Search

Controlled delivery of proteins has immense potential for the treatment of various human diseases, but effective strategies for their delivery are required before this potential can be fully realized. Recent research has identified hydrogels as a promising option for the controlled delivery of therapeutic proteins, owing to their ability to respond to diverse chemical and biological stimuli, as well as their customizable properties that allow for desired delivery rates. This study utilized alginate and chitosan as model polymers to investigate the effects of hydrogel properties on protein release rates. The results demonstrated that polymer properties, concentration, and crosslinking density, as well as their responses to pH, can be tailored to regulate protein release rates. The study also revealed that hydrogels may be combined to create double-network hydrogels to provide an additional metric to control protein release rates. Furthermore, the hydrogel scaffolds were also found to preserve the long-term function and structure of encapsulated proteins before their release from the hydrogels. In conclusion, this research demonstrates the significance of integrating porosity and response to stimuli as orthogonal control parameters when designing hydrogel-based scaffolds for therapeutic protein release. [ABSTRACT FROM AUTHOR]

The stability of adsorbed proteins is increased by controlling the heterogeneity of the surface by creating raftlike domains in a soft liposomal membrane. The studies have shown that creating domains on which an enzyme can adsorb has increased the stability of that enzyme under denaturing conditions and that the size of these domains has a major effect on the degree of stability imparted by adsorption.

Single-walled carbon nanotubes (SWNTs) that provide a high intrinsic surface area without intraparticle diffusional limitations, are studied. In conclusion, the unique interaction of three properties afforded by nanomaterial such as SWNTs, high surface area, ability to assemble at an aqueous-organic interface, and absence of intraparticle diffusional limitations are demonstrated.

Post cryopreservation viability of human embryonic kidney (HEK) cells under two-dimensional (2D) and three-dimensional (3D) culture conditions was studied using trehalose as the sole cryoprotective agent. An L9(34) Taguchi design was used to optimize the cryoprotection cocktail seeding process prior to slow-freezing with the specific aim of maximizing cell viability measured 7 days post thaw, using the combinatorial cell viability andin-vitrocytotoxicity WST assay. At low (200 mM) and medium (800 mM) levels of trehalose concentration, encapsulation in alginate offered a greater protection to cryopreservation. However, at the highest trehalose concentration (1200 mM) and in the absence of the pre-incubation step, there was no statistical difference at the 95% CI (p = 0.0212) between the viability of the HEK cells under 2D and 3D culture conditions estimated to be 17.9 ± 4.6% and 14.0 ± 3.6%, respectively. A parallel comparison between cryoprotective agents conducted at the optimal levels of the L9study, using trehalose, dimethylsulfoxide and glycerol in alginate microcapsules yielded a viability of 36.0 ± 7.4% for trehalose, in average 75% higher than the results associated with the other two cell membrane-permeating compounds. In summary, the effectiveness of trehalose has been demonstrated by the fact that 3D cell cultures can readily be equilibrated with trehalose before cryopreservation, thus mitigating the cytotoxic effects of glycerol and dimethylsulfoxide. [ABSTRACT FROM AUTHOR]

There is an immediate need to develop highly predictive in vitro cell-based assays that provide reliable information on cancer drug efficacy and toxicity. Development of biomaterial-based three-dimensional (3D) cell culture models as drug screening platforms has recently gained much scientific interest as 3D cultures of cancer cells have been shown to more adequately mimic the in vivo tumor conditions. Moreover, it has been recognized that the biophysical and biochemical properties of the 3D microenvironment can play key roles in regulating various cancer cell fates, including their response to chemicals. In this study, we employed alginate-based scaffolds of varying mechanical stiffness and adhesive ligand presentation to further explore the role of 3D microenvironmental cues on glioblastoma cell response to cytotoxic compounds. Our experiments suggested the ability of both matrix stiffness and cell-matrix adhesions to strongly influence cell responses to toxins. Cells were found to be more susceptible to the toxins when cultured in softer matrices that emulated the stiffness of brain tissue. Furthermore, the effect of matrix stiffness on differential cell responses to toxins was negated by the presence of the adhesive ligand RGD, but regained when integrin-based cellmatrix interactions were inhibited. This study therefore indicates that both 3D matrix stiffness and cell-matrix adhesions are important parameters in the design of more predictive in vitro platforms for drug development and toxicity screening. [ABSTRACT FROM AUTHOR]

A desire to replicate the structural and functional complexity of proteins with structured, sequence‐specific oligomers motivates study of the structural features of water‐soluble peptoids (N‐substituted glycine oligomers). Understanding the molecular‐level details of peptoid self‐assembly in water is essential to advance peptoids' application as novel materials. Peptoid 1, an amphiphilic, putatively helical peptoid previously studied in our laboratory, shows evidence of self‐association in aqueous solution. In this work, we evaluate how changes to aqueous solution conditions influence the self‐association of 1. We report that changes to pH influence the fluorescence and CD spectroscopic features as well as the peptoid's interaction with a solvatochromic fluorophore and its apparent size as estimated by size exclusion chromatography. Addition of guanidine hydrochloride and ammonium sulfate also modulate spectroscopic features of the peptoid, its interaction with a solvatochromic fluorophore, and its elution in size exclusion chromatography. These data suggest that the ordering of the self‐assembly changes in response to pH and with solvent additives and is more ordered at higher pH and in the presence of guanidine hydrochloride. The deeper understanding of the self‐association of 1 afforded by these studies informs the design of new stimuli‐responsive peptoids with stable tertiary or quaternary structures. [ABSTRACT FROM AUTHOR]