Alginate Beads Containing Cerium-Doped Mesoporous Glass and Curcumin: Delivery and Stabilization of Therapeutics

Cancer is a leading cause of death worldwide, its genesis and progression are caused by homeostatic errors, and reactive oxygen species play a major role in promoting aberrant cancer homeostasis. In this scenario, curcumin could be an interesting candidate due to its versatile antioxidant, anti-inflammatory, anti-tumor, anti-HIV, and anti-infection properties. Nonetheless, the major problem related to its use is its poor oral bioavailability, which can be overcome by encapsulating it into small particles, such as hydrogel beads containing mesoporous silica. In this work, various systems have been synthesized: starting from mesoporous silica glasses (MGs), cerium-containing MGs have been produced; then, these systems have been loaded with 4 to 6% of curcumin. Finally, various MGs at different compositions have been included in alginate beads. In vitro studies showed that these hybrid materials enable the stabilization and effective delivery of curcumin and that a synergic effect can be achieved if Ce3+/Ce4+ and curcumin are both part of the beads. From swelling tests, it is possible to confirm a controlled curcumin release compartmentalized into the gastrointestinal tract. For all beads obtained, a curcumin release sufficient to achieve the antioxidant threshold has been reached, and a synergic effect of cerium and curcumin is observed. Moreover, from catalase mimetic activity tests, we confirm the well-known catalytic activity of the couple Ce3+/Ce4+. In addition, an extremely good radical scavenging effect of curcumin has been demonstrated. In conclusion, these systems, able to promote an enzymatic-like activity, can be used as drug delivery systems for curcumin-targeted dosing.

[1]  Huatian Wang,et al.  Emulsion-based delivery systems for curcumin: Encapsulation and interaction mechanism between debranched starch and curcumin. , 2020, International journal of biological macromolecules.

[2]  C. Brinker,et al.  Sol–Gel‐Based Advanced Porous Silica Materials for Biomedical Applications , 2020, Advanced Functional Materials.

[3]  M. Vallet‐Regí,et al.  Cerium (III) and (IV) containing mesoporous glasses/alginate beads for bone regeneration: bioactivity, biocompatibility and reactive oxygen species activity. , 2019, Materials science & engineering. C, Materials for biological applications.

[4]  N. Škalko-Basnet,et al.  Interpreting non-linear drug diffusion data: Utilizing Korsmeyer-Peppas model to study drug release from liposomes. , 2019, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[5]  Devanand L. Luthria,et al.  Curcumin: Biological, Pharmaceutical, Nutraceutical, and Analytical Aspects , 2019, Molecules.

[6]  I. Texier,et al.  Lipid Nanoparticles and Their Hydrogel Composites for Drug Delivery: A Review , 2018, Pharmaceuticals.

[7]  D. Mcclements,et al.  Impact of Delivery System Type on Curcumin Bioaccessibility: Comparison of Curcumin-Loaded Nanoemulsions with Commercial Curcumin Supplements. , 2018, Journal of agricultural and food chemistry.

[8]  D. Kalman,et al.  Curcumin: A Review of Its’ Effects on Human Health , 2017, Foods.

[9]  Lili Tang,et al.  The tumor microenvironment and inflammatory breast cancer , 2017, Journal of Cancer.

[10]  D. Mcclements Recent progress in hydrogel delivery systems for improving nutraceutical bioavailability , 2017 .

[11]  P. Luches,et al.  Cerium-doped bioactive 45S5 glasses: spectroscopic, redox, bioactivity and biocatalytic properties , 2017, Journal of Materials Science.

[12]  P. Luches,et al.  Evidence of catalase mimetic activity in Ce(3+)/Ce(4+) doped bioactive glasses. , 2015, The journal of physical chemistry. B.

[13]  L. Xue,et al.  Therapeutic Effects of Curcumin on Alzheimer's Disease , 2014 .

[14]  Jiashing Yu,et al.  Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres , 2014, International journal of nanomedicine.

[15]  K. Zandi,et al.  A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin , 2014, BioMed research international.

[16]  H. M. Shewan,et al.  Review of techniques to manufacture micro-hydrogel particles for the food industry and their applications , 2013 .

[17]  M. Vallet‐Regí,et al.  Curcumin release from cerium, gallium and zinc containing mesoporous bioactive glasses , 2013 .

[18]  S. Zinjarde,et al.  Curcumin conjugated silica nanoparticles for improving bioavailability and its anticancer applications. , 2013, Journal of agricultural and food chemistry.

[19]  J. Zhao,et al.  Adsorption Properties toward Trivalent Rare Earths by Alginate Beads Doping with Silica , 2013 .

[20]  M. Vallet‐Regí,et al.  Structural and in vitro study of cerium, gallium and zinc containing sol–gel bioactive glasses , 2012 .

[21]  Hailong Yu,et al.  Improving the oral bioavailability of curcumin using novel organogel-based nanoemulsions. , 2012, Journal of agricultural and food chemistry.

[22]  D. Mooney,et al.  Alginate: properties and biomedical applications. , 2012, Progress in polymer science.

[23]  D. Raja,et al.  Effect of Formulation Variables on Rifampicin Loaded Alginate Beads , 2012, Iranian journal of pharmaceutical research : IJPR.

[24]  D. Mcclements,et al.  Structured biopolymer-based delivery systems for encapsulation, protection, and release of lipophilic compounds , 2011 .

[25]  D. Mcclements,et al.  Controlling lipid digestion by encapsulation of protein-stabilized lipid droplets within alginate–chitosan complex coacervates , 2011 .

[26]  Malavasi Gianluca,et al.  The role of coordination chemistry in the development of innovative gallium-based bioceramics: the case of curcumin , 2011 .

[27]  S. Mandal,et al.  Development and evaluation of calcium alginate beads prepared by sequential and simultaneous methods , 2010 .

[28]  A. Józkowicz,et al.  Oxidative stress in tumor angiogenesis- therapeutic targets. , 2010, Current pharmaceutical design.

[29]  María Vallet-Regí,et al.  Sol-gel silica-based biomaterials and bone tissue regeneration. , 2010, Acta biomaterialia.

[30]  María Vallet-Regí,et al.  New developments in ordered mesoporous materials for drug delivery , 2010 .

[31]  V. Basile,et al.  Curcumin derivatives: molecular basis of their anti-cancer activity. , 2009, Biochemical pharmacology.

[32]  K. No,et al.  Monitoring of Swelling and Degrading Behavior of Alginate Beads using Optical Tweezers , 2009 .

[33]  Robert A Newman,et al.  Bioavailability of curcumin: problems and promises. , 2007, Molecular pharmaceutics.

[34]  C. Porter,et al.  Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs , 2007, Nature Reviews Drug Discovery.

[35]  Ricky A. Sharma,et al.  Pharmacokinetics and pharmacodynamics of curcumin. , 2007, Advances in experimental medicine and biology.

[36]  I. Gülçin Comparison of in vitro antioxidant and antiradical activities of L-tyrosine and L-Dopa , 2006, Amino Acids.

[37]  Olivier De Wever,et al.  Role of tissue stroma in cancer cell invasion , 2003, The Journal of pathology.

[38]  T Kitsugi,et al.  Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W. , 1990, Journal of biomedical materials research.