Pharmacokinetic availability of proteolytic enzymes after oral administration: a narrative review of the literature

Orally administered serine and cysteine proteolytic enzymes are used extensively in the therapy of various inflammatory conditions. However, due to their protein nature, there have been concerns about these enzymes undergoing digestion or biotransformation in the gut and the resultant amount of active enzyme reaching blood circulation and at the site of inflammation. Research has shown that orally administered serine and cysteine proteases are able to pass through the mucosal barrier of the gastrointestinal tract and reach the blood and lymph as intact, high molecular weight and physiologically active forms. These have been studied in in vitro, animal models and further confirmed in human studies. Despite high inter-individual variability, the maximum plasma levels of the free proteases follow dose linearity. They circulate bound to plasma anti-proteases and are detectable in clinically significant concentrations. Targeted studies also indicate that paracellular transport mechanism may play a significant role in the absorption of these molecules. We present a summary of the existing knowledge from these studies

A comparative analysis of pain reduction following a single intra-articular injection of platelet-rich plasma, steroid or normal saline in chronic external shoulder impingement syndrome

Background: Shoulder impingement is a common diagnosis for patients with pain and dysfunction of shoulder joint. Due to its chronicity of clinical manifestation of the impingement syndrome, there is a need to find new therapies that collaborate to improve pain management. Methods: A hospital based descriptive, epidemiological study was conducted with 150 patients. The patients were divided in the following three groups of 50 patients each: Platelet-rich plasma (PRP) group: 50 patients received PRP, steroid group: 50 patients received steroid injection normal saline group: 50 patients received normal saline injection. Baseline visual analogue scale (VAS) score on overhead activities were recorded. After the 4th week, 12th week, and 24th week, patients were examined in the outpatient clinic. The main outcome measure was pain with overhead activities using a VAS. Results: The VAS score improved significantly in PRP group and Steroid group compared to normal saline group at the 4th week, 12th-week and 24th-week follow-up periods post injection, as per ANOVA test (p<0.05). Conclusions: PRP and steroids, both can be considered effective methods to treat pain in chronic shoulder impingement syndrome (SIS) and less invasive compared to surgical treatment. They improve the pain and hence shoulder function in chronic impingement syndrome

Composite supramolecular nanoassemblies with independent stimulus sensitivities

U.S. Army Research Office; National Science Foundation; Chinese National Science Foundation [51173135]; PHaSE Energy Frontier Research Centre; Basic Energy Sciences of the U.S. Department of Energy; NSF-IGERT programNanoscale assemblies with stimuli-sensitive features have attracted significant attention due to implications in a variety of areas ranging from materials to biology. Recently, there have been excellent developments in obtaining nanoscale structures that are concurrently sensitive to multiple stimuli. Such nanostructures are primarily focused on a single nanostructure containing an appropriate combination of functional groups within the nanostructure. In this work, we outline a simple approach to bring together two disparate supramolecular assemblies that exhibit very different stimuli-sensitive characteristics. These composite nanostructures comprise a block copolymer micelle core and nanogel shell, both of which can preserve their respective morphology and stimulus sensitivities. The block copolymer is based on poly(2-(diisopropylamino) ethylmethacrylate-b-2-aminoethylmethacrylate hydrochloride), which contains a pH-sensitive hydrophobic block. Similarly, the redox-sensitive nanogel is derived from a poly(oligoethyleneglycolmonomethylethermethacrylate-co-glycidylmethacrylate-co-pyridyldisulfide ethylmethacrylate) based random copolymer. In addition to the independent pH-response of the micellar core and redox-sensitivity of the nanogel shell in the composite nanostructures, the synergy between the micelles and the nanogels have been demonstrated through a robust charge generation in the nanogels during the disassembly of the micelles. The supramolecular assembly and disassembly have been characterized using transmission electron microscopy, dynamic light scattering, zeta potential measurements, fluorescence spectroscopy and cellular uptake

Tethered tertiary amines as solid-state n-type dopants for solution-processable organic semiconductors

A scarcity of stable n-type doping strategies compatible with facile processing has been a major impediment to the advancement of organic electronic devices. Localizing dopants near the cores of conductive molecules can lead to improved efficacy of doping. We and others recently showed the effectiveness of tethering dopants covalently to an electron-deficient aromatic molecule using trimethylammonium functionalization with hydroxide counterions linked to a perylene diimide core by alkyl spacers. In this work, we demonstrate that, contrary to previous hypotheses, the main driver responsible for the highly effective doping observed in thin films is the formation of tethered tertiary amine moieties during thin film processing. Furthermore, we demonstrate that tethered tertiary amine groups are powerful and general n-doping motifs for the successful generation of free electron carriers in the solid-state, not only when coupled to the perylene diimide molecular core, but also when linked with other small molecule systems including naphthalene diimide, diketopyrrolopyrrole, and fullerene derivatives. Our findings help expand a promising molecular design strategy for future enhancements of n-type organic electronic materials

BODIPY-based panchromatic π-conjugated polymers for organic photovoltaics

In a highly interdisciplinary field, such as organic photovoltaics (OPVs), developing a predictive understanding of the relationship between molecular structures, morphology of the photoactive layer and the ultimate device performance is the key to unlocking the vast potential of this field. Although isolated examples of high-performance organic molecules are prevalent in the literature, the reasons for their superior performance are not well understood. The function of an OPV device is dependent of four key processes: (i) light absorption, (ii) charge separation, (iii) charge transport, and (iv) charge collection. While the first three are material-dependent factors, charge collection depends on the nature of the interfaces involved. We have thus investigated a new class of semiconductor molecules based on BODIPY dyes with the aim of understanding how variations in the molecular structure affect the optoelectronic and transport properties of the molecules. First-generation pi-conjugated polymers based on the BODIPY core possess broad and intense absorption spectra. Additionally, the frontier molecular orbital (FMO) energy levels of the polymers can be tuned by a judicious choice of the comonomers. Electron-deficient comonomers with electron affinities higher than that of the BODIPY core, predominantly afford n-type polymers. A unique feature of these semiconductors is their panchromatic absorption spectrum that spans throughout the visible region. Thus these polymers can be considered to be potential electron acceptors in all-polymer solar cells. Copolymerization of BODIPY with electron-rich comonomers, on the other hand, only results in p-type semiconductors. Furthermore, the highest occupied molecular orbital (HOMO) of these polymers is found to correlate with the ionization potential of the electron-rich monomer. Having said that, the lowest unoccupied molecular orbital (LUMO) energy level does not change. Thus for the first time, a correlation between theoretical calculations and experimental observations has been demonstrated for predicting the FMO energy levels of BODIPY-based semiconducting polymers. Second-generation copolymers based on an unsubstituted BODIPY core retain the broad absorption characteristics of the first-generation polymers. In addition, due to reduced electron density on the BODIPY core, the HOMO energy level of the resulting polymers is reduced thereby imparting enhanced oxidative stability to these polymers. Charge transport measurements through thick films (∼1 micron) reveal only p-channel activity with hole mobilities comparable to some of the high-performance polymers reported in literature. Preliminary bulk-heterojunction OPV devices fabricated with these polymers show modest power conversion efficiencies. We believe that understanding the morphology of the active layer in relation to the polymer structure will help improve future molecular designs and eventually, device performance