Sodium alginate-guar gum and carbopol based methotrexate loaded mucoadhesive microparticles for colon delivery
An in vitro evaluation
DOI:
https://doi.org/10.1590/s2175-97902020000419147Keywords:
Methotrexate. Mucoadhesive microparticles. Colorectal cancer. Sodium alginate. Guar gum. Colon.Abstract
Methotrexate (MTX) is famous for its therapeutic potential against different cancers including colorectal cancer. Goal of the present investigation was to formulate MTX loaded mucoadhesive microparticles for colon targeting. The optimized formulation (MTX-MS2) was composed of mucoadhesive polymers (sodium alginate, guar gum and carbopol 940) in an appropriate ratio. MTXMS2 was developed by ionic-gelation method. The suitable particle size and zeta potential were found to be 21.10 ± 0.18 μm and 3.01 ± 0.16 mV for MTX-MS2 respectively. The % yield (98.60 ± 2.12), % entrapment efficiency (97.98 ± 1.22) and % drug loading (1.04 ± 0.03) were estimated for MTXMS2. The swelling index (0.99 ± 0.04 θ) and mucoadhesion (97.29 ± 4.61%) were significantly (***P ˂ 0.01) achieved with MTX-MS2 as compared to other formulations. The optimum drug release (96.07 ± 4.52%) was significantly achieved with MTX-MS2 at simulated gastric fluid (pH 7.4) for 36 h in a sustained manner. This profile may be attributed towards excellent mucoadhesivness of the
polymers used in the formulation. Therefore, the current investigation suggests that mucoadhesive carrier system could be promising approach for colon delivery. Thus, the proposed work would be helpful for the treatment of colorectal cancer.
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Agüero L, Zaldivar-Silva D, Peña L, Dias ML. Alginate microparticles as oral colon drug delivery device: A review. Carbohydr Polym. 2017;168:32-43.
Ahmad MZ, Akhter S, Anwar M, Ahmad FJ. Assam Bora rice starch based biocompatible mucoadhesive microsphere for targeted delivery of 5-fluorouracil in colorectal cancer. Mol Pharm. 2012; 9(11):2986-94.
Akala EO, Elekwachi O, Chase V, Johnson H, Marjorie L, Scott K. Organic redox initiated polymerization process for the fabrication of hydrogel for colon specific drug delivery. Drug Dev Ind Pharm. 2003;29:375-386.
Amin ML, Ahmed T, Mannan MA. Development of floatingmucoadhesive microsphere for site specific release of metronidazole. Adv Pharm Bull. 2016; 6(2):195-200.
Amit C, Upendra N, Bhavya R, Neha G. Development and evaluation of mucoadhesive microspheres of levofloxacin hydrochloride. J Drug Delivery Ther. 2012;2(6):21-24.
Anande NM, Jain SK, Jain NK. Con-A conjugated mucoadhesive microspheres for the colonic delivery of diloxanide furoate. Int J Pharm. 2008;359:182-189.
Andrews GP, Laverty TP, Jones DS. Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm. 2009;71:505-18.
Ayyappan S, Sundaraganesan N, Aroulmoji V, Murano E, Sebastian S. Molecular structure, vibrational spectra and DFT molecular orbital calculations (TD-DFT and NMR) of the antiproliferative drug methotrexate. Spectrochim Acta, Part A. 2010;77:264-275.
Bak A, Ashford M, Brayden DJ. Local delivery of macromolecules to treat diseases associated with the colon. Adv Drug Deliv Rev. 2018;136-137:2-27.
Chaurasia M, Chourasia MK, Jain NK, Jain A, Soni V, Gupta Y, et al. Methotrexate bearing calcium pectinate microspheres: A platform to achieve colon-specific drug release. Curr Drug Delivery. 2008;5:215-219.
Chen J, Li X, Chen L, Xie F. Starch film-coated microparticles for oral colon-specific drug delivery. Carbohydr Polym. 2018;191:242-254.
Choudhury PK, Murthy PM, Tripathy NK, Patra BS. Formulation and development of enteric coated matrix tablets for colon drug delivery of ornidazole. Asian J Pharm Clin Res. 2012;5(3):86-89.
Gaba P, Singh S, Gaba M, Gupta GD. Galactomannan gum coated mucoadhesive microspheres of glipizide for treatment of type 2 diabetes mellitus, In vitro and in vivo evaluation. Saudi Pharm J. 2011;19:143-152.
George A, Shah PA, Shrivastav PS. Guar gum: Versatile natural polymer for drug delivery applications. Eur Polym J. 2019;112:722-735.
Guo JH. Carbopol polymers for pharmaceutical drug delivery applications. Drug Deliv Technol. 2003;3:1-4.
Guzmán ML, Romanuk˜ CB, Sanchez MF, Luciani-Giacobbe LC, Alarcón-Ramirez LP, Battistini FD, et al. MicroRNA26b represses colon cancer cell proliferation by inhibiting lymphoid enhancer factor 1 expression. Drug Deliv Transl Res. 2018;8:123-31.
Hua S, Marks E, Schneider JJ, Keely S. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease. Nanomedicine. 2015;11(5):111732.
International Agency for Cancer Research (IARC), World Health Organization (WHO), Globocan, 2018, Updated September 2018. Available from: http://gco.iarc.fr/today/data/factsheets/cancers/10_8_9-Colorectum-fact-sheet.pdf . Accessed date: January 25, 2019.
» http://gco.iarc.fr/today/data/factsheets/cancers/10_8_9-Colorectum-fact-sheet.pdf
Jelvehgari M, Mobaraki V, Montazam SH. Preparation and evaluation of mucoadhesive beads/discs of alginate and algino-pectinate of piroxicam for colon-specific drug delivery via oral route. Jundishapur J Nat Pharm Prod. 2014;9(4):e16576.
Kang JH, Hwang JY, Seo JW, Kim HS, Shin US. Small intestine- and colon-specific smart oral drug delivery system with controlled release characteristic. Mater Sci Eng C Mater Biol Appl. 2018;91:247-254.
Lanjhiyana SK, Garabadu D, Lanjhiyana S, Ahirwar B, Arya A. In-vitro and in-vivo release studies of methotrexate from novel enteric coated time-dependent microbial-triggered drug delivery systems for colon specific. Int J Pharm Sci Rev Res. 2010;5(1):124-130.
Ma ZG, Ma R, Xiao XL, Zhang YH, Zhang XZ, Hu N, et al. Azo polymeric micelles designed for colon-targeted dimethyl fumarate delivery for colon cancer therapy. Acta Biomater. 2016;44:323-31.
Malik RK, Malik P, Gulati N, Nagaich U. Fabrication and in vitro evaluation of mucoadhesive ondansetron hydrochloride beads for the management of emesis in chemotherapy. Int J Pharm Investig. 2013;3(1):42-46.
Mansuri S, Kesharwani P, Jain K, Tekade RK, Jain NK. Mucoadhesion: A promising approach in drug delivery system. React Funct Polym. 2016;100:151-172.
Muramatsu N, Kondo J. An approach to prepare microparticles of uniform size. J Microencapsul. 1995;12(2):129-36.
Oliveira AR, Caland LB, Oliveira EG, Egito EST, Pedrosa MFF, Júnior AAS. HPLC-DAD and UV-Vis spectrophotometric methods for methotrexate assay in different biodegradable microparticles. J Braz Chem Soc. 2015;26(4):649-659.
Prajapati V, Bansal M, Sharma PK. Mucoadhesive buccal patches and use of natural polymer in its preparation - A review. Int J PharmTech Res. 2012;4(2):582-589.
Preisig D, Roth R, Tognola S, Varum FJ, Bravo R, Cetinkaya Y, et al. Mucoadhesive microparticles for local treatment of gastrointestinal diseases. Eur J Pharm Biopharm. 2016;105:156-65.
Singla AK, Chawla M, Singh A. Potential applications of carbomer in oral mucoadhesive controlled drug delivery system: A review. Drug Dev Ind Pharm. 2000;26:913-24.
Tao Y, Lu Y, Sun Y, Gu B, Lu W, Pan J. Development of mucoadhesive microspheres of acyclovir with enhanced bioavailability. Int J Pharm. 2009;378:30-36.
Teruel AH, Pérez-Esteve É, González-Álvarez I, GonzálezÁlvarez M, Costero AM, Ferri D, et al. Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: New approaches for inflammatory bowel diseases treatment. J Control Release. 2018;281:58-69.
Wong TW, Colombo G, Sonvico F. Pectin matrix as oral drug delivery vehicle for colon cancer treatment. AAPS PharmSciTech. 2011;12(1):201-214.
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