Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation.

Long-lasting vaginal dosage forms could improve the therapeutic efficacy of vaginal microbicides, but achieving long-term delivery to the vaginal canal has been a significant challenge. To advance understanding of vaginal dosage retention and biodistribution, we describe a method of noninvasive imaging with Zr-labeled bioadhesive nanoparticles (BNPs) in non-human primates. We additionally examined the safety of repeated BNP application.

Branching in poly(amine-co-ester) polyplexes impacts mRNA transfection.

Branching is a key structural parameter of polymers, which can have profound impacts on physicochemical properties. It has been demonstrated that branching is a modulating factor for mRNA delivery and transfection using delivery vehicles built from cationic polymers, but the influence of polymer branching on mRNA delivery remains relatively underexplored compared to other polymer features such as monomer composition, hydrophobicity, pKa, or the type of terminal group. In this study, we examined the impact of branching on the physicochemical properties of poly(amine-co-esters) (PACE) and their efficiency in mRNA transfection in vivo and in vitro under various conditions.

Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination.

An inhalable platform for messenger RNA (mRNA) therapeutics would enable minimally invasive and lung-targeted delivery for a host of pulmonary diseases. Development of lung-targeted mRNA therapeutics has been limited by poor transfection efficiency and risk of vehicle-induced pathology. Here, we report an inhalable polymer-based vehicle for delivery of therapeutic mRNAs to the lung.

Inhalable polymer nanoparticles for versatile mRNA delivery and mucosal vaccination.

Unlabelled: An inhalable platform for mRNA therapeutics would enable minimally invasive and lung targeted delivery for a host of pulmonary diseases. Development of lung targeted mRNA therapeutics has been limited by poor transfection efficiency and risk of vehicle-induced pathology. Here we report an inhalable polymer-based vehicle for delivery of therapeutic mRNAs to the lung.

PEGylation of poly(amine-co-ester) polyplexes for tunable gene delivery.

There is growing interest in PEGylation of cationic polymeric vehicles for gene delivery in order to improve vehicle stability and reduce toxicity, but little is known about the effects of PEG coatings on transfection. We used a polymer from the poly(amine-co-ester) (PACE) family blended with PEG-conjugated PACE at different ratios in order to explore the effects of polyplex PEGylation on the transfection efficiency of plasmid DNA, mRNA, and siRNA in vitro and mRNA in vivo. We discovered that concentrations of PACE-PEG as low as 0.

Optimizing biodegradable nanoparticle size for tissue-specific delivery.

Nanoparticles (NPs) are promising vehicles for drug delivery because of their potential to target specific tissues [1]. Although it is known that NP size plays a critical role in determining their biological activity, there are few quantitative studies of the role of NP size in determining biodistribution after systemic administration. Here, we engineered fluorescent, biodegradable poly(lactic-co-glycolic acid) (PLGA) NPs in a range of sizes (120-440nm) utilizing a microfluidic platform and used these NPs to determine the effect of diameter on bulk tissue and cellular distribution after systemic administration.