Oleophylic Nanospheres Self-Assembly by Emulsion Technique Utilizing the Automatic Nanoscalar Interfacial Alternation (ANIAE)

Author(s): Hao Ran, Weibin Liu*, Xin Pan*, Chuanbin Wu*, Guilan Quan, Ying Huang, Yingtong Cui

Journal Name: Current Pharmaceutical Biotechnology

Volume 22 , Issue 1 , 2021

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Graphical Abstract:


Background: The administration of many pharmaceutical active ingredients is often performed by the injection of an aqueous-based solution. Numerous active ingredients are however, insoluble in water, which complicates their administration and restricts their efficacy.

Objective: The current solutions are hindered by both, a time-consuming manufacturing process and unsuitability for hydrophilic and hydrophobic materials.

Methods: Emulsions of oleophilic active ingredients and polyprotein microspheres are an important step to overcome insolubility issues.

Results: Polyprotein microspheres offer a versatile modifiable morphology, thermal responsivity, and size variation, which allows for the protection and release of assembled biomaterials. In addition, nanospheres present promising cell phagocytosis outcomes in vivo.

Conclusion: In this research, a reproducible multifunctional approach, to assemble nanospheres in one step, using a technique termed “automatic nanoscalar interfacial alternation in emulsion” (ANIAE) was developed, incorporating a thermally controlled release mechanism for the assembled target active ingredients. These results demonstrate a viable, universal, multifunctional principal for the pharmaceutical industry.

Keywords: Self-Assembly, oleophilic nanospheres, polyprotein, ANIAE, thermally controlled release, assembled biomaterials.

Zheng, Z.; Zhang, X.; Carbo, D.; Clark, C.; Nathan, C.; Lvov, Y. Sonication-assisted synthesis of polyelectrolyte-coated curcumin nanoparticles. Langmuir, 2010, 26(11), 7679-7681.
[http://dx.doi.org/10.1021/la101246a] [PMID: 20459072]
Guha, I.F.; Anand, S.; Varanasi, K.K. Creating nanoscale emulsions using condensation. Nat. Commun., 2017, 8(1), 1371.
[http://dx.doi.org/10.1038/s41467-017-01420-8] [PMID: 29118327]
Aboalnaja, K.O.; Yaghmoor, S.; Kumosani, T.A.; McClements, D.J. Utilization of nanoemulsions to enhance bioactivity of pharmaceuticals, supplements, and nutraceuticals: Nanoemulsion delivery systems and nanoemulsion excipient systems. Expert Opin. Drug Deliv., 2016, 13(9), 1327-1336.
[http://dx.doi.org/10.1517/17425247.2016.1162154] [PMID: 26984045]
Saifullah, M.; Shishir, M.R.I.; Ferdowsi, R.; Rahman, T.M.R.; Van Vuong, Q. Micro and nano encapsulation, retention and controlled release of flavor and aroma compounds: A critical review. Trends Food Sci. Technol., 2019, 86, 230-251.
Sinha, S.; Schreiner, A.J.; Biernaskie, J.; Nickerson, D.; Gabriel, V.A. Treating pain on skin graft donor sites: Review and clinical recommendations. J. Trauma Acute Care Surg., 2017, 83(5), 954-964.
[http://dx.doi.org/10.1097/TA.0000000000001615] [PMID: 28598907]
Larsen, S.W.; Østergaard, J.; Poulsen, S.V.; Schulz, B.; Larsen, C. Diflunisal salts of bupivacaine, lidocaine and morphine. Use of the common ion effect for prolonging the release of bupivacaine from mixed salt suspensions in an in vitro dialysis model. Eur. J. Pharm. Sci., 2007, 31(3-4), 172-179.
[http://dx.doi.org/10.1016/j.ejps.2007.03.005] [PMID: 17462869]
Liu, X.; Ma, X.; Kun, E.; Guo, X.; Yu, Z.; Zhang, F. Influence of lidocaine forms (salt vs. freebase) on properties of drug-eudragit® L100-55 extrudates prepared by reactive melt extrusion. Int. J. Pharm., 2018, 547(1-2), 291-302.
[http://dx.doi.org/10.1016/j.ijpharm.2018.06.009] [PMID: 29883791]
Lemo, N.; Vnuk, D.; Radisic, B.; Skender, L.; Karacic, V.; Brcic, I. Determination of the toxic dose of lidocaine in dogs and its corresponding serum concentration. Vet. Rec., 2007, 160(11), 374-375.
[http://dx.doi.org/10.1136/vr.160.11.374] [PMID: 17369479]
Riblet, L.A.W.; Tuttle, W.W. Investigation of the amygdaloid and olfactory electrographic response in the cat after toxic dosage of lidocaine. Electroencephalogr. Clin. Neurophysiol., 1970, 28(6), 601-608.
[http://dx.doi.org/10.1016/0013-4694(70)90202-6] [PMID: 4192836]
Gil-Gouveia, R.; Goadsby, P.J. Neuropsychiatric side-effects of lidocaine: Examples from the treatment of headache and a review. Cephalalgia, 2009, 29(5), 496-508.
[http://dx.doi.org/10.1111/j.1468-2982.2008.01800.x] [PMID: 19250287]
Venturi, F.; Blocker, T.; Dees, D.D.; Madsen, R.; Brinkis, J. Corneal anesthetic effect and ocular tolerance of 3.5% lidocaine gel in comparison with 0.5% aqueous proparacaine and 0.5% viscous tetracaine in normal canines. Vet. Ophthalmol., 2017, 20(5), 405-410.
[http://dx.doi.org/10.1111/vop.12440] [PMID: 27981712]
Oki, T.; Nagai, S.; Yoshinaga, M.; Nishiba, Y.; Suda, I. Contribution of beta carotene to radical scavenging capacity varies among orange-fleshed sweet potato cultivars. Food Sci. Technol. Int. Tokyo, 2006, 12(2), 156-160.
Liang, R.; Han, R-M.; Fu, L-M.; Ai, X-C.; Zhang, J-P.; Skibsted, L.H. Baicalin in radical scavenging and its synergistic effect with β-carotene in antilipoxidation. J. Agric. Food Chem., 2009, 57(15), 7118-7124.
[http://dx.doi.org/10.1021/jf9013263] [PMID: 19722585]
Strobel, M.; Tinz, J.; Biesalski, H.K. The importance of beta-carotene as a source of vitamin A with special regard to pregnant and breastfeeding women. Eur. J. Nutr., 2007, 46(Suppl. 1), I1-I20.
[http://dx.doi.org/10.1007/s00394-007-1001-z] [PMID: 17665093]
Olabinri, B.M.; Odetola, A.A.; Adebamowo, C.A. Changes in levels of serum beta-carotene vitamin A and cholesterol in breast cancer of pre and post menopausal Nigerian women. Biokemistri, 2016, 15(1), 22-26.
Druesne-Pecollo, N.; Latino-Martel, P.; Norat, T.; Barrandon, E.; Bertrais, S.; Galan, P.; Hercberg, S. Beta-carotene supplementation and cancer risk: A systematic review and metaanalysis of randomized controlled trials. Int. J. Cancer, 2010, 127(1), 172-184.
[http://dx.doi.org/10.1002/ijc.25008] [PMID: 19876916]
Raeburn, J.; Zamith Cardoso, A.; Adams, D.J. The importance of the self-assembly process to control mechanical properties of low molecular weight hydrogels. Chem. Soc. Rev., 2013, 42(12), 5143-5156.
[http://dx.doi.org/10.1039/c3cs60030k] [PMID: 23571407]
Ficheux, M.F.; Bonakdar, L.; Leal-Calderon, F.; Bibette, J. Some stability criteria for double emulsions. Langmuir, 1998, 14(10), 2702-2706.
Tjipto, E.; Cadwell, K.D.; Quinn, J.F.; Johnston, A.P.R.; Abbott, N.L.; Caruso, F. Tailoring the interfaces between nematic liquid crystal emulsions and aqueous phases via layer-by-layer assembly. Nano Lett., 2006, 6(10), 2243-2248.
[http://dx.doi.org/10.1021/nl061604p] [PMID: 17034091]
Mao, L.; Song, M. Structuring food emulsions to improve nutrient delivery during digestion. Food Eng. Rev., 2015, 7(4), 439-451.
Chan, E.S. Preparation of Ca-alginate beads containing high oil content: Influence of process variables on encapsulation efficiency and bead properties. Carbohydr. Polym., 2011, 84(4), 1267-1275.
Kihara, Y.; Ichikawa, T.; Abe, S.; Nemoto, N.; Ishihara, T.; Hirano, N.; Haruki, M. Synthesis of alkyne-functionalized amphiphilic polysiloxane polymers and formation of nanoemulsions conjugated with bioactive molecules by click reactions. Polym. J., 2013, 46(3), 175-183.
Deshpande, S.; Caspi, Y.; Meijering, A.E.; Dekker, C. Octanol-assisted liposome assembly on chip. Nat. Commun., 2016, 7(773), 10447.
[http://dx.doi.org/10.1038/ncomms10447] [PMID: 26794442]
Nii, T.; Ishii, F. Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method. Int. J. Pharm., 2005, 298(1), 198-205.
[http://dx.doi.org/10.1016/j.ijpharm.2005.04.029] [PMID: 15951143]
Sukhorukov, G.B.; Möhwald, H. Multifunctional cargo systems for biotechnology. Trends Biotechnol., 2007, 25(3), 93-98.
[http://dx.doi.org/10.1016/j.tibtech.2006.12.007] [PMID: 17207546]
Bédard, M.F.; Braun, D.; Sukhorukov, G.B.; Skirtach, A.G. Toward self-assembly of nanoparticles on polymeric microshells: near-IR release and permeability. ACS Nano, 2008, 2(9), 1807-1816.
[http://dx.doi.org/10.1021/nn8002168] [PMID: 19206419]
Franceschi, E.; Cesaro, A.M.D.; Ferreira, S.R.S.; Oliveira, J.V. Precipitation of β-carotene microparticles from SEDS technique using supercritical CO2. J. Food Eng., 2009, 95(4), 656-663.
Majorek, K.A.; Porebski, P.J.; Dayal, A.; Zimmerman, M.D.; Jablonska, K.; Stewart, A.J.; Chruszcz, M.; Minor, W. Structural and immunologic characterization of bovine, horse, and rabbit serum albumins. Mol. Immunol., 2012, 52(3-4), 174-182.
[http://dx.doi.org/10.1016/j.molimm.2012.05.011] [PMID: 22677715]
Priamo, W.L.; Cezaro, A.M.D.; Benetti, S.C.; Oliveira, J.V.; Ferreira, S.R.S. In vitro release profiles of β-carotene encapsulated in PHBV by means of supercritical carbon dioxide micronization technique. J. Supercrit. Fluids, 2011, 56(2), 137-143.
Serrano-Luginbühl, S.; Ruiz-Mirazo, K.; Ostaszewski, R.; Gallou, F.; Walde, P. Soft and dispersed interface-rich aqueous systems that promote and guide chemical reactions. Nat. Rev. Chem., 2018, 2(10), 306-327.
Grigoriev, D.; Miller, R.; Shchukin, D.; Möhwald, H. Interfacial assembly of partially hydrophobic silica nanoparticles induced by ultrasonic treatment. Small, 2007, 3(4), 665-671.
[http://dx.doi.org/10.1002/smll.200600613] [PMID: 17340665]
Zhao, Y.; Liu, J.; Chen, Z.; Zhu, X.; Möller, M. Hybrid nanostructured particles via surfactant-free double miniemulsion polymerization. Nat. Commun., 2018, 9(1), 1918.
[http://dx.doi.org/10.1038/s41467-018-04320-7] [PMID: 29765045]
Chen, Q.; Xu, Y.; Cao, X.; Qin, L.; An, Z. Core Cross-Linked Star (CCS) polymers with temperature and salt dual responsiveness: Synthesis, formation of High Internal Phase Emulsions (HIPEs) and triggered demulsification. Polym. Chem., 2013, 5(1), 175-185.
Kumar, A.; Montemagno, C.; Choi, H-J. Smart microparticles with a pH-responsive macropore for targeted oral drug delivery. Sci. Rep., 2017, 7(1), 3059.
[http://dx.doi.org/10.1038/s41598-017-03259-x] [PMID: 28596597]
Xia, Z.; McClements, D.J.; Xiao, H. Influence of physical state of β-carotene (crystallized versus solubilized) on bioaccessibility. J. Agric. Food Chem., 2015, 63(3), 990-997.
[http://dx.doi.org/10.1021/jf504673v] [PMID: 25560778]
Huyskens, P.L.; Haulait-Pirson, M.C.; Vandevyvere, P.; Seghers, K.; Zeegers-Huyskens, T.R. Segregation of molecules in binary solvent mixtures without H bonds. A quantitative treatment based on the theory of mobile order and disorder. J. Chem. Soc., Faraday Trans., 1998, 94(24), 3587-3594.
McClements, D.J.; Gumus, C.E. Natural emulsifiers - Biosurfactants, phospholipids, biopolymers, and colloidal particles: Molecular and physicochemical basis of functional performance. Adv. Colloid Interface Sci., 2016, 234, 3-26.
[http://dx.doi.org/10.1016/j.cis.2016.03.002] [PMID: 27181392]
Johnson, E. The role of carotenoids in human health. Nutr. Clin. Care, 2002, 5, 56-65.
Dragosavac, M.M.; Holdich, R.G.; Vladisavljević, G.T.; Sovilj, M.N. Stirred cell membrane emulsification for multiple emulsions containing unrefined pumpkin seed oil with uniform droplet size. J. Membr. Sci., 2012, 392-393, 122-129.
Imasaka, Y.; Sano, M.; Suzuki, M.; Hanabusa, K. Gel-emulsions prepared using a low-molecular-weight gelator and their use in the synthesis of porous polymers. Polym. J., 2018, 50(5), 397-406.
Zhang, H.; Wang, D.; Butler, R.; Campbell, N.L.; Long, J.; Tan, B.; Duncalf, D.J.; Foster, A.J.; Hopkinson, A.; Taylor, D.; Angus, D.; Cooper, A.I.; Rannard, S.P. Formation and enhanced biocidal activity of water-dispersable organic nanoparticles. Nat. Nanotechnol., 2008, 3(8), 506-511.
[http://dx.doi.org/10.1038/nnano.2008.188] [PMID: 18685640]

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Year: 2021
Published on: 02 June, 2020
Page: [182 - 190]
Pages: 9
DOI: 10.2174/1389201021666200602134054
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