Alginate-coated chitosan nanoparticles protect protein drugs from acid degradation in gastric media

Journal of Pharmaceutical Investigation - Tập 52 - Trang 465-476 - 2022
Phuong Tran1, Jeong-Sook Park1
1College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea

Tóm tắt

The aim of this study was to design and evaluate chitosan nanoparticles (CS NPs) coated with alginate which protect protein drugs from acid degradation.K The model protein drug used was bovine serum albumin (BSA). BSA-loaded CS NPs (BSA-CS NPs) were prepared using the ionic gelation method with sodium tripolyphosphate and the surface of the BSA-CS NPs were coated with sodium alginate (Alg). The optimized alginate-coated BSA-CS NPs (Alg-BSA-CS NPs) were evaluated for BSA degradation in an acidic medium. The encapsulation efficiency (EE), particle size, polydispersity index, and zeta potential of the prepared Alg-BSA-CS NPs were 95.2%, 476.4 nm, 0.24, and − 53.8 mV, respectively. An in vitro release study showed that the initial burst release of BSA from the BSA-CS NPs was higher than that from the Alg-BSA-CS NPs. Cytotoxicity analysis revealed that the Alg-BSA-CS NPs were non-toxic to Caco-2 cells. The in vitro cellular uptake of the Alg-BSA-CS NPs in Caco-2 cells was significantly higher than that of the BSA-CS NPs and free BSA. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis showed that the Alg-BSA-CS NPs protected BSA from degradation in an acidic environment. Alg-BSA-CS NPs are suitable for the oral delivery of protein drugs by preventing protein degradation in acidic environments.

Tài liệu tham khảo

Agnihotri SA, Mallikarjuna NN, Aminabhavi TM (2004) Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release 100:5–28. https://doi.org/10.1016/j.jconrel.2004.08.010 Al-Tahami K, Singh J (2007) Smart polymer based delivery systems for peptides and proteins. Recent Pat Drug Deliv Formul 1:65–71. https://doi.org/10.2174/187221107779814113 Amidi M, Mastrobattista E, Jiskoot W, Hennink WE (2010) Chitosan-based delivery systems for protein therapeutics and antigens. Adv Drug Deliv Rev 62:59–82. https://doi.org/10.1016/j.addr.2009.11.009 Bagre AP, Jain K, Jain NK (2013) Alginate coated chitosan core shell nanoparticles for oral delivery of enoxaparin: in vitro and in vivo assessment. Int J Pharm 456:31–40. https://doi.org/10.1016/j.ijpharm.2013.08.037 Berthold A, Cremer K, Kreuter J (1996) Preparation and characterization of chitosan microspheres as drug carrier for prednisolone sodium phosphate as model for anti-inflammatory drugs. J Control Release 39:17–25. https://doi.org/10.1016/0168-3659(95)00129-8 Bronze-Uhle E, Costa BC, Ximenes VF, Lisboa-Filho PN (2016) Synthetic nanoparticles of bovine serum albumin with entrapped salicylic acid. Nanotechnol Sci Appl 10:11–21. https://doi.org/10.2147/NSA.S117018 Calvo P, Remuñán-López C, Vila-Jato JL, Alonso MJ (1997) Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers. J Appl Polym Sci 63:125–132. https://doi.org/10.1002/(SICI)1097-4628(19970103)63:1%3c125::AID-APP13%3e3.0.CO;2-4 Coppi G, Iannuccelli V, Leo E et al (2001) Chitosan-alginate microparticles as a protein carrier. Drug Dev Ind Pharm 27:393–400. https://doi.org/10.1081/DDC-100104314 Cui Z, Mumper RJ (2001) Chitosan-based nanoparticles for topical genetic immunization. J Control Release 75:409–419. https://doi.org/10.1016/S0168-3659(01)00407-2 Fan W, Yan W, Xu Z, Ni H (2012) Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique. Colloids Surfaces B Biointerfaces 90:21–27. https://doi.org/10.1016/j.colsurfb.2011.09.042 Fan YF, Wang YN, Fan YG, Ma J (2006) Preparation of insulin nanoparticles and their encapsulation with biodegradable polyelectrolytes via the layer-by-layer adsorption. Int J Pharm 324:158–167. https://doi.org/10.1016/j.ijpharm.2006.05.062 Ferreira Tomaz A, Sobral de Carvalho S, Cardoso Barbosa R et al (2018) Ionically crosslinked chitosan membranes used as drug carriers for cancer therapy application. Materials (basel) 11:2051. https://doi.org/10.3390/ma11102051 Frokjaer S, Otzen DE (2005) Protein drug stability: a formulation challenge. Nat Rev Drug Discov 4:298–306. https://doi.org/10.1038/nrd1695 Gan Q, Wang T, Cochrane C, McCarron P (2005) Modulation of surface charge, particle size and morphological properties of chitosan–TPP nanoparticles intended for gene delivery. Colloids Surfaces B Biointerfaces 44:65–73. https://doi.org/10.1016/j.colsurfb.2005.06.001 Ghormade V, Deshpande MV, Paknikar KM (2011) Perspectives for nano-biotechnology enabled protection and nutrition of plants. Biotechnol Adv 29:792–803. https://doi.org/10.1016/j.biotechadv.2011.06.007 Illum L, Jabbal-Gill I, Hinchcliffe M et al (2001) Chitosan as a novel nasal delivery system for vaccines. Adv Drug Deliv Rev 51:81–96. https://doi.org/10.1016/S0169-409X(01)00171-5 ISO-10993-5 (2009) Biological evaluation of medical devices-Part 5: Tests for in vitro cytotoxicity Jain S, Rathi VV, Jain AK et al (2012) Folate-decorated PLGA nanoparticles as a rationally designed vehicle for the oral delivery of insulin. Nanomedicine (lond) 7:1311–1337. https://doi.org/10.2217/nnm.12.31 Katuwavila NP, Perera ADLC, Samarakoon SR et al (2016) Chitosan-alginate nanoparticle system efficiently delivers doxorubicin to MCF-7 cells. J Nanomater 2016:1–12. https://doi.org/10.1155/2016/3178904 Kumari A, Yadav SK, Yadav SC (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surfaces B Biointerfaces 75:1–18. https://doi.org/10.1016/j.colsurfb.2009.09.001 Kurz D, Ciulla T (2002) Novel approaches for retinal drug delivery. Ophthalmol Clin North Am 15:405–410. https://doi.org/10.1016/S0896-1549(02)00034-2 Lee B-J, Min G-H (1996) Oral controlled release of melatonin using polymer-reinforced and coated alginate beads. Int J Pharm 144:37–46. https://doi.org/10.1016/S0378-5173(96)04723-0 Li T, Shi X-W, Du Y-M, Tang Y-F (2007) Quaternized chitosan/alginate nanoparticles for protein delivery. J Biomed Mater Res Part A 83A:383–390. https://doi.org/10.1002/jbm.a.31322 Li X, Kong X, Shi S et al (2008) Preparation of alginate coated chitosan microparticles for vaccine delivery. BMC Biotechnol 8:89. https://doi.org/10.1186/1472-6750-8-89 Loutfy SA, Alam El-Din HM, Elberry MH et al (2016) Synthesis, characterization and cytotoxic evaluation of chitosan nanoparticles: in vitro liver cancer model. Adv Nat Sci Nanosci Nanotechnol 7:035008. https://doi.org/10.1088/2043-6262/7/3/035008 Mohanraj VJ, Barnes TJ, Prestidge CA (2010) Silica nanoparticle coated liposomes: a new type of hybrid nanocapsule for proteins. Int J Pharm 392:285–293. https://doi.org/10.1016/j.ijpharm.2010.03.061 Mueller EA, Kovarik JM, van Bree JB et al (1994) Improved dose linearity of cyclosporine pharmacokinetics from a microemulsion formulation. Pharm Res 11:301–304. https://doi.org/10.1023/a:1018923912135 Muheem A, Shakeel F, Jahangir MA et al (2016) A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives. Saudi Pharm J 24:413–428. https://doi.org/10.1016/j.jsps.2014.06.004 Müller RH, Mäder K, Gohla S (2000) Solid lipid nanoparticles (SLN) for controlled drug delivery—a review of the state of the art. Eur J Pharm Biopharm 50:161–177. https://doi.org/10.1016/s0939-6411(00)00087-4 Nayar S, Mir A, Ashok A et al (2010) Bovine serum albumin binding and drug delivery studies with PVA-ferrofluid. J Bionic Eng 7:29–34. https://doi.org/10.1016/S1672-6529(09)60188-8 Okada E, Sasaki S, Ishii N et al (1997) Intranasal immunization of a DNA vaccine with IL-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens. J Immunol 159:3638–3647 Othayoth R, Mathi P, Bheemanapally K et al (2015) Characterization of vitamin–cisplatin-loaded chitosan nano-particles for chemoprevention and cancer fatigue. J Microencapsul 32:578–588. https://doi.org/10.3109/02652048.2015.1065921 Park JH, Saravanakumar G, Kim K, Kwon IC (2010) Targeted delivery of low molecular drugs using chitosan and its derivatives. Adv Drug Deliv Rev 62:28–41. https://doi.org/10.1016/j.addr.2009.10.003 Park K, Kwon IC, Park K (2011) Oral protein delivery: current status and future prospect. React Funct Polym 71:280–287. https://doi.org/10.1016/j.reactfunctpolym.2010.10.002 Patil S, Narvekar A, Puranik A et al (2019) Formulation of therapeutic proteins: strategies for developing oral protein formulations. In: Bachhav Y (ed) Innovative dosage forms: design and development at early stage. Wiley, Hoboken, pp 391–432 Raj L, Jonisha R, Revathi B, Jayalakshmy E (2015) Preparation and characterization of BSA and chitosan nanopartices for sustainable delivery system for quercetin. J Appl Pharm Sci. https://doi.org/10.7324/JAPS.2015.50701 Retnakumari A, Setua S, Menon D et al (2010) Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging. Nanotechnology 21:055103. https://doi.org/10.1088/0957-4484/21/5/055103 Safdar R, Omar AA, Arunagiri A et al (2019) Potential of chitosan and its derivatives for controlled drug release applications—a review. J Drug Deliv Sci Technol 49:642–659. https://doi.org/10.1016/j.jddst.2018.10.020 Sahu SK, Prusty AK (2010) Design and evaluation of a nanoparticulate system prepared by biodegradable polymers for oral administration of protein drugs. Pharmazie 65:824–829 Sarmento B, Martins S, Ferreira D, Souto EB (2007) Oral insulin delivery by means of solid lipid nanoparticles. Int J Nanomed 2:743–749 Shu X, Zhu K (2002) Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure. Int J Pharm 233:217–225. https://doi.org/10.1016/S0378-5173(01)00943-7 Sinha V, Singla A, Wadhawan S et al (2004) Chitosan microspheres as a potential carrier for drugs. Int J Pharm 274:1–33. https://doi.org/10.1016/j.ijpharm.2003.12.026 Su F-Y, Lin K-J, Sonaje K et al (2012) Protease inhibition and absorption enhancement by functional nanoparticles for effective oral insulin delivery. Biomaterials 33:2801–2811. https://doi.org/10.1016/j.biomaterials.2011.12.038 Takka S, Gürel A (2010) Evaluation of chitosan/alginate beads using experimental design: formulation and in vitro characterization. AAPS PharmSciTech 11:460–466. https://doi.org/10.1208/s12249-010-9406-z Torchilin VP, Lukyanov AN (2003) Peptide and protein drug delivery to and into tumors: challenges and solutions. Drug Discov Today 8:259–266. https://doi.org/10.1016/S1359-6446(03)02623-0 Tran P, Park J-S (2021) Formulation of solid dispersion to improve dissolution and oral bioavailability of poorly soluble dexibuprofen. Pharm Dev Technol 26:422–430. https://doi.org/10.1080/10837450.2021.1884259 Wang L-Y, Ma G-H, Su Z-G (2005) Preparation of uniform sized chitosan microspheres by membrane emulsification technique and application as a carrier of protein drug. J Control Release 106:62–75. https://doi.org/10.1016/j.jconrel.2005.04.005 Zohri M, Nomani A, Gazori T et al (2011) Characterization of chitosan/alginate self-assembled nanoparticles as a protein carrier. J Dispers Sci Technol 32:576–582. https://doi.org/10.1080/01932691003757314