Chemical bath deposition of SnO2films on PEN/ITO substrates for efficient flexible perovskite solar cells.

Flexible perovskite solar cells (f-PSCs) have achieved significant success. However, high-quality tin dioxide (SnO2) electron transport layers (ETLs) fabricated via chemical bath deposition (CBD) have not been achieved on flexible PEN/ITO substrates. This limitation is primarily due to the corrosion of the poor-quality ITO layer by the strongly acidic CBD solution. Here, we analyzed the reasons for the poor corrosion resistance of ITO films on PEN substrate from multiple perspectives, such as element composition, microstructure, and crystallinity. Then, we proposed a modified CBD method for SnO2films suitable for flexible PEN/ITO substrates. We employed SnCl2·2H2O as the tin source and regulated the pH of the CBD solution by NH3·H2O, which effectively avoided the corrosion of the ITO layer by the CBD solution and achieved high-quality SnO2films on the ITO layers. Compared to the commercial SnO2dispersion, the SnO2films prepared by this method have smaller grains and higher transmittance. As a result, we achieved an unprecedented power conversion efficiency (PCE) of 20.71% for f-PSCs fabricated on PEN/ITO substrates with SnO2ETLs by CBD method. This breakthrough facilitates the development of high-performance f-PSCs by a low-cost and large-scale chemical bath deposition of high-quality ETLs on flexible substrates.

Investigation on the Combined Effect of Hydroxypropyl Beta-Cyclodextrin (HPßCD) and Polysorbate in Monoclonal Antibody Formulation.

Monoclonal antibodies require careful formulation due to their inherent stability limitations. Polysorbates are commonly used to stabilize mAbs, but they are prone to degradation, which results in unwanted impurities. KLEPTOSE® HPßCD (hydroxypropyl beta-cyclodextrin) has functioned as a stable stabilizer for protein formulations in our previous research. The current study investigates the collaborative impact of combining polysorbates and HPßCD as excipients in protein formulations. The introduction of HPßCD in formulations showed it considerably reduced aggregation in two model proteins, bevacizumab and ipilimumab, following exposure to various stress conditions. The diffusion interaction parameter revealed a reduction in protein-protein interactions by HPßCD. In bevacizumab formulations, the subvisible particle counts per 0.4 mL of samples in commercial formulations vs. formulations containing both HPßCD and polysorbates subjected to distinct stressors were as follows: agitation, 87,308 particles vs. 15,350 particles; light, 25,492 particles vs. 6765 particles; and heat, 1775 particles vs. 460 particles. Isothermal titration calorimetry (ITC) measurement indicated a weak interaction between PS 80 and HPßCD, with a KD value of 74.7 ± 7.5 µM and binding sites of 5 × 10-3. Surface tension measurements illustrated that HPßCD enhanced the surface activity of polysorbates. The study suggests that combining these excipients can improve mAb stability in formulations, offering an alternative for the biopharmaceutical industry.

Polysorbates versus Hydroxypropyl Beta-Cyclodextrin (HPßCD): Comparative Study on Excipient Stability and Stabilization Benefits on Monoclonal Antibodies.

Polysorbates (PS 20 and PS 80) are the most widely used surfactants in biopharmaceutical formulations to protect proteins from denaturation, aggregation, and surface adsorption. To date, around 70% of marketed therapeutic antibodies contain either PS 20 or PS 80 in their formulations. However, polysorbates are chemically diverse mixtures, which are prone to degradation by oxidation and hydrolysis to produce peroxides and fatty acids, which, in turn, induce protein oxidation, aggregation, and insoluble particle formation. These will negatively impact protein quality and stability. Thus, polysorbate degradation has emerged as one of the major challenges in the development and commercialization of therapeutic protein products. KLEPTOSE® HPßCD (hydroxypropyl beta-cyclodextrin), a new multifunctional excipient, has been shown to provide protein stabilization functions in biopharmaceutical downstream processes and in their final formulations. This study aims to evaluate HPßCD, a new molecule of its class, against polysorbates as a stabilizer in biologics formulations. In this study, the chemical stability of KLEPTOSE® HPßCDs is compared with polysorbates (20 and 80) under various stress conditions. When subjected to heat stress, HPßCDs show little change in product recovery (90.7-100.7% recovery for different HPßCDs), while polysorbates 20 and 80 show significant degradation, with only 11.5% and 7.3% undegraded product remaining, respectively. When subjected to other chemical stressors, namely, autoclave, light, and oxidative stresses, HPßCD remains almost stable, while polysorbates show more severe degradation, with 95.5% to 98.8% remaining for polysorbate 20 and 85.5% to 97.4% remaining for polysorbate 80. Further, profiling characterization and degradation analysis reveal that chemical structures of HPßCDs remain intact, while polysorbates undergo significant hydrolytic degradation and oxidation. Lastly, the physicochemical stability of monoclonal antibodies in formulations is investigated. When subjected to light stress, adalimumab, as a model mAb, formulated in the presence of HPßCD, shows a significant decrease in protein aggregation, and superior monomer and total protein recovery compared to PS 80-containing formulations. HPßCD also reduces both agitation and thermal stress-induced protein aggregation and prevents subvisible particle formation compared to PS 80.

Pristine Gellan Gum-Collagen Interpenetrating Network Hydrogels as Mechanically Enhanced Anti-inflammatory Biologic Wound Dressings for Burn Wound Therapy.

Gellan gum is a biologically inert natural polymer that is increasingly favored as a material-of-choice to form biorelevant hydrogels. However, as a burn wound dressing, native gellan gum hydrogels do not drive host's biology toward regeneration and are mechanically inadequate wound barriers. To overcome these issues, we fabricateda gellan gum-collagen full interpenetrating network (full-IPN) hydrogel that can house adipose-derived mesenchymal stem cells (ADSCs) and employ their multilineage differentiation potential and produce wound-healing paracrine factors to reduce inflammation and promote burn wound regeneration. Herein, a robust temperature-dependent simultaneous IPN (SIN) hydrogel fabrication process was demonstrated using applied rheology for the first time. Subsequently after fabrication, mechanical characterization assays showed that the IPN hydrogels were easy to handle without deforming and retained sufficient mass to effect ADSCs' anti-inflammation property in a simulated wound environment. The IPN hydrogels' increased stiffness proved conducive for mechanotransduced cell adhesion. Scanning electron microscopy revealed theIPN's porous network, which enabled encapsulated ADSCs to spread and proliferate, for up to 3 weeks of culture, further shown by cells' dynamic filopodia extension observed in 3D confocal images. Successful incorporation of ADSCs accorded the IPN hydrogels with biologic wound-dressing properties, which possess the ability to promote human dermal fibroblast migration and secrete an anti-inflammatory paracrine factor, TSG-6 protein, as demonstrated in the 2D scratch wound assay and ELISA, respectively. More importantly, upon application onto murine full thickness burn wounds, our biologic wound dressing enhanced early wound closure, reduced inflammation, and promoted complete skin regeneration. Altogether, our results highlight the successful mechanical and biological enhancement of the inert matrix of gellan gum. Through completely natural procedures, a highly applicable biologic wound dressing is introduced for cell-based full thickness burn wound therapy.

Chlorella vulgaris Extract as a Serum Replacement That Enhances Mammalian Cell Growth and Protein Expression.

The global cell culture market is experiencing significant growth due to the rapid advancement in antibody-based and cell-based therapies. Both rely on the capacity of different living factories, namely prokaryotic and eukaryotic cells, plants or animals for reliable and mass production. The ability to improve production yield is of important concern. Among many strategies pursued, optimizing the complex nutritional requirements for cell growth and protein production has been frequently performed via culture media component titration and serum replacement. The addition of specific ingredients into culture media to modulate host cells' metabolism has also recently been explored. In this study, we examined the use of extracted bioactive components of the microalgae Chlorella vulgaris, termed chlorella growth factor (CGF), as a cell culture additive for serum replacement and protein expression induction. We first established a chemical fingerprint of CGF using ultraviolet-visible spectroscopy and liquid chromatography-mass spectrometry and evaluated its ability to enhance cell proliferation in mammalian host cells. CGF successfully promoted the growth of Chinese hamster ovary (CHO) and mesenchymal stem cells (MSC), in both 2D and 3D cell cultures under reduced serum conditions for up to 21 days. In addition, CGF preserved cell functions as evident by an increase in protein expression in CHO cells and the maintenance of stem cell phenotype in MSC. Taken together, our results suggest that CGF is a viable culture media additive and growth matrix component, with wide ranging applications in biotechnology and tissue engineering.

Biomimicry of microbial polysaccharide hydrogels for tissue engineering and regenerative medicine - A review.

Hydrogels as artificial biomaterial scaffolds offer a much favoured 3D microenvironment for tissue engineering and regenerative medicine (TERM). Towards biomimicry of the native ECM, polysaccharides from Nature have been proposed as ideal surrogates given their biocompatibility. In particular, derivatives from microbial sources have emerged as economical and sustainable biomaterials due to their fast and high yielding production procedures. Despite these merits, microbial polysaccharides do not interact biologically with human tissues, a critical limitation hampering their translation into paradigmatic scaffolds for in vitro 3D cell culture. To overcome this, chemical and biological functionalization of polysaccharide scaffolds have been explored extensively. This review outlines the most recent strategies in the preparation of biofunctionalized gellan gum, xanthan gum and dextran hydrogels fabricated exclusively via material blending. Using inorganic or organic materials, we discuss the impact of these approaches on cell adhesion, proliferation and viability of anchorage-dependent cells for various TERM applications.'

Impact of Physicochemical Properties of Cellulosic Polymers on Supersaturation Maintenance in Aqueous Drug Solutions.

The precipitation inhibitory effect of cellulosic polymers in relation to their physicochemical properties was studied. Using a poorly water-soluble model drug, griseofulvin, the precipitation inhibitory effect of a series of hydroxypropyl methylcellulose (HPMC) and methylcellulose polymers was studied using solvent-shift method. The extent of supersaturation maintenance of each polymer was then quantified by the parameter, supersaturation factor (SF). Partial least square (PLS) regression analysis was employed to understand the relative contribution from viscosity, hydroxypropyl content (HC), methoxyl content, methoxyl/hydroxypropyl ratio, and drug-polymer interaction parameter (χ) on SF. All grades of cellulosic polymers effectively prolonged supersaturation of griseofulvin. PLS regression analysis revealed that HC and χ appeared to have the strongest influence on SF response. A regression model of SF = 1.65-0.16 χ + 0.05 HC with a high correlation coefficient, r of 0.921, was obtained. Since the value of χ is inversely related to the strength of drug-polymer interaction, the result shows that SF increases with increasing drug-polymer interaction and increasing HC. As such, it can be implied that strong drug-polymer interaction and presence of hydroxypropyl groups in cellulosic polymers for hydrogen bonding are two key parameters for effective supersaturation maintenance. This knowledge on the relative contribution of polymer physicochemical properties on precipitation inhibition will allow the selection of suitable cellulosic polymers for systematic development of supersaturating drug delivery systems.

High drug load, stable, manufacturable and bioavailable fenofibrate formulations in mesoporous silica: a comparison of spray drying versus solvent impregnation methods.

Encapsulation of drugs in mesoporous silica using co-spray drying process has been recently explored as potential industrial method. However, the impact of spray drying on manufacturability, physiochemical stability and bioavailability in relation to conventional drug load processes are yet to be fully investigated. Using a 2(3) factorial design, this study aims to investigate the effect of drug-loading process (co-spray drying and solvent impregnation), mesoporous silica pore size (SBA-15, 6.5 nm and MCM-41, 2.5 nm) and percentage drug load (30% w/w and 50% w/w) on material properties, crystallinity, physicochemical stability, release profiles and bioavailability of fenofibrate (FEN) loaded into mesoporous silica. From the scanning electronic microscopy (SEM) images, powder X-ray diffraction and Differential scanning calorimetry measurements, it is indicated that the co-spray drying process was able to load up to 50% (w/w) FEN in amorphous form onto the mesoporous silica as compared to the 30% (w/w) for solvent impregnation. The in vitro dissolution rate of the co-spray dried formulations was also significantly (p = 0.044) better than solvent impregnated formulations at the same drug loading. Six-month accelerated stability test at 40 °C/75 RH in open dish indicated excellent physical and chemical stability of formulations prepared by both methods. The amorphous state of FEN and the enhanced dissolution profiles were well preserved, and very low levels of degradation were detected after storage. The dog data for the three selected co-spray-dried formulations revealed multiple fold increment in FEN bioavailability compared to the reference crystalline FEN. These results validate the viability of co-spray-dried mesoporous silica formulations with high amorphous drug load as potential drug delivery systems for poorly water soluble drugs.

Effect of binders on the release rates of direct molded verapamil tablets using twin-screw extruder in melt granulation.

Conventional manufacturing of pharmaceutical tablets often involves single processes such as blending, granulation, milling and direct compression. A process that minimizes and incorporates all these in a single continuous step is desirable. The concept of omitting milling step followed by direct-molding of tablets utilizing a twin-screw extruder in a melt granulation process using thermoplastic binders was explored. The objective of this study was to investigate the effect of combining hydrophilic binder (HPMC K4M, PEO 1M), and hydrophobic binder (Compritol® ATO 888, Precirol® ATO 5) on the release profiles of direct-molded tablets and direct-compressed tablets from milled extrudates using a quality-by-design approach. It was identified that hydrophilic binder type and process significantly affects (p=0.005) the release profiles of verapamil. Moreover, two-way interaction analysis demonstrated that the combination of process with type of hydrophilic polymer (p=0.028) and the type of hydrophilic polymer with polymer ratio (p=0.033) significantly affected the release profiles. The formulation release kinetics correlated to Higuchi release model and the mechanism correlated to a non-Fickian release mechanism. The results of the present study indicated that direct-molded tablets with different release profiles can be manufactured without milling process and through a continuous melt granulation using twin-screw extruder with appropriate thermoplastic binder ratio.