FORMULATION AND DEVELOPMENT OF GALLEN GUM LOADED SELF-ASSEMBLED MIXED MICELLES SYSTEM BASED ON FLAVONOID PHOSPHOLIPID COMPLEX

MANJUSHA A. BHANGE; ANIL M. PETHE; AMRAPALI JADHAV; HARSHADA KANADJE

doi:10.22159/ijap.2023v15i3.46795

Authors

MANJUSHA A. BHANGE Department of Pharmaceutics, Datta Meghe College of Pharmacy, DMIHER (DU), Sawangi, Wardha-442001, Maharashtra, India https://orcid.org/0000-0003-4332-9474
ANIL M. PETHE Department of Pharmaceutics, Datta Meghe College of Pharmacy, DMIHER (DU), Sawangi, Wardha-442001, Maharashtra, India
AMRAPALI JADHAV Department of Pharmaceutics, Government College of Pharmacy, Aurangabad, Maharashtra, India
HARSHADA KANADJE Department of Pharmaceutical Quality Assurance, DBSS’s Rajarshi Shahu College of Pharmacy, Buldana, Maharashtra, India

DOI:

https://doi.org/10.22159/ijap.2023v15i3.46795

Keywords:

QCT, Phospholipids S-75, Phospholipids S-100, Solvent evapouration method, Mixed micells

Abstract

Objective: Research on the development of pharmaceutical self-assembled mixed micells systems is in that they have the advantage of keeping the drug's encapsulating qualities while also enhancing its physicochemical characteristics. The goal of this study was to make the class II biopharmaceutical quercetin more soluble in water and more bioavailable when taken orally (QCT). The enhancement of encapsulation and flavonoids loading within mixed micelles using solvent evapouration technique.

Methods: In the present study, pharmaceutical mixed micells of a BCS class II drug, QCT were prepared using solvent evapouration technique method. Prepared mixed micells were characterized using Critical micelle concentration (CMC), Fourier Transform Infrared (FT-IR), Particle size and zeta potential, Powder X-Ray Diffract meter (PXRD), In vitro dissolution, Transmission electron microscopy (TEM). In addition In vitro drug release studies were also performed.

Results: The results of the characterization studies indicated the designing of gallen gum loaded self-assembled mixed micelles system based on flavonoid phospholipid complex. The CMC of LS-75 and LS-100 binary mixture had shows good results to be 0.0013%. The FTIR spectra of complex showed characteristic peak of QCT shows abundant effect on O-H (aromatic), C-O (aromatic), C-C, and aromatic C-O is observed at 3282.2, 1620.1, 1058.7, and 1162.2 respectively. The average particle size of design-optimized quercetin mixed micells (QCT-MMs) was demonstrated to be ~116.1 nm, as evaluated by Malvern. From the obtained particle size, it indicated that the particle size of QCT in QCT-MMs was widely distributed. The polydispersity index (PDI) for QCT-MMs was found in the range of ~ 1.000, zeta potential value for QCT-MMs as evaluated by Malvern was observed to be ~-99.2 mV. The P-XRD, SEM, showed good powder diffraction results with having good flow property. Also formulation were evaluated for the In vitro drug dissolution study for rate of extent of drug release and dissolution rate release of QCT from QCT-MMs was sustained up to 72 h. TEM images of QCT-MMs, where the micelles exhibited relatively regular dark stained shapes appearing more or less spherical or spheroid.

Conclusion: It can be concluded that the QCT-MMs enhance the aqueous solubility of the QCT and increased the bioavailability and retention time.

Downloads

Download data is not yet available.

References

Hemant K, Abhay R, Praveen S, Swati U, Hemanth KS. Cancer nanotechnology: nanoparticulate drug delivery for the treatment of cancer. Int J Pharm Pharm Sci 2022;7(3):40-6.

Zheng G, Chen J, Li H, Glickson JD. Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents. Proc Natl Acad Sci USA. 2005;102(49):17757-62. doi: 10.1073/pnas.0508677102, PMID 16306263.

Molavi O, Ma Z, Mahmud A, Alshamsan A, Samuel J, Lai R. Polymeric micelles for the solubilization and delivery of STAT3 inhibitor cucurbitacins in solid tumors. Int J Pharm. 2008;347(1-2):118-27. doi: 10.1016/j.ijpharm.2007.06.032, PMID 17681440.

Kazunori K, Yokoyama M, Masayuki Y, Teruo O, Yasuhisa S. Block copolymer micelles as vehicles for drug delivery. J Control Release. 1993;24(1-3):119-32. doi: 10.1016/0168-3659(93)90172-2.

Kim S, Shi Y, Kim JY, Park K, Cheng JX. Overcoming the barriers in micellar drug delivery: loading efficiency, in vivo stability, and micelle–cell interaction. Expert Opin Drug Deliv. 2010;7(1):49-62. doi: 10.1517/17425240903380446, PMID 20017660.

Xiong XB, Falamarzian A, Garg SM, Lavasanifar A. Engineering of amphiphilic block copolymers for polymeric micellar drug and gene delivery. J Control Release. 2011;155(2):248-61. doi: 10.1016/j.jconrel.2011.04.028, PMID 21621570.

Senthil Kumar Raju. Biogenic synthesis of copper nanoparticles and their biological applications: an overview. Int J Pharm Pharm Sci. 2022;14(3):8-26. doi:10.22159/ijpps.2022v14i3.43842.

Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol. 2011;6(12):815-23. doi: 10.1038/nnano.2011.166, PMID 22020122.

Khan YY, Suvarna V. Liposomes containing phytochemicals for cancer treatment-an update. Int J Curr Pharm Sci. 2017;9(1). doi: 10.22159/ijcpr.2017v9i1.16629.

Telange DR, Patil AT, Pethe AM, Fegade H, Anand S, Dave VS. Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential. Eur J Pharm Sci. 2017;108:36-49. doi: 10.1016/j.ejps.2016.12.009. PMID 27939619.

Sivapriya V, Ponnarmadha S, Azeezand NA, Sudarshanadeepa V. Novel nanocarriers for ethnopharmacological formulations. Int J App Pharm. 2018;10( 4):26-30. doi: 10.22159/ ijap.2018v10i4.26081.

Senthil Kumar Raju. Biogenic synthesis of copper nanoparticles and their biological applications: an overview. Int J Pharm Pharm Sci. 2022;14(3):8-26. doi:10.22159/ ijpps.2022v14i3.43842.

Gautam A, Bepler G. Suppression of lung tumor formation by the regulatory subunit of ribonucleotide reductase. Cancer Res. 2006;66(13):6497-502. doi: 10.1158/0008-5472.CAN-05-4462, PMID 16818620.

Merlo LMF, Pepper JW, Reid BJ, Maley CC. Cancer as an evolutionary and ecological process. Nat Rev Cancer. 2006;6(12):924-35. doi: 10.1038/nrc2013, PMID 17109012.

Sub K, Park W, Hu J, Han Y, Na K. Biomaterials a cancer-recognizable MRI contrast agents using pH-responsive polymeric micelle. Biomaterials. 2014;35(1):337-43. https://doi.org/10.1016/j.biomaterials.2013.10.004

Gao Y, Li Z, Xie X, Wang C, You J, Mo F. Dendrimeric anticancer prodrugs for targeted delivery of ursolic acid to folate receptor-expressing cancer cells: synthesis and biological evaluation. Eur J Pharm Sci. 2015;70:55-63. doi: 10.1016/j.ejps.2015.01.007. PMID 25638419.

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1-3):3-26. doi: 10.1016/s0169-409x(00)00129-0. PMID 11259830.

B Jeevana Jyothi. Development and in vitro evaluation of phytosomes of naringin. Asian J Pharm Clin Res. 2019;12(9):252-6. doi: 10.22159/ajpcr.2019.v12i9.34798.

Giordano KF, Jatoi A. The cancer anorexia/weight loss syndrome: therapeutic challenges. Curr Oncol Rep. 2005;7(4):271-6. doi: 10.1007/s11912-005-0050-9, PMID 15946586.

Park JH, Lee S, Kim J, Park K, Kim K, Kwon IC. Polymeric nanomedicine for cancer therapy. Prog Polym Sci. 2008;33(1):113-37. doi: 10.1016/j.progpolymsci.2007.09.003.

Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces. 2010;75(1):1-18. doi: 10.1016/j.colsurfb.2009.09.001, PMID 19782542.

Schoellhammer CM, Blankschtein D, Langer R. Skin permeabilization for transdermal drug delivery: recent advances and future prospects. Expert Opin Drug Deliv. 2014;11(3):393-407. doi: 10.1517/17425247.2014.875528, PMID 24392787.

Donnelly RF, Singh TRR, Garland MJ, Migalska K, Majithiya R, McCrudden CM. Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery. Adv Funct Mater. 2012;22(23):4879-90. doi: 10.1002/adfm.201200864, PMID 23606824.

Brambilla D, Luciani P, Leroux JC. Breakthrough discoveries in drug delivery technologies: the next 30 y. J Control Release. 2014;190:9-14. doi: 10.1016/j.jconrel.2014.03.056. PMID 24794899.

Salam AE WH, El-Helaly SN. Preparation of novel phospholipid-based sono complexes for improved intestinal permeability of rosuvastatin. Int J Pharm. 2018;548(1):375-84. doi: 10.1016/j.ijpharm.2018.07.005.

Yang X, Hou Y, Gong T, Sun L, Xue J, Guo Y. Concentration-dependent rheological behavior and gelation mechanism of high acyl gellan aqueous solutions. Int J Biol Macromol. 2019;131:959-70. doi: 10.1016/j.ijbiomac.2019.03.137, PMID 30910680.

Zoratto N, Grillo I, Matricardi P, Dreiss CA. Supramolecular gels of cholesterol-modified gellan gum with disc-like and worm-like micelles. J Colloid Interface Sci. 2019;556:301-12. doi: 10.1016/j.jcis.2019.08.057, PMID 31454622.

Hsu MF, Tyan YS, Chien YC, Lee MW. Hyaluronic acid-based nano-sized drug carrier-containing Gellan gum microspheres as potential multifunctional embolic agent. Sci Rep. 2018;8(1):731. doi: 10.1038/s41598-018-19191-7. PMID 29335649.

Mandal A, Bisht R, Rupenthal ID, Mitra AK. Polymeric micelles for ocular drug delivery: from structural frameworks to recent preclinical studies. J Control Release. 2017;248:96-116. doi: 10.1016/j.jconrel.2017.01.012, PMID 28087407.

Khalid A, Zia M. Recent trends on gellan Gum blends with natural and synthetic polymers: a review. Int J Biol Macromol. 2018;109:1068-87. doi: 10.1016/j.ijbiomac.2017.11.099.

Duan Y, Cai X, Du H, Zhai G. Novel in situ gel systems based on P123/TPGS mixed micelles and gellan gum for ophthalmic delivery of curcumin. Colloids Surf B Biointerfaces. 2015;128:322-30. doi: 10.1016/j.colsurfb.2015.02.007. PMID 25707750.

Maiti S, Chakravorty A, Chowdhury M. Gellan co-polysaccharide micellar solution of budesonide for allergic anti-rhinitis: an in vitro appraisal. Int J Biol Macromol. 2014;68:241-6. doi: 10.1016/j.ijbiomac.2014.05.003. PMID 24820153.

Arrigo GD, Navarro G, Di C, Matricardi P, Torchilin V. Gellan gum nano hydrogel containing anti-inflammatory and anticancer drugs: a multi-drug delivery system for combination therapy in cancer treatment. Eur J Pharm Biopharm. 2013;11:1-9. doi: 10.1016/j.ejpb.2013.11.001.