Honokiol/Magnolol-Loaded Self-Assembling Lecithin-Based Mixed Polymeric Micelles (lbMPMs) for Improving Solubility to Enhance Oral Bioavailability
This study was intended to utilize lecithin-based mixed polymeric micelles ( MPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications. Lecithin was selected to increase the volume of the core...
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| Published in | International journal of nanomedicine Vol. 16; pp. 651 - 665 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New Zealand
Dove Medical Press Limited
01.01.2021
Taylor & Francis Ltd Dove Dove Medical Press |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1178-2013 1176-9114 1178-2013 |
| DOI | 10.2147/IJN.S290444 |
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| Abstract | This study was intended to utilize lecithin-based mixed polymeric micelles (
MPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications.
Lecithin was selected to increase the volume of the core of
MPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor
and Pluronic
series) were included with lecithin for screening and optimization.
After preliminary evaluation and subsequentially optimization, two
MPMs formulations composed of honokiol/magnolol:lecithin:NaDOC (
MPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 (
MPMs[PP123]) in respective ratios of 6:2:5 and 1:1:10 were optimally obtained with the mean particle sizes of 80-150 nm, encapsulation efficacy (EEs) of >90%, and drug loading (DL) of >9.0%. These
MPMs efficiently stabilized honokiol/magnolol in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C. PK study demonstrated that
MPMs[NaDOC] showed much improvement in enhancing bioavailability than that by
MPMs[PP123] for both honokiol and magnolol. The absolute bioavailability for honokiol and magnolol after intravenous administration of
MPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol. For oral administration with
MPMs[NaDOC], the absolute bioavailability of honokiol was 4.8%, and the absolute and relative bioavailability of magnolol were 20.1% and 2.9-fold increase, respectively.
Overall, honokiol/magnolol loaded in
MPMs[NaDOC] showed an improvement of solubility with suitable physical characteristics leading to enhance honokiol and magnolol bioavailability and facilitating their wider application as therapeutic agents for treating human disorders. |
|---|---|
| AbstractList | Objective: This study was intended to utilize lecithin-based mixed polymeric micelles (lbMPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications. Methods: Lecithin was selected to increase the volume of the core of lbMPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor®, and Pluronic® series) were included with lecithin for screening and optimization. Results: After preliminary evaluation and subsequentially optimization, two lbMPMs formulations composed of honokiol/magnolol:lecithin:NaDOC (lbMPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 (lbMPMs[PP123]) in respective ratios of 6:2:5 and 1:1:10 were optimally obtained with the mean particle sizes of 80– 150 nm, encapsulation efficacy (EEs) of > 90%, and drug loading (DL) of > 9.0%. These lbMPMs efficiently stabilized honokiol/magnolol in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C. PK study demonstrated that lbMPMs[NaDOC] showed much improvement in enhancing bioavailability than that by lbMPMs[PP123] for both honokiol and magnolol. The absolute bioavailability for honokiol and magnolol after intravenous administration of lbMPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol. For oral administration with lbMPMs[NaDOC], the absolute bioavailability of honokiol was 4.8%, and the absolute and relative bioavailability of magnolol were 20.1% and 2.9-fold increase, respectively. Conclusion: Overall, honokiol/magnolol loaded in lbMPMs[NaDOC] showed an improvement of solubility with suitable physical characteristics leading to enhance honokiol and magnolol bioavailability and facilitating their wider application as therapeutic agents for treating human disorders. Objective: This study was intended to utilize lecithin-based mixed polymeric micelles (IbMPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications. Methods: Lecithin was selected to increase the volume of the core of IbMPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor[R], and Pluronic[R] series) were included with lecithin for screening and optimization. Results: After preliminary evaluation and subsequentially optimization, two IbMPMs formulations composed of honokiol/magnolol:lecithin:NaDOC (lbMPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 (lbMPMs[PP123]) in respective ratios of 6:2:5 and 1:1:10 were optimally obtained with the mean particle sizes of 80-150 nm, encapsulation efficacy (EEs) of >90%, and drug loading (DL) of >9.0%. These IbMPMs efficiently stabilized honokiol/magnolol in phosphate-buffered saline (PBS) at room temperature or 4 [degrees]C and in fetal bovine serum or PBS at 37 [degrees]C. PK study demonstrated that lbMPMs[NaDOC] showed much improvement in enhancing bioavailability than that by lbMPMs[PP123] for both honokiol and magnolol. The absolute bioavailability for honokiol and magnolol after intravenous administration of lbMPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol. For oral administration with lbMPMs[NaDOC], the absolute bioavailability of honokiol was 4.8%, and the absolute and relative bioavailability of magnolol were 20.1% and 2.9-fold increase, respectively. Conclusion: Overall, honokiol/magnolol loaded in lbMPMs[NaDOC] showed an improvement of solubility with suitable physical characteristics leading to enhance honokiol and magnolol bioavailability and facilitating their wider application as therapeutic agents for treating human disorders. Keywords: lecithin, mixed polymeric micelles, honokiol, magnolol, sodium deoxycholate, pluronic This study was intended to utilize lecithin-based mixed polymeric micelles ( MPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications. Lecithin was selected to increase the volume of the core of MPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor and Pluronic series) were included with lecithin for screening and optimization. After preliminary evaluation and subsequentially optimization, two MPMs formulations composed of honokiol/magnolol:lecithin:NaDOC ( MPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 ( MPMs[PP123]) in respective ratios of 6:2:5 and 1:1:10 were optimally obtained with the mean particle sizes of 80-150 nm, encapsulation efficacy (EEs) of >90%, and drug loading (DL) of >9.0%. These MPMs efficiently stabilized honokiol/magnolol in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C. PK study demonstrated that MPMs[NaDOC] showed much improvement in enhancing bioavailability than that by MPMs[PP123] for both honokiol and magnolol. The absolute bioavailability for honokiol and magnolol after intravenous administration of MPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol. For oral administration with MPMs[NaDOC], the absolute bioavailability of honokiol was 4.8%, and the absolute and relative bioavailability of magnolol were 20.1% and 2.9-fold increase, respectively. Overall, honokiol/magnolol loaded in MPMs[NaDOC] showed an improvement of solubility with suitable physical characteristics leading to enhance honokiol and magnolol bioavailability and facilitating their wider application as therapeutic agents for treating human disorders. This study was intended to utilize lecithin-based mixed polymeric micelles (lbMPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications.OBJECTIVEThis study was intended to utilize lecithin-based mixed polymeric micelles (lbMPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications.Lecithin was selected to increase the volume of the core of lbMPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor®, and Pluronic® series) were included with lecithin for screening and optimization.METHODSLecithin was selected to increase the volume of the core of lbMPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor®, and Pluronic® series) were included with lecithin for screening and optimization.After preliminary evaluation and subsequentially optimization, two lbMPMs formulations composed of honokiol/magnolol:lecithin:NaDOC (lbMPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 (lbMPMs[PP123]) in respective ratios of 6:2:5 and 1:1:10 were optimally obtained with the mean particle sizes of 80-150 nm, encapsulation efficacy (EEs) of >90%, and drug loading (DL) of >9.0%. These lbMPMs efficiently stabilized honokiol/magnolol in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C. PK study demonstrated that lbMPMs[NaDOC] showed much improvement in enhancing bioavailability than that by lbMPMs[PP123] for both honokiol and magnolol. The absolute bioavailability for honokiol and magnolol after intravenous administration of lbMPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol. For oral administration with lbMPMs[NaDOC], the absolute bioavailability of honokiol was 4.8%, and the absolute and relative bioavailability of magnolol were 20.1% and 2.9-fold increase, respectively.RESULTSAfter preliminary evaluation and subsequentially optimization, two lbMPMs formulations composed of honokiol/magnolol:lecithin:NaDOC (lbMPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 (lbMPMs[PP123]) in respective ratios of 6:2:5 and 1:1:10 were optimally obtained with the mean particle sizes of 80-150 nm, encapsulation efficacy (EEs) of >90%, and drug loading (DL) of >9.0%. These lbMPMs efficiently stabilized honokiol/magnolol in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C. PK study demonstrated that lbMPMs[NaDOC] showed much improvement in enhancing bioavailability than that by lbMPMs[PP123] for both honokiol and magnolol. The absolute bioavailability for honokiol and magnolol after intravenous administration of lbMPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol. For oral administration with lbMPMs[NaDOC], the absolute bioavailability of honokiol was 4.8%, and the absolute and relative bioavailability of magnolol were 20.1% and 2.9-fold increase, respectively.Overall, honokiol/magnolol loaded in lbMPMs[NaDOC] showed an improvement of solubility with suitable physical characteristics leading to enhance honokiol and magnolol bioavailability and facilitating their wider application as therapeutic agents for treating human disorders.CONCLUSIONOverall, honokiol/magnolol loaded in lbMPMs[NaDOC] showed an improvement of solubility with suitable physical characteristics leading to enhance honokiol and magnolol bioavailability and facilitating their wider application as therapeutic agents for treating human disorders. Hong-Liang Lin,1 Wen-Ting Cheng,2 Ling-Chun Chen,3 Hsiu-O Ho,2 Shyr-Yi Lin,4,5 Chien-Ming Hsieh2 1School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, Republic of China; 2School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan, Republic of China; 3Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu 30015, Taiwan, Republic of China; 4Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan, Republic of China; 5Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, Republic of ChinaCorrespondence: Shyr-Yi Lin; Chien-Ming Hsieh 250 Wu-Hsing Street, Taipei 11031, Taiwan, Republic of ChinaTel +886-2-27361661 ext 6112Fax +886-2-23771942Email sylin@tmu.edu.tw; cmhsieh@tmu.edu.twObjective: This study was intended to utilize lecithin-based mixed polymeric micelles (lbMPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications.Methods: Lecithin was selected to increase the volume of the core of lbMPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor®, and Pluronic® series) were included with lecithin for screening and optimization.Results: After preliminary evaluation and subsequentially optimization, two lbMPMs formulations composed of honokiol/magnolol:lecithin:NaDOC (lbMPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 (lbMPMs[PP123]) in respective ratios of 6:2:5 and 1:1:10 were optimally obtained with the mean particle sizes of 80- 150 nm, encapsulation efficacy (EEs) of > 90%, and drug loading (DL) of > 9.0%. These lbMPMs efficiently stabilized honokiol/magnolol in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C. PK study demonstrated that lbMPMs[NaDOC] showed much improvement in enhancing bioavailability than that by lbMPMs[PP123] for both honokiol and magnolol. The absolute bioavailability for honokiol and magnolol after intravenous administration of lbMPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol. For oral administration with lbMPMs[NaDOC], the absolute bioavailability of honokiol was 4.8%, and the absolute and relative bioavailability of magnolol were 20.1% and 2.9-fold increase, respectively.Conclusion: Overall, honokiol/magnolol loaded in lbMPMs[NaDOC] showed an improvement of solubility with suitable physical characteristics leading to enhance honokiol and magnolol bioavailability and facilitating their wider application as therapeutic agents for treating human disorders.Keywords: lecithin, mixed polymeric micelles, honokiol, magnolol, sodium deoxycholate, pluronic |
| Audience | Academic |
| Author | Cheng, Wen-Ting Chen, Ling-Chun Hsieh, Chien-Ming Lin, Hong-Liang Ho, Hsiu-O Lin, Shyr-Yi |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33536753$$D View this record in MEDLINE/PubMed |
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| Snippet | This study was intended to utilize lecithin-based mixed polymeric micelles (
MPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to... Objective: This study was intended to utilize lecithin-based mixed polymeric micelles (IbMPMs) for enhancing the solubility and bioavailability of honokiol and... Objective: This study was intended to utilize lecithin-based mixed polymeric micelles (lbMPMs) for enhancing the solubility and bioavailability of honokiol and... This study was intended to utilize lecithin-based mixed polymeric micelles (lbMPMs) for enhancing the solubility and bioavailability of honokiol and magnolol... Hong-Liang Lin,1 Wen-Ting Cheng,2 Ling-Chun Chen,3 Hsiu-O Ho,2 Shyr-Yi Lin,4,5 Chien-Ming Hsieh2 1School of Pharmacy, College of Pharmacy, Kaohsiung Medical... |
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| SubjectTerms | Administration, Oral Angiogenesis Animals Bioavailability Biological Availability Biphenyl Compounds - blood Biphenyl Compounds - chemistry Biphenyl Compounds - pharmacokinetics Biphenyl Compounds - pharmacology Cancer Chromatography Deoxycholic acid Drug delivery systems Drug Liberation Hemodialysis honokiol Humans Lecithin Lecithins - chemistry Ligands Lignans - blood Lignans - chemistry Lignans - pharmacokinetics Lignans - pharmacology magnolol Male Micelles mixed polymeric micelles Original Research Particle Size pluronic Polymers Polymers - chemistry Rats Rats, Sprague-Dawley sodium deoxycholate Solubility Thin films |
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| Title | Honokiol/Magnolol-Loaded Self-Assembling Lecithin-Based Mixed Polymeric Micelles (lbMPMs) for Improving Solubility to Enhance Oral Bioavailability |
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