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Full-Text Articles in Medicine and Health Sciences
Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang
Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang
Pharmacy Faculty Articles and Research
The cellular delivery of cell-impermeable and water-insoluble molecules remains an ongoing challenge to overcome. Previously, we reported amphipathic cyclic peptides c[WR]4 and c[WR]5 consisting of alternate arginine and tryptophan residues as nuclear-targeting molecular transporters. These peptides contain an optimal balance of positive charge and hydrophobicity, which is required for interactions with the phospholipid bilayer to facilitate their application as a drug delivery system. To further optimize them, we synthesized and evaluated a multivalent tricyclic peptide as an efficient molecular transporter. The monomeric cyclic peptide building blocks were synthesized using Fmoc/tBu solid-phase chemistry and cyclization in the …
Ligand-Installed Polymeric Nanocarriers For Combination Chemotherapy, Xinyuan Xi
Ligand-Installed Polymeric Nanocarriers For Combination Chemotherapy, Xinyuan Xi
Theses & Dissertations
Combination chemotherapy remains the mainstay of cancer treatment because such strategy targets different cell signaling pathways to decrease the likelihood of developing protective mechanisms by cancer cells, thereby delaying the onset of recurrence and prolonging the survival. The co-delivery of binary drug combination via a single nanocarrier provides benefits in reducing dose-limiting toxicities, improving the pharmacokinetic properties of the cargo, spatial-temporal synchronization of drug exposure, and synergistic therapeutic effects. Rational design of such regimen is crucial for maximizing the therapeutic effects since only certain drug ratios exposed to the target might be synergistic while other ratios exert additive or even …
Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi
Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi
Pharmacy Faculty Articles and Research
COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics. To this end, the innate RNA interference (RNAi) mechanism can be employed to develop front line therapies against …
Comparative Molecular Transporter Properties Of Cyclic Peptides Containing Tryptophan And Arginine Residues Formed Through Disulfide Cyclization, Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari, Keykavous Parang
Comparative Molecular Transporter Properties Of Cyclic Peptides Containing Tryptophan And Arginine Residues Formed Through Disulfide Cyclization, Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari, Keykavous Parang
Pharmacy Faculty Articles and Research
We have previously reported cyclic cell-penetrating peptides [WR]5 and [WR]4 as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)xC] and linear counterparts (C(WR)xC), where x = 4–5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast …
Recent Advances In Stimuli-Responsive Drug Release And Targeting Concepts Using Mesoporous Silica Nanoparticles, Ghada G. Abdo, Moustafa M. Zagho, Ashraf Khalil
Recent Advances In Stimuli-Responsive Drug Release And Targeting Concepts Using Mesoporous Silica Nanoparticles, Ghada G. Abdo, Moustafa M. Zagho, Ashraf Khalil
Faculty Publications
Being a developed and promising approach, nanotechnology has attracted a lot of attention in biomedical and pharmaceutical therapy applications. Among nanostructured materials, mesoporous silica nanoparticles (MSNs) are effectively used as nanocarriers for drug delivery systems. MSNs can be tailored-designed by different synthetic techniques. Their morphological characteristics dictate the type of application of such materials. Recently, polymer-based materials have been employed to functionalize the MSNs surface. These modified nanocarriers are loaded with the drug and can unload their “cargo” upon exposure to either endogenous or exogenous types of stimuli. In this study, different targeting concepts, including passive, active, vascular, nuclear, and …
Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann
Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann
Electronic Theses and Dissertations
Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …
Gsk3787-Loaded Poly(Ester Amide) Particles For Intra-Articular Drug Delivery, Ian J. Villamagna, Danielle M. Mcrae, Aneta Borecki, Xueli Mei, François Lagugné-Labarthet, Frank Beier, Elizabeth Gillies
Gsk3787-Loaded Poly(Ester Amide) Particles For Intra-Articular Drug Delivery, Ian J. Villamagna, Danielle M. Mcrae, Aneta Borecki, Xueli Mei, François Lagugné-Labarthet, Frank Beier, Elizabeth Gillies
Physiology and Pharmacology Publications
© 2020 by the authors. Osteoarthritis (OA) is a debilitating joint disorder affecting more than 240 million people. There is no disease modifying therapeutic, and drugs that are used to alleviate OA symptoms result in side effects. Recent research indicates that inhibition of peroxisome proliferator-activated receptor ffi (PPARffi) in cartilage may attenuate the development or progression of OA. PPARffi antagonists such as GSK3787 exist, but would benefit from delivery to joints to avoid side effects. Described here is the loading of GSK3787 into poly(ester amide) (PEA) particles. The particles contained 8 wt. % drug and had mean diameters of about …
Formulation Strategies To Enhance Solubility And Permeability Of Small Molecules For Drug Delivery Applications, Pradeep Kumar Bolla
Formulation Strategies To Enhance Solubility And Permeability Of Small Molecules For Drug Delivery Applications, Pradeep Kumar Bolla
Open Access Theses & Dissertations
All the new chemical entities/drug molecules intended for therapeutic use must be administered using an appropriate delivery system/dosage form to achieve maximum bioavailability. However, designing a drug delivery system is complex as several factors such as lipophilicity, molecular mass, crystallinity, ionic charge, polymorphic forms and hydrogen bonding) affect the solubility and permeability of these molecules. Biopharmaceutics drug classification system (BCS) categorizes the existing drugs into four classes based on the aqueous solubility and membrane permeability and it is reported that >70% of the drugs are poorly soluble and belong to BCS class II and BCS class IV. Several physical, chemical …