Biodegradable polymer-based microneedle (MN) patches enable self-administered, long-acting drug delivery. Controlled drug release from MNs requires controlled material distribution and minimal porosity in the MNs. MN detachment in the skin requires MNs without film formation beyond the MN base. To achieve these goals, we studied solvent removal dynamics during MN patch fabrication by a solvent-casting method to better control distribution of polymer and drug in the MN patch mold. More specifically, we designed casting solvents to control (i) solvent evaporation rate, (ii) solvent absorption rate into polydimethylsiloxane (PDMS) molds, and (iii) solubility of biodegradable polymer (poly (lactic acid)) and drug (etonogestrel, for long-acting contraception) in the solvent. We found that polymer film formation was prevented by using solvents with minimal mold absorption and moderate evaporation rates. We further demonstrated that solvent-nonsolvent mixtures titrated to the solubility limit of the polymer and beyond the solubility limit of the drug (forming a suspension of fine precipitate) also produced MNs without films. This occurred even when using solvents that absorbed into the molds. To better achieve sustained drug release, we showed that centrifuge-based casting and heat annealing reduced surface and bulk MN porosity. The resulting MNs achieved efficient detachment in porcine skin and sustained release of etonogestrel for two months in-vitro. This study establishes a framework to control solvent removal dynamics during MN patch fabrication to optimize biodegradable polymer MNs for long-acting delivery of etonogestrel and other drugs.
Nasal administration is investigated as an effective mucosal site suitable for non-invasive vaccine delivery and able to elicit both systemic and mucosal immunity. Delivery of proteins across the epithelial barrier is a key point to induce an immune response. In this framework, nanogels are properly designed to present the delivered antigen to the immune system, promoting their targeting to specific immune populations. Nanogels for nasal administration based on dextran sulfate and ϵ-poly-L-lysine have been prepared by polyelectrolyte complexation. To unlock the potential of mucosal vaccination, we evaluated nanogel for their ability to enhance antigen delivery across mucus barriers and promote immune activation. Using fluorescein-labelled ovalbumin as a model antigen, we investigated how nanogel governs antigen transport, cellular uptake, and presentation. Produced results showed that nanogel combines favourable physicochemical properties with mucoadhesive behaviour, enabling efficient interaction with the mucus layer. This translates into enhanced uptake and controlled intracellular trafficking in murine Bone Marrow-derived-Dendritic Cells, ultimately promoting effective antigen cross-presentation. Importantly, intranasal administration in vivo revealed prolonged antigen retention within the airway mucosa compared to the free antigen, indicating sustained local antigen availability. In addition, studies in human monocyte-derived macrophages provided preliminary information on the inflammatory response and intracellular fate of the nanogels in a human-relevant system. Together, these findings contribute to the preliminary preclinical characterization of the nanogel platform, while further studies are required to establish its immunogenicity and vaccine efficacy.
Pressurised Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel drug delivery system for treating peritoneal metastasis. No PIPAC-specific formulation is available, stability data under PIPAC conditions are lacking, and the drugs are used off-label. 85
Long-acting injectable formulations have emerged as promising systems for managing chronic psychiatric conditions by reducing dosing frequency and improving patient adherence. Oral antidepressants such as citalopram hydrobromide require daily administration, posing a significant risk of non-compliance in patients with Major Depressive Disorder (MDD). This study aimed to develop and characterize a poly (lactic-co-glycolic acid) (PLGA)-based in situ forming implant (ISFI) for the sustained parenteral delivery of citalopram hydrobromide over 10 days. Systematic formulation screening across polymers, solvents, and lipid excipients identified the optimized formulation (F4) composition, which was evaluated for viscosity, syringeability, in vitro drug release, ex vivo depot formation, release kinetics, cytotoxicity, and in vivo pharmacokinetic prediction. The optimized formulation exhibited Newtonian flow behavior (viscosity 0.35 Pa.s) with a maximum expulsion force of 16.49 N through a 20G needle, confirming adequate injectability. The in vitro release profile demonstrated a moderate initial burst of 13
The field of drug delivery is undergoing rapid transformation, driven by advances in biotherapeutics, new modalities, and innovative delivery technologies. However, translating these scientific breakthroughs into patient-centric therapies requires overcoming significant scientific, translational, and organizational barriers. This perspective piece provides insights from a multidisciplinary panel of leaders in biopharma, academia, and start-up innovation, focusing on the most promising opportunities and persistent challenges in the field. The discussion highlights the renewed and increased focus on subcutaneous and microneedle-based delivery systems, the evolving role of nanoparticle delivery, and the importance of aligning research with clinical and market needs through early cross-sector collaboration. The panel underscored the need for early stakeholder engagement, transparent communication, and iterative feedback to integrate business case considerations from the outset and foster successful partnerships. Various collaborative models that include pre-competitive consortia, open innovation incubators, public-private partnerships, and entrepreneurial training, are discussed for their effectiveness in bridging the gap between academic discovery and clinical translation. Ultimately, the advancement of drug delivery depends on multidisciplinary collaboration, robust translational frameworks, and sustained investment in innovative, patient-focused solutions that address real-world needs and improve patient outcomes.
