Vitamin B3 Containing Polymers for Nanodelivery

Abstract

Polymeric nanoparticles with an integrated dual delivery system, facilitating controlled release of bioactive molecules and drugs, offer therapeutic advantages. Key design targets include high biocompatibility, cellular uptake, and encapsulating efficiency. In this study, we synthesized a diverse polymer library derived from niacin, a vitamin B3 integral to metabolic pathways and therapeutics. The library comprised poly(2‐(acryloyloxy)ethyl nicotinate), poly(2‐acrylamidoethyl nicotinate), and poly(N‐(2‐acrylamidoethyl)nicotinamide), with varying hydrophilicity in the backbone and pendant group linker. Polymers with higher hydrophobicity were formulated into nanoparticles with diameters below 150 nm, exhibiting a homogeneous spherical distribution, as confirmed by dynamic light scattering and scanning electron microscopy respectively. Encapsulation studies using the model drug neutral lipid orange (NLO) revealed a significant influence of the polymer backbone on efficiency, ranging from 46% for the ester backbone to 96% for the acrylamide backbone. Biological investigations showed that the nanoparticles were non‐toxic up to 300 µg mL−1 and exhibited superior cellular uptake. Interestingly, poly(2‐(acryloyloxy)ethyl nicotinate) and poly(2‐acrylamidoethyl nicotinate) boosted the metabolic activity of the cells. This is attributed to the cellular release of niacin, a precursor to nicotinamide adenine dinucleotide (NAD), a central coenzyme in metabolism. The results underline the potential of nutrient‐derived polymers as pro‐nutrient and drug delivery materials.This article is protected by copyright. All rights reserved

Optimizing Biocompatibility and Gene Delivery with DMAEA and DMAEAm: A Niacin-Derived Copolymer Approach

“…This phenomenon can be attributed to AAEN, as its homopolymer nanoparticles demonstrated a similar enhancement of cellular metabolism. 39 Additionally, this effect was similarly more pronounced with AAEN compared to AEN. Surprisingly, C1 was notably cytotoxic.…”

“…In our previous study, PAAEN demonstrated superior attributes in both encapsulation and cellular uptake when compared to PAEN. 39 Therefore, to further explore the potential applications of niacin-derived polymers as gene carriers, a copolymer library was conducted following initial investigations into the transfection efficiency of the A and B series, which resulted in the identification and selection of the optimal ratio. Analysis of molar mass distributions of the polymers using SEC revealed monomodal distributions, as depicted in Figure 1B.…”

“…A similar tendency to lose cargo due to T g was observed in our previous study on PAEN with small molecular weight model drugs. 39 Since cellular internalization of polyplexes is strongly influenced by their size, 52 the sizes of polyplexes for all polymers formulated at N*/P 20 were determined using DLS. As shown in Figure 2D, the hydrodynamic diameters of the polyplexes ranged between 64 and 109 nm, which is suitable for controlled cellular uptake through endocytosis.…”

“…To elaborate further, hydrophobic homopolymers derived from niacin were investigated. 39 The rationale was to utilize niacin, a natural compound, to improve nanoparticle formation, biocompatibility, and uptake profiles of polymers by harnessing the intrinsic advantages of the natural compound. Poly[2-acrylamidoethyl nicotinate] (PAAEN) and poly [2-(acryloyloxy)ethyl nicotinate] (PAEN) emerged as the top performers, with their nanoparticles showcasing high biocompatibility and enhanced uptake profiles, making them promising candidates for gene delivery if their attributes can be retained.…”

“…Poly[2-acrylamidoethyl nicotinate] (PAAEN) and poly [2-(acryloyloxy)ethyl nicotinate] (PAEN) emerged as the top performers, with their nanoparticles showcasing high biocompatibility and enhanced uptake profiles, making them promising candidates for gene delivery if their attributes can be retained. 39 In this study, we investigate a copolymer library comprising niacin-derived monomers (AAEN or AEN) in combination with either DMAEAm or DMAEA. The latter is incorporated to harness its charge-shifting property and compare its performance to that of the hydrolytically stable DMAEAm.…”