Formulation and Characterization of Alginate Coated Chitosan Nanoparticles as Therapeutic Protein for Oral Delivery System
DOI:
https://doi.org/10.48048/tis.2022.5797Keywords:
Alginate, BSA, Chitosan, Lysozyme, Nanoparticle, Oral deliveryAbstract
Nanoparticles have been promptly studied and developed for oral protein delivery. Selection of excipients and formulation method depends on the physicochemical characteristics of the protein carried. Therefore, this study aims to design a formulation and characterize the alginate coated chitosan nanoparticles which carried different protein. Alginate coated chitosan nanoparticles were formed using an ionic gelation method. Optimization was done by varying the parameter such as crosslinker concentration, agitation method, rate, and time. The results show that chitosan nanoparticles formed by sonication using sodium tripolyphosphate (STPP): chitosan (1:0.8) was the best method to form nanoparticles. The particle size and polydispersity index (PDI) of bovine serum albumin (BSA) and lysozyme nanoparticles were 812.2 nm and 0.412 for BSA while 793.3 nm and 0.438 for lysozyme. Encapsulation efficiency (EE) of BSA is 52 % and lysozyme is 68 %. In vitro tests on acidic/gastric conditions showed that lysozyme (±32 %) was released faster than BSA (±10 %) during the 24 h incubation. Under neutral/terminal intestine conditions, percentage of BSA (±17 %) release is slightly higher than lysozyme (±13 %) for 8 h incubation period. It was concluded that the formulation of alginate coated chitosan nanoparticles in this study appears to be more effective for BSA delivery than lysozyme.
HIGHLIGHTS
- Nanoparticle vesicular system is an effective approach for protein drug delivery system
- Factors affecting the formation of chitosan nanoparticle are crosslinker concentration, agitation method, rate, and time
- Alginate coated chitosan nanoparticle was more effective for oral delivery of BSA compared to lysozyme
GRAPHICAL ABSTRACT
Downloads
Metrics
References
Z Antosova, M Mackova, V Kral and T Macek. Therapeutic application of peptides and proteins: Parenteral forever? Trends Biotechnol. 2009; 27, 628-35.
SJ Cao, S Xu, HM Wang, Y Ling, J Dong, RD Xia, and XH Sun. Nanoparticles: Oral Delivery for protein and peptide drugs. AAPS PharmSciTech 2019; 20, 190.
MSH Akash, K Rehman, M Tariq and S Chen. Development of therapeutic proteins: Advances and challenges. Turkish J. Biol. 2015; 39, 343-58.
C Ye and S Venkatraman. The long-term delivery of proteins and peptides using Micro/Nanoparticles: Overview and perspectives. Ther. Deliv. 2019; 10, 269-72.
SS Usmani, G Bedi, JS Samuel, S Singh, S Kalra, P Kumar, AA Ahuja, M Sharma, A Gautam and GPS Raghava. THPdb: Database of FDA-approved peptide and protein therapeutics. PLoS One 2017; 12, e0181748.
JEV Ramirez, LA Sharpe and NA Peppas. Current state and challenges in developing oral vaccines. Adv. Drug Deliv. Rev. 2017; 114, 116-31.
E Criscuolo, V Caputo, RA Diotti, GA Sautto, GA Kirchenbaum and N Clementi. Alternative methods of vaccine delivery: An overview of edible and intradermal vaccines. J. Immunol. Res. 2019; 2019, 8303648.
AK Dinda, M Bhat, S Srivastava, SK Kottarath and CK Prashant. Novel nanocarrier for oral hepatitis B vaccine. Vaccine 2016; 34, 3076-81.
G Bayramoǧlu, B Kaya and MY Arica. Procion brown Mx-5br Attached and lewis metals ion-immobilized poly(hydroxyethyl methacrylate)/chitosan ipns membranes: Their lysozyme adsorption equilibria and kinetics characterization. Chem. Eng. Sci. 2002; 57, 2323-34.
X Zeng and E Ruckenstein. Cross-linked macroporous chitosan anion-exchange membranes for protein separations. J. Memb. Sci. 1998; 148, 195-205.
QY Deng, CR Zhou and BH Luo. Preparation and characterization of chitosan nanoparticles containing lysozyme. Pharm. Biol. 2006; 44, 336-42.
S Jesus, AP Marques, A Duarte, E Soares, JP Costa, M Colaço, M Schmutz, C Som, G Borchard, P Wick and O Borges. Chitosan nanoparticles: Shedding light on immunotoxicity and hemocompatibility. Front. Bioeng. Biotechnol. 2020; 8, 100.
M Yanat and K Schroën. Preparation methods and applications of chitosan nanoparticles; with an outlook toward reinforcement of biodegradable packaging. React. Funct. Polym. 2021; 161, 104849.
M Soltanzadeh, SH Peighambardoust, B Ghanbarzadeh, M Mohammadi and JM Lorenzo. Chitosan nanoparticles as a promising nanomaterial for encapsulation of pomegranate (Punica Granatum L.) peel extract as a natural source of antioxidants. Nanomaterials 2021; 11, 1439.
M George and TE Abraham. Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan - a review. J. Contr. Release 2006; 114, 1-14.
X Meng, P Li, Q Wei and HX Zhang. pH sensitive alginate-chitosan hydrogel beads for carvedilol delivery. Pharm. Dev. Tech. 2011; 16, 22-8.
K Sonaje, K Lin, MT Tseng, S Wey, F Su, E Chuang, C Hsu, C Chen and H Sung. Biomaterials effects of chitosan-nanoparticle-mediated tight junction opening on the oral absorption of endotoxins. Biomaterials 2011; 32, 8712-21.
G Coppi, V Iannuccelli, E Leo, MT Bernabei and R Cameroni. Chitosan-alginate microparticles as a protein carrier. Drug Dev. Ind. Pharm. 2001; 27, 393-400.
B Kim, T Bowersock, P Griebel, A Kidane, LA Babiuk, M Sanchez, S Attah-Poku, RS Kaushik, and GK Mutwiri. Mucosal immune responses following oral immunization with rotavirus antigens encapsulated in alginate microspheres. J. Contr. Release 2002; 85, 191-202.
O Borges, J Tavares, AD Sousa,G Borchard, HE Junginger and A Cordeiro-da-Silva. Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate-coated chitosan nanoparticles. Eur. J. Pharm. Sci. 2007; 32, 278-90.
F Sarei, N Dounighi, H Zolfagharian, P Khaki and S Bidhendi. Alginate nanoparticles as a promising adjuvant and vaccine delivery system. Indian J. Pharm. Sci. 2013; 75, 442-9.
XY Li, XY Kong, S Shi, XL Zheng, G Guo, YQ Wei and ZY Qian. Preparation of alginate coated chitosan microparticles for vaccine delivery. BMC Biotechnol. 2008; 8, 89.
R Fernandez-Urrusuno, P Calvo, C Remunan-Lopez, JL Vila-Jato and MJ Alonso. Enhancement of nasal absorption of insulin using chitosan nanoparticles. Pharm. Res. 1999; 16, 1576-81.
P Calvo, C Remunan-Lopez, JL Vila-Jato and MJ Alonso. Chitosan and chitosan/ethylene oxide-propylene oxide block copolymer nanoparticles as novel carriers for protein and vaccine. Pharm. Res. 1997; 14, 1431-6.
N Sawtarie, Y Cai and Y Lapitsky. Preparation of Chitosan/tripolyphosphate nanoparticles with highly tunable size and low polydispersity. Colloid. Surface. B Biointerfac. 2017; 157, 110-7.
RM Saeed, I Dmour and MO Taha. Stable chitosan-based nanoparticles using polyphosphoric acid or hexametaphosphate for tandem ionotropic/covalent crosslinking and subsequent investigation as novel vehicles for drug delivery. Front. Bioeng. Biotechnol. 2020; 8, 4.
NK Al-Nemrawi, SSM Alsharif and RH Dave. Preparation of chitosan-tpp nanoparticles: The Influence of chitosan polymeric properties and formulation variables. Int. J. Appl. Pharm. 2018; 10, 60-5.
W Fan, W Yan, Z Xu and H Ni. Colloids and surfaces B: Biointerfaces formation mechanism of monodisperse , low molecular weight chitosan nanoparticles by ionic gelation technique. Colloid. Surface. B Biointerfac. 2012; 90, 21-7.
P Calvo, C Remuñán-López, JL Vila-Jato and MJ Alonso. Novel hydrophilic chitosan - polyethylene oxide nanoparticles as protein carriers. J. Appl. Polym. Sci. 1997; 63, 125-32.
SS Shen, JJ Yang, CX Liu and RB Bai. Immobilization of copper ions on chitosan/cellulose acetate blend hollow fiber membrane for protein adsorption. RSC Adv. 2017; 7, 10424-31.
P Sacco, M Borgogna, A Travan, E Marsich, S Paoletti, F Asaro, M Grassi and I Donati. Polysaccharide-based networks from homogeneous chitosan-tripolyphosphate hydrogels: synthesis and characterization. Biomacromolecules 2014; 15, 3396-405.
P Sacco, F Furlani, GD Marzo, E Marsich, S Paoletti and I Donati. Concepts for developing physical gels of chitosan and of chitosan derivatives. Gels 2018; 4, 67.
H Katas, Z Hussain and TC Ling. Chitosan nanoparticles as a percutaneous drug delivery system for hydrocortisone. J. Nanomater. 2012; 2012, 372725.
MA Torres, MM Beppu and CC Santana. Characterization of chemically modified chitosan microspheres as adsorbents using standard proteins (bovine serum albumin and lysozyme). Brazilian J. Chem. Eng. 2007; 24, 325-36.
UK Aravind, J Mathew and CT Aravindakumar. Transport studies of BSA, lysozyme and ovalbumin through chitosan/polystyrene sulfonate multilayer membrane. J. Memb. Sci. 2007; 299, 146-55.
K Itoyama and S Tokura. Adsorption behavior of lysozyme onto carboxylated chitosan beads. Sen’i Gakkaishi 1994; 50, 118-23.
T Wu, J Huang, Y Jiang, Y Hu, X Ye, D Liu and J Chen. Formation of hydrogels based on chitosan/alginate for the delivery of lysozyme and their antibacterial activity. Food Chem. 2018; 240, 361-9.
O Borges, A Cordeiro-da-Silva, SG Romeijn, M Amidi, AD Sousa, G Borchard and HE Junginger. Uptake Studies in rat peyer’s patches, cytotoxicity and release studies of alginate coated chitosan nanoparticles for mucosal vaccination. J. Contr. Release 2006; 114, 348-58.
F Alqahtani, F Aleanizy, EE Tahir, H Alhabib, R Alsaif, G Shazly, H Alqahtani, I Alsarra and J Mahdavi. Antibacterial activity of chitosan nanoparticles against pathogenic n. gonorrhoea. Int. J. Nanomed. 2020; 15, 7877-87.
N Nwe, T Furuike and H Tamura. The mechanical and biological properties of chitosan scaffolds for tissue regeneration templates are significantly enhanced by chitosan from gongronella butleri. Materials 2009; 2, 374-98.
C Yomota, K Tetsuo and K Toshio. Studies on degradation of chitosan films by lysozyme and release of loaded chemical. Yakugaku Zasshi 1990; 110, 442-8.
JW Oh, SC Chun and M Chandrasekaran. Preparation and in vitro characterization of chitosan nanoparticles and their broad-spectrum antifungal action compared to antibacterial activities against phytopathogens of tomato. Agronomy 2019; 9, 21.
O Borges, G Borchard, JC Verhoef, AD Sousa and HE Junginger. Preparation of coated nanoparticles for a new mucosal vaccine delivery system. Int. J. Pharm. 2005; 299, 155-66.
NP Katuwavila, ADLC Perera, SR Samarakoon, P Soysa, V Karunaratne, GAJ Amaratunga and DN Karunaratne. Chitosan-alginate nanoparticle system efficiently delivers doxorubicin to MCF-7 cells. J. Nanomater. 2016; 2016, 3178904.
Y Xu and Y Du. Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles. Int. J. Pharm. 2003; 250, 215-26.
G Lawrie, I Keen, B Drew, A Chandler-Temple, L Rintoul, P Fredericks and L Grøndahl. Interactions between Alginate and chitosan biopolymers characterized using FTIR and XPS. Biomacromolecules 2007; 8, 2533-41.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
