{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T21:51:37Z","timestamp":1788558697065,"version":"build-2803163510"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Ministry of Health's National Medical Research Council","award":["IRG NMRC\/1187\/2008 (R-148-000-114-213)"],"award-info":[{"award-number":["IRG NMRC\/1187\/2008 (R-148-000-114-213)"]}]},{"name":"GEA-NUS PPRL","award":["N-148-000-008-001"],"award-info":[{"award-number":["N-148-000-008-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Chlorin e6 is a poorly water-soluble photoactive drug. Its monomers form aggregates at the tumour physiological pH, which drastically reduces its photodynamic efficacy. This study aimed to improve the dissolution rate and photodynamic efficacy of chlorin e6 by nanosuspension formulation using biodegradable sucrose esters as drug carrier.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A modified emulsion-solvent diffusion method was used to prepare the nanosuspension, where amount of Ce6, ratio of sucrose monopalmitate to sucrose monolaurate as carrier and ratio of dichloromethane to acetone as solvent, were varied using central composite design. Particle size, zeta potential, encapsulation efficiency and in vitro drug release characteristics of the nanosuspensions were evaluated. The formulation was optimised by response surface methodology and its photodynamic efficacy evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>The optimised nanosuspension had mean particle size of ~200 nm, 88% drug encapsulation efficiency and faster drug release compared to pure Ce6. Spectroscopic studies showed that Ce6 exists in monomeric form in the carrier, which facilitated a remarkable increase in cellular uptake, in vitro singlet oxygen generation and cytotoxicity to oral squamous carcinoma cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The dissolution rate and photodynamic efficacy of Ce6 were markedly improved by formulating the drug as a nanosuspension with sucrose esters as drug carrier.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.12947","type":"journal-article","created":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T05:20:21Z","timestamp":1529990421000},"page":"1152-1163","source":"Crossref","is-referenced-by-count":4,"title":["Improvement in dissolution rate and photodynamic efficacy of chlorin e6 by sucrose esters as drug carrier in nanosuspension formulation: optimisation and <i>in vitro<\/i> characterisation"],"prefix":"10.1093","volume":"70","author":[{"given":"Shubhajit","family":"Paul","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Minnesota , Minneapolis, MN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Wan Sia","family":"Heng","sequence":"additional","affiliation":[{"name":"GEANUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore , Singapore,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2229-7784","authenticated-orcid":false,"given":"Lai Wah","family":"Chan","sequence":"additional","affiliation":[{"name":"GEANUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore , Singapore,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,9,1]]},"reference":[{"key":"2024103012294372900_jphp12947-cit-0001","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/j.1440-1681.2006.04406.x","article-title":"Art and science of photodynamic therapy","volume":"5\u20136","author":"Pervaiz","year":"2006","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2024103012294372900_jphp12947-cit-0002","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.1021\/jm040074b","article-title":"Current clinical and preclinical photosensitizers for use in photodynamic therapy","volume":"16","author":"Detty","year":"2004","journal-title":"J Med Chem"},{"key":"2024103012294372900_jphp12947-cit-0003","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S1011-1344(96)07430-1","article-title":"In vitro photo-activation of newly synthesized chlorin derivatives with red-light-emitting diodes","volume":"1","author":"Colasanti","year":"1997","journal-title":"J Photochem Photobiol B"},{"key":"2024103012294372900_jphp12947-cit-0004","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S1011-1344(99)00130-X","article-title":"Acid-base properties of chlorin e6: relation to cellular uptake","volume":"1\u20133","author":"Cunderlikova","year":"1999","journal-title":"J Photochem Photobiol B"},{"key":"2024103012294372900_jphp12947-cit-0005","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jphotobiol.2008.06.004","article-title":"Toward understanding the high PDT efficacy of chlorin e6-polyvinylpyrrolidone formulations: photophysical and molecular aspects of photosensitizer-polymer interaction in vitro","volume":"3","author":"Isakau","year":"2008","journal-title":"J Photochem Photobiol B"},{"key":"2024103012294372900_jphp12947-cit-0006","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/lsm.1900170103","article-title":"Clinical and preclinical photodynamic therapy","volume":"1","author":"Fisher","year":"1995","journal-title":"Lasers Surg Med"},{"key":"2024103012294372900_jphp12947-cit-0007","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s10895-013-1236-4","article-title":"Elucidation of monomerization effect of PVP on chlorin e6 aggregates by spectroscopic, chemometric, thermodynamic and molecular simulation studies","volume":"5","author":"Paul","year":"2013","journal-title":"J Fluoresc"},{"key":"2024103012294372900_jphp12947-cit-0008","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/jphp.12535","article-title":"pH-dependent complexation of hydroxypropyl-beta-cyclodextrin with chlorin e6: effect on solubility and aggregation in relation to photodynamic efficacy","volume":"4","author":"Paul","year":"2016","journal-title":"J Pharm Pharmacol"},{"key":"2024103012294372900_jphp12947-cit-0009","doi-asserted-by":"crossref","first-page":"250","DOI":"10.31768\/2312-8852.2015.37(4):250-254","article-title":"Chlorin e6 combined with albumin nanoparticles as a potential composite photosensitizer for photodynamic therapy of tumors","volume":"4","author":"Shton","year":"2015","journal-title":"Exp Oncol"},{"key":"2024103012294372900_jphp12947-cit-0010","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ijpharm.2005.03.020","article-title":"Skin permeation enhancement by sucrose esters: a pH-dependent phenomenon","volume":"1\u20132","author":"Cazares-Delgadillo","year":"2005","journal-title":"Int J Pharm"},{"key":"2024103012294372900_jphp12947-cit-0011","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1248\/bpb.28.1689","article-title":"Effect of sucrose fatty acid esters on transdermal permeation of lidocaine and ketoprofen","volume":"9","author":"Okamoto","year":"2005","journal-title":"Biol Pharm Bull"},{"key":"2024103012294372900_jphp12947-cit-0012","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1021\/bc034038n","article-title":"Pyropheophorbide 2-deoxyglucosamide: a new photosensitizer targeting glucose transporters","volume":"4","author":"Zhang","year":"2003","journal-title":"Bioconjug Chem"},{"key":"2024103012294372900_jphp12947-cit-0013","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.colsurfa.2014.03.051","article-title":"Elucidating chlorin e6\u2013sucrose ester interaction using coarse-grain modeling and fluorescence spectroscopic technique","author":"Paul","year":"2014","journal-title":"Colloids Surf A"},{"key":"2024103012294372900_jphp12947-cit-0014","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1007\/s11095-011-0428-3","article-title":"Formulation, biological and pharmacokinetic studies of sucrose ester-stabilized nanosuspensions of oleanolic acid","volume":"8","author":"Li","year":"2011","journal-title":"Pharm Res"},{"key":"2024103012294372900_jphp12947-cit-0015","doi-asserted-by":"crossref","first-page":"4228","DOI":"10.1021\/bm501258s","article-title":"Photochemically triggered cytosolic drug delivery using pH-Responsive hyaluronic acid nanoparticles for light-induced cancer therapy","volume":"11","author":"Lee","year":"2014","journal-title":"Biomacromolecules"},{"key":"2024103012294372900_jphp12947-cit-0016","doi-asserted-by":"crossref","first-page":"17117","DOI":"10.1021\/acsami.8b06299","article-title":"Multifunctional micelles dually responsive to hypoxia and singlet oxygen: enhanced photodynamic therapy via interactively triggered photosensitizer delivery","volume":"10","author":"Li","year":"2018","journal-title":"ACS Appl Mater Interfaces"},{"key":"2024103012294372900_jphp12947-cit-0017","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1021\/acs.biomac.8b00290","article-title":"Miktoarm amphiphilic block copolymer with singlet oxygen-labile stereospecific beta-aminoacrylate junction: synthesis, self-assembly, and photodynamically triggered drug release","volume":"19","author":"Saravanakumar","year":"2018","journal-title":"Biomacromolecules"},{"key":"2024103012294372900_jphp12947-cit-0018","doi-asserted-by":"crossref","first-page":"6063","DOI":"10.1039\/c0cc05662f","article-title":"Supramolecular polymeric micelles by the host-guest interaction of star-like calix[4]arene and chlorin e6 for photodynamic therapy","volume":"21","author":"Tu","year":"2011","journal-title":"Chem Commun"},{"key":"2024103012294372900_jphp12947-cit-0019","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1093\/jnci\/80.5.330","article-title":"In vitro characterization of monoaspartyl chlorin e6 and diaspartyl chlorin e6 for photodynamic therapy","volume":"5","author":"Roberts","year":"1988","journal-title":"J Natl Cancer Inst"},{"key":"2024103012294372900_jphp12947-cit-0020","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.jfoodeng.2005.11.024","article-title":"Modeling and optimization I: usability of response surface methodology","volume":"3","author":"Ba\u015f","year":"2007","journal-title":"J Food Eng"},{"key":"2024103012294372900_jphp12947-cit-0021","first-page":"611","article-title":"Preparation and characterization of solid lipid nanoparticles containing cyclosporine by the emulsification-diffusion method","volume":"5","author":"Urban-Morlan","year":"2010","journal-title":"Int J Nanomedicine"},{"key":"2024103012294372900_jphp12947-cit-0022","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/j.1751-1097.1978.tb06972.x","article-title":"A new method for the detection of singlet oxygen in aqueous solutions","volume":"4\u20135","author":"Kralji\u0107","year":"1978","journal-title":"Photochem Photobiol"},{"key":"2024103012294372900_jphp12947-cit-0023","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0378-5173(99)00187-8","article-title":"Preparation of poly(dl-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method","volume":"2","author":"Murakami","year":"1999","journal-title":"Int J Pharm"},{"key":"2024103012294372900_jphp12947-cit-0024","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1080\/00032719.2013.867503","article-title":"Comparison of full factorial design, central composite design, and box-behnken design in chromatographic method development for the determination of fluconazole and its impurities","volume":"8","author":"Raki\u0107","year":"2014","journal-title":"Anal Lett"},{"key":"2024103012294372900_jphp12947-cit-0025","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1080\/02652040600682390","article-title":"Celecoxib-loaded poly(D, L-lactide-co-glycolide) nanoparticles prepared using a novel and controllable combination of diffusion and emulsification steps as part of the salting-out procedure","volume":"5","author":"Mccarron","year":"2006","journal-title":"J Microencapsul"},{"key":"2024103012294372900_jphp12947-cit-0026","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.spl.2008.10.032","article-title":"Lack-of-fit testing in errors-in-variables regression model with validation data","volume":"6","author":"Song","year":"2009","journal-title":"Stat Probab Lett"},{"key":"2024103012294372900_jphp12947-cit-0027","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.talanta.2014.01.034","article-title":"Experimental design and multiple response optimization. Using the desirability function in analytical methods development","volume":"124","author":"Vera Candioti","year":"2014","journal-title":"Talanta"},{"key":"2024103012294372900_jphp12947-cit-0028","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1517\/17425247.1.1.141","article-title":"Particle uptake by Peyer's patches: a pathway for drug and vaccine delivery","volume":"1","author":"Shakweh","year":"2004","journal-title":"Expert Opin Drug Deliv"},{"key":"2024103012294372900_jphp12947-cit-0029","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1023\/A:1014276917363","article-title":"Production and characterization of a budesonide nanosuspension for pulmonary administration","volume":"2","author":"Jacobs","year":"2002","journal-title":"Pharm Res"},{"key":"2024103012294372900_jphp12947-cit-0030","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.saa.2010.03.037","article-title":"FTIR spectra and normal-mode analysis of chlorin e6 and its degradation-induced impurities","volume":"3","author":"Gladkova","year":"2010","journal-title":"Spectrochim Acta A Mol Biomol Spectrosc"},{"key":"2024103012294372900_jphp12947-cit-0031","first-page":"2710","article-title":"Lysosomal localization and mechanism of uptake of Nile blue photosensitizers in tumor cells","volume":"10","author":"Lin","year":"1991","journal-title":"Cancer Res"},{"key":"2024103012294372900_jphp12947-cit-0032","first-page":"340","article-title":"Photophysical evaluation of mTHPC-loaded HSA nanoparticles as novel PDT delivery systems","volume":"3","author":"25Chen","year":"2010","journal-title":"J Photochem Photobiol B"},{"key":"2024103012294372900_jphp12947-cit-0033","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.ijpharm.2010.11.023","article-title":"Photosensitizer loaded HSA nanoparticles II: in vitro investigations","volume":"1\u20132","author":"Preuss","year":"2011","journal-title":"Int J Pharm"},{"key":"2024103012294372900_jphp12947-cit-0034","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.addr.2010.10.008","article-title":"PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect","volume":"3","author":"Acharya","year":"2011","journal-title":"Adv Drug Deliv Rev"},{"key":"2024103012294372900_jphp12947-cit-0035","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/cbic.200600454","article-title":"Control and selectivity of photosensitized singlet oxygen production: challenges in complex biological systems","volume":"5","author":"Clo","year":"2007","journal-title":"ChemBioChem"},{"key":"2024103012294372900_jphp12947-cit-0036","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1016\/j.actbio.2011.07.033","article-title":"Criteria impacting the cellular uptake of nanoparticles: a study emphasizing polymer type and surfactant effects","volume":"12","author":"Musyanovych","year":"2011","journal-title":"Acta Biomater"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.12947","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/70\/9\/1152\/60223785\/jphp12947.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/70\/9\/1152\/60223785\/jphp12947.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T17:30:51Z","timestamp":1730309451000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/70\/9\/1152\/6121740"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,1]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9,1]]},"published-print":{"date-parts":[[2018,9,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jphp.12947","relation":{},"ISSN":["2042-7158","0022-3573"],"issn-type":[{"value":"2042-7158","type":"electronic"},{"value":"0022-3573","type":"print"}],"subject":[],"published-other":{"date-parts":[[2018,9]]},"published":{"date-parts":[[2018,9,1]]}}}