REVIEW | doi:10.20944/preprints201706.0032.v1
Subject: Chemistry And Materials Science, Organic Chemistry Keywords: water-solubility; porphyrin; chlorin; bacteriochlorin; PEGylation; bioconjugation; photodynamic therapy; bioimaging
Online: 6 June 2017 (07:51:04 CEST)
The increasing popularity of porphyrins and hydroporphyrins for application in a variety of biomedical (photodynamic therapy, fluorescence tagging and imaging, photoacoustic imaging) and technical (chemosensing, catalysis, light harvesting) applications is also associated with the growing number of methodologies that enable their solubilization in aqueous media. Natively, the vast majority of synthetic porphyrinic compounds are not water-soluble. Moreover, any water-solubility imposes several restrictions on the synthetic chemist on when to install solubilizing groups in the synthetic sequence, and how to isolate and purify these compounds. This review summarizes the chemical modifications to render synthetic porphyrins water-soluble, with a focus on the work since 2000. Where available, practical data such as solubility, indicators for the degree of aggregation, and special notes for the practicioner are listed. We hope that this review will guide synthetic chemists through the many strategies known to make porphyrins and hydroporphyrins water soluble.
ARTICLE | doi:10.20944/preprints201806.0415.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: PEGylation; safety; pediatric; biologics; polyethylene glycol; excipient; conjugation; polysorbate; hemophilia; rurioctocog alfa pegol
Online: 26 June 2018 (12:15:59 CEST)
Polyethylene glycol (PEG) is an inert, water soluble polymer, used for decades in pharmaceuticals. Although PEG is considered safe, concerns persist about the potential adverse effects of long-term exposure to PEG-containing therapies, specifically in children, following the introduction of PEGylated recombinant factor products used for the treatment of hemophilia. Given the absence of long-term surveillance data, and to evaluate the potential risk, we estimated PEG exposure in the pediatric population receiving US Food and Drug Administration-approved parenteral therapies with pediatric indications. We used a range of pediatric weights and doses based on prescribing information (PI) or treatment guidelines. PIs and reporting websites were searched for information about adverse events (AEs). For a child weighing 50 kg on the highest prophylactic dose of a FVIII product, the range of total PEG exposure was 40–21,840 mg/year; for FIX products, the range was 13–1342 mg/year; and for other products, the range was 383–26,743 mg/year, primarily as a derivative excipient. No AE patterns attributable to PEG were found for any of these products, including potential renal, neurological, or hepatic AEs. Our analyses suggest the pediatric population has had substantial exposure to PEG for several decades, with no evidence of adverse consequences.
REVIEW | doi:10.20944/preprints202108.0447.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Interferons; IFNα; IFNß; IFNγ; antiviral; antiproliferative; immunomodulator; PEGylation; formulation; encapsulate IFNs; drug delivery system; liposomes; polymeric micelles; microparticles; nanoparticles
Online: 23 August 2021 (13:51:44 CEST)
Interferons (IFNs) are cytokines involved in the immune response that act on innate and adaptive immunity. These proteins are natural cell-signaling glycoproteins expressed in response to viral infections, tumors, and biological inducers and constitute the first line of defense of vertebrates against infectious agents. They have been marketed for more than 30 years with considerable impact on the global therapeutic protein market thanks to their diversity in terms of biological activities. They have been used as single agents or with combination treatment regimens, demonstrating promising clinical results, resulting in 22 different formulations approved by regulatory agencies. The 163 clinical trials with currently active IFNs reinforce their importance as therapeutics for human health. However, their application has presented difficulties due to the molecules’ size, sensitivity to degradation, and rapid elimination from the bloodstream. For some years now, work has been underway to obtain new drug delivery systems to provide adequate therapeutic concentrations for these cytokines, decrease their toxicity and prolong their half-life in the circulation. Although different research groups have presented various formulations that encapsulate IFNs, to date, there is no formulation approved for use in humans. The current review exhibits an updated summary of all encapsulation forms presented in the scientific literature for these cytokines IFNα, IFNß, and IFNγ, from the year 1996 to the year 2021, considering parameters such as: encapsulating matrix, route of administration, and encapsulation.
ARTICLE | doi:10.20944/preprints202202.0262.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Ruthenium complex; Carbon monoxide releasing molecule; Hydrophilicity, PEGylation
Online: 22 February 2022 (03:38:19 CET)
The poor water-solubility and instability of Ru(II) carbonyl complex hamper the therapeutic application as CO releasing materials (CO-RMs). To enhance the hydrophilicity and bio-utility of CO, a robust Ru(I) carbonyl sawhorse skeleton were grafted with water-soluble PEGlyated sidearms. Twelve PEGlyted sawhorse Ru2(CO)4 complexes were prepared with satisfactory yields and characterized by IR and 1H- and 13C- NMR. X-ray diffraction analysis of CO-RM 8, 13 and 14 revealed the featured diruthenium sawhorse skeleton and PEGylated axial ligands. The ﬂask-shaking method measures the hydrophilicity of CO-RMs, indicating that both bridging carboxylate ligand and PEGlyated axial ligands regulate the hydrophilicity of these CO-RMs. Under photolysis conditions, CO-RM 4-13 sustainable released therapeutic amounts of CO in myoglobin assay. The correlation of the CO release kinetics and hydrophilicity of CO-RMs demonstrated that the more hydrophilic CO-RM released CO faster. The biological test found the low cytotoxic CO-RM 4 showed a specific anticancer activity toward HT-29 tumour cells.