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

다국어 초록 (Multilingual Abstract)

Purpose 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).
Methods 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.
Results The encapsulation efficiency (EE), particle size, polydispersity index, and zeta potential of the prepared Alg-BSACS 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.
Conclusion Alg-BSA-CS NPs are suitable for the oral delivery of protein drugs by preventing protein degradation in acidic environments.

참고문헌 (Reference)

1 Park JH, "Targeted delivery of low molecular drugs using chitosan and its derivatives" 62 : 28-41, 2010

2 Bronze-Uhle E, "Synthetic nanoparticles of bovine serum albumin with entrapped salicylic acid" 10 : 11-21, 2016

3 Loutfy SA, "Synthesis, characterization and cytotoxic evaluation of chitosan nanoparticles : in vitro liver cancer model" 7 : 035008-, 2016

4 Müller RH, "Solid lipid nanoparticles(SLN)for controlled drug delivery—a review of the state of the art" 50 : 161-177, 2000

5 Al-Tahami K, "Smart polymer based delivery systems for peptides and proteins" 1 : 65-71, 2007

6 Mohanraj VJ, "Silica nanoparticle coated liposomes : a new type of hybrid nanocapsule for proteins" 392 : 285-293, 2010

7 Agnihotri SA, "Recent advances on chitosan-based micro-and nanoparticles in drug delivery" 100 : 5-28, 2004

8 Tao Li, "Quaternized chitosan/alginate nanoparticles for protein delivery" Wiley 83A (83A): 383-390, 2007

9 Frokjaer S, "Protein drug stability : a formulation challenge" 4 : 298-306, 2005

10 Su F-Y, "Protease inhibition and absorption enhancement by functional nanoparticles for effective oral insulin delivery" 33 : 2801-2811, 2012

11 Wang L-Y, "Preparation of uniform sized chitosan microspheres by membrane emulsification technique and application as a carrier of protein drug" 106 : 62-, 2005

12 Fan YF, "Preparation of insulin nanoparticles and their encapsulation with biodegradable polyelectrolytes via the layer-by-layer adsorption" 324 : 158-167, 2006

13 Li X, "Preparation of alginate coated chitosan microparticles for vaccine delivery" 8 : 89-, 2008

14 Berthold A, "Preparation and characterization of chitosan microspheres as drug carrier for prednisolone sodium phosphate as model for anti-inflammatory drugs" 39 : 17-25, 1996

15 L. Raj, "Preparation and characterization of BSA and chitosan nanopartices for sustainable delivery system for quercetin" Journal of Applied Pharmaceutical Science 001-005, 2015

16 Safdar R, "Potential of chitosan and its derivatives for controlled drug release applications—a review" 49 : 642-659, 2019

17 Ghormade V, "Perspectives for nano-biotechnology enabled protection and nutrition of plants" 29 : 792-803, 2011

18 Torchilin VP, "Peptide and protein drug delivery to and into tumors : challenges and solutions" 8 : 259-266, 2003

19 Park K, "Oral protein delivery : current status and future prospect" 71 : 280-287, 2011

20 Sarmento B, "Oral insulin delivery by means of solid lipid nanoparticles" 2 : 743-749, 2007

21 Lee B-J, "Oral controlled release of melatonin using polymer-reinforced and coated alginate beads" 144 : 37-46, 1996

22 Calvo P, "Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers" 63 : 125-132, 1997

23 Kurz D, "Novel approaches for retinal drug delivery" 15 : 405-410, 2002

24 Retnakumari A, "Molecular-receptorspecific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging" 21 : 055103-, 2010

25 Gan Q, "Modulation of surface charge, particle size and morphological properties of chitosan–TPP nanoparticles intended for gene delivery" 44 : 65-73, 2005

26 Ferreira Tomaz A, "Ionically crosslinked chitosan membranes used as drug carriers for cancer therapy application" 11 : 2051-, 2018

27 Okada E, "Intranasal immunization of a DNA vaccine with IL-12-and granulocyte-macrophage colonystimulating factor(GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens" 159 : 3638-3647, 1997

28 Patil S, "Innovative dosage forms: design and development at early stage" Wiley 391-432, 2019

29 Mueller EA, "Improved dose linearity of cyclosporine pharmacokinetics from a microemulsion formulation" 11 : 301-304, 1994

30 "ISO-10993-5 (2009) Biological evaluation of medical devices-Part 5:Tests for in vitro cytotoxicity"

31 Tran P, "Formulation of solid dispersion to improve dissolution and oral bioavailability of poorly soluble dexibuprofen" 26 : 422-430, 2021

32 Fan W, "Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique" 90 : 21-27, 2012

33 Jain S, "Folate-decorated PLGA nanoparticles as a rationally designed vehicle for the oral delivery of insulin" 7 : 1311-1337, 2012

34 Takka S, "Evaluation of chitosan/alginate beads using experimental design : formulation and in vitro characterization" 11 : 460-466, 2010

35 Sahu SK, "Design and evaluation of a nanoparticulate system prepared by biodegradable polymers for oral administration of protein drugs" 65 : 824-829, 2010

36 Shu X, "Controlled drug release properties of ionically cross-linked chitosan beads : the influence of anion structure" 233 : 217-225, 2002

37 Amidi M, "Chitosanbased delivery systems for protein therapeutics and antigens" 62 : 59-82, 2010

38 Katuwavila NP, "Chitosanalginate nanoparticle system efficiently delivers doxorubicin to MCF-7 cells" 2016 : 1-12, 2016

39 Cui Z, "Chitosan-based nanoparticles for topical genetic immunization" 75 : 409-419, 2001

40 Coppi G, "Chitosan-alginate microparticles as a protein carrier" 27 : 393-400, 2001

41 Sinha V, "Chitosan microspheres as a potential carrier for drugs" 274 : 1-33, 2004

42 Illum L, "Chitosan as a novel nasal delivery system for vaccines" 51 : 81-96, 2001

43 Othayoth R, "Characterization of vitamin–cisplatin-loaded chitosan nano-particles for chemoprevention and cancer fatigue" 32 : 578-588, 2015

44 Zohri M, "Characterization of chitosan/alginate self-assembled nanoparticles as a protein carrier" 32 : 576-582, 2011

45 Nayar S, "Bovine serum albumin binding and drug delivery studies with PVA-ferrofluid" 7 : 29-34, 2010

46 Kumari A, "Biodegradable polymeric nanoparticles based drug delivery systems" 75 : 1-18, 2010

47 Bagre AP, "Alginate coated chitosan core shell nanoparticles for oral delivery of enoxaparin : in vitro and in vivo assessment" 456 : 31-40, 2013

48 Muheem A, "A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives" 24 : 413-428, 2016