Oral Delivery of Teriparatide Using a Nanoemulsion System: Design, in Vitro and in Vivo Evaluation

Bashar M. Altaani; Ammar M. Almaaytah; Suha Dadou; Khouloud Alkhamis; Mousa H. Daradka; Wael Hananeh

doi:10.1007/s11095-020-02793-0

Oral Delivery of Teriparatide Using a Nanoemulsion System: Design, in Vitro and in Vivo Evaluation

Bashar M. Altaani^*, Ammar M. Almaaytah, Suha Dadou, Khouloud Alkhamis, Mousa H. Daradka, Wael Hananeh

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Purpose: Investigate the possibility of delivering teriparatide orally using nanoemulsion.

Method: Teriparatide was allowed to interact with chitosan in the presence of HPβCD. The formed polyelectrolyte complex (PEC) was characterized by DSC, FTIR, DLS and for entrapment efficiency. PEC was the incorporated in an oil phase consisting of Oleic Acid, Labrasol and Plurol Oleique to form a nanoemulsion. This preparation was characterized for refractive index, viscosity, pH, conductivity, particle size, and morphology. Bioavailability of the preparation was evaluated using rabbits against SC injection. The efficacy of the formula was tested using ovariectomized rats (an osteoporosis animal model) and mechanical and histological tests were conducted on their bones. The stability of the preparation was evaluated by storing samples at 4^o C, 25^o C and 40^o C for three months.

Results: PEC testing demonstrate a complex formation with particle size of 208 nm, zeta potential of +17 mV and entrapment efficiency of 49%. For the nanoemulsion, the results demonstrate the formation of a nano-sized dispersed system (108 nm) with a drug loading of 98% and a percent protection of 90% and 71% in SGF and SIF respectively. Bioavailability results showed a sustained release profile was achieved following the oral formulation administration. Efficacy studies showed improvement in the strength, thickness and connectivity of bones. Short-term stability study demonstrated that the nanoemulsion is mostly stable at 4^o C.

Conclusion: These findings demonstrate the ability of delivering Teriparatide orally using oleic acid based dispersion in combination with chitosan PEC.

Original language	English
Article number	80
Journal	Pharmaceutical Research
Volume	37
Issue number	4
DOIs	https://doi.org/10.1007/s11095-020-02793-0
Publication status	Published - 06 Apr 2020
Externally published	Yes

Bibliographical note

Funding Information:
The author wish to thanks Deanship of Research for providing the funding for this work (169/2012). The authors wish to thank Dr. Faisal Athamneh from Faculty of Chemistry, Jordan University of Science and Technology for his help. The authors are also thankful for Dr. Munther Al-Shami for his help in the pharmacokinetic statistics. The authors further wish to thank Dr. Adnan Badwan from the Jordanian Pharmaceutical Manufacturing Company (JPM)?and Dr Adnan Dakkuri from Feris State University for providing valuable suggestions and guidance for this research.

Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

Nanoemulsion
Oral delivery of peptides
Osteoporosis
Polyelectrolyte complex
Teriparatide

ASJC Scopus subject areas

Biotechnology
Molecular Medicine
Pharmacology
Pharmaceutical Science
Organic Chemistry
Pharmacology (medical)

Access to Document

10.1007/s11095-020-02793-0Licence: Unspecified

Cite this

@article{b44dbc054ccb43ebb83a3c21c5ce7ce1,

title = "Oral Delivery of Teriparatide Using a Nanoemulsion System: Design, in Vitro and in Vivo Evaluation",

abstract = "Purpose: Investigate the possibility of delivering teriparatide orally using nanoemulsion. Method: Teriparatide was allowed to interact with chitosan in the presence of HPβCD. The formed polyelectrolyte complex (PEC) was characterized by DSC, FTIR, DLS and for entrapment efficiency. PEC was the incorporated in an oil phase consisting of Oleic Acid, Labrasol and Plurol Oleique to form a nanoemulsion. This preparation was characterized for refractive index, viscosity, pH, conductivity, particle size, and morphology. Bioavailability of the preparation was evaluated using rabbits against SC injection. The efficacy of the formula was tested using ovariectomized rats (an osteoporosis animal model) and mechanical and histological tests were conducted on their bones. The stability of the preparation was evaluated by storing samples at 4o C, 25o C and 40o C for three months. Results: PEC testing demonstrate a complex formation with particle size of 208 nm, zeta potential of +17 mV and entrapment efficiency of 49%. For the nanoemulsion, the results demonstrate the formation of a nano-sized dispersed system (108 nm) with a drug loading of 98% and a percent protection of 90% and 71% in SGF and SIF respectively. Bioavailability results showed a sustained release profile was achieved following the oral formulation administration. Efficacy studies showed improvement in the strength, thickness and connectivity of bones. Short-term stability study demonstrated that the nanoemulsion is mostly stable at 4o C. Conclusion: These findings demonstrate the ability of delivering Teriparatide orally using oleic acid based dispersion in combination with chitosan PEC.",

keywords = "Nanoemulsion, Oral delivery of peptides, Osteoporosis, Polyelectrolyte complex, Teriparatide",

author = "Altaani, {Bashar M.} and Almaaytah, {Ammar M.} and Suha Dadou and Khouloud Alkhamis and Daradka, {Mousa H.} and Wael Hananeh",

note = "Funding Information: The author wish to thanks Deanship of Research for providing the funding for this work (169/2012). The authors wish to thank Dr. Faisal Athamneh from Faculty of Chemistry, Jordan University of Science and Technology for his help. The authors are also thankful for Dr. Munther Al-Shami for his help in the pharmacokinetic statistics. The authors further wish to thank Dr. Adnan Badwan from the Jordanian Pharmaceutical Manufacturing Company (JPM)?and Dr Adnan Dakkuri from Feris State University for providing valuable suggestions and guidance for this research. Publisher Copyright: {\textcopyright} 2020, Springer Science+Business Media, LLC, part of Springer Nature. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = apr,

day = "6",

doi = "10.1007/s11095-020-02793-0",

language = "English",

volume = "37",

journal = "Pharmaceutical Research",

issn = "0724-8741",

publisher = "Springer New York",

number = "4",

}

TY - JOUR

T1 - Oral Delivery of Teriparatide Using a Nanoemulsion System: Design, in Vitro and in Vivo Evaluation

AU - Altaani, Bashar M.

AU - Almaaytah, Ammar M.

AU - Dadou, Suha

AU - Alkhamis, Khouloud

AU - Daradka, Mousa H.

AU - Hananeh, Wael

N1 - Funding Information: The author wish to thanks Deanship of Research for providing the funding for this work (169/2012). The authors wish to thank Dr. Faisal Athamneh from Faculty of Chemistry, Jordan University of Science and Technology for his help. The authors are also thankful for Dr. Munther Al-Shami for his help in the pharmacokinetic statistics. The authors further wish to thank Dr. Adnan Badwan from the Jordanian Pharmaceutical Manufacturing Company (JPM)?and Dr Adnan Dakkuri from Feris State University for providing valuable suggestions and guidance for this research. Publisher Copyright: © 2020, Springer Science+Business Media, LLC, part of Springer Nature. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/4/6

Y1 - 2020/4/6

N2 - Purpose: Investigate the possibility of delivering teriparatide orally using nanoemulsion. Method: Teriparatide was allowed to interact with chitosan in the presence of HPβCD. The formed polyelectrolyte complex (PEC) was characterized by DSC, FTIR, DLS and for entrapment efficiency. PEC was the incorporated in an oil phase consisting of Oleic Acid, Labrasol and Plurol Oleique to form a nanoemulsion. This preparation was characterized for refractive index, viscosity, pH, conductivity, particle size, and morphology. Bioavailability of the preparation was evaluated using rabbits against SC injection. The efficacy of the formula was tested using ovariectomized rats (an osteoporosis animal model) and mechanical and histological tests were conducted on their bones. The stability of the preparation was evaluated by storing samples at 4o C, 25o C and 40o C for three months. Results: PEC testing demonstrate a complex formation with particle size of 208 nm, zeta potential of +17 mV and entrapment efficiency of 49%. For the nanoemulsion, the results demonstrate the formation of a nano-sized dispersed system (108 nm) with a drug loading of 98% and a percent protection of 90% and 71% in SGF and SIF respectively. Bioavailability results showed a sustained release profile was achieved following the oral formulation administration. Efficacy studies showed improvement in the strength, thickness and connectivity of bones. Short-term stability study demonstrated that the nanoemulsion is mostly stable at 4o C. Conclusion: These findings demonstrate the ability of delivering Teriparatide orally using oleic acid based dispersion in combination with chitosan PEC.

AB - Purpose: Investigate the possibility of delivering teriparatide orally using nanoemulsion. Method: Teriparatide was allowed to interact with chitosan in the presence of HPβCD. The formed polyelectrolyte complex (PEC) was characterized by DSC, FTIR, DLS and for entrapment efficiency. PEC was the incorporated in an oil phase consisting of Oleic Acid, Labrasol and Plurol Oleique to form a nanoemulsion. This preparation was characterized for refractive index, viscosity, pH, conductivity, particle size, and morphology. Bioavailability of the preparation was evaluated using rabbits against SC injection. The efficacy of the formula was tested using ovariectomized rats (an osteoporosis animal model) and mechanical and histological tests were conducted on their bones. The stability of the preparation was evaluated by storing samples at 4o C, 25o C and 40o C for three months. Results: PEC testing demonstrate a complex formation with particle size of 208 nm, zeta potential of +17 mV and entrapment efficiency of 49%. For the nanoemulsion, the results demonstrate the formation of a nano-sized dispersed system (108 nm) with a drug loading of 98% and a percent protection of 90% and 71% in SGF and SIF respectively. Bioavailability results showed a sustained release profile was achieved following the oral formulation administration. Efficacy studies showed improvement in the strength, thickness and connectivity of bones. Short-term stability study demonstrated that the nanoemulsion is mostly stable at 4o C. Conclusion: These findings demonstrate the ability of delivering Teriparatide orally using oleic acid based dispersion in combination with chitosan PEC.

KW - Nanoemulsion

KW - Oral delivery of peptides

KW - Osteoporosis

KW - Polyelectrolyte complex

KW - Teriparatide

U2 - 10.1007/s11095-020-02793-0

DO - 10.1007/s11095-020-02793-0

M3 - Article

C2 - 32253527

AN - SCOPUS:85083071303

SN - 0724-8741

VL - 37

JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 4

M1 - 80

ER -

Oral Delivery of Teriparatide Using a Nanoemulsion System: Design, in Vitro and in Vivo Evaluation

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Fingerprint

Cite this