Biology subjects

Hayward, A. M.

Publications and source records attributed to Hayward, A. M..

4 recordsLinked to original sources

bioRxiv2025

Monolithic Shape-Shifting Absorbable Implants for Long-Term Contraception

Reversible contraceptives empower women to prevent unintended pregnancies and enable family planning. However, the need for frequent dosing with pills or injections often leads to suboptimal medication adherence and reduced effectiveness-an issue common to many chronic conditions. Long-acting drug delivery implants offer a compelling alternative by enabling autonomous, multi-year drug release, thereby improving real-world adherence and treatment outcomes. However, user acceptability and access are limited by need for invasive insertion and surgical end-of-life removal, particularly in low-resource settings, as well as by limited drug loading and suboptimal drug utilization efficiency, which constrain both the duration of therapy and the range of drugs that can be effectively delivered. To address these limitations, we developed the Monolithic Shape-shifting Absorbable Implants for Chronic Care (MoSAIC) platform-a minimally invasive, fully bioresorbable system that integrates compacted drug formulations with a space-efficient device architecture. This approach reduces implant size, eliminates the need for surgical removal, and prolongs therapeutic duration compared to existing implants. We develop compacted formulations of the contraceptive drug levonorgestrel (LNG), and other poorly water-solubility drugs, demonstrating exceptional drug loading (100% w/w) and multi-year sustained drug release via surface-mediated dissolution in rats. When incorporated into MoSAIC devices, these formulations enable high-efficiency drug loading and zero-order drug release kinetics with geometrically tunable rates and durations. As a result, MoSAIC systems can be designed to be smaller, less invasive, and/or longer lasting than current contraceptive implants such as Jadelle(R) and Nexplanon(R). The MoSAIC platform expands access to reversible contraception and supports long-term medication adherence, with the potential to improve health outcomes and quality of life. More broadly, it provides a flexible approach for delivering other potent, low-solubility therapeutics and lays the foundation for a "dose it and forget it" paradigm in chronic disease management, where adherence is designed into the therapy itself.

bioengineering↗

bioRxiv2023

A Vibrating Ingestible BioElectronic Stimulator Modulates Gastric Stretch Receptors for Illusory Satiety

Effective therapies for obesity either require invasive surgical or endoscopic interventions or high patient adherence, making it challenging for the nearly 42% of American adults who suffer from obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. Here we developed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill - an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release as well as yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake ([~]40%, p< 0.0001) and minimized the weight gain rate (p< 0.03) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.

pathology↗

bioRxiv2022

A machine learning liver-on-a-chip system for safer drug formulation

Drug metabolism leads to biotransformations of pharmaceutical substances that alter drug efficacy, toxicity, as well as drug interactions. Modeling these processes ex vivo stands to greatly accelerate our capacity to develop safe and efficacious drugs and formulations. Recognizing the liver as the primary site of drug metabolism, here we report a novel whole-tissue ex vivo liver screening platform that enabled modeling of hepatic metabolism and tracking of hepatotoxic drug metabolites. We applied the system for the characterization of acetaminophen (APAP) metabolism and identified interactions that can mitigate the generation of toxic metabolites ex vivo. Combining our experimental platform with state-of-the-art machine learning, we validated two novel functional excipients that can prevent APAP hepatotoxicity in vivo in mice. To assess translational potential, we prototyped a novel solid dosage form with controlled release of both APAP and our functional excipients. Our this platform provides innovative potential access to actionable data on drug metabolism to support the development of new therapeutic approaches.

bioengineering↗

bioRxiv2019

Computationally guided high-throughput design of self-assembling drug nanoparticles

Nanoformulations are transforming our capacity to effectively deliver and treat a myriad of conditions. However, many nanoformulation approaches still suffer from high production complexity and low drug loading. One potential solution relies on harnessing co-assembly of drugs and small molecular excipients to facilitate nanoparticle formation through solvent exchange without the need for chemical synthesis, generating nanoparticles with up to 95% drug loading. However, there is currently no understanding which of the millions of possible combinations of small molecules can result in the formation of these nanoparticles. Here we report the development of a high-throughput screening platform coupled to machine learning to enable the rapid evaluation of such nanoformulations. Our platform identified 101 novel self-assembling drug nanoparticles from 2.1 million pairings derived from 788 candidate drugs with one of 2686 excipients, spanning treatments for multiple diseases and often harnessing well-known food additives, vitamins, or approved drugs as carrier materials - with potential for accelerated approval and translation. Given their long-term stability and potential for clinical impact, we further characterize novel sorafenib-glycyrrhizin and terbinafine-taurocholic acid nanoparticles ex vivo and in vivo. We anticipate that this platform could accelerate the development of safer and more efficacious nanoformulations with high drug loadings for a wide range of therapeutics.

bioengineering↗