization of chitosan nanoparticles loaded with amoxicillin. Int Res J Phar 2:145–511
Zurück zum Zitat Laffleur F, Hintzen F, Shahnaz G, Rahmat D, Leithner K, Bernkop-Schnürch A (2014) Development and in vitro evaluation of slippery nanoparticles for enhanced diffusion through native mucus. Nanomedicine 9(3):387–396 Laffleur F, Hintzen F, Shahnaz G, Rahmat D, Leithner K, Bernkop-Schnürch A (2014) Development and in vitro evaluation of slippery nanoparticles for enhanced diffusion through native mucus. Nanomedicine 9(3):387–396
Zurück zum Zitat Lai SK, Wang Y-Y, Hanes J (2009) Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 61(2):158–171 Lai SK, Wang Y-Y, Hanes J (2009) Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 61(2):158–171
Zurück zum Zitat Lam HT, Leonaviciute G, Zupančič O, Bernkop-Schnürch A (2017) Thiomers: impact of in situ cross-linkers on mucoadhesive properties. Eur J Pharm Sci 106:41–48 Lam HT, Leonaviciute G, Zupančič O, Bernkop-Schnürch A (2017) Thiomers: impact of in situ cross-linkers on mucoadhesive properties. Eur J Pharm Sci 106:41–48
Zurück zum Zitat Marques MR, Loebenberg R, Almukainzi M (2011) Simulated biological fluids with possible application in dissolution testing. Dissolution Technol 18(3):15–28 Marques MR, Loebenberg R, Almukainzi M (2011) Simulated biological fluids with possible application in dissolution testing. Dissolution Technol 18(3):15–28
Zurück zum Zitat Mehta SB, Carpenter JF, Randolph TW (2016) Colloidal instability fosters agglomeration of subvisible particles created by rupture of gels of a monoclonal antibody formed at silicone oil-water interfaces. J Pharm Sci 105(8):2338–2348 Mehta SB, Carpenter JF, Randolph TW (2016) Colloidal instability fosters agglomeration of subvisible particles created by rupture of gels of a monoclonal antibody formed at silicone oil-water interfaces. J Pharm Sci 105(8):2338–2348
Zurück zum Zitat Metin AÜ, Alver E (2016) Fibrous polymer-grafted chitosan/clay composite beads as a carrier for immobilization of papain and its usability for mercury elimination. Bioprocess Biosyst Eng 39(7):1137–1149 Metin AÜ, Alver E (2016) Fibrous polymer-grafted chitosan/clay composite beads as a carrier for immobilization of papain and its usability for mercury elimination. Bioprocess Biosyst Eng 39(7):1137–1149
Zurück zum Zitat Müller C, Leithner K, Hauptstein S, Hintzen F, Salvenmoser W, Bernkop-Schnürch A (2013) Preparation and characterization of mucus-penetrating papain/poly (acrylic acid) nanoparticles for oral drug delivery applications. J Nanopart Res 15(1):1353 Müller C, Leithner K, Hauptstein S, Hintzen F, Salvenmoser W, Bernkop-Schnürch A (2013) Preparation and characterization of mucus-penetrating papain/poly (acrylic acid) nanoparticles for oral drug delivery applications. J Nanopart Res 15(1):1353
Zurück zum Zitat Müller C, Perera G, König V, Bernkop-Schnürch A (2014) Development and in vivo evaluation of papain-functionalized nanoparticles. Eur J Pharm Biopharm 87(1):125–131 Müller C, Perera G, König V, Bernkop-Schnürch A (2014) Development and in vivo evaluation of papain-functionalized nanoparticles. Eur J Pharm Biopharm 87(1):125–131
Zurück zum Zitat Narkar M, Sher P, Pawar A (2010) Stomach-specific controlled release gellan beads of acid-soluble drug prepared by ionotropic gelation method. AAPS PharmSciTech 11(1):267–277 Narkar M, Sher P, Pawar A (2010) Stomach-specific controlled release gellan beads of acid-soluble drug prepared by ionotropic gelation method. AAPS PharmSciTech 11(1):267–277
Zurück zum Zitat Novelli F, De Santis S, Punzi P, Giordano C, Scipioni A, Masci G (2017) Self-assembly and drug release study of linear l, d-oligopeptide-poly (ethylene glycol) conjugates. New Biotechnol 37(5):99–107 Novelli F, De Santis S, Punzi P, Giordano C, Scipioni A, Masci G (2017) Self-assembly and drug release study of linear l, d-oligopeptide-poly (ethylene glycol) conjugates. New Biotechnol 37(5):99–107
Zurück zum Zitat Rajinikanth P, Balasubramaniam J, Mishra B (2007) Development and evaluation of a novel floating in situ gelling system of amoxicillin for eradication of Helicobacter pylori. Int J Pharm 335(1):114–122 Rajinikanth P, Balasubramaniam J, Mishra B (2007) Development and evaluation of a novel floating in situ gelling system of amoxicillin for eradication of Helicobacter pylori. Int J Pharm 335(1):114–122
Zurück zum Zitat Rossi A, Conti C, Colombo G, Castrati L, Scarpignato C, Barata P, Sandri G, Caramella C, Bettini R, Buttini F (2016) Floating modular drug delivery systems with buoyancy independent of release mechanisms to sustain amoxicillin and clarithromycin intra-gastric concentrations. Drug Dev Ind Pharm 42(2):332–339 Rossi A, Conti C, Colombo G, Castrati L, Scarpignato C, Barata P, Sandri G, Caramella C, Bettini R, Buttini F (2016) Floating modular drug delivery systems with buoyancy independent of release mechanisms to sustain amoxicillin and clarithromycin intra-gastric concentrations. Drug Dev Ind Pharm 42(2):332–339
Zurück zum Zitat Sambuy Y, De Angelis I, Ranaldi G, Scarino M, Stammati A, Zucco F (2005) The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol Toxicol 21(1):1–26 Sambuy Y, De Angelis I, Ranaldi G, Scarino M, Stammati A, Zucco F (2005) The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol Toxicol 21(1):1–26
Zurück zum Zitat Shahnaz G, Perera G, Sakloetsakun D, Rahmat D, Bernkop-Schnürch A (2010) Synthesis, characterization, mucoadhesion and biocompatibility of thiolated carboxymethyl dextran–cysteine conjugate. J Control Release 144(1):32–38 Shahnaz G, Perera G, Sakloetsakun D, Rahmat D, Bernkop-Schnürch A (2010) Synthesis, characterization, mucoadhesion and biocompatibility of thiolated carboxymethyl dextran–cysteine conjugate. J Control Release 144(1):32–38
Zurück zum Zitat Sigurdsson HH, Kirch J, Lehr C-M (2013) Mucus as a barrier to lipophilic drugs. Int J Pharm 453(1):56–64 Sigurdsson HH, Kirch J, Lehr C-M (2013) Mucus as a barrier to lipophilic drugs. Int J Pharm 453(1):56–64
Zurück zum Zitat Sohail MF, Javed I, Hussain SZ, Sarwar S, Akhtar S, Nadhman A, Batool S, Bukhari NI, Saleem RSZ, Hussain I (2016) Folate grafted thiolated chitosan enveloped nanoliposomes with enhanced oral bioavailability and anticancer activity of docetaxel. J Mater Chem B 4(37):6240–6248 Sohail MF, Javed I, Hussain SZ, Sarwar S, Akhtar S, Nadhman A, Batool S, Bukhari NI, Saleem RSZ, Hussain I (2016) Folate grafted thiolated chitosan enveloped nanoliposomes with enhanced oral bioavailability and anticancer activity of docetaxel. J Mater Chem B 4(37):6240–6248
Zurück zum Zitat Umamaheshwari R, Ramteke S, Jain NK (2004) Anti-Helicobacter pylori effect of mucoadhesive nanoparticles bearing amoxicillin in experimental gerbils model. AAPS PharmSciTech 5(2):60–68 Umamaheshwari R, Ramteke S, Jain NK (2004) Anti-Helicobacter pylori effect of mucoadhesive nanoparticles bearing amoxicillin in experimental gerbils model. AAPS PharmSciTech 5(2):60–68
Zurück zum Zitat Vetter A, Martien R, Bernkop-Schnürch A (2010) Thiolated polycarbophil as an adjuvant for permeation enhancement in nasal delivery of antisense oligonucleotides. J Pharm Sci 99(3):1427–1439 Vetter A, Martien R, Bernkop-Schnürch A (2010) Thiolated polycarbophil as an adjuvant for permeation enhancement in nasal delivery of antisense oligonucleotides. J Pharm Sci 99(3):1427–1439
Zurück zum Zitat Zazo H, Colino CI, Lanao JM (2016) Current applications of nanoparticles in infectious diseases. J Control Release 224:86–102 Zazo H, Colino CI, Lanao JM (2016) Current applications of nanoparticles in infectious diseases. J Control Release 224:86–102
Metadaten
Titel
Design of enzyme decorated mucopermeating nanocarriers for eradication of H. pylori infection
verfasst von
Hajra Zafar
Maria Hassan Kiani
Faisal Raza
Aisha Rauf
Iqra Chaudhery
Nasir Mahmood Ahmad
Sohail Akhtar
Gul Shahnaz
Publikationsdatum
01.01.2020
Verlag
Springer Netherlands
Erschienen in
Journal of Nanoparticle Research / Ausgabe 1/2020
Print ISSN: 1388-0764
Elektronische ISSN: 1572-896X
DOI
https://doi.org/10.1007/s11051-019-4719-7

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