bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.01.19.700335

Layer-by-Layer Polymeric Films: A Novel Approach to Buccal GLP-1 Delivery

Pantazoglou, E.·Bahuon, F.·Andresen, A. K.·Tollemeto, M.·Zhang, Z.·Tzitzigiannis, I.·Ezazi, N. Z.·Sacramento, M. M. A.·Mano, J. F.·Untracht, G. R.·Andersen, P. E.·van de Weert, M.·Berthelsen, R.·Buckley, S. T.·Hosta-Rigau, L.·Jacobsen, J.·Hagner Nielsen, L.
View original source ↗Export metadata ↓

Abstract

Buccal delivery offers a promising alternative to oral drug administration by enabling direct systemic absorption and avoiding first-pass metabolism. Multilayer polymeric films represent a promising strategy for the sequential delivery of drug and absorption enhancer in the oral cavity. Here, dual- and triple-layer films were fabricated via slot-die coating, incorporating a GLP-1 receptor agonist (GLP-1-RA) and the penetration enhancer sodium glycodeoxycholate (GDC). These were co-loaded in dual-layer films or compartmentalized in triple-layer films. Scanning electron microscopy and optical coherence tomography confirmed well-defined, distinct layers with thicknesses suitable for buccal administration (339 {+/-} 10.24 {micro}m and 487 {+/-} 36.5 {micro}m for dual- and triple-layer films, respectively). Both designs exhibited good mucoadhesion and mucosal compatibility, and preserved the secondary structure of GLP-1-RA. In vitro release studies showed rapid diffusion of GDC and GLP-1-RA from dual-layer films, whereas triple-layer films enabled sustained, sequential release of GDC and GLP-1-RA. Ex vivo porcine buccal mucosa studies showed higher GLP-1-RA and GDC flux from triple-layer films compared to dual-layer films. The films also did not compromise epithelial integrity, in contrast to the direct application of GLP-1-RA and GDC, which caused significant epithelial disruption. These results demonstrate that multilayer film architecture and spatial layering can be harnessed to control release kinetics, maximize peptide penetration, and minimize tissue stress, offering a versatile platform for safe and effective peptide delivery. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/700335v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@76858borg.highwire.dtl.DTLVardef@1397e74org.highwire.dtl.DTLVardef@19d1841org.highwire.dtl.DTLVardef@a369c5_HPS_FORMAT_FIGEXP M_FIG C_FIG

Explore related subjects

bioengineeringPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Pantazoglou, E., Bahuon, F., Andresen, A. K., Tollemeto, M., Zhang, Z., Tzitzigiannis, I., Ezazi, N. Z., Sacramento, M. M. A., Mano, J. F., Untracht, G. R., Andersen, P. E., van de Weert, M., Berthelsen, R., Buckley, S. T., Hosta-Rigau, L., Jacobsen, J., Hagner Nielsen, L.. 2026-01-22. Layer-by-Layer Polymeric Films: A Novel Approach to Buccal GLP-1 Delivery. https://doi.org/10.64898/2026.01.19.700335

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Wall stiffening is a primary contributor to motility loss in Crohn's disease: an electromechanical modeling study

Fibrotic strictures are among the most disabling complications of Crohn's disease, permanently narrowing the bowel and impairing motility, yet no approved therapy reverses them. Chronic inflammation alters pacemaker-network coupling, smooth-muscle excitability, and calcium-dependent contractility, while fibrosis thickens the bowel wall, narrows the lumen, and changes tissue mechanics. The relative contributions of these coupled electrical, contractile, and structural alterations to motility loss remain unclear. To address this gap, we develop an integrated electromechanical finite-element framework for fibrostenosing Crohn's disease that couples a fibrosis-driven growth model with a FitzHugh-Nagumo electromechanical model. A full-factorial 25 design of experiments is used to quantify the relative effects of electrical diffusivity, excitation threshold, peak active stress, wall stiffness, and hypertrophic remodeling on cyclic lumen-volume deformation. Motility is quantified by the standard deviation of lumen volume over one contraction cycle. Within the parameter ranges examined, increased wall stiffness emerged as the dominant contributor to motility loss, followed by impaired smooth-muscle contractility. Changes in excitation threshold, hypertrophic remodeling, and electrical diffusivity produced substantially smaller effects. Pairwise interactions were small relative to the dominant main effects, indicating that the mechanisms contributed largely through their individual effects. Our findings suggest that limiting wall stiffening while preserving smooth-muscle contractile function may provide a therapeutic strategy for maintaining intestinal motility in fibrostenosing Crohn's disease.

bioengineering↗
bioRxiv2026

Lactate Receptor Activation Alleviates Senescence and Preserves Homeostasis of Aged Arteries

Arteries are among the first tissues to exhibit age-related dysfunction, yet the metabolic mechanisms driving vascular senescence remain poorly understood. Here, analysis of human aortic transcriptomic data identified HCAR1, encoding the lactate receptor GPR81, as one of the genes most significantly downregulated with age. We therefore investigated whether age-associated loss of GPR81 contributes to cellular senescence within the vessel wall. Senescent human endothelial cells and vascular smooth muscle cells accumulated neutral and oxidized lipids and exhibited increased labile iron and ferroptosis. Silencing GPR81 in early-passage cells recapitulated this metabolic phenotype together with multiple hallmarks of cellular senescence. Moreover, endothelial-specific deletion of GPR81 in young mice was sufficient to induce senescent cell accumulation, impaired lipid homeostasis, endothelial dysfunction, and elastin disorganization. Conversely, pharmacological activation of GPR81 with the agonist CHBA restored fatty acid metabolism, promoted glycolytic reprogramming, and attenuated ferroptotic stress and senescence-associated phenotypes. In lamin A knock-in (LAKI) progeroid mice, CHBA reduced arterial lipid accumulation and cellular senescence, shifted vascular cell composition toward a youthful state, improved endothelial integrity, and restored extracellular matrix homeostasis. Together, these findings identify age-associated loss of GPR81 as a driver of vascular metabolic dysfunction and cellular senescence and establish pharmacological GPR81 activation as a promising therapeutic strategy for preserving vascular homeostasis and mitigating age-associated cardiovascular disease.

bioengineering↗
bioRxiv2026

Targeted and bilateral blood flow monitoring in middle cerebral artery using diffuse correlation spectroscopy

Objective: To develop and validate a dual-probe Diffuse Correlation Spectroscopy (DCS) system for non-invasive and simultaneous, monitoring of cerebral blood flow (CBF) in the bilateral Middle Cerebral Artery (MCA) territories, and expanding the utility of conventional DCS limited to cortical-volume-based CBF measurements to vessel-specific cerebral perfusion monitoring. Methods: A dual-probe DCS system was designed for non-invasive monitoring of MCA-specific perfusion. Probe placement and protocol optimization study has been performed using anatomical landmarks, motor and speech activation tasks in healthy volunteers. System stability and repeatability were further evaluated in a pilot cohort of 30 healthy (age, 25{+/-}7 years) participants using optimized probe position and protocol. A bilateral MCA ischemic Lacunar Infract stroke case report also validated the feasibility of the system in clinical settings. Results: Measurements demonstrated superior sensitivity towards MCA-territory perfusion at targeted probe locations compared to off-MCA positions. In pilot cohort, significant increase of 30.34 {+/-} 21.56% and 36.48 {+/-} 21.22% in rCBF corresponding to hand squeeze and speech task respectively showed reproducible physiological responsiveness of the system (p<0.001). Measurement done on a patient with bilateral MCA ischemic Lacunar Infract stroke showed a significant change of 30% during speech for both the MCAs but no significant change is observed for hand squeeze tasks. Conclusion: The custom built dual-probe DCS system enables non-invasive, operator-independent, targeted and continuous monitoring of rCBF within bilateral MCA territories. Significance: This approach enables the potential use of DCS system for bilateral and vessel-specific monitoring of cerebral perfusion in the MCA territories.

bioengineering↗