Oral absorption studies of lipid-polylysine conjugates of thyrotropin releasing hormone (TRH1) and luteinizing hormone releasing hormone (LHRH1) |
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| Affiliation: | 1. The School of Pharmacy, University of London, 29–39 Brunswick Square, London, WCIN IAX, UK;2. Uppsala University, Biomedicum, Box 580, S-751 23, Uppsala, Sweden;1. Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;2. Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA;1. Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland;2. Department of Ophthalmology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland;1. Servei de Dermatologia, Hospital Universitari GermansTrias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, España;2. Servicio de Dermatología, Hospital de Jaén, Jaén, España;3. Servicio de Dermatología, Hospital Universitario La Paz, Madrid, España;4. Servicio de Dermatología, Hospital General de Valencia, Valencia, España;5. Servicio de Dermatología, Hospital Universitari Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, Barcelona, España;6. Servicio de Dermatología, Hospital Universitario de Navarra, Pamplona, España;1. Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences – Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, United States;2. Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, United States;1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY;2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY;3. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;1. Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, 240 E. Huron St, Chicago, IL 60611, USA;2. Department of Otolaryngology, Northwestern University Feinberg School of Medicine, 675 N St. Clair St Suite 15-200, Chicago, IL 60611, USA |
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| Abstract: | The lipoamino acids and their oligomers provide an excellent means of enhancing peptide lipophilicity and also helping to increase the stability of the peptide and protect it from enzymatic degradation. Thyrotropin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) were extended on the N-terminal with one and two lipoamino acids and labelled with the 3H-acetyl group. TRH and LHRH conjugates were also prepared where the compounds were extended with two lipoamino acids, a polylysine unit and the N-terminal labelled with the 3H-acetyl group. The higher lipophilicity resulted in a higher Caco-2 cell association and also a higher rate of oral uptake. The addition of the polylysine system increased the water solubility, as well as the oral uptake of the conjugates. The conjugates developed have been absorbed and detected after oral administration and appear to be stable for a considerable time in vivo. |
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