{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T14:09:19Z","timestamp":1773670159555,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T00:00:00Z","timestamp":1545004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The goal of this work was to comprehensive study the transport properties of controlled-release systems for the safe and reliable delivery of drugs. Special emphasis has been placed on the measurement of the diffusion of drugs, alone or in combination with carrier molecules for enhanced solubility and facilitated transport. These studies have provided detailed comprehensive information\u2014both kinetic and thermodynamic\u2014for the design and operation of systems for the controlled release and delivery of drugs. Cyclodextrins are among the most important carriers used in these systems. The basis for their popularity is the ability of these materials to solubilize poorly soluble drugs, generally resulting in striking increases in their water solubilities. The techniques used in these investigations include pulse voltammetry, nuclear magnetic resonance (NMR) and Raman spectroscopy, ultrasonic relaxation, and dissolution kinetics. Transport in these systems is a mutual diffusion process involving coupled fluxes of drugs and carrier molecules driven by concentration gradients. Owing to a strong association in these multicomponent systems, it is not uncommon for a diffusing solute to drive substantial coupled fluxes of other solutes, mixed electrolytes, or polymers. Thus, diffusion data, including cross-diffusion coefficients for coupled transport, are essential in order to understand the rates of many processes involving mass transport driven by chemical concentration gradients, as crystal growth and dissolution, solubilization, membrane transport, and diffusion-limited chemical reactions are all relevant to the design of controlled-release systems. While numerous studies have been carried out on these systems, few have considered the transport behavior for controlled-release systems. To remedy this situation, we decided to measure mutual diffusion coefficients for coupled diffusion in a variety of drug\u2013carrier solutions. In summary, the main objective of the present work was to understand the physical chemistry of carrier-mediated transport phenomena in systems of controlled drug release.<\/jats:p>","DOI":"10.3390\/biom8040178","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T03:12:30Z","timestamp":1545102750000},"page":"178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Transport Properties for Pharmaceutical Controlled-Release Systems: A Brief Review of the Importance of Their Study in Biological Systems"],"prefix":"10.3390","volume":"8","author":[{"given":"Ana C. F.","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Department of Chemistry, Coimbra Chemistry Centre, University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"given":"Miguel A.","family":"Esteso","sequence":"additional","affiliation":[{"name":"U.D. Qu\u00edmica F\u00edsica, Universidad de Alcal\u00e1, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.molliq.2010.04.020","article-title":"Differential mutual diffusion coefficients of binary and ternary systems measured by the open-ended conductimetric capillary cell and by the Taylor technique","volume":"156","author":"Ribeiro","year":"2010","journal-title":"J. Mol. Liquids"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.ijpharm.2014.12.053","article-title":"Transport properties in aqueous ethambutol dihydrochloride","volume":"479","author":"Cabral","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6885","DOI":"10.1021\/j100380a063","article-title":"Diffusion Coefficients in Systems with inclusion-compounds 1 \u03b1-cyclodextrin-l-phenylalanine water at 25-degrees-C","volume":"94","author":"Paduano","year":"1990","journal-title":"J. Phys. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1007\/BF00972961","article-title":"Diffusion Coefficients of the System \u03b1-Cyclodextrin-n-ButylureaWater at 25 \u00b0C","volume":"24","author":"Paduano","year":"1995","journal-title":"J. Solut. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5023","DOI":"10.1021\/jp972356b","article-title":"Diffusion Coefficients of the Ternary System \u03b1-Cyclodextrin Sodium Benzenesulfonate Water at 25 degrees C: The Effect of Chemical Equilibrium and Complex Formation on the Diffusion Coefficients of a Ternary System","volume":"102","author":"Paduano","year":"1998","journal-title":"J. Phys. Chem. B"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1039\/a903989i","article-title":"Equilibrium Properties of the System (Dibutyl L-tartrate)-(\u03b1- Cyclodextrin)-(water) at 25 \u00b0C, A 1H NMR and UV Study","volume":"1","author":"Paduano","year":"1999","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0168-3659(93)90167-4","article-title":"Controlling diffusion","volume":"24","author":"Wesselingh","year":"1993","journal-title":"J. Control Release"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10680","DOI":"10.1021\/la801636u","article-title":"Modulation of drug transport properties by multicomponent diffusion in surfactant aqueous solutions","volume":"24","author":"Zhang","year":"2008","journal-title":"Langmuir"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1021\/la803664g","article-title":"Diffusion of an Ionic Drug in Micellar Aqueous Solutions","volume":"25","author":"Zhang","year":"2009","journal-title":"Langmuir"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ijpharm.2013.02.049","article-title":"Mass transport techniques as a tool for a better understanding of the structure of l-dopa aqueous solutions","volume":"447","author":"Barros","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jct.2013.12.010","article-title":"Diffusion of levodopa in aqueous solutions of hydrochloric acid at 25 degrees C","volume":"72","author":"Barros","year":"2014","journal-title":"J. Chem. Thermodyn."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1021\/je900853f","article-title":"Quaternary diffusion coefficients of \u03b2-cyclodextrin + kcl + caffeine + water at 298.15 K using a Taylor dispersion method","volume":"55","author":"Ribeiro","year":"2010","journal-title":"J. Chem. Eng. Data"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jct.2012.11.033","article-title":"Multicomponent Diffusion in Cyclodextrin-Drug- Salt-water systems. 2-hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2CD) +KCl + theophylline + water, and \u03b2-cyclodextrin (\u03b2CD) + KCl + theophylline + water","volume":"59","author":"Santos","year":"2012","journal-title":"J. Chem. Thermodyn."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.foodchem.2009.05.026","article-title":"Interaction between copper chloride and caffeine as seen by diffusion at 25 \u00b0C and 37 \u00b0C","volume":"118","author":"Ribeiro","year":"2010","journal-title":"Food Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1021\/je800728b","article-title":"Diffusion coefficients of the ternary system \u03b2-cyclodextrin + caffeine + water at 298.15 K","volume":"54","author":"Ribeiro","year":"2009","journal-title":"J. Chem. Eng. Data"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.jct.2009.06.005","article-title":"Diffusion coefficients of the ternary system (2-hydroxypropyl-\u03b2-cyclodextrin plus caffeine plus water) at T = 298.15 K","volume":"41","author":"Ribeiro","year":"2009","journal-title":"J. Chem. Thermodyn."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1021\/je2013928","article-title":"A comparison between the diffusion properties of theophylline\/\u03b2-cyclodextrin and theophylline\/2- hydroxypropyl-\u03b2\u2013cyclodextrin in aqueous systems","volume":"57","author":"Santos","year":"2012","journal-title":"J. Chem. Eng. Data"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1021\/je060092t","article-title":"Binary diffusion coefficients for aqueous solutions of \u03b2-cyclodextrin at temperatures from 298.15 k and 312.15 K","volume":"51","author":"Ribeiro","year":"2006","journal-title":"J. Chem. Eng. Data"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1021\/je900221m","article-title":"Binary mutual diffusion coefficients of isoniazid aqueous solutions at 298.15 and 310.15 K","volume":"54","author":"Ribeiro","year":"2009","journal-title":"J. Chem. Eng. Data"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1021\/je060474z","article-title":"Binary mutual diffusion coefficients of aqueous solutions of \u03b1-cyclodextrin, 2-hydroxypropyl-\u03b1-cyclodextrin and 2-hydroxypropyl-\u03b2-cyclodextrin at temperatures from 298.15K to 312.15 K","volume":"52","author":"Ribeiro","year":"2007","journal-title":"J. Chem. Eng. Data"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1021\/je700598v","article-title":"Some transport properties of \u03b3 cyclodextrin aqueous solutions at 298.15 K and 310.15 K","volume":"53","author":"Ribeiro","year":"2008","journal-title":"J. Chem. Eng. Data"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jct.2012.03.014","article-title":"Diffusion coefficients of paracetamol in aqueous solutions","volume":"54","author":"Ribeiro","year":"2012","journal-title":"J. Chem. Thermodyn."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0167-7322(01)00268-9","article-title":"Diffusion coefficients of sodium dodecylsulfate in aqueous solutions and in aqueous solutions of sucrose","volume":"94","author":"Ribeiro","year":"2001","journal-title":"J. Mol. Liquids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0167-7322(02)00069-7","article-title":"Diffusion Coefficients of sodium dodecylsulfate in aqueous solutions and in aqueous solutions of b-cyclodextrin","volume":"102","author":"Ribeiro","year":"2003","journal-title":"J. Mol. Liquids"},{"key":"ref_25","unstructured":"Tyrrell, H.J.V., and Harris, K.R. (1984). Diffusion in Liquids, Butterworths. [2nd ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1007\/s10953-014-0268-y","article-title":"Multicomponent Taylor Dispersion Coefficients","volume":"43","author":"Chen","year":"2014","journal-title":"J. Solut. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.molliq.2010.03.011","article-title":"Mutual diffusion with equal eigenvalues in solutions of strongly associated surfactants. A new kind of multicomponent diffusion","volume":"156","author":"Wygnal","year":"2010","journal-title":"J. Mol. Liquids"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1021\/je900700g","article-title":"Measurement of Ternary Mutual Diffusion Coefficients from Ill-Conditioned Taylor Dispersion Profiles in Cases of Identical or Nearly Identical Eigenvalues of the Diffusion Coefficient Matrix","volume":"55","author":"Ray","year":"2010","journal-title":"J. Chem. Eng. Data"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8173","DOI":"10.1039\/b906452d","article-title":"Coupled mutual diffusion in solutions of micelles and solubilizates","volume":"11","author":"Everist","year":"2019","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s10953-005-9000-2","article-title":"Diffusion coefficients for binary, ternary, and polydisperse solutions from peak-width analysis of Taylor dispersion profiles","volume":"35","author":"Callendar","year":"2006","journal-title":"J. Solut. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1021\/je800767e","article-title":"Thermodynamic Stability and the Origins of Incongruent and Strongly Coupled Diffusion in Solutions of Micelles, Solubilizates, and Microemulsions","volume":"54","author":"Moulins","year":"2009","journal-title":"J. Chem. Eng. Data"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10296","DOI":"10.1021\/jp0214662","article-title":"Incongruent diffusion (Negative main mutual diffusion coefficient) for a ternary mixed surfactant system","volume":"106","author":"MacEwan","year":"2002","journal-title":"J. Phys. Chem. B"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17969","DOI":"10.1021\/jp4062576","article-title":"Structural and Electronic Properties of Poly(9,9-dialkylfluorene)-Based Alternating Copolymers in Solution: An NMR Spectroscopy and Density Functional Theory Study","volume":"115","author":"Justino","year":"2013","journal-title":"J. Phys. Chem. C"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1039\/c2dt32587j","article-title":"Structural and photophysical studies on gallium(III) 8-hydroxyquinoline-5-sulfonates. Does excited state decay involve ligand photolabilisation?","volume":"42","author":"Ramos","year":"2013","journal-title":"Dalton Trans."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3581","DOI":"10.1016\/j.poly.2006.07.006","article-title":"Association between ammonium monovanadate and \u03b2 cyclodextrin as seen by NMR and transport techniques","volume":"25","author":"Ribeiro","year":"2006","journal-title":"Polyhedron"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11310","DOI":"10.1021\/jp802963x","article-title":"Thermodynamic and kinetic characterization of host-guest association between bolaform surfactants and \u03b1- and \u03b2-cyclodextrins","volume":"112","author":"Nilsson","year":"2008","journal-title":"J. Phys. Chem. B"},{"key":"ref_37","first-page":"396","article-title":"Transport properties of cyclodextrins. Intermolecular diffusion coefficients","volume":"14","author":"Ribeiro","year":"2008","journal-title":"J. Balkan Tribol. Assoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1039\/C4CS00153B","article-title":"Self-assembled capsules based on tetrafunctionalized calix[4]resorcinarene cavitands","volume":"44","author":"Kobayashi","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1070\/RC2011v080n01ABEH004127","article-title":"Chemistry of calix[4]resorcinarenes","volume":"80","author":"Jain","year":"2011","journal-title":"Russ. Chem. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"398","DOI":"10.2174\/157019309789371604","article-title":"Introduction to the Chirality of Resorcinarenes","volume":"6","author":"Iwanek","year":"2009","journal-title":"Mini Rev. Org. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S1472-7862(03)00068-6","article-title":"Cation-pi interactions in neutral calix[4]resorcinarenes","volume":"2","author":"Atwood","year":"2003","journal-title":"J. Supramol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1039\/C6SC04854D","article-title":"A resorcinarene for inhibition of A\u03b2 fibrillation","volume":"8","author":"Han","year":"2017","journal-title":"Chem. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pedro-Hern\u00e1ndez, L.D., Mart\u00ednez-Klimova, E., Cortez-Maya, S., Mendonza, S., Ram\u00edrez-\u00c1pan, T., and Mart\u00ednez-Garc\u00eda, M. (2017). Synthesis, characterization, and nanomedical applications of conjugates between resorcinarene-dendrimers and Ibuprofen. Nanomaterials, 7.","DOI":"10.3390\/nano7070163"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/8\/4\/178\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:34:35Z","timestamp":1760196875000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/8\/4\/178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,17]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["biom8040178"],"URL":"https:\/\/doi.org\/10.3390\/biom8040178","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,17]]}}}