Steroid-eluting contact lenses for corneal and intraocular inflammation.

Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation.

Enhancement of covalent aggregate quantification of protein therapeutics by non-reducing capillary gel electrophoresis using sodium hexadecyl sulfate (CE-SHS).

Capillary gel electrophoresis (CGE) using sodium dodecyl sulfate (CGE-SDS or CE-SDS) is commonly used in the biotechnology industry to assess the purity of a complex therapeutic during manufacturing process optimization and also for commercial release and stability testing. However, for therapeutic proteins mAb-1 and mAb-2, non-reducing (NR) CE-SDS yielded higher than expected % aggregate which considerably lowered its apparent purity relative to the purity reported by other complementary methods, such as Size Exclusion Chromatography (SEC). Furthermore, a strong protein load dependence on aggregate levels was observed which prevented any reasonable assessment of the true purity value.

Minimization of artifact protein aggregation using tetradecyl sulfate and hexadecyl sulfate in capillary gel electrophoresis under reducing conditions.

In the biopharmaceutical industry, CE-SDS assesses the purity, heterogeneity, and stability of therapeutic proteins. However, for mAb-1 and mAb-2, typical CE-SDS under reducing conditions produced atypical protein peak profiles, which led to biased purity results, thus were not acceptable for biologics manufacturing. This bias was caused by the formation of method-induced higher molecular weight artifacts, the levels of which correlated with protein concentration.

Synthesis and application of β-carbolines as novel multi-functional anti-Alzheimer's disease agents.

The design, synthesis and assessment of β-carboline core-based compounds as potential multifunctional agents against several processes that are believed to play a significant role in Alzheimer's disease (AD) pathology, are described. The activity of the compounds was determined in Aβ self-assembly (fibril and oligomer formation) and cholinesterase (AChE, BuChE) activity inhibition, and their antioxidant properties were also assessed. To obtain insight into the mode of action of the compounds, HR-MS studies were carried out on the inhibitor-Aβ complex formation and molecular docking was performed on inhibitor-BuChE interactions.

Sulfonamides as multifunctional agents for Alzheimer's disease.

Sulfonamide linker-based inhibitors with extended linear structure were designed and synthesized with the aim of producing multifunctional agents against several processes involved in the pathology of Alzheimer's disease (AD). The potency of the compounds were assessed in the inhibition of Aβ self-assembly (fibril and oligomer formation), in modulating cholinesterase (AChE, BuChE) activity, and scavenging free radicals. Several compounds exhibited promising Aβ self-assembly and cholinesterase inhibition and in parallel, showed good free radical scavenging properties.

Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer's disease.

A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (Aβ) self-assembly and the disassembly of preformed Aβ oligomers. Several compounds showed excellent potential as multifunctional compounds for AD.

Diaryl hydrazones as multifunctional inhibitors of amyloid self-assembly.

The design and application of an effective, new class of multifunctional small molecule inhibitors of amyloid self-assembly are described. Several compounds based on the diaryl hydrazone scaffold were designed. Forty-four substituted derivatives of this core structure were synthesized using a variety of benzaldehydes and phenylhydrazines and characterized.

Pharmacophore Modeling, virtual and in vitro screening for acetylcholinesterase inhibitors and their effects on amyloid-β self- assembly.

One of the most promising methods of unveiling the pharmacology of marketed drugs is to screen them against new biological targets. In an attempt to find inhibitors for acetylcholinesterase (AChE), the Drug Bank Database and natural alkaloids with other known medicinal values were screened through a four-point pharmacophore built in this study. The development of the pharmacophore was based on a structurally diverse set of reported AChE inhibitors and was validated using a separate set of known inhibitors.