TY - JOUR
T1 - Engineered Nano-carrier systems for the oral targeted delivery of follicle stimulating Hormone
T2 - Development, characterization, and, assessment of in vitro and in vivo performance and targetability
AU - Raut, Sushil Yadaorao
AU - Fu, Kengyen
AU - Taichun, Huang
AU - Gahane, Avinash
AU - Chaudhari, Dasharath
AU - Kushwah, Varun
AU - Suresh Managuli, Renuka
AU - Hegde, Aswathi R.
AU - Jain, Sanyog
AU - Kalthur, Guruprasad
AU - Bandu Joshi, Manjunath
AU - Chang, Hsin I.
AU - Dai, Niann Tzyy
AU - Mutalik, Srinivas
N1 - Funding Information:
The authors are thankful to Nano mission, Department of Science and Technology, Government of India, New Delhi for providing financial support for the research project (DST/NM/NT/2018/133). The authors express their gratitude to Manipal Academy of Higher Education, Manipal for providing Dr. TMA Pai Doctoral Fellowship. The authors are grateful to i) Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, ii) National Defense Medical Center, Taipei, Taiwan, iii) Indian Institute of Technology Kanpur, India, iv) National Institute of Pharmaceutical Education and Research, Punjab, India, and v) Kasturba Medical College Manipal, Manipal, and vi) National Chiayi University, Chiayi City, Taiwan for providing necessary facilities and support.
Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/4/25
Y1 - 2023/4/25
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ijpharm.2023.122868
DO - 10.1016/j.ijpharm.2023.122868
M3 - Article
C2 - 36958606
AN - SCOPUS:85151471077
SN - 0378-5173
VL - 637
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 122868
ER -