Skip to content
#diffusion models Open access

The design and optimization of a chitosan-based lamotrigine-loaded intranasal mucoadhesive nanomicelle solution using response surface methodology and artificial neural networks

Aug 2026 · Figshare
Advanced Drug Delivery Systems

Abstract

The study aimed to develop and optimize chitosan-based mucoadhesive nanomicelles for intranasal delivery of lamotrigine (LTG), to enhance epilepsy treatment, bypass the blood-brain barrier, and potentially improve brain targeting. LTG-loaded nanomicelles were prepared using thin-film hydration and optimized using a central composite design, response surface methodology, and artificial neural networks. The formulation included D-ɑ-tocopheryl polyethylene glycol succinate, Poloxamer 407, chitosan, and glycerol. Critical quality attributes assessed were micelle size (MS), polydispersity index (PDI), Zeta potential (ZP), pH, LTG content, transmittance, in vitro mucoadhesion, LTG release, and 28-day stability. The MS, PDI, ZP, pH, and LTG content of the optimized mucoadhesive nanomicelles was 31.28 ± 0.34 nm, 0.487 ± 0.00, +31.37 ± 1.97 mV, 4.61 ± 0.01, and 2.89 ± 0.01 mg/mL, respectively. The transmittance was 98.50 ± 0.10%, and significant in vitro mucoadhesion, with reduced migration, was observed for mucin-containing gels. LTG release (96.94% at 6 hours) followed the Higuchi diffusion model, with sufficient LTG released at 40 minutes to potentially reach the minimum effective concentration, based on in vitro release data alone. The formulation remained stable for 28 days at 4 °C and 25 °C. Chitosan-based mucoadhesive nanomicelles are a promising intranasal delivery system for LTG, with the potential for brain targeting, controlled LTG release, and improved epilepsy management.

View source

Similar papers

Modeling Environmentally Driven Seasonal Moisture Migration and Ground Movements in Expansive Clays

This paper describes the formulation of a numerical model for simulating environmentally driven one-dimensional (1D) ground movements of expansive clay. The formulation is based on a finite-element model that simulates the redistribution of matric suction through a diffusion-type equation, explicitly accounting for volume changes due to wetting and drying of the clay. We synthesize and modify highly nonlinear constitutive relationships for (1) hysteretic soil water retention; (2) reversible soil shrinkage and expansion of clay; and (3) hydraulic conductivity, explicitly incorporating desiccation cracks through a multidomain framework and assuming a critical surface crack depth. These models are well-calibrated to published laboratory tests on a reference expansive clay, Denver bentonite. We demonstrate capabilities of the proposed formulation to simulate the response of a homogeneous expansive clay to periods of drying and wetting, considering the initial matric suction, saturated hydraulic conductivity of the intact clay, and critical crack depth as three primary sources of uncertainty. We compare ensemble model simulations with measured ground movements from an instrumented expansive clay test site in Texas over a 3-year period using detailed records of potential evapotranspiration and precipitation. By assigning weights to the ensemble simulations based on their performance, we constrain the ranges of the three key uncertain parameters. The results showed very reasonable first-order agreement with the measured data and highlight the potential of the proposed formulation. We anticipate that more reliable predictions can be achieved through direct measurements of actual in situ evaporation rates and local soil properties.

Mahdi Seyyedan, Jiali Ma, Ivo Rosa Montenegro et al. · 1 citation
#diffusion models Review Open access Sep 2026

Modelling the impact of temperature on nanocarrier behavior: Thermodynamics, structural transitions, and drug release.

A rational design for next-generation thermo-responsive nanocarriers is proposed, in which polymer chemistry, nanoparticle structure, experimental characterization, and mechanistic modelling are integrated from the earliest stages of material development.

M. Schifone, Giuseppe Nunziata, Filippo Rossi · 1 citation
#diffusion models Open access Aug 2026

The Economics of Artificial Intelligence: Scaling, Verification, Assignment, Capital, Growth, and Value

This paper develops the economics of artificial intelligence as a single connected structure, from the physics of the production function to the aggregate growth constraint and the valuation of the firms building and adopting it. Part I derives the cost of capability from scaling laws, shows why deployed models are systematically overtrained, and estimates the task-success slope directly from 23,235 public evaluation runs: $\hat\beta=0.83$ with no detectable release-date trend. Part II treats market structure: minimum efficient scale, the two-tier equilibrium in which open weights contest the trailing edge but never the frontier, and inference as a capacity-constrained short-run market that rations rather than prices. Part III is the core. We replace the standard automation assignment rule with one that prices reliability, obtaining an automation calendar $t_{\mathrm{aut}}=t_{1/2}+(\tau/\beta)\log_2\gamma$ in which verification cost, not task difficulty, sets the date; derive optimal checkpoint spacing $k^\star\approx\sqrt{v_{\mathrm{ver}}/\lambda}$; and prove the exact best-of-$k$ result. Against a sound verifier, sampling divides the reliability lag by $k$ in the small-$k$ regime and does better outside it; against an unsound verifier, it leaves an error floor that no amount of sampling removes. Part IV aggregates: diffusion inherits its time dispersion from verification costs, and revenue growth is governed by the density of tasks at the current threshold. Part V proves a Baumol bound --- with elasticity of substitution below one, aggregate growth converges to that of the least automatable essential input --- and states three jointly necessary conditions for explosive growth. Part VI treats measurement, policy, and financial markets. Part VII states the investment bridge: technological importance, industry profit, and security return are distinct objects, and a coherent valuation must respect the automation calendar, rent migration, capital consumption, and expectations already in price. The full valuation architecture is reserved for a separate companion paper. Part VIII states eighteen open problems.

Miquel Noguer Alonso · 0 citations

Related blog posts