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Cannabidiol (CBD) has been recognized for its numerous therapeutic benefits, such as neuroprotection, anti-inflammatory effects, and cardioprotection. However, CBD has some limitations, including unpredictable pharmacokinetics and low oral bioavailability. To overcome the challenges associated with CBD delivery, we employed Design of Experiments (DoE), lipid carriers, and 3D printing techniques to optimize and develop buccal film loaded with CBD-NLCs. Three-factor Box-Behnken Design was carried out to optimise the NLCs and analyse the effect of independent factors on dependent factors. The emulsification-ultrasonication technique was used to prepare the NLCs. A pressure-assisted micro-syringe printing technique was used to produce the films. The produced films were studied for physicochemical, and mechanical properties, release profiles, and predicted in vivo performance. The observed particle size of the NLCs ranged from 12.17 to 84.91 nm whereas the PDI varied from 0.099 to 0.298. Lipid and sonication time positively affected the particle size whereas the surfactant concentration was inversely related. CBD was incorporated into the optimal formulation and the observed particle size, PDI, and zeta potential for the CBD-NLCs were 94.2 ± 0.47 nm, 0.11 ± 0.01 and − 11.8 ± 0.52 mV. Hydroxyethyl cellulose (HEC)-based gel containing the CBD-NLCs was prepared and used as a feed for 3D printing. The CBD-NLCs film demonstrated a slow and sustained in vitro release profile (84. 11 ± 7.02% in 6 h). The predicted AUC0–10 h, Cmax, and Tmax were 201.5 µg·h/L, 0.74 µg/L, and 1.28 h for a film with 0.4 mg of CBD, respectively. The finding demonstrates that a buccal film of CBD-NLCs can be fabricated using 3D printing. [ABSTRACT FROM AUTHOR]

Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy. From the initial screening of polymers for their potential to improve the solubility and stability, Soluplus (SOL) was selected. The optimized NCF demonstrated over 20,000-fold improvement in aqueous solubility as a result of amorphization, hydrogen bonding interaction, and micellization determined using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy. Moreover, the greater stabilizing effect in alkaline pH and light was observed. Furthermore, significant enhancement of dissolution and permeability of CUR across everted sacs of rat small intestine were noticed. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 117 and 17-fold in case of NCF and physical mixture of CUR and SOL compared to CUR suspension. These results suggest NCF identified as a promising new approach for repositioning of CUR for pharmaceutical application by enhancing the oral bioavailability of CUR. The findings herein stimulate further in vivo evaluations and clinical tests of NCF. [ABSTRACT FROM AUTHOR]

A first of its kind, simple, rapid, and sensitive liquid chromatography mass spectrometry (LC-MS/MS) method was developed and validated for quantification of perindopril and perindoprilat in both human plasma and breast milk. The analytes and internal standards (phenazone and acetyl salicylic acid) were extracted from biological matrices by protein precipitation. A Phenomenex® C-18 column was used to provide an appropriate chromatographic separation of the analytes, followed by detection with tandem mass spectrometry. Gradient chromatographic and mass spectrometric detection conditions with mobile phases (A: 5% methanol + 0.1% formic acid in water v/ v, and B: 95% methanol + 0.1% formic acid in water v/ v) were developed to achieve a LOQ of 0.5 ng/mL in both human plasma and milk. The method was suitable of evaluating clinical samples. The mass transition was followed as m/z 369.10/172.00 for perindopril, m/z 339.00/168.10 for perindoprilat, m/z 188.90/55.95 for phenazone, and m/z 179.04/137.02 for acetyl salicylic acid. The developed method was optimized and validated with a linear range of 0.1-200 ng/mL ( r = better than 0.99 for both perindopril and perindoprilat). The precision and accuracy values were within 15% CV. The overall recovery of the analytes was 80-110%. The method has good specificity and repeatability. Stability studies were conducted in both human plasma and bovine milk for up to 3 months, at the storage conditions of 25, 4, and −80 °C. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) mostly affects the elderly population and is frequently diagnosed at an advanced stage. Self-expanding metal stents (SEMS) are the most popular mode of palliation, but they are associated with reocclusion caused by tumor growth. To overcome this problem, docetaxel (DTX)-loaded polyurethane formulations were prepared for stent application. The films were evaluated against the cancer cell lines, OE-19 and OE-21, and normal esophageal cell line Het-1A. The DTX and the formulations were evaluated in vitro for the cytotoxicity and in vivo in nude mice. It was found that DTX and the formulations have a weak activity against the EC cell lines and an even weaker activity against Het-1A cell line. Preliminary in vivo studies showed skin toxicity in nude mice necessitating modification of the formulation. Reevaluation in a mouse xenograft model resulted in toxicity at high dose formulations while the low dose formulation exhibited modest advantage over commercial IV formulation; however, there was no significant difference between the commercial IV and blank formulation. DTX combination with an anti-cancer agent having complementary mode of action and non-overlapping toxicity could yield better outcome in future. [ABSTRACT FROM AUTHOR]