المؤلفون: Ari-Pekka Forsback, Panu Noppari, Jesse Viljanen, Jari Mikkola, Mika Jokinen, Lasse Leino, Simon Bjerregaard, Camilla Borglin, Janet Halliday

المصدر: Nanomaterials, Vol 11, Iss 6, p 1578 (2021)

مصطلحات موضوعية: controlled release, silica hydrogel, silica microparticles, silica nanoparticles, triptorelin, Chemistry, QD1-999

الوصف: Triptorelin acetate was encapsulated into silica microparticles by spray-drying a mixture of colloidal silica sol and triptorelin acetate solution. The resulting microparticles were then combined with another silica sol containing silica nanoparticles, which together formed an injectable silica-triptorelin acetate depot. The particle size and surface morphology of the silica-triptorelin acetate microparticles were characterized together with the in vitro release of triptorelin, injectability and rheology of the final injectable silica-triptorelin acetate depot. In vivo pharmacokinetics and pharmacodynamics of the silica-triptorelin acetate depot and Pamorelin® were evaluated and compared in Sprague-Dawley male rats after subcutaneous administration. Serum samples up to 91 days were collected and the plasma concentrations of triptorelin and testosterone were analyzed with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In vivo pharmacokinetics showed that injections of the silica-triptorelin acetate depot gave 5-fold lower Cmax values than the corresponding Pamorelin® injections. The depot also showed a comparable sustained triptorelin release and equivalent pharmacodynamic effect as the Pamorelin® injections. Detectable triptorelin plasma concentrations were seen with the depot after the 91-day study period and testosterone plasma concentrations remained below the human castration limit for the same period.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2079-4991/11/6/1578Test; https://doaj.org/toc/2079-4991Test

الوصول الحر: https://doaj.org/article/a168b40f965b4abd86250b44c9f32ffcTest

المؤلفون: Sofie Trier, Lars Linderoth, Simon Bjerregaard, Thomas Lars Andresen, Ulrik Lytt Rahbek

المصدر: PLoS ONE, Vol 9, Iss 10, p e109939 (2014)

مصطلحات موضوعية: Medicine, Science

الوصف: BACKGROUND: Acylation of peptide drugs with fatty acid chains has proven beneficial for prolonging systemic circulation as well as increasing enzymatic stability without disrupting biological potency. Acylation has furthermore been shown to increase interactions with the lipid membranes of mammalian cells. The extent to which such interactions hinder or benefit delivery of acylated peptide drugs across cellular barriers such as the intestinal epithelia is currently unknown. The present study investigates the effect of acylating peptide drugs from a drug delivery perspective. PURPOSE: We hypothesize that the membrane interaction is an important parameter for intestinal translocation, which may be used to optimize the acylation chain length for intestinal permeation. This work aims to characterize acylated analogues of the intestinotrophic Glucagon-like peptide-2 by systematically increasing acyl chain length, in order to elucidate its influence on membrane interaction and intestinal cell translocation in vitro. RESULTS: Peptide self-association and binding to both model lipid and cell membranes was found to increase gradually with acyl chain length, whereas translocation across Caco-2 cells depended non-linearly on chain length. Short and medium acyl chains increased translocation compared to the native peptide, but long chain acylation displayed no improvement in translocation. Co-administration of a paracellular absorption enhancer was found to increase translocation irrespective of acyl chain length, whereas a transcellular enhancer displayed increased synergy with the long chain acylation. CONCLUSIONS: These results show that membrane interactions play a prominent role during intestinal translocation of an acylated peptide. Acylation benefits permeation for shorter and medium chains due to increased membrane interactions, however, for longer chains insertion in the membrane becomes dominant and hinders translocation, i.e. the peptides get 'stuck' in the cell membrane. Applying a transcellular absorption enhancer increases the dynamics of membrane insertion and detachment by fluidizing the membrane, thus facilitating its effects primarily on membrane associated peptides.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC4190408?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/a915abac3436473e9afd7af20a5a21c4Test

المؤلفون: Tobias Siefen, Simon Bjerregaard, Camilla Borglin, Alf Lamprecht

المصدر: Journal of Controlled Release. 348:745-759

مصطلحات موضوعية: Cartilage, Articular, Biological Products, Drug Delivery Systems, Osteoarthritis, Synovial Membrane, Humans, Pharmaceutical Science, Injections, Intra-Articular

الوصف: Intraarticular (IA) injections provide the opportunity to deliver biologics directly to their site of action for a local and efficient treatment of osteoarthritis. However, the synovial joint is a challenging site of administration since the drug is rapidly eliminated across the synovial membrane and has limited distribution into cartilage, resulting in unsatisfactory therapeutic efficacy. In order to rationally develop appropriate drug delivery systems, it is essential to thoroughly understand the unique biopharmaceutical environments and kinetics in the joint to adequately simulate them in relevant experimental models. This review presents a detailed view on articular kinetics and drug-tissue interplay of IA administered drugs and summarizes how these can be translated into reasonable formulation strategies by identification of key factors through which the joint residence time can be prolonged and specific structures can be targeted. In this way, pros and cons of the delivery approaches for biologics will be evaluated and the extent to which biorelevant models are applicable to gain mechanistic insights and ameliorate formulation design is discussed.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a400a90f7c6879a150fd55be7ef28d0cTest
https://doi.org/10.1016/j.jconrel.2022.06.015Test

مستخلص: The present invention relates to a method for spray-drying of protein solutions and the spray-dried protein product. The invention also relates to pharmaceutical compositions containing such spray-dried protein, to methods of treating diabetes and hyperglycaemia using the spray-dried protein of the invention and to the use of such spray-dried protein in the treatment of diabetes and hyperglycaemia.

المؤلفون: Camilla Borglin, Janet A. Halliday, Panu Noppari, Ari-Pekka Forsback, Jesse Viljanen, Jari Mikkola, Simon Bjerregaard, Lasse Leino, Mika Jokinen

المساهمون: DelSiTech Ltd, School common, CHEM, Ferring Pharmaceuticals, Ferring Controlled Therapeutics Limited, Department of Chemical and Metallurgical Engineering, Aalto-yliopisto, Aalto University

المصدر: Nanomaterials, Vol 11, Iss 1578, p 1578 (2021)
Nanomaterials
Volume 11
Issue 6

مصطلحات موضوعية: Depot, General Chemical Engineering, Colloidal silica, Cmax, Silica hydrogel, silica nanoparticles, Article, In vivo, Silica microparticles, medicine, Controlled release, silica microparticles, General Materials Science, QD1-999, silica hydrogel, Chromatography, Chemistry, triptorelin, Triptorelin, Silica nanoparticles, Pharmacodynamics, Particle size, controlled release, medicine.drug

الوصف: Funding Information: Funding: Funding support from Ferring Pharmaceutical A/S is acknowledged. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Triptorelin acetate was encapsulated into silica microparticles by spray-drying a mixture of colloidal silica sol and triptorelin acetate solution. The resulting microparticles were then combined with another silica sol containing silica nanoparticles, which together formed an injectable silica-triptorelin acetate depot. The particle size and surface morphology of the silica-triptorelin acetate microparticles were characterized together with the in vitro release of triptorelin, injectability and rheology of the final injectable silica-triptorelin acetate depot. In vivo pharmacokinetics and pharmacodynamics of the silica-triptorelin acetate depot and Pamorelin® were evaluated and compared in Sprague-Dawley male rats after subcutaneous administration. Serum samples up to 91 days were collected and the plasma concentrations of triptorelin and testosterone were analyzed with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In vivo pharmacokinetics showed that injections of the silica-triptorelin acetate depot gave 5-fold lower Cmax values than the corresponding Pamorelin® injections. The depot also showed a comparable sustained triptorelin release and equivalent pharmacodynamic effect as the Pamorelin® injections. Detectable triptorelin plasma concentrations were seen with the depot after the 91-day study period and testosterone plasma concentrations remained below the human castration limit for the same period.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::45152f929cb2643305fde744c76bba8aTest
https://www.mdpi.com/2079-4991/11/6/1578Test

مستخلص: Pharmaceutical formulations of GLP-1 compounds and methods for preparation thereof.

المؤلفون: Marie-Louise Hartoft-Nielsen, Astrid Breitschaft, Simon Bjerregaard Jensen, Tine A. Bækdal, Camilla Hauge

مصطلحات موضوعية: Adult, Male, Glucagon-Like Peptides, Levothyroxine, Administration, Oral, Pharmacology, Toxicology, Single Center, Multiple dose, Pharmacokinetics, Humans, Hypoglycemic Agents, Medicine, Drug Interactions, Dosing, Cross-Over Studies, business.industry, Semaglutide, Healthy subjects, General Medicine, Thyroxine, stomatognathic diseases, Female, Open label, business, Tablets, medicine.drug

الوصف: Oral semaglutide comprises the glucagon-like peptide-1 analog, semaglutide, and sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). Levothyroxine has similar dosing conditions to oral semaglutide. This trial investigated if oral semaglutide co-administered with levothyroxine affects thyroxine (T4) exposure and if multiple placebo tablets co-administered with oral semaglutide affect semaglutide exposure. In this one-sequence crossover trial, 45 healthy subjects received levothyroxine (600 μg single-dose) alone, or with concomitant SNAC 300 mg or concomitant oral semaglutide 14 mg at steady-state. Subjects also received oral semaglutide 14 mg at steady-state alone or with five placebo tablets once-daily for 5 weeks. A 33% increase in total T4 exposure was observed with levothyroxine/oral semaglutide vs levothyroxine alone, but baseline-corrected maximum concentration (Cmax) was unaffected. SNAC alone did not affect total T4 exposure, whereas Cmax was slightly decreased. A 34% decrease in semaglutide exposure was observed when oral semaglutide was co-administered with placebo tablets, and Cmax also decreased. Levothyroxine pharmacokinetics were influenced by co-administration with oral semaglutide. Monitoring of thyroid parameters should be considered when treating patients with both oral semaglutide and levothyroxine. Oral semaglutide exposure was influenced by co-administration with multiple tablets, which is addressed in the dosing guidance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9c91aa49d5021653d53a1105a228823Test

مستخلص: Pharmaceutical formulations of GLP-1 compounds and methods for preparation thereof.

مستخلص: Pharmaceutical formulations of GLP-1 compounds and methods for preparation thereof.

مستخلص: Pharmaceutical formulations of GLP-1 compounds and methods for preparation thereof.