Tracing the architecture of caffeic acid phenethyl ester cocrystals: studies on crystal structure, solubility, and bioavailability implications

YesCaffeic acid phenethyl ester (CAPE) is a polyphenolic active compound present in popular apiproduct, ‘propolis’ obtained from beehives. Though it has broad therapeutic capability, the bioavailability of CAPE is limited due to poor solubility. In this study, we report novel cocrystals of CAPE engineered using coformers such as caffeine (CAF), isonicotinamide (INIC), nicotinamide (NIC) with enhanced solubility and bioavailability of CAPE. The cocrystals were prepared by microwave-assisted cocrystallization and characterized using PXRD, DSC and Raman spectroscopy. PXRD and DSC confirm the successful formation and phase purity of CAPE-CAF, CAPE-INIC and CAPE-NIC cocrystals. Raman spectra of CAPE cocrystals complement these results in confirming the formation of novel crystalline phases. CAPE-NIC cocrystal was further subjected to X-ray crystallography to understand its molecular arrangement and hydrogen bonding in the crystal structure. The CAPE-NIC cocrystal structure is found to be stabilized by a rare 1,2-benzenediol-amide heterosynthon. Cocrystallization of CAPE with NIC improved its aqueous solubility and pharmacokinetic profile thereby demonstrating 2.76 folds escalation in bioavailability.We thank UKIERI: UK-India Education and Research Initiative (TPR26) and EPSRC (EP/J003360/1, EP/L027011/1) for providing financial support during this study

Liquid crystalline phase as a probe for crystal engineering of lactose: carrier for pulmonary drug delivery

noThe current work was undertaken to assess suitability of liquid crystalline phase for engineering of lactose crystals and their utility as a carrier in dry powder inhalation formulations. Saturated lactose solution was poured in molten glyceryl monooleate which subsequently transformed into gel. The gel microstructure was analyzed by PPL microscopy and SAXS. Lactose particles recovered from gels after 48 h were analyzed for polymorphism using techniques such as FTIR, XRD, DSC and TGA. Particle size, morphology and aerosolisation properties of prepared lactose were analyzed using Anderson cascade impactor. In situ seeding followed by growth of lactose crystals took place in gels with cubic microstructure as revealed by PPL microscopy and SAXS. Elongated (size approximately 71 mum) lactose particles with smooth surface containing mixture of alpha and beta-lactose was recovered from gel, however percentage of alpha-lactose was more as compared to beta-lactose. The aerosolisation parameters such as RD, ED, %FPF and % recovery of lactose recovered from gel (LPL) were found to be comparable to Respitose(R) ML001. Thus LC phase (cubic) can be used for engineering of lactose crystals so as to obtain particles with smooth surface, high elongation ratio and further they can be used as carrier in DPI formulations

Can green synthesized propolis loaded silver nanoparticulate gel enhance wound healing caused by burns?

NoNanotechnology can offer new opportunities in the fight against infection. The aim of current work was to investigate an eco-friendly method for synthesis of silver nanoparticles (AgNP) which have the ability to load lipophilic compounds onto their surface. Pharmaceutically acceptable hydrophilic lipid (Gelucire® 50/13) has been used as a reducing agent for in situ reduction of silver nitrate so as to obtain silver nanoparticles. Propolis is used as model molecule for loading onto surface of AgNP owing to its well reported broad range of pharmacological activities including anti-inflammatory, antioxidant and antimicrobial activity. Propolis loaded silver nanoparticles (PLSN) were prepared and characterized for silver content, surface plasmon resonance, particle size, XRD, FTIR, TEM, antibacterial activity and burn wound healing in wistar rats. Propolis constituents were successfully loaded onto surface of AgNP using the proposed conceptual method. The formation of PLSN having size 24.3 ± 2.5 nm was confirmed using surface plasmon resonance, FTIR, XRD and TEM. The combination of propolis with AgNP significantly reduced minimum inhibitory concentration of AgNP alone when tested against Staphylococcus aureus. PLSN gel showed comparable burn wound healing in wistar rats when tested against marketed silver sulfadiazine gel. The use of Gelucire® as solubilizing agent for lipophillic drugs was effectively utilized for loading lipophillic constituents of propolis onto the AgNP. This potentially provides an effective method for the green synthesis of AgNP which can be used to load lipophillic molecules onto their surface whenever such combination is required

Global circumferential and radial strain among patients with immune checkpoint inhibitor myocarditis

BACKGROUND Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS. OBJECTIVES This study aimed to detail the role of GCS and GRS in ICI myocarditis. METHODS In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death. RESULTS Cases and controls were similar in age (66 15 years vs 63 12 years; P ¼ 0.20), sex (male: 73% vs 61%; P ¼ 0.20) and cancer type (P ¼ 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% 3.4% vs 23.5% 3.8%; P ¼ 0.14; GRS: 45.5% 6.2% vs 43.6% 8.8%; P ¼ 0.24). Overall, 56% (n ¼ 42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% 4.2% vs 23.6% 3.0%; P < 0.001; GRS: 28.6% 6.7% vs 47.0% 7.4%; P < 0.001). Over a median follow-up of 30 days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95% CI: 1.6-15.0]; P ¼ 0.005) and GRS (HR: 3.9 [95% CI: 1.4-10.8]; P ¼ 0.008) below the median was associated with an increased event rate. In receiveroperating characteristic (ROC) curves, GCS (AUC: 0.80 [95% CI: 0.70-0.91]) and GRS (AUC: 0.76 [95% CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95% CI: 0.58-0.82]), LVEF (AUC: 0.69 [95% CI: 0.56-0.81]), and age (AUC: 0.54 [95% CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P ¼ 0.04) and GCS over cTnT (P ¼ 0.002). CONCLUSIONS GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance. (J Am Coll Cardiol Img 2022;15:1883–1896) © 2022 the American College of Cardiology Foundation. Published by Elsevier. All rights reserved