A comprehensive mathematical model of drug release kinetics from nano-liposomes, derived from optimization studies of cationic PEGylated liposomal doxorubicin formulations for drug-gene delivery

Fateme Haghiralsadat, Ghasem Amoabediny, Marco N. Helder, Samira Naderinezhad, Mohammad Hasan Sheikhha, Tymour Forouzanfar, Behrouz Zandieh-doulabi

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

This study focuses on the development of a universal mathematical model for drug release kinetics from liposomes to allow in silico prediction of optimal conditions for fine-tuned controlled drug release. As a prelude for combined siRNA-drug delivery, nanoliposome formulations were optimized using various mole percentages of a cationic lipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) in the presence or absence of 3 mol% distearoyl phosphoethanolamine, polyethylene glycol (PEG–2000mDSPE). Outcome parameters were particle size, zeta potential, entrapment efficiency, in vitro drug release, and tumor cell kill efficiency. The optimized formula (containing 20% DOTAP with 3% DSPE-mPEG(2000) was found to be stable for six months, with round-shaped particles without aggregate formation, an average diameter of 71 nm, a suitable positive charge, and 89% drug encapsulation efficiency (EE). The 41% drug release during 6 h confirmed controlled release. Furthermore, the release profiles as functions of pH and temperature were investigated and the kinetics of the drug release could adequately be fitted to Korsmeyer–Peppas’ model by multiple regression analysis. The statistical parameters confirmed good conformity of final models. Functionality of the novel cationic liposome formulations (± DOX) was tested on osteosarcoma (OS) cell lines. Increased OS cell toxicity (1.3-fold) was observed by the DOX-loaded vs. the free DOX. A feasibility pilot showed that siRNA could be loaded efficiently as well. In conclusion, we have established a predictive mathematical model for the fine-tuning of controlled drug release from liposomal formulations, while creating functional drug-delivery liposomes with potential for siRNA co-delivery to increase specificity and efficacy. (Figure presented.)

Original languageEnglish
Pages (from-to)169-177
Number of pages9
JournalArtificial Cells, Nanomedicine and Biotechnology
Volume46
Issue number1
DOIs
Publication statusPublished - Feb 2018

Cite this

@article{f36870c339c24e2f8c8f2d658d1c5e9c,
title = "A comprehensive mathematical model of drug release kinetics from nano-liposomes, derived from optimization studies of cationic PEGylated liposomal doxorubicin formulations for drug-gene delivery",
abstract = "This study focuses on the development of a universal mathematical model for drug release kinetics from liposomes to allow in silico prediction of optimal conditions for fine-tuned controlled drug release. As a prelude for combined siRNA-drug delivery, nanoliposome formulations were optimized using various mole percentages of a cationic lipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) in the presence or absence of 3 mol{\%} distearoyl phosphoethanolamine, polyethylene glycol (PEG–2000mDSPE). Outcome parameters were particle size, zeta potential, entrapment efficiency, in vitro drug release, and tumor cell kill efficiency. The optimized formula (containing 20{\%} DOTAP with 3{\%} DSPE-mPEG(2000) was found to be stable for six months, with round-shaped particles without aggregate formation, an average diameter of 71 nm, a suitable positive charge, and 89{\%} drug encapsulation efficiency (EE). The 41{\%} drug release during 6 h confirmed controlled release. Furthermore, the release profiles as functions of pH and temperature were investigated and the kinetics of the drug release could adequately be fitted to Korsmeyer–Peppas’ model by multiple regression analysis. The statistical parameters confirmed good conformity of final models. Functionality of the novel cationic liposome formulations (± DOX) was tested on osteosarcoma (OS) cell lines. Increased OS cell toxicity (1.3-fold) was observed by the DOX-loaded vs. the free DOX. A feasibility pilot showed that siRNA could be loaded efficiently as well. In conclusion, we have established a predictive mathematical model for the fine-tuning of controlled drug release from liposomal formulations, while creating functional drug-delivery liposomes with potential for siRNA co-delivery to increase specificity and efficacy. (Figure presented.)",
keywords = "Cationic liposome, drug release kinetics, mathematical modelling, siRNA delivery, thermo and pH sensitivity",
author = "Fateme Haghiralsadat and Ghasem Amoabediny and Helder, {Marco N.} and Samira Naderinezhad and Sheikhha, {Mohammad Hasan} and Tymour Forouzanfar and Behrouz Zandieh-doulabi",
year = "2018",
month = "2",
doi = "10.1080/21691401.2017.1304403",
language = "English",
volume = "46",
pages = "169--177",
journal = "Artificial Cells, Nanomedicine and Biotechnology",
issn = "2169-1401",
publisher = "Informa Healthcare",
number = "1",

}

A comprehensive mathematical model of drug release kinetics from nano-liposomes, derived from optimization studies of cationic PEGylated liposomal doxorubicin formulations for drug-gene delivery. / Haghiralsadat, Fateme; Amoabediny, Ghasem; Helder, Marco N.; Naderinezhad, Samira; Sheikhha, Mohammad Hasan; Forouzanfar, Tymour; Zandieh-doulabi, Behrouz.

In: Artificial Cells, Nanomedicine and Biotechnology, Vol. 46, No. 1, 02.2018, p. 169-177.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A comprehensive mathematical model of drug release kinetics from nano-liposomes, derived from optimization studies of cationic PEGylated liposomal doxorubicin formulations for drug-gene delivery

AU - Haghiralsadat, Fateme

AU - Amoabediny, Ghasem

AU - Helder, Marco N.

AU - Naderinezhad, Samira

AU - Sheikhha, Mohammad Hasan

AU - Forouzanfar, Tymour

AU - Zandieh-doulabi, Behrouz

PY - 2018/2

Y1 - 2018/2

N2 - This study focuses on the development of a universal mathematical model for drug release kinetics from liposomes to allow in silico prediction of optimal conditions for fine-tuned controlled drug release. As a prelude for combined siRNA-drug delivery, nanoliposome formulations were optimized using various mole percentages of a cationic lipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) in the presence or absence of 3 mol% distearoyl phosphoethanolamine, polyethylene glycol (PEG–2000mDSPE). Outcome parameters were particle size, zeta potential, entrapment efficiency, in vitro drug release, and tumor cell kill efficiency. The optimized formula (containing 20% DOTAP with 3% DSPE-mPEG(2000) was found to be stable for six months, with round-shaped particles without aggregate formation, an average diameter of 71 nm, a suitable positive charge, and 89% drug encapsulation efficiency (EE). The 41% drug release during 6 h confirmed controlled release. Furthermore, the release profiles as functions of pH and temperature were investigated and the kinetics of the drug release could adequately be fitted to Korsmeyer–Peppas’ model by multiple regression analysis. The statistical parameters confirmed good conformity of final models. Functionality of the novel cationic liposome formulations (± DOX) was tested on osteosarcoma (OS) cell lines. Increased OS cell toxicity (1.3-fold) was observed by the DOX-loaded vs. the free DOX. A feasibility pilot showed that siRNA could be loaded efficiently as well. In conclusion, we have established a predictive mathematical model for the fine-tuning of controlled drug release from liposomal formulations, while creating functional drug-delivery liposomes with potential for siRNA co-delivery to increase specificity and efficacy. (Figure presented.)

AB - This study focuses on the development of a universal mathematical model for drug release kinetics from liposomes to allow in silico prediction of optimal conditions for fine-tuned controlled drug release. As a prelude for combined siRNA-drug delivery, nanoliposome formulations were optimized using various mole percentages of a cationic lipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) in the presence or absence of 3 mol% distearoyl phosphoethanolamine, polyethylene glycol (PEG–2000mDSPE). Outcome parameters were particle size, zeta potential, entrapment efficiency, in vitro drug release, and tumor cell kill efficiency. The optimized formula (containing 20% DOTAP with 3% DSPE-mPEG(2000) was found to be stable for six months, with round-shaped particles without aggregate formation, an average diameter of 71 nm, a suitable positive charge, and 89% drug encapsulation efficiency (EE). The 41% drug release during 6 h confirmed controlled release. Furthermore, the release profiles as functions of pH and temperature were investigated and the kinetics of the drug release could adequately be fitted to Korsmeyer–Peppas’ model by multiple regression analysis. The statistical parameters confirmed good conformity of final models. Functionality of the novel cationic liposome formulations (± DOX) was tested on osteosarcoma (OS) cell lines. Increased OS cell toxicity (1.3-fold) was observed by the DOX-loaded vs. the free DOX. A feasibility pilot showed that siRNA could be loaded efficiently as well. In conclusion, we have established a predictive mathematical model for the fine-tuning of controlled drug release from liposomal formulations, while creating functional drug-delivery liposomes with potential for siRNA co-delivery to increase specificity and efficacy. (Figure presented.)

KW - Cationic liposome

KW - drug release kinetics

KW - mathematical modelling

KW - siRNA delivery

KW - thermo and pH sensitivity

UR - http://www.scopus.com/inward/record.url?scp=85017186647&partnerID=8YFLogxK

U2 - 10.1080/21691401.2017.1304403

DO - 10.1080/21691401.2017.1304403

M3 - Article

VL - 46

SP - 169

EP - 177

JO - Artificial Cells, Nanomedicine and Biotechnology

JF - Artificial Cells, Nanomedicine and Biotechnology

SN - 2169-1401

IS - 1

ER -