Abstract
Herein, we used tri-ureasil organic–inorganic hybrid material (tU5000) in order to enhance the solubility of nonsteroidal anti-inflammatory drugs and fine tuning the drug delivery profile. For the first time, we used tU5000 as a film-forming agent in order to provide an alternative vehicle for transdermal drug delivery systems which the cell viability of practically 100 % for the highest and the lowest tested concentrations of pure tU5000 indicated that the material was not cytotoxic. The physicochemical properties of the tU5000 drug carrier and drug-loaded hybrids were systematically studied using powder X-ray diffraction, differential scanning calorimetry, small-angle X-ray scattering, and Fourier-transform infrared spectroscopy. The structural changes of tU5000 as well as the relationships between the drug content and in vitro drug release behaviors were investigated. The results showed that the ibu molecules were homogeneously distributed in the tU5000 xerogels contributing to fine-tuning the drug delivery profile. Considering the ability to incorporated high drug content, simple and mild preparation procedure by one-pot sol–gel route, high stability of the materials, sustained-release property, this class of hybrid based on polymers and inorganic compounds may have potential applications in the design of pharmaceutical formulation as ophthalmic (contact lenses), transdermal (patches) and implantable (soft tissue) drug delivery systems.
Similar content being viewed by others
References
Sanchez C, Belleville P, Popall M, Nicole L (2011) Applications of advanced hybrid organic–inorganic nanomaterials: from laboratory to market. Chem Soc Rev 40:696–753
Sanchez C, Julian B, Belleville P, Popall M (2005) Applications of hybrid organic–inorganic nanocomposites. J Mater Chem 15:3559–3592
Sanchez C, Soler-Illia GJAA, Ribot F, Lalot T, Mayer CR, Cabuil V (2001) Designed hybrid organic-inorganic nanocomposites from functional nanobuilding blocks. Chem Mater 13:3061–3083
Kickelbick G (2006) Hybrid materials. Wiley-VCH, Weinheim
Soler-Illia GJAA, Azzaroni O (2011) Multifunctional hybrids by combining ordered mesoporous materials and macromolecular building blocks. Chem Soc Rev 40:1107–1150
Mehdi A, Reye C, Corriu RJP (2011) From molecular chemistry to hybrid nanomaterials. Design and functionalization. Chem Soc Rev 40:563–574
Harrisson S, Nicolas J, Maksimenko A, Bui DT, Mougin J, Couvreur P (2013) Nanoparticles with in vivo anticancer activity from polymer prodrug amphiphiles prepared by living radical polymerization. Angew Chem Int Ed 52:1678–1682
Ge Z, Liu S (2013) Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specific drug delivery and enhanced imaging performance. Chem Soc Rev 42:7289–7325
Laine L, Smith R, Min K, Chen C, Dubois RW (2006) Systematic review: the lower gastrointestinal adverse effects of non-steroidal antiinflammatory drugs. Aliment Pharmacol Ther 24:751–767
Narayanan D, Geena MG, Lakshmi H, Koyakutty M, Nair S, Menon D (2013) Poly-(ethylene glycol) modified gelatin nanoparticles for sustained delivery of the anti-inflammatory drug ibuprofen-sodium: an in vitro and in vivo analysis. Nanomedicine 9:818–828
Crielaard BJ, Lammers T, Schiffelers RM, Storm GJ (2012) Drug targeting systems for inflammatory disease: one for all, all for one. J Control Release 161:225–234
Rosario-Meléndez R, Yu W, Uhrich KE (2013) Biodegradable polyesters containing ibuprofen and naproxen as pendant groups. Biomacromolecules 14:3542–3548
Gao Q, Xu Y, Wu D, Shen W, Deng F (2010) Synthesis. Characterization, and in Vitro pH-controllable drug release from mesoporous silica spheres with switchable gates langmuir 26:17133–17138
Yu D, Williams GR, Yang J, Wang X, Yang J, Li X (2011) Solid lipid nanoparticles self-assembled from electrosprayed polymer-based microparticles. J Mater Chem 21:15957–15961
Lamprecht A, Saumet J, Roux J, Benoit J (2004) Lipid nanocarriers as drug delivery system for ibuprofen in pain treatment. Int J Pharm 278:407–414
Jia H, Kerr LL (2013) Sustained ibuprofen release using composite poly(lactic-co-glycolic acid)/titanium dioxide nanotubes from Ti implant surface. J Pharm Sci 102:2341–2348
Mirzaagha B (2008) Design, synthesis and in vitro evaluation of vinyl ether type polymeric prodrugs of ibuprofen, ketoprofen and naproxen. Int J Pharm 356:167–173
Yang P, Gai S, Lin J (2012) Functionalized mesoporous silica materials for controlled drug delivery. Chem Soc Rev 41:3679–3698
Vallet-Regi M, Colilla M, Gonzalez B (2001) Medical applications of organic–inorganic hybrid materials within the field of silica-based bioceramics. Chem Soc Rev 40:596–607
Zhu Y, Shi J, Shen W, Dong X, Feng J, Ruan M, Li Y (2005) Stimuli-responsive controlled drug release from a hollow mesoporous silica sphere/polyelectrolyte multilayer core-shell structure. Angew Chem Int Ed 44:5083–5087
Balas F, Manzano M, Horcajada P, Vallet-Regi M (2006) Confinement and controlled release of bisphosphonates on ordered mesoporous silica-based materials. J Am Chem Soc 128:8116–8117
Vallet-Regi M (2006) Ordered mesoporous materials in the context of drug delivery systems and bone tissue engineering. Chem Eur J 12:5934–5943
Makiko F, Naohide H, Kumi S (2000) Effect of fatty acid Esters on permeation of ketoprofen through hairless rat skin. Int J Pharm 205:117–125
Vergote GJ, Vervaet C, Driessche IV (2001) An oral controlled release matrix pellet formulation containing nanocrystalline ketoprofen. Int J Pharm 219:81–87
Perioli L, Ambrogi V, Bernardini C (2004) Potential prodrugs of non-steroidal anti-inflammatory agents for targeted drug delivery to the CNS. Eur J Med Chem 39:715–727
Chie K, Kenji K, Kazuo M (2009) Synthesis of polyamidoamine dendrimers having poly(ethylene glycol) grafts and their ability to encapsulate anticancer drugs. Bioconjug Chem 11:910–917
Koç FE, Senel M (2013) Solubility enhancement of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) using polypolypropylene oxide core PAMAM dendrimers. Int J Pharm 451:18–22
Molina EF, Marçal L, Carvalho HWP, Nassar EJ, Ciuffi KJ (2013) Tri-ureasil gel as a multifunctional organic–inorganic hybrid matrix. Polym Chem 4:1575–1582
Nolasco MM, Vaz PM, Freitas VT, Lima PP, Andre PS, Ferreira RAS, Vaz PD, Ribeiro-Claro P, Carlos LD (2013) Engineering highly efficient Eu(III)-based tri-ureasil hybrids toward luminescent solar concentrators. J Mater Chem A 1:7339–7350
Berridge MV, Herst PM, Tan AS (2005) Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev 11:127–152
Bernas T, Dobrucki J (1999) Reduction of a tetrazolium salt, CTC, by intact HepG2 human hepatoma cells: subcellular localisation of reducing systems. Biochim Biophys Acta 1451:73–81
Chujo Y, Saegusa T (1992) Adv Polym Sci 100:11–13
Freitas VT, Lima PP, Bermudez VZ, Ferreira RAS, Carlos LD (2012) Boosting the emission quantum yield of urea cross-linked tripodal poly(oxypropylene)/siloxane hybrids through the variation of catalyst concentration. Eur J Inorg Chem 32:5390–5395
Newman A, Engers D, Bates S, Ivanisevic I, Kelly RC, Zografi G (2008) Characterization of amorphous API: polymer mixtures using X-ray powder diffraction. J Pharm Sci 97:4840–4856
Mahieu A, Willart J, Dudognon E, Danède F, Descamps MA (2013) New protocol to determine the solubility of drugs into polymer matrixes. Mol Pharm 10:560–566
Kianfar F, Antonijevic MD, Chowdhry BZ, Boateng JS (2011) Formulation development of a carrageenan based delivery system for buccal drug delivery using ibuprofen as a model drug. J Biomater Nanobiotech 2:582–595
Dahmouche K, Santilli CV, Pulcinelli SH, Craievich AF (1999) Small-angle X-ray scattering study of sol–gel-derived siloxane–PEG and siloxane–PPG hybrid materials. J Phys Chem B 103:4937–4942
Freer AA, Bunyan JM, Shankland N, Sheen DB (1993) Structure of (S)-(+)-ibuprofen. Acta Crystallogr Sect C 49:1378–1380
Levin CS, Kundu J, Janesko BG, Scuseria GE, Raphael RM, Halas NJ (2008) Interactions of ibuprofen with hybrid lipid bilayers probed by complementary surface-enhanced vibrational spectroscopies. J Phys Chem B 112:14168–14175
Yoon S, Ichikawa K, MacKnight WJ, Hsu SL (1995) Spectroscopic analysis of chain conformation of poly(propylene oxide)-based polymer electrolytes. Macromolecules 28:4278–4283
Zea Bermudez V, Carlos LD, Alcacer L (1999) Sol–gel derived urea cross-linked organically modified silicates. 1. Room temperature mid-infrared spectra. Chem Mater 11:569–580
Molina EF, Pulcinelli SH, Santilli CV, Briois V (2012) Ligand exchange inducing efficient incorporation of CisPt derivatives into Ureasil–PPO hybrid and their interactions with the multifunctional hybrid network. J Phys Chem B 116:7931–7939
Molina EF, Pulcinelli SH, Santilli CV, Blanchandin S, Briois V (2010) Controlled cisplatin delivery from Ureasil-PEO1900 hybrid matrix. J Phys Chem B 114:3461–3466
Lopes L, Molina EF, Chiavacci LA, Santilli CV, Briois V, Pulcinelli SH (2012) Drug–matrix interaction of sodium diclofenac incorporated into ureasil-poly(ethylene oxide) hybrid materials. RSC Advances 2:5629–5636
Lemaire V (2003) Structural modeling of drug release from biodegradable porous matrices based on a combined diffusion/erosion process. Int J Pharm 258:95–107
Kim S, Ha J, Lee Y (2000) Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)/poly(ϵ-caprolactone) (PCL) amphiphilic block copolymeric nanospheres: II. Thermo-responsive drug release behaviors. J Control Release 65:345–358
Zuleger S, Lippold BC (2001) Polymer particle erosion controlling drug release. I. Factors influencing drug release and characterization of the release mechanism. Int J Pharm 217:139–152
Siepmann J, Peppas NA (2012) Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliver Rev 64:163–174
Ritger PL, Peppas NA (1987) A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release 5:37–42
Siepmann J, Peppas NA (2001) Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose. Adv Drug Deliver Rev 48:139–157
Yang YQ, Guo XD, Lin WJ, Zhang LJ, Zhang CY, Qian Y (2012) Amphiphilic copolymer brush with random pH-sensitive/hydrophobic structure: synthesis and self-assembled micelles for sustained drug delivery. Soft Matter 8:454–464
Acknowledgments
The authors would like to thank the financial support received from the Brazilian agencies CAPES, CNPq, and FAPESP (project number 2013/02613-0). We thank the Brazilian Synchrotron Light Laboratory (LNLS) for SAXS measurements and the D01A-SAXS1 beamline staff for all assistance with the X-ray scattering experiments. We would also like to thank Leila A. Chiavacci for allowing us to use their laboratory premises (UNESP/Araraquara) during the UV–vis release experiments.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Caravieri, B.B., de Oliveira, P.F., Furtado, R.A. et al. Solubility enhancement of ibuprofen using tri-ureasil-PPO hybrid: structural, cytotoxic, and drug release investigation. J Sol-Gel Sci Technol 72, 627–636 (2014). https://doi.org/10.1007/s10971-014-3485-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10971-014-3485-3