Threading the needle: Achieving simplicity and performance in cellulose alkanoate ω-carboxyalkanoates for amorphous solid dispersion.

Most active pharmaceutical ingredients (APIs) suffer from poor water solubility, often keeping them from reaching patients. To overcome the issues of poor drug solubility and subsequent low bioavailability, amorphous solid dispersions (ASDs) have garnered much attention. Cellulose ester derivatives are of interest for ASD applications as they are benign, sustainable-based, and successful in commercial drug delivery systems, e.g. in osmotic pump systems and as commercial ASD polymers. Synthesis of carboxy-pendant cellulose esters is a challenge, due in part to competing reactions between carboxyls and hydroxyls, forming ester crosslinks. Herein we demonstrate proof-of-concept for a scalable synthetic route to simple, yet highly promising ASD polymers by esterifying cellulose polymers through ring-opening of cyclic succinic or glutaric anhydride. We describe the complexity of such ring-opening reactions, not previously well-described, and report ways to avoid gelation. We report synthesis, characterization, and preliminary in vitro ASD evaluations of fifteen such derivatives. Synthetic routes were designed to accommodate these criteria: no protecting groups, no metal catalysts, mild conditions with standard reagents, simple purification, and one-pot synthesis. Finally, these designed ASD polymers included members that maintained fast-crystallizing felodipine in solution and release it from an ASD at rather high 20 % drug loading (DL).

Chemical synthesis of polysaccharide-protein and polysaccharide-peptide conjugates: A review.

Polysaccharides are abundant natural polymers, which in nature are at times covalently modified with peptides and proteins. Polysaccharide-protein or polysaccharide-peptide conjugates, natural or otherwise, may have increased solubility, improved emulsion properties, prolonged circulation time, reduced immunogenicity, and enhanced selectivity for targeting specific tissues compared to native peptides and proteins. In this paper, we will review recent advances in synthetic methods for producing polysaccharide-protein conjugates and discuss their advantages with a focus on drug targeting.

Enhanced chemoresistance of squamous carcinoma cells grown in 3D cryogenic electrospun scaffolds.

It is critically important to study head and neck squamous cell carcinoma tumorigenic mechanisms in order to gain a better understanding of tumor development, progression, and treatment. Unfortunately, a representative three-dimensional (3D) model for these evaluations has yet to be developed. The purpose of this study was to replicate tumor extracellular matrix (ECM) morphology utilizing electrospinning technology. First, the tumor ECM was evaluated by decellularizing tumor samples and analyzing the fibrous structure of the ECM by scanning electron microscopy. Cryogenic electrospun silk scaffolds were then fabricated to mimic the tumor ECM, and were found to be similar in fiber orientation and fiber dimensions to the native tumor ECM. Tumor cells were cultured on these ECM mimicking scaffolds and compared to an in vivo model of the same derivative human tumor in terms of proliferation and differentiation. The tumor cells in the 3D model show similar phenotypes to those found in vivo, contrasting to the same cells grown in two-dimensional (2D) culture. The sensitivity of the tumor cells to paclitaxel was compared between 2D culture and 3D culture. The results indicate that increased drug concentrations, orders of magnitude higher than the IC90 for 2D culture, had minimal effects on HN12 cell viability in the 3D model. In conclusion, an in vitro tumor model has been developed that will allow for a better understanding of tumor biology and aid chemotherapeutic drug development and accurate evaluation of drug efficacy.