Although bioactive polymers such as cationic polymers have demonstrated potential as drug carriers and nonviral gene delivery vectors, high toxicity and uncontrolled, instantaneous cellular interactions of those vectors have hindered the successful implementation in vivo. Fine control over the cellular interactions of a potential drug/gene delivery vector would be thus desirable. Herein we have designed nanohybrid systems (100-150 nm in diameter) that combine the polycations with protective outer layers consisting of biodegradable polymeric nanoparticles (NPs) or liposomes. A commonly used polycation polyethylenimine (PEI) was employed after conjugation with rhodamine (RITC). The PEI-RITC conjugates were then encapsulated into: i) polymeric NPs made of either polylactide-co-glycolide (PLGA) or polyethylene glycol-bpolylactide-co-glycolide (PEG-PLGA); or ii) PEGylated liposomes, resulting in three nanohybrid systems. Through the nano-hybridization, both cellular uptake and cytotoxicity of the nanohybrids were kinetically controlled. The cytotoxicity assay using MCF-7 cells revealed that liposomebased nanohybrids exhibited the least toxicity, followed by PEG-PLGA-and PLGA-based NPs after 24 hr incubation. The different kinetics of cellular uptake was also observed; the liposomebased systems being the fastest and PLGA-based systems being the slowest. The results present a potential delivery platform with enhanced control over its biological interaction kinetics and passive targeting capability through size control.

Nanomedicine has had a profound impact on the treatment of many diseases especially cancer. However, synthesis of multifunctional nanoscale drug carriers often requires multistep coupling and purification reactions, which can pose major scale-up challenges. Here we leveraged bioinspired oxidation-triggered polymerization of catechols to synthesize nanoparticles (NPs) from the plant polyphenol quercetin (QCT) loaded with a hydrophobic anti-cancer drug, curcumin, and functionalized with poly(ethylene glycol) (PEG) for steric stabilization in one reaction step.NPs were formed by base-catalyzed oxidative self-polymerization of QCT in the presence of curcumin and thiol-terminated PEG upon mixing in a universal solvent (dimethyl sulfoxide), followed by self-assembly with the gradual addition of water. Dynamic light scattering and X-ray photoelectron spectroscopy were used to confirm NP PEGylation. Drug loading was verified by UV-Vis spectroscopy. Curcumin-loaded NPs were efficiently internalized by CT26 murine colon cancer cells as determined by flow cytometry and confocal microscopy. NPs also demonstrated sustained release and potent cytotoxicity in vitro. Moreover, in vivo imaging of CT26 tumorbearing Balb/c mice following tail vein injection of DiR-labeled QCT NPs showed steady tumor accumulation of the NPs up to 24 h. This was further supported by significant tumor uptake of curcumin-loaded QCT NPs as measured by flow cytometry analysis of tumor homogenates. Our findings present a greener synthetic route for the fabrication of drug-loaded surface functionalized NPs from poorly water-soluble plant polyphenols such as QCT as promising anti-cancer delivery systems.

Plant polyphenols have attracted attention in recent years due to their ability to undergo oxidative coupling reactions enabled by the presence of multiple phenolic hydroxyl groups, forming chemically versatile coatings and biocompatible nanoparticles (NPs) for various applications. The aim of this study was to investigate whether coffee bean aqueous extracts, which are known to be rich in polyphenols, could serve as a natural source of NP building blocks. Extracts were prepared by heating ground Arabica beans of varying roasting degrees in water with or without the addition of sodium metaperiodate or copper sulfate as an oxidizing agent, followed by filtration. NP formation was verified by dynamic light scattering and transmission electron microscopy, which revealed the presence of nano-sized particles with varying sizes and polydispersities as a function of the coffee type and oxidizing agent used. NP colors ranged from light to medium to dark brown, and particle sizes were between 44 and 250 nm with relatively low polydispersity indices. In vitro antioxidant assays showed that oxidizing agent-treated coffee NPs had lower antioxidant potency compared to air-oxidized NPs, but the free-radical scavenging activity was still retained. Coffee NPs exhibited no antimicrobial activity against common bacterial and fungal strains. Cell viability assays demonstrated that the NPs were biocompatible in human dermal fibroblasts, while exhibiting antiproliferative activity against MCF7 breast cancer cells, particularly copper sulfate-oxidized NPs. This study presents a facile and economical method to produce template-free antioxidant NPs that may be explored for various applications such as drug delivery and cosmetics.

Melanin-mimetic polydopamine nanoparticles (PDA NPs) are emerging as promising candidates for topical and transdermal drug delivery because they mimic melanin, a naturally occurring skin pigment. However, our knowledge of their interactions with human skin remains limited. Hence, we set out to investigate the role of PDA NP surface chemistry in modulating their skin deposition. PDA NPs were synthesized by base-catalyzed oxidative self-polymerization of dopamine and functionalized with poly­(ethylene glycol) (PEG) bearing different termini to obtain neutral, anionic, cationic, and hydrophobic PEGylated NPs. NPs were characterized by dynamic light scattering, transmission electron microscopy, Fourier transform-infrared spectroscopy, and X-ray photoelectron spectroscopy. The NPs were then labeled with rhodamine B, and their skin interactions were investigated both in vitro, using a Strat-M membrane, and ex vivo, using excised whole thickness human skin. In vitro diffusion studies revealed that the NPs did not permeate transdermally, rather the NPs accumulated in the Strat-M membrane after 24 h of incubation. Membrane deposition of the NPs showed a strong dependence on surface chemistry, with anionic (unmodified and carboxyl-terminated PEGylated) NPs achieving the highest accumulation, followed by neutral and cationic NPs, whereas hydrophobic NPs achieved the lowest degree of accumulation. In ex vivo permeation studies, we observed that surface modification of PDA NPs with PEG serving as an antifouling coating is essential to maintaining colloidal stability upon skin contact. Moreover, anionic PEGylated NPs were able to achieve 78% skin accumulation, which was significantly higher than neutral and cationic NPs (51 and 34% accumulation, respectively). Our findings provide important insights into the role of surface chemistry in enhancing the skin accumulation of melanin-mimetic PDA NPs as potential sunscreens and carriers for skin-targeted treatments.

Over the last few decades, nanotechnology has given rise to promising new therapies and diagnostic tools for a wide range of diseases, especially cancer. The unique properties of nanocarriers such as liposomes, polymeric nanoparticles, micelles, and bioconjugates have mainly been exploited to enhance drug solubility, dissolution, and bioavailability. The most important advantage offered by nanotechnology is the ability to specifically target organs, tissues, and individual cells, which ultimately reduces the systemic side effects and improves the therapeutic index of drug molecules. The contribution of medicinal chemistry to nanotechnology is evident in the abundance of new active molecules that are being discovered but are faced with tremendous delivery challenges by conventional formulation strategies. Additionally, medicinal chemistry plays a crucial role in all the steps involved in the preparation of nanocarriers, where structure-activity relationships of the drug molecule as well as the nanocarrier are harnessed to enhance the design, efficacy, and safety of nanoformulations. The aim of this review is to provide an overview of the contributions of medicinal chemistry to nanotechnology, from supplying drug candidates and inspiring high-throughput nanocarrier design strategies, to structure-activity relationship elucidation and construction of computational models for better understanding of nanocarrier physicochemical properties and biological behavior. These two fields are undoubtedly interconnected and we will continue to see the fruits of that communion for years to come.

The coronavirus disease 2019 (COVID-19) pandemic is being considered one of the most challenging global crises that the world has experienced in recent history, causing ripple effects and major disruption across all aspects of our daily lives, especially education. Many countries around the world, including Jordan, have instituted shutdown of academic institutions as an early measure to curb the spread of the virus. The rapid response came at a price: Having to transition to remote teaching and learning without the proper tools and technological support. Here we present a glimpse of the efforts undertaken by chemistry instructors at a Pharmacy School in Jordan to ensure the continuity of student learning and achieve educational outcomes during these unprecedented times. By sharing our experiences, we hope to contribute to the collective insights of chemistry instructors around the world in the face of this universal struggle, so that we may all be better prepared for future disruptive events.

Coal tar (CT) is a commonly used therapeutic agent in psoriasis treatment. CT formulations currently in clinical use have limitations such as toxicity and skin staining properties, leading to patient nonadherence. The purpose of this study was to develop a nanoparticle (NP) formulation for CT based on biocompatible poly(lactide- co -glycolide) (PLGA). CT was entrapped in PLGA NPs by nanoprecipitation, and the resulting NPs were characterized using dynamic light scattering and high-performance liquid chromatography (HPLC) to determine the particle size and CT loading efficiency, respectively. In vitro biocompatibility of the NPs was examined in human dermal fibroblasts. Permeation, washability, and staining experiments were carried out using skin-mimetic Strat-M membranes in Franz diffusion cells. The optimal CT-loaded PLGA NPs achieved 92% loading efficiency and were 133 nm in size with a polydispersity index (PDI) of 0.10 and a zeta potential of −40 mV, promoting colloidal stability during storage. CT NPs significantly reduced the cytotoxicity of crude CT in human dermal fibroblasts, maintaining more than 75% cell viability at the highest concentration tested, whereas an equivalent concentration of CT was associated with 28% viability. Permeation studies showed that only a negligible amount of CT NPs could cross the Strat-M membrane after 24 h, with 97% of the applied dose found accumulated within the membrane. The superiority of CT NPs was further demonstrated by the notably diminished staining ability and enhanced washability compared to those of crude CT. Our findings present a promising CT nanoformulation that can overcome its limitations in the treatment of psoriasis and other skin disorders.

Amphotericin B (AmB) is one of the first-line treatments for systemic fungal infections, yet it suffers from doselimiting systemic toxicity and high cost of less toxic lipid-based formulations. Here, we report on a facile approach to synthesize an AmB-loaded nanomedicine by leveraging plant-inspired oxidative self-polymerization of the ubiquitous polyphenol quercetin (QCT). Polymerized QCT nanoparticles (pQCT NPs) were formed, loaded with AmB, and functionalized with poly(ethylene glycol) (PEG) to impart steric stability in a simple procedure that relied on mixing followed by dialysis. The AmB-loaded NPs (AmB@pQCT-PEG NPs) were characterized by a drug loading efficiency of more than 90%, a particle size of around 160 nm, a polydispersity index of 0.07, and a partially negative surface charge. AmB release from the NPs was sustained over several days and followed the Korsmeyer−Peppas model with a release exponent (n) value >0.85, denoting drug release by polymer relaxation and swelling. A hemolysis assay revealed the NPs to be highly biocompatible, with negligible hemolytic activity and 30−60% hemolysis after 1 and 24 h of incubation with erythrocytes, respectively, across a wide concentration range (6.25−100.00 μg/mL). Conversely, equivalent concentrations of free AmB caused 90−100% hemolysis within the same timeframe. Importantly, AmB@pQCT-PEG NPs outperformed free AmB in microbial susceptibility assays on Candida albicans, achieving a minimum inhibitory concentration of 62.5 ng/mL after 48 h of incubation, which was 2-fold lower than the free drug. Our results demonstrate that pQCT NPs may serve as a viable AmB delivery platform for the treatment of fungal infections and potentially other AmB-susceptible pathogens.