| Events
2nd AAU International Conference on Pharmacy and Biomedical Sciences
January 22-23, 2025
Abu Dhabi, UAE
Invited lecture:
Lipid-based Nanocarriers for Oral Peptide Drug Delivery: Hype or Hope?
Prof. Dr. A. Bernkop-Schnürch
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Discovery & Development Europe 2025: Formulation & Drug Delivery Congress
July 1-2, 2025
Basel, Switzerland
Invited lecture:
Oral Delivery Of Peptide And Protein Drugs – Oral Delivery of GLP-1 Analogues
Prof. Dr. A. Bernkop-Schnürch
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8th European Cyclodextrin Conference
September 9-12, 2025
Milano, Italy
Invited lecture:
Thiolated Cyclodextrins in Drug Delivery
Prof. Dr. A. Bernkop-Schnürch
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Proof of Efficacy
Mucoadhesion and controlled drug release in human volunteers
Ocular Inserts
The mucoadhesive properties
and the potential to provide a controlled drug release out of thiolated
polymers were recently demonstrated in human volunteers. Due to the
mucoadhesive properties of the delivery system lasting for at least 8 hours
and a controlled release of the model drug sodium fluorescein, a constant
level of the test compound could be maintained in the tear fluid/cornea for
numerous hours (blue graph). In contrast, using the same polymeric carrier
matrix without thiol groups, the effect was gone within an hour (grey graph) [Hornof, M.D., Weyenberg, W., Ludwig, A., and Bernkop–Schnürch, A. (2003). A mucoadhesive ocular insert: Development and in vivo evaluation in humans. J. Control. Rel,. 89, 419].
Oral
bioavailability of hydrophilic macromolecular drugs
Low Molecular Weight
Heparin (LMWH)
The oral bioavailability of
LMWH is negligible, as this hydrophilic macro-molecule can only hardly pass
the gastrointestinal absorption membrane. Even by the use of
well-established drug
delivery systems with permeation enhancing properties the uptake of LMWH is
poor as recently shown in rats (grey graph). Utilizing the
thiomer-technology, however, the plasma LMWH level can be strongly improved (blue graph) reaching an absolute oral bioavailability of at least 20%. For
more details please read Kast et al. [Kast, C.E., Guggi, D., Langoth, N. and Bernkop-Schnürch, A. (2003) Development and in vivo evaluation of an oral delivery system for low molecular weight heparin based on thiolated polycarbophil. Pharm. Res., 20, 931].
Oral
bioavailability of efflux pump substrates
Rhodamine 123
Rhodamine 123 is a
well-known substrate of P-glycoprotein (P-gp). Due to the activity of P-gp in the GI-tract its oral bioavailability is
comparatively very poor (grey graph). Studies in rats, however, demonstrated
that by the co-administration of thiolated polymers its oral uptake can even
be more than 1.6-fold improve (blue graph) [Föger F., Schmitz Th., Kafedjiiski K. and Bernkop-Schnürch A. (2006) In vivo evaluation of an oral delivery system for P-gp substrates based on thiolated chitosan, Biomaterials, 27, 4250].
Pharmacological efficacy of orally given peptide drugs
Insulin
Because of enzymatic
degradation in the gastrointestinal tract and poor absorption form the
intestine orally administered
insulin has no effect on the blood glucose level. Accordingly, the effect of
orally administered insulin on the glucose level of diabetic mice is also of
no significance (grey graph). In contrast, a significant reduction of the
glucose level is achieved by incorporating the peptide in a thiolated
polymer (blue graph). Utilizing the thiomer-technology a pharmacological efficacy of
the oral formulation versus s.c. injection of 7% was reached. For more
details please read Caliceti et al. [Calceti P., Salmaso S., Walker G., and Bernkop-Schnürch A. (2004) Development and in vivo evaluation of an oral insulin-PEG delivery system. Eur. J. Pharm. Sci., 22, 315].
Antide
The therapeutic peptide
antide is an antagonist of gonadotropin hormone-releasing hormone, which has
been studied for the treatment of prostate and breast cancer, endometriosis
and uterine fibrosis. When being orally administered with state-of-the-art
delivery systems (grey graph), the peptide drug does not at all reach the
systemic circulation. Utilizing the thiomer-technology, however, an absolute
and relative (vs subcutaneous) bioavailability of 1% and 3% was achieved in
pigs, respectively (blue graph) [Bernkop-Schnürch A., Pinter Y., Guggi D., Kahlbacher H., Schoffmann G., Schuh M., Schmerold I., Del Curto M.D., D'Antonio M., Esposito P., and Huck C. (2005) The use of thiolated polymers as carrier matrix in oral peptide delivery--proof of concept. J. Control. Release., 106, 26].
In another study oral administration of antide in solution led to a bioavailability of 0.03% in rats. In contrast, with antide incorporated in matrix tablets comprising a preactivated thiolated polymer a bioavailability of 10.9% could be reached resulting in a 421-fold increased area under the plasma concentration time curve compared to the antide solution [Dünnhaupt, S., Barthelmes, J., Iqbal, J., Perera, G., Thurner, C.C., Friedl, H. and Bernkop-Schnürch, A. (2012) In vivo evaluation of an oral drug delivery system for peptides based on S-protected thiolated chitosan. J. Control. Release., 160, 477].
Salmon Calcitonin
Biofeedback studies in rats
showed, that the calcium level cannot be lowered by the oral administration
of salmon calcitonin using well-established delivery systems (grey graph).
In contrast, a pharmacological efficacy of 1.3% was achieved in rats by
utilizing a thiolated polymer as drug carrier matrix (blue graph). For more details please read Guggi et al. [Guggi D., Krauland A.H., and Bernkop-Schnürch A. (2003) Systemic peptide delivery via the stomach: in vivo evaluation of an oral dosage form for salmon calcitonin. J. Control. Release, 92, 125].
Bioavailability of nasally administered peptide drugs
Human
Growth Hormon (hGH)
Because of its comparatively
high molecular mass being in the range of 22 kDa, hGH is not absorbed from
the nasal cavity in significant quantities (grey graph). Utilizing a thiomer
as auxiliary agent, however, an absolute nasal bioavailability of 2.6% was
reached (blue graph). More recent studies showed that by
making use of another thiomer formulation an even higher nasal
bioavailability for hGH in the range of 8% can be gained [Leitner V.M., Guggi D. and Bernkop-Schnürch A. (2004) Thiomers in noninvasive polypeptide delivery: in vitro and in vivo characterization of a polycarbophil-cysteine /glutathione gel formulation for human growth hormone. J. Pharm. Sci,. 93, 1682; Leitner V.M., Guggi D., Krauland A.H. and Bernkop-Schnürch A. (2004) Nasal delivery of human growth hormone: in vitro and in vivo evaluation of a thiomer/glutathione microparti-culate delivery system. J. Control. Release., 100, 87].
Bioavailability of buccally administered peptide drugs
Pituitary
Adenylate Cyclase-Activating Polypeptide (PACAP)
PACAP is a therapeutic
peptide useful for the treatment of type 2 diabetes. Utilizing unmodified
chitosan or other state-of-the-art auxiliary agents the peptide is not at
all uptaken from the buccal mucosa (grey graph). In contrast, when being
incorporated in thiolated chitosan and applied in form of buccal patches an
absolute bioavailability of at least 1% was achieved in pigs (blue graph) [Langoth, N., Kahlbacher, H., Schöffmann, G., Schmerold, I., Schuh, M., Franz, S., Kurka, P. and Bernkop-Schnürch, a. (2006) Thiolated chitosans: design and in vivo evaluation of a mucoadhesive buccal peptide drug delivery system, Pharm. Res., 23, 573].
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News
Thiomatrix joined the EU-project TENTACLE (101191747) focusing on the use of thiomers for in situ bioprinting.
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