Biology subjects

Kelley, J.

Publications and source records attributed to Kelley, J..

4 recordsLinked to original sources

bioRxiv2026

Biodegradable Nanoparticle-in-Implant Platform for Sustained and Light-Boosted Pirfenidone Delivery

Vocal fold (VF) fibrosis is a major cause of persistent dysphonia due to excessive extracellular matrix deposition and tissue stiffening that disrupt normal vocal fold vibration. Current treatment approaches are limited by the need for repeated local injections and inadequate long-term therapeutic control. Pirfenidone (PFD), an FDA-approved antifibrotic agent, has demonstrated potential for reducing fibrosis; however, its short half-life and systemic adverse effects limit conventional administration strategies. In this study, we developed a sustained and near-infrared (NIR)-responsive local delivery platform by integrating PFD-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles into biodegradable PLGA implants for dose-controllable antifibrotic delivery. PFD-loaded PLGA nanoparticles were fabricated using an oil-in-water emulsion solvent evaporation method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Nanoparticles with small, medium, and large hydrodynamic diameters were generated to evaluate the effect of particle size on release behavior. Gold nanorods (AuNRs) were incorporated to enable photothermal NIR-triggered release enhancement. The nanoparticles were subsequently loaded into non-porous PLGA (90:10) implants and evaluated for long-term in vitro release under physiological conditions with and without pulsed 1064 nm laser irradiation. The nanoparticle-loaded implants demonstrated sustained PFD release for over 190 days with minimal initial burst release (<2.5%). NIR irradiation enhanced PFD release compared with non-irradiated controls across all nanoparticle sizes. Smaller nanoparticles produced greater cumulative release than medium and large nanoparticles due to shorter diffusion pathways and larger surface-area-to-volume ratios. Prior to implant fracture, cumulative PFD release reached approximately 20.2%, 14.8%, and 12.3% of total loading for small, medium, and large nanoparticle groups under 2-min irradiation conditions, respectively. Dialysis membrane studies further demonstrated that the PLGA capsule acted as an additional diffusion barrier that substantially prolonged release compared with nanoparticles alone. Overall, this study demonstrates a hybrid nanoparticle-in-implant strategy capable of providing sustained and irradiation-enhanced local PFD delivery with tunable release characteristics. These findings support the potential of biodegradable, dose-controllable implant systems for long-term management of vocal fold fibrosis while reducing the need for repeated interventions.

bioengineering↗

bioRxiv2026

Croconium Dye Thermosensitive Liposomes for Light Activated Drug Release

This study investigates a novel light-activated drug delivery system designed to produce on-demand drug release. The light-activated system was developed by incorporating a photostable photothermal agent, croconium dye, into liposomes to enable thermally triggered drug release. The drug release from the liposomes was determined at three powers of 210, 295, and 380 mW under 0-, 1-, and 2-minute light irradiation. A continuous wave 808 nm laser was used as the light source. Dexamethasone sodium phosphate (DSP) released from the liposomes was tunable depending on the power and irradiation time with a range of 1 -19 g released depending on irradiation power and time. For local temperature measurement during the photothermal activation, polymerized 10, 12 - Pentacosadiynoic acid (PCDA) was incorporated in the lipid bilayer. Under heating polymerized PCDA undergoes a transition into a red phase from a blue phase. Utilizing the spectrum changes under known temperatures a regression model was developed to calculate the local temperature of the liposomes under irradiation. The ability of the liposomes to release DSP under irradiation in the presence of a phantom tissue was tested under different attenuation coefficients to match various common biological tissues. The liposomes were still able to release DSP in the presence of tissue phantoms for a certain thickness of the tissue. Finally, the cytotoxicity of the liposomes with the croconium dye for chemical and thermal toxicity was determined. The liposomes displayed good biocompatibility with Human Microvascular Endothelial Cell line-1 (HMEC-1). The results support the use of croconium dye as a potential alternative to commonly photothermal agents used in drug delivery such as metal nanoparticles. Future work will focus on optimization of absorbance spectrum for drug release, and in vivo studies for efficacy and safety.

bioengineering↗

bioRxiv2025

Distinct mechanisms mediate dopamine-octopamine opponency in an insect model of olfaction

Neuromodulators play a key role in determining how an organism processes and responds to sensory cues. Often, different neuromodulators act on the same set of neural circuits to produce diverging behavioral outcomes. In this study, we examined how dopamine and octopamine alter odor-driven neural activity in a peripheral olfactory circuit (the antennal lobe) and thereby alter behavioral responses in an opposing manner. Our results indicate that dopamine suppressed GABAergic local neuron activity during odor stimulation. Releasing the antennal lobe network from inhibition increased the principal neural activity for all odorants and led to nonspecific increases in a behavioral appetitive response. Octopamine, on the other hand, did not alter the GABAergic inhibition in the antennal lobe but still reduced the odor- evoked principal neural activity and the behavioral responses elicited by all odorants. Thus, both dopamine and octopamine used distinct mechanisms (altering recurrent inhibition vs intrinsic excitability) to mediate opponent changes in odor-evoked neural activity and behavioral outcomes.

neuroscience↗

bioRxiv2024

Investigating the Functional Role of the DI-DII Linker in Nav1.5 Channel Function

The cardiac voltage-gated sodium channel, Nav1.5 initiates the cardiac action potential. Its dysfunction can lead to dangerous arrhythmias, sudden cardiac arrest, and death. The functional Nav1.5 core consists of four homologous repeats (I, II, III, and IV), each formed from a voltage sensing and a pore domain. The channel also contains three cytoplasmic linkers (I-II, II-III, and III-IV). While Nav1.5 structures have been published, the I-II and II-III linkers have remained absent, are predicted to be disordered, and their functional role is not well understood. We divided the I-II linker into eight regions ranging in size from 32 to 52 residues, chosen based on their distinct properties. Since these regions had unique sequence properties, we hypothesized that they may have distinct effects on channel function. We tested this hypothesis with experiments with individual Nav1.5 constructs with each region deleted. These deletions had small effects on channel gating, though two (430 - 457del and 556 - 607del) reduced peak current. Phylogenetic analysis of the I-II linker revealed five prolines (P627, P628, P637, P640, P648) that were conserved in mammals but absent from the Xenopus sequence. We created mutant channels, where these were replaced with their Xenopus counterparts. The only mutation that had a significant effect on channel gating was P627S, which depolarized channel activation (10.13 +/- 2.28 mV). Neither a phosphosilent (P627A) nor a phosphomimetic (P627E) mutation had a significant effect, suggesting that either phosphorylation or another specific serine property is required. Since deletion of large regions had little effect on channel gating while a point mutation had a conspicuous impact, the I-II linker role may be to facilitate interactions with other proteins. Variants may have a larger impact if they create or disrupt these interactions, which may be key in evaluating pathogenicity of variants.

physiology↗