Formulation and Characterization of a Pluronic F127 Polymeric Micelle as a Nanocarrier for Berberine Delivery

Noora Kadhim Hadi Alyasari(1*), Anwar Jasib Almzaiel(2)

(1) Department of Physiology, Pharmacology, and Biochemistry, College of Veterinary Medicine, University of Al-Qadisiyah, Diwaniyah 58002, Iraq
(2) Department of Biochemistry, College of Medicine, University of Al-Qadisiyah, Diwaniyah 58002, Iraq
(*) Corresponding Author


Berberine's (Ber’s) lower water solubility, which leads to low bioavailability, poses substantial delivery-related barriers to its therapeutic efficacy. Thus, a new approach to improving Ber's delivery and bioavailability is required. In this study, a Pluronic F127 micelle containing Ber (mBer) was formulated using thin-film hydration technique with the intention of resolving challenging issues associated with Ber delivery. The micelle was tested for drug loading and retention efficiency, size, zeta potential, shape, in vitro release, and in vitro toxicity. The spherical micelles that were made had an average encapsulation efficiency of 85%, a hydrodynamic size of 82.2 nm, a polydispersity of 0.176, and a zeta potential of −47.4 mV. The results of Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) indicated that Ber was physically entrapped and in an amorphous state within the synthesized micelles. Compared to the free Ber solution, the in vitro release of Ber from micelles exhibited both short-term rapid release and sustained release. The mBer was shown to be relatively non-toxic to blood cells via an in vitro hemolysis assay. Our findings showed that polymeric F127 micelles could be a simple nanocarrier for Ber delivery, which can be used to enhance the therapeutic efficiency of Ber.


Berberine; Pluronic F127; micelles; polymeric drug delivery systems; nanoparticles

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[1] Wang, K., Feng, X., Chai, L., Cao, S., and Qiu, F., 2017, The metabolism of berberine and its contribution to the pharmacological effects, Drug Metab. Rev., 49 (2), 139–157.

[2] Javed Iqbal, M., Quispe, C., Javed, Z., Sadia, H., Qadri, Q.R., Raza, S., Salehi, B., Cruz-Martins, N., Abdulwanis Mohamed, Z., Sani Jaafaru, M., and Sharifi-Rad, J., 2021, Nanotechnology-based strategies for berberine delivery system in cancer treatment: Pulling strings to keep berberine in power, Front. Mol. Biosci., 7, 624494.

[3] Li, Z., Wang, Y., Xu, Q., Ma, J., Li, X., Yan, J., Tian, Y., Wen, Y., and Chen, T., 2023, Berberine and health outcomes: An umbrella review, Phytother. Res., 37 (5), 2051–2066.

[4] Szaniawska, M., Szymczyk, K., Zdziennicka, A., and Jańczuk, B., 2023, Thermodynamic parameters of berberine with Kolliphor mixtures adsorption and micellization, Molecules, 28 (7), 3115.

[5] Li, X., Shi, L., Shi, N., Chen, W., Qu, X., Li, Q., Duan, X., Li, X., and Li, Q., 2023, Multiple stimulus-response berberine plus baicalin micelles with particle size-charge-release triple variable properties for breast cancer therapy, Drug Dev. Ind. Pharm., 49 (2), 189–206.

[6] Calvo, A., Moreno, E., Larrea, E., Sanmartín, C., Irache, J.M., and Espuelas, S., 2020, Berberine-loaded liposomes for the treatment of Leishmania infantum-infected BALB/c mice, Pharmaceutics, 12 (9), 858.

[7] Negut, I., and Bita, B., 2023, Polymeric micellar systems—A special emphasis on “smart” drug delivery, Pharmaceutics, 15 (3), 976.

[8] Pham, D.T., Chokamonsirikun, A., Phattaravorakarn, V., and Tiyaboonchai, W., 2021, Polymeric micelles for pulmonary drug delivery: A comprehensive review, J. Mater. Sci., 56 (3), 2016–2036.

[9] Hwang, D., Ramsey, J.D., and Kabanov, A.V., 2020, Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval, Adv. Drug Delivery Rev., 156, 80–118.

[10] Ahmad, Z., Shah, A., Siddiq, M., and Kraatz, H.B., 2014, Polymeric micelles as drug delivery vehicles, RSC Adv., 4 (33), 17028–17038.

[11] Shin, H.C., Alani, A.W.G., Rao, D.A., Rockich, N.C., and Kwon, G.S., 2009, Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs, J. Controlled Release, 140 (3), 294–300.

[12] Chiappetta, D.A., and Sosnik, A., 2007, Poly (ethylene oxide)–poly (propylene oxide) block copolymer micelles as drug delivery agents: Improved hydrosolubility, stability and bioavailability of drugs, Eur. J. Pharm. Biopharm., 66 (3), 303–317.

[13] Bodratti, A.M., and Alexandridis, P., 2018, Formulation of poloxamers for drug delivery, J. Funct. Biomater., 9 (1), 11.

[14] Gutiérrez-Saucedo, R.A., Gómez-López, J.C., Villanueva-Briseño, A.A., Topete, A., Soltero-Martínez, J.F.A., Mendizábal, E., Jasso-Gastinel, C.F., Taboada, P., and Figueroa-Ochoa, E.B., 2023, Pluronic F127 and P104 polymeric micelles as efficient nanocarriers for loading and release of single and dual antineoplastic drugs, Polymers, 15 (10), 2249.

[15] Oerlemans, C., Bult, W., Bos, M., Storm, G., Nijsen, J.F.W., and Hennink, W.E., 2010, Polymeric micelles in anticancer therapy: Targeting, imaging and triggered release, Pharm. Res., 27 (12), 2569–2589.

[16] Younis, F.A., Saleh, S.R., El-Rahman, S.S.A., Newairy, A.S.A., El-Demellawy, M.A., and Ghareeb, D.A., 2022, Preparation, physicochemical characterization, and bioactivity evaluation of berberine-entrapped albumin nanoparticles, Sci. Rep., 12 (1), 17431.

[17] Liu, C.S., Zheng, Y.R., Zhang, Y.F., and Long, X.Y., 2016, Research progress on berberine with a special focus on its oral bioavailability, Fitoterapia, 109, 274–282.

[18] Pan, G., Wang, G.J., Liu, X.D., Fawcett, J.P., and Xie, Y.Y., 2002, The involvement of P‐glycoprotein in berberine absorption, Pharmacol. Toxicol., 91 (4), 193–197.

[19] Niu, J., Yuan, M., Chen, C., Wang, L., Tang, Z., Fan, Y., Liu, X., Ma, Y.J., and Gan, Y., 2020, Berberine-loaded thiolated Pluronic F127 polymeric micelles for improving skin permeation and retention, Int. J. Nanomed., 15, 9987–10005.

[20] Massella, D., Celasco, E., Salaün, F., Ferri, A., and Barresi, A.A., 2018, Overcoming the limits of flash nanoprecipitation: Effective loading of hydrophilic drug into polymeric nanoparticles with controlled structure, Polymers, 10 (10), 1092.

[21] Patel, V., Ray, D., Bahadur, A., Ma, J., Aswal, V.K., and Bahadur, P., 2018, Pluronic®-bile salt mixed micelles, Colloids Surf., B, 166, 119–126.

[22] Carvalho, P.M., Felício, M.R., Santos, N.C., Gonçalves, S., and Domingues, M.M., 2018, Application of light scattering techniques to nanoparticle characterization and development, Front. Chem., 6, 237.

[23] Sahibzada, M.U.K., Sadiq, A., Faidah, H.S., Khurram, M., Amin, M.U., Haseeb, A., and Kakar, M., 2018, Berberine nanoparticles with enhanced in vitro bioavailability: Characterization and antimicrobial activity, Drug Des., Dev. Ther., 12, 303–312.

[24] Vuddanda, P.R., Rajamanickam, V.M., Yaspal, M., and Singh, S., 2014, Investigations on agglomeration and haemocompatibility of vitamin E TPGS surface modified berberine chloride nanoparticles, Biomed Res. Int., 2014, 951942.

[25] Shen, R., Kim, J.J., Yao, M., and Elbayoumi, T.A., 2016, Development and evaluation of vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate-mixed polymeric phospholipid micelles of berberine as an anticancer nanopharmaceutical, Int. J. Nanomed., 11, 1687–1700.

[26] Willard, C.A., 2020, Statistical Methods: An Introduction to Basic Statistical Concepts and Analysis, Routledge, New York, US.

[27] Lapteva, M., Mondon, K., Möller, M., Gurny, R., and Kalia, Y.N., 2014, Polymeric micelle nanocarriers for the cutaneous delivery of tacrolimus: A targeted approach for the treatment of psoriasis, Mol. Pharmaceutics, 11 (9), 2989–3001.

[28] Basalious, E.B., and Shamma, R.N., 2015, Novel self-assembled nano-tubular mixed micelles of Pluronics P123, Pluronic F127 and phosphatidylcholine for oral delivery of nimodipine: In vitro characterization, ex vivo transport and in vivo pharmacokinetic studies, Int. J. Pharm., 493 (1-2), 347–356.

[29] Alalaiwe, A., Wang, P.W., Lu, P.L., Chen, Y.P., Fang, J.Y., and Yang, S.C., 2018, Synergistic anti-MRSA activity of cationic nanostructured lipid carriers in combination with oxacillin for cutaneous application, Front. Microbiol., 9, 1493.

[30] Shanmugam, S., Park, J.H., Kim, K.S., Piao, Z.Z., Yong, C.S., Choi, H.G., and Woo, J.S., 2011, Enhanced bioavailability and retinal accumulation of lutein from self-emulsifying phospholipid suspension (SEPS), Int. J. Pharm., 412 (1-2), 99–105.

[31] Kanoujia, J., Kushwaha, P.S., and Saraf, S.A., 2014, Evaluation of gatifloxacin pluronic micelles and development of its formulation for ocular delivery, Drug Delivery Transl. Res., 4 (4), 334–343.

[32] Zhang, M., Gao, S., Yang, D., Fang, Y., Lin, X., Jin, X., Liu, Y., Liu, X., Su, K., and Shi, K., 2021, Influencing factors and strategies of enhancing nanoparticles into tumors in vivo, Acta Pharm. Sin. B, 11 (8), 2265–2285.

[33] Bachhav, Y.G., Mondon, K., Kalia, Y.N., Gurny, R., and Möller, M., 2011, Novel micelle formulations to increase cutaneous bioavailability of azole antifungals, J. Controlled Release, 153 (2), 126–132.

[34] Rizvi, S.A.A., and Saleh, A.M., 2018, Applications of nanoparticle systems in drug delivery technology, Saudi Pharm. J., 26 (1), 64–70.

[35] Souza, T.G.F., Ciminelli, V.S.T., and Mohallem, N.D.S., 2016, A comparison of TEM and DLS methods to characterize size distribution of ceramic nanoparticles, J. Phys.: Conf. Ser., 733 (1), 012039.

[36] Karolewicz, B., Górniak, A., Owczarek, A., Zurawska-Płaksej, E., Piwowar, A., and Pluta, J., 2014, Thermal, spectroscopic, and dissolution studies of ketoconazole-Pluronic F127 system, J. Therm. Anal. Calorim., 115 (3), 2487–2493.

[37] Koide, T., Iwata, M., Maekawa, K., Saito, H., Tanimoto, T., and Okada, S., 2001, Berberine hydrochloride reference standard (Control 001) of National Institute of Health Sciences, Bull. Natl. Inst. Health Sci., 119, 97–100.

[38] Gurunath, S., Pradeep Kumar, S., Basavaraj, N.K., and Patil, P.A., 2013, Amorphous solid dispersion method for improving oral bioavailability of poorly water-soluble drugs, J. Pharm. Res., 6 (4), 476–480.

[39] Sotoudegan, F., Amini, M., Faizi, M., and Aboofazeli, R., 2016, Nimodipine-loaded Pluronic® block copolymer micelles: Preparation, characterization, in-vitro and in-vivo studies, Iran. J. Pharm. Res., 15 (4), 641.

[40] Ding, Y., Wang, C., Wang, Y., Xu, Y., Zhao, J., Gao, M., Ding, Y., Peng, J., and Li, L., 2018, Development and evaluation of a novel drug delivery: Soluplus®/TPGS mixed micelles loaded with piperine in vitro and in vivo, Drug Dev. Ind. Pharm., 44 (9), 1409–1416.

[41] Saorin, G., Mauceri, M., Cavarzerani, E., Caligiuri, I., Bononi, G., Granchi, C., Bartoletti, M., Perin, T., Tuccinardi, T., Canzonieri, V., Adeel, M., and Rizzolio, F., 2023, Enhanced activity of a Pluronic F127 formulated Pin1 inhibitor for ovarian cancer therapy, J. Drug Delivery Sci. Technol., 87, 104718.

[42] de la Harpe, K.M., Kondiah, P.P.D., Choonara, Y.E., Marimuthu, T., du Toit, L.C., and Pillay, V., 2019, The hemocompatibility of nanoparticles: A review of cell-nanoparticle interactions and hemostasis, Cells, 8 (10), 1209.

[43] Ritz, S., Schöttler, S., Kotman, N., Baier, G., Musyanovych, A., Kuharev, J., Landfester, K., Schild, H., Jahn, O., Tenzer, S., and Mailänder, V., 2015, Protein corona of nanoparticles: distinct proteins regulate the cellular uptake, Biomacromolecules, 16 (4), 1311–1321.

[44] Sun, H., Lv, L., Bai, Y., Yang, H., Zhou, H., Li, C., and Yang, L., 2018, Nanotechnology-enabled materials for hemostatic and anti-infection treatments in orthopedic surgery, Int. J. Nanomed., 13, 8325–8338.


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