The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles

Research output: Contribution to journalJournal articleResearchpeer-review

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The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles. / Liu, Jingying; Christophersen, Philip C; Yang, Mingshi; Nielsen, Hanne M; Mu, Huiling.

In: Drug Development and Industrial Pharmacy, Vol. 43, No. 12, 12.2017, p. 2032-2042.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Liu, J, Christophersen, PC, Yang, M, Nielsen, HM & Mu, H 2017, 'The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles', Drug Development and Industrial Pharmacy, vol. 43, no. 12, pp. 2032-2042. https://doi.org/10.1080/03639045.2017.1361967

APA

Liu, J., Christophersen, P. C., Yang, M., Nielsen, H. M., & Mu, H. (2017). The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles. Drug Development and Industrial Pharmacy, 43(12), 2032-2042. https://doi.org/10.1080/03639045.2017.1361967

Vancouver

Liu J, Christophersen PC, Yang M, Nielsen HM, Mu H. The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles. Drug Development and Industrial Pharmacy. 2017 Dec;43(12):2032-2042. https://doi.org/10.1080/03639045.2017.1361967

Author

Liu, Jingying ; Christophersen, Philip C ; Yang, Mingshi ; Nielsen, Hanne M ; Mu, Huiling. / The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles. In: Drug Development and Industrial Pharmacy. 2017 ; Vol. 43, No. 12. pp. 2032-2042.

Bibtex

@article{a9919fc8caa74eec9bc4cefbae4b33c7,
title = "The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles",
abstract = "OBJECTIVE: The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM.METHODS: Labeled lysozyme was incorporated into SLM prepared with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS), and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water (s/o/w) method. The distribution of lysozyme in SLM and the release of the protein from SLM were evaluated by confocal laser scanning microscopy. The storage stability of SLM was characterized by HPLC, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy.RESULTS: Lysozyme was displayed as small scattered domains inside GDS and GMS SLM, whereas it was incorporated in the core of TG14 SLM formulated by the w/o/w method or evenly distributed in TG14 SLM prepared by the s/o/w method. Stability study at 37 °C revealed that only TG14 SLM made by the w/o/w method was able to maintain the lysozyme amount both on the particle surface and released from the SLM. Elevated storage temperature induced polymorphic transition of lipids in GDS and GMS SLM, which was, however, not remarkable for the TG14 SLM.CONCLUSIONS: Lipid excipients and particle preparation methods were found to differently affect the lysozyme distribution in SLM, owning to varied storage stabilities of the lipids. The present study provides updated knowledge for rational development of lipid-based formulations for oral delivery of peptide or protein drugs.",
keywords = "Administration, Oral, Calorimetry, Differential Scanning, Chemistry, Pharmaceutical, Drug Delivery Systems, Excipients, Lipids, Microscopy, Electron, Scanning, Muramidase, Proteins, Triglycerides, X-Ray Diffraction, Journal Article",
author = "Jingying Liu and Christophersen, {Philip C} and Mingshi Yang and Nielsen, {Hanne M} and Huiling Mu",
year = "2017",
month = "12",
doi = "10.1080/03639045.2017.1361967",
language = "English",
volume = "43",
pages = "2032--2042",
journal = "Drug Development and Industrial Pharmacy",
issn = "0363-9045",
publisher = "Taylor & Francis",
number = "12",

}

RIS

TY - JOUR

T1 - The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles

AU - Liu, Jingying

AU - Christophersen, Philip C

AU - Yang, Mingshi

AU - Nielsen, Hanne M

AU - Mu, Huiling

PY - 2017/12

Y1 - 2017/12

N2 - OBJECTIVE: The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM.METHODS: Labeled lysozyme was incorporated into SLM prepared with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS), and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water (s/o/w) method. The distribution of lysozyme in SLM and the release of the protein from SLM were evaluated by confocal laser scanning microscopy. The storage stability of SLM was characterized by HPLC, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy.RESULTS: Lysozyme was displayed as small scattered domains inside GDS and GMS SLM, whereas it was incorporated in the core of TG14 SLM formulated by the w/o/w method or evenly distributed in TG14 SLM prepared by the s/o/w method. Stability study at 37 °C revealed that only TG14 SLM made by the w/o/w method was able to maintain the lysozyme amount both on the particle surface and released from the SLM. Elevated storage temperature induced polymorphic transition of lipids in GDS and GMS SLM, which was, however, not remarkable for the TG14 SLM.CONCLUSIONS: Lipid excipients and particle preparation methods were found to differently affect the lysozyme distribution in SLM, owning to varied storage stabilities of the lipids. The present study provides updated knowledge for rational development of lipid-based formulations for oral delivery of peptide or protein drugs.

AB - OBJECTIVE: The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM.METHODS: Labeled lysozyme was incorporated into SLM prepared with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS), and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water (s/o/w) method. The distribution of lysozyme in SLM and the release of the protein from SLM were evaluated by confocal laser scanning microscopy. The storage stability of SLM was characterized by HPLC, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy.RESULTS: Lysozyme was displayed as small scattered domains inside GDS and GMS SLM, whereas it was incorporated in the core of TG14 SLM formulated by the w/o/w method or evenly distributed in TG14 SLM prepared by the s/o/w method. Stability study at 37 °C revealed that only TG14 SLM made by the w/o/w method was able to maintain the lysozyme amount both on the particle surface and released from the SLM. Elevated storage temperature induced polymorphic transition of lipids in GDS and GMS SLM, which was, however, not remarkable for the TG14 SLM.CONCLUSIONS: Lipid excipients and particle preparation methods were found to differently affect the lysozyme distribution in SLM, owning to varied storage stabilities of the lipids. The present study provides updated knowledge for rational development of lipid-based formulations for oral delivery of peptide or protein drugs.

KW - Administration, Oral

KW - Calorimetry, Differential Scanning

KW - Chemistry, Pharmaceutical

KW - Drug Delivery Systems

KW - Excipients

KW - Lipids

KW - Microscopy, Electron, Scanning

KW - Muramidase

KW - Proteins

KW - Triglycerides

KW - X-Ray Diffraction

KW - Journal Article

U2 - 10.1080/03639045.2017.1361967

DO - 10.1080/03639045.2017.1361967

M3 - Journal article

VL - 43

SP - 2032

EP - 2042

JO - Drug Development and Industrial Pharmacy

JF - Drug Development and Industrial Pharmacy

SN - 0363-9045

IS - 12

ER -

ID: 185404422