Doxorubicin-Loaded Multivesicular Liposomes (DepoFoam) as a Sustained Release Carrier Intended for Locoregional Delivery in Cancer Treatment: Development, Characterization, and Cytotoxicity Evaluation.
Doxorubicin
Drug Delivery
Intratumoral Injection
Locoregional
Multivesicular Liposomes
Journal
Iranian journal of pharmaceutical research : IJPR
ISSN: 1726-6890
Titre abrégé: Iran J Pharm Res
Pays: Netherlands
ID NLM: 101208407
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
received:
20
12
2022
revised:
15
01
2023
accepted:
22
01
2023
entrez:
10
3
2023
pubmed:
11
3
2023
medline:
11
3
2023
Statut:
epublish
Résumé
Despite the advantages of direct intratumoral (IT) injection, the relatively rapid withdrawal of most anti-cancer drugs from the tumor due to their small molecular size limits the effectiveness of this method of administration. To address these limitations, recently, increasing attention has been directed to using slow-release biodegradable delivery systems for IT injection. This study aimed to develop and characterize a doxorubicin-loaded DepoFoam system as an efficient controlled-release carrier to be employed for locoregional drug delivery in cancer treatment. Major formulation parameters, including the molar ratio of cholesterol to the main lipid [Chol/egg phosphatidylcholine (EPC)], triolein (TO) content, and lipid-to-drug molar ratio (L/D), were optimized using a two-level factorial design approach. The prepared batches were evaluated for encapsulation efficiency (EE) and percentage of drug release (DR) after 6 and 72 hours as dependent variables. The optimum formulation (named DepoDOX) was further evaluated in terms of particle size, morphology, zeta potential, stability, Fourier-transform infrared spectroscopy, in vitro cytotoxicity, and hemolysis. The analysis of factorial design indicated that TO content and L/D ratio had a negative effect on EE; between these two, TO content had the greatest effect. The TO content was also the most significant component, with a negative effect on the release rate. The ratio of Chol/EPC showed a dual effect on the DR rate. Using a higher percentage of Chol slowed down the initial release phase of the drug; nevertheless, it accelerated the DR rate in the later slow phase. DepoDOX were spherical and honeycomb-like structures (≈ 9.81 μm) with a desired sustained release profile, as DR lasted 11 days. Its biocompatibility was confirmed by the results of cytotoxicity and hemolysis assays. The in vitro characterization of optimized DepoFoam formulation demonstrated its suitability for direct locoregional delivery. DepoDOX, as a biocompatible lipid-based formulation, showed appropriate particle size, high capability for encapsulating doxorubicin, superior physical stability, and a markedly prolonged DR rate. Therefore, this formulation could be considered a promising candidate for locoregional drug delivery in cancer treatment.
Sections du résumé
Background
UNASSIGNED
Despite the advantages of direct intratumoral (IT) injection, the relatively rapid withdrawal of most anti-cancer drugs from the tumor due to their small molecular size limits the effectiveness of this method of administration. To address these limitations, recently, increasing attention has been directed to using slow-release biodegradable delivery systems for IT injection.
Objectives
UNASSIGNED
This study aimed to develop and characterize a doxorubicin-loaded DepoFoam system as an efficient controlled-release carrier to be employed for locoregional drug delivery in cancer treatment.
Methods
UNASSIGNED
Major formulation parameters, including the molar ratio of cholesterol to the main lipid [Chol/egg phosphatidylcholine (EPC)], triolein (TO) content, and lipid-to-drug molar ratio (L/D), were optimized using a two-level factorial design approach. The prepared batches were evaluated for encapsulation efficiency (EE) and percentage of drug release (DR) after 6 and 72 hours as dependent variables. The optimum formulation (named DepoDOX) was further evaluated in terms of particle size, morphology, zeta potential, stability, Fourier-transform infrared spectroscopy, in vitro cytotoxicity, and hemolysis.
Results
UNASSIGNED
The analysis of factorial design indicated that TO content and L/D ratio had a negative effect on EE; between these two, TO content had the greatest effect. The TO content was also the most significant component, with a negative effect on the release rate. The ratio of Chol/EPC showed a dual effect on the DR rate. Using a higher percentage of Chol slowed down the initial release phase of the drug; nevertheless, it accelerated the DR rate in the later slow phase. DepoDOX were spherical and honeycomb-like structures (≈ 9.81 μm) with a desired sustained release profile, as DR lasted 11 days. Its biocompatibility was confirmed by the results of cytotoxicity and hemolysis assays.
Conclusions
UNASSIGNED
The in vitro characterization of optimized DepoFoam formulation demonstrated its suitability for direct locoregional delivery. DepoDOX, as a biocompatible lipid-based formulation, showed appropriate particle size, high capability for encapsulating doxorubicin, superior physical stability, and a markedly prolonged DR rate. Therefore, this formulation could be considered a promising candidate for locoregional drug delivery in cancer treatment.
Identifiants
pubmed: 36896322
doi: 10.5812/ijpr-134190
pmc: PMC9990514
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e134190Informations de copyright
Copyright © 2023, Author(s).
Déclaration de conflit d'intérêts
Conflict of Interests: The authors declare that there is no conflict of interest regarding the present study.
Références
Nanotechnology. 2013 Feb 8;24(5):055706
pubmed: 23324261
Drug Dev Ind Pharm. 2013 Feb;39(2):197-204
pubmed: 22443684
Pharmaceutics. 2020 Aug 05;12(8):
pubmed: 32764318
Front Pharmacol. 2013 May 07;4:57
pubmed: 23675348
J Mol Biol. 1964 May;8:660-8
pubmed: 14187392
Clin Ther. 2016 Jul;38(7):1551-66
pubmed: 27158009
Eur J Pharm Biopharm. 2015 Aug;94:521-31
pubmed: 26170161
Biophys J. 2008 Sep;95(5):2318-24
pubmed: 18515370
Molecules. 2019 May 05;24(9):
pubmed: 31060345
Iran J Pharm Res. 2015 Winter;14(Suppl):33-42
pubmed: 26185503
J Control Release. 2019 Dec 10;315:23-30
pubmed: 31629038
Mini Rev Med Chem. 2018;18(4):324-344
pubmed: 27804889
Sci Technol Adv Mater. 2021 Jun 24;22(1):522-531
pubmed: 34220340
J Biomed Mater Res A. 2020 May;108(7):1444-1458
pubmed: 32246745
Bioinformatics. 2020 Jul 1;36(Suppl_1):i482-i489
pubmed: 32657359
Drug Dev Ind Pharm. 2006 Jul;32(6):699-707
pubmed: 16885125
J Pharm Pharmacol. 2014 Sep;66(9):1231-9
pubmed: 24716458
CA Cancer J Clin. 2022 Jan;72(1):7-33
pubmed: 35020204
CA Cancer J Clin. 2021 May;71(3):209-249
pubmed: 33538338
Drug Deliv. 2016 Nov;23(9):3358-3363
pubmed: 27099000
AAPS PharmSciTech. 2005 Sep 20;6(1):E35-41
pubmed: 16353961
Drug Deliv. 2018 Nov;25(1):1372-1383
pubmed: 29869520
Pharmaceutics. 2017 Mar 27;9(2):
pubmed: 28346375
Methods Mol Biol. 2011;731:237-45
pubmed: 21516412
J Pharm Sci. 2006 Jun;95(6):1173-6
pubmed: 16639718
Biochim Biophys Acta. 1983 Mar 9;728(3):339-48
pubmed: 6824663
Drug Dev Ind Pharm. 2021 Aug;47(8):1290-1301
pubmed: 34620021
Int J Cancer. 2000 Nov 15;88(4):645-51
pubmed: 11058884
Pharmacol Rev. 1999 Dec;51(4):691-743
pubmed: 10581328
J Control Release. 2010 Feb 25;142(1):101-7
pubmed: 19819274
Int J Pharm. 2018 Mar 25;539(1-2):139-146
pubmed: 29353083
J Pharm Sci. 1998 Nov;87(11):1341-6
pubmed: 9811487
Drug Dev Ind Pharm. 2010 Jul;36(7):823-31
pubmed: 20515403
J Clin Oncol. 1999 May;17(5):1435-41
pubmed: 10334528
J Vet Intern Med. 2020 Jul;34(4):1563-1569
pubmed: 32442344
J Pharm Sci. 2004 Jul;93(7):1718-24
pubmed: 15176061
Prog Lipid Res. 2002 Sep;41(5):392-406
pubmed: 12121719
J Food Sci. 2019 Sep;84(9):2572-2583
pubmed: 31436862