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Engineered Nano-carrier systems for the oral targeted delivery of follicle stimulating Hormone: Development, characterization, and, assessment of in vitro and in vivo performance and targetability
[Display omitted] Follicle stimulating hormone (FSH) is widely used for the treatment of female infertility, where the level of FSH is suboptimal due to which arrest in follicular development and anovulation takes place. Currently, only parenteral formulations are available for FSH in the market. Du...
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| Published in: | International journal of pharmaceutics 2023-04, Vol.637, p.122868-122868, Article 122868 |
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| creator | Raut, Sushil Yadaorao Fu, Kengyen Taichun, Huang Gahane, Avinash Chaudhari, Dasharath Kushwah, Varun Suresh Managuli, Renuka Hegde, Aswathi R. Jain, Sanyog Kalthur, Guruprasad Bandu Joshi, Manjunath Chang, Hsin-I. Dai, Niann-Tzyy Mutalik, Srinivas |
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Follicle stimulating hormone (FSH) is widely used for the treatment of female infertility, where the level of FSH is suboptimal due to which arrest in follicular development and anovulation takes place. Currently, only parenteral formulations are available for FSH in the market. Due to the drawbacks of parenteral administration and the high market shares of FSH, there is a need for easily accessible oral formulation. Therefore, enteric coated capsules filled with FSH loaded nanostructured lipid carriers (NLCs) or liposomes were prepared. Preliminary studies such as circular dichroism, SDS-PAGE, FTIR and ELISA were conducted to analyze FSH. Prepared formulations were optimized with respect to the size, polydispersity index, zeta potential, and entrapment efficiency using the design of experiments. Optimized formulations were subjected to particle counts and distribution analysis, TEM analysis, in vitro drug release, dissolution of enteric coated capsules, cell line studies, everted sac rat's intestinal uptake study, pharmacokinetics, pharmacodynamics, and stability studies. In the case of liposomes, RGD conjugation was done by carbodiimide chemistry and conjugation was confirmed by FTIR, 1HNMR and Raman spectroscopy. The prepared formulations were discrete and spherical. The release of FSH from enteric coated capsules was slow and sustained. The increased permeability of nano-formulations was observed in Caco-2 monoculture as well as in Caco-2 and Raji-B co-culture models. NLCs and liposomes showed an improvement in oral bioavailability and efficacy of FSH in rats. This may be due to mainly chylomicron-assisted lymphatic uptake of NLCs; whereas, in the case of liposomes, RGD-based targeting of β1 integrins of M cells on Peyer's patches may be the main reason for the better effect by FSH. FSH was found to be stable chemically and conformationally. Overall, the study reveals the successful development and evaluation of FSH loaded NLCs and liposomes. |
| doi_str_mv | 10.1016/j.ijpharm.2023.122868 |
| format | article |
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Follicle stimulating hormone (FSH) is widely used for the treatment of female infertility, where the level of FSH is suboptimal due to which arrest in follicular development and anovulation takes place. Currently, only parenteral formulations are available for FSH in the market. Due to the drawbacks of parenteral administration and the high market shares of FSH, there is a need for easily accessible oral formulation. Therefore, enteric coated capsules filled with FSH loaded nanostructured lipid carriers (NLCs) or liposomes were prepared. Preliminary studies such as circular dichroism, SDS-PAGE, FTIR and ELISA were conducted to analyze FSH. Prepared formulations were optimized with respect to the size, polydispersity index, zeta potential, and entrapment efficiency using the design of experiments. Optimized formulations were subjected to particle counts and distribution analysis, TEM analysis, in vitro drug release, dissolution of enteric coated capsules, cell line studies, everted sac rat's intestinal uptake study, pharmacokinetics, pharmacodynamics, and stability studies. In the case of liposomes, RGD conjugation was done by carbodiimide chemistry and conjugation was confirmed by FTIR, 1HNMR and Raman spectroscopy. The prepared formulations were discrete and spherical. The release of FSH from enteric coated capsules was slow and sustained. The increased permeability of nano-formulations was observed in Caco-2 monoculture as well as in Caco-2 and Raji-B co-culture models. NLCs and liposomes showed an improvement in oral bioavailability and efficacy of FSH in rats. This may be due to mainly chylomicron-assisted lymphatic uptake of NLCs; whereas, in the case of liposomes, RGD-based targeting of β1 integrins of M cells on Peyer's patches may be the main reason for the better effect by FSH. FSH was found to be stable chemically and conformationally. Overall, the study reveals the successful development and evaluation of FSH loaded NLCs and liposomes.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2023.122868</identifier><identifier>PMID: 36958606</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Administration, Oral ; Animals ; Caco-2 Cells ; Capsules ; Chylomicron ; Drug Carriers - chemistry ; Female ; Follicle Stimulating Hormone ; Humans ; Liposomes ; Nanostructured lipid carriers ; Nanostructures - chemistry ; Oligopeptides ; Particle Size ; Peyer’s patches ; Rats ; RGD peptide</subject><ispartof>International journal of pharmaceutics, 2023-04, Vol.637, p.122868-122868, Article 122868</ispartof><rights>2023 Elsevier B.V.</rights><rights>Copyright © 2023 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-ccbc91373021b94d2025d8fb080083f00914a7015e76091bd81281278eed65693</citedby><cites>FETCH-LOGICAL-c365t-ccbc91373021b94d2025d8fb080083f00914a7015e76091bd81281278eed65693</cites><orcidid>0000-0002-0636-6674 ; 0000-0002-0688-9563 ; 0000-0002-0642-1928</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36958606$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Raut, Sushil Yadaorao</creatorcontrib><creatorcontrib>Fu, Kengyen</creatorcontrib><creatorcontrib>Taichun, Huang</creatorcontrib><creatorcontrib>Gahane, Avinash</creatorcontrib><creatorcontrib>Chaudhari, Dasharath</creatorcontrib><creatorcontrib>Kushwah, Varun</creatorcontrib><creatorcontrib>Suresh Managuli, Renuka</creatorcontrib><creatorcontrib>Hegde, Aswathi R.</creatorcontrib><creatorcontrib>Jain, Sanyog</creatorcontrib><creatorcontrib>Kalthur, Guruprasad</creatorcontrib><creatorcontrib>Bandu Joshi, Manjunath</creatorcontrib><creatorcontrib>Chang, Hsin-I.</creatorcontrib><creatorcontrib>Dai, Niann-Tzyy</creatorcontrib><creatorcontrib>Mutalik, Srinivas</creatorcontrib><title>Engineered Nano-carrier systems for the oral targeted delivery of follicle stimulating Hormone: Development, characterization, and, assessment of in vitro and in vivo performance and targetability</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
Follicle stimulating hormone (FSH) is widely used for the treatment of female infertility, where the level of FSH is suboptimal due to which arrest in follicular development and anovulation takes place. Currently, only parenteral formulations are available for FSH in the market. Due to the drawbacks of parenteral administration and the high market shares of FSH, there is a need for easily accessible oral formulation. Therefore, enteric coated capsules filled with FSH loaded nanostructured lipid carriers (NLCs) or liposomes were prepared. Preliminary studies such as circular dichroism, SDS-PAGE, FTIR and ELISA were conducted to analyze FSH. Prepared formulations were optimized with respect to the size, polydispersity index, zeta potential, and entrapment efficiency using the design of experiments. Optimized formulations were subjected to particle counts and distribution analysis, TEM analysis, in vitro drug release, dissolution of enteric coated capsules, cell line studies, everted sac rat's intestinal uptake study, pharmacokinetics, pharmacodynamics, and stability studies. In the case of liposomes, RGD conjugation was done by carbodiimide chemistry and conjugation was confirmed by FTIR, 1HNMR and Raman spectroscopy. The prepared formulations were discrete and spherical. The release of FSH from enteric coated capsules was slow and sustained. The increased permeability of nano-formulations was observed in Caco-2 monoculture as well as in Caco-2 and Raji-B co-culture models. NLCs and liposomes showed an improvement in oral bioavailability and efficacy of FSH in rats. This may be due to mainly chylomicron-assisted lymphatic uptake of NLCs; whereas, in the case of liposomes, RGD-based targeting of β1 integrins of M cells on Peyer's patches may be the main reason for the better effect by FSH. FSH was found to be stable chemically and conformationally. Overall, the study reveals the successful development and evaluation of FSH loaded NLCs and liposomes.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Caco-2 Cells</subject><subject>Capsules</subject><subject>Chylomicron</subject><subject>Drug Carriers - chemistry</subject><subject>Female</subject><subject>Follicle Stimulating Hormone</subject><subject>Humans</subject><subject>Liposomes</subject><subject>Nanostructured lipid carriers</subject><subject>Nanostructures - chemistry</subject><subject>Oligopeptides</subject><subject>Particle Size</subject><subject>Peyer’s patches</subject><subject>Rats</subject><subject>RGD peptide</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNqFkctu1DAUhi0EosPAI4C8ZNEMdjxxHDaoKqVFqmADa8uxT6YeOfZgeyINz8eD4TRDt0i-n-9cfH6E3lKyoYTyD_uN3R8eVBw3NanZhta14OIZWlHRsoptW_4crQhrRdXQll2gVyntCSG8puwlumC8awQnfIX-3Pid9QARDP6mfKi0itFCxOmUMowJDyHi_AA4ROVwVnEHuaAGnJ0gnnAYCuGc1Q5wynY8OpWt3-G7EMfg4SP-DBO4cBjB50usS8FKZ4j2d8GCv8TKm7KkBCnNyBzPejzZHMNsWy5TwAeIpZJReQ2P70slqrfO5tNr9GJQLsGb875GP7_c_Li-q-6_3369vrqvNONNrrTudUdZy0hN-25rSuMaI4aeCEIEGwjp6Fa1hDbQ8nLujaB1Ga0AMLzhHVuj90vcQwy_jpCyHG3S4JzyEI5J1u1j-LrMNWoWVMeQUoRBHqIdVTxJSuQsoNzLs4ByFlAuAha_d-cUx34E8-T1T7ECfFoAKB-dilIyaQulLcZG0FmaYP-T4i8vxbMO</recordid><startdate>20230425</startdate><enddate>20230425</enddate><creator>Raut, Sushil Yadaorao</creator><creator>Fu, Kengyen</creator><creator>Taichun, Huang</creator><creator>Gahane, Avinash</creator><creator>Chaudhari, Dasharath</creator><creator>Kushwah, Varun</creator><creator>Suresh Managuli, Renuka</creator><creator>Hegde, Aswathi R.</creator><creator>Jain, Sanyog</creator><creator>Kalthur, Guruprasad</creator><creator>Bandu Joshi, Manjunath</creator><creator>Chang, Hsin-I.</creator><creator>Dai, Niann-Tzyy</creator><creator>Mutalik, Srinivas</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0636-6674</orcidid><orcidid>https://orcid.org/0000-0002-0688-9563</orcidid><orcidid>https://orcid.org/0000-0002-0642-1928</orcidid></search><sort><creationdate>20230425</creationdate><title>Engineered Nano-carrier systems for the oral targeted delivery of follicle stimulating Hormone: Development, characterization, and, assessment of in vitro and in vivo performance and targetability</title><author>Raut, Sushil Yadaorao ; 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Follicle stimulating hormone (FSH) is widely used for the treatment of female infertility, where the level of FSH is suboptimal due to which arrest in follicular development and anovulation takes place. Currently, only parenteral formulations are available for FSH in the market. Due to the drawbacks of parenteral administration and the high market shares of FSH, there is a need for easily accessible oral formulation. Therefore, enteric coated capsules filled with FSH loaded nanostructured lipid carriers (NLCs) or liposomes were prepared. Preliminary studies such as circular dichroism, SDS-PAGE, FTIR and ELISA were conducted to analyze FSH. Prepared formulations were optimized with respect to the size, polydispersity index, zeta potential, and entrapment efficiency using the design of experiments. Optimized formulations were subjected to particle counts and distribution analysis, TEM analysis, in vitro drug release, dissolution of enteric coated capsules, cell line studies, everted sac rat's intestinal uptake study, pharmacokinetics, pharmacodynamics, and stability studies. In the case of liposomes, RGD conjugation was done by carbodiimide chemistry and conjugation was confirmed by FTIR, 1HNMR and Raman spectroscopy. The prepared formulations were discrete and spherical. The release of FSH from enteric coated capsules was slow and sustained. The increased permeability of nano-formulations was observed in Caco-2 monoculture as well as in Caco-2 and Raji-B co-culture models. NLCs and liposomes showed an improvement in oral bioavailability and efficacy of FSH in rats. This may be due to mainly chylomicron-assisted lymphatic uptake of NLCs; whereas, in the case of liposomes, RGD-based targeting of β1 integrins of M cells on Peyer's patches may be the main reason for the better effect by FSH. FSH was found to be stable chemically and conformationally. Overall, the study reveals the successful development and evaluation of FSH loaded NLCs and liposomes.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>36958606</pmid><doi>10.1016/j.ijpharm.2023.122868</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0636-6674</orcidid><orcidid>https://orcid.org/0000-0002-0688-9563</orcidid><orcidid>https://orcid.org/0000-0002-0642-1928</orcidid></addata></record> |
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| ispartof | International journal of pharmaceutics, 2023-04, Vol.637, p.122868-122868, Article 122868 |
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| source | ScienceDirect Freedom Collection 2022-2024 |
| subjects | Administration, Oral Animals Caco-2 Cells Capsules Chylomicron Drug Carriers - chemistry Female Follicle Stimulating Hormone Humans Liposomes Nanostructured lipid carriers Nanostructures - chemistry Oligopeptides Particle Size Peyer’s patches Rats RGD peptide |
| title | Engineered Nano-carrier systems for the oral targeted delivery of follicle stimulating Hormone: Development, characterization, and, assessment of in vitro and in vivo performance and targetability |
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