33 research outputs found
Pharmacy students’ perceptions and attitudes towards experiential training in Jordan and United Kingdom
Purpose: To examine the quality of pharmaceutical experiential training by developing an experiential training survey.
Methods: An online survey was placed on E-learning platforms in Jordan and UK to develop a validated instrument that can assess pharmacy students' perceptions of the experiential program implemented in their curricula.
Results: A total of 377 students from Jordan (250 students) and the UK (127 students) completed the survey. Principal component analysis was used to conduct exploratory factor analysis and to assess the factor structure for the data. A two-factor model was applied to the data obtained from the students. These factors included students’ feelings toward experiential training (Perceiver Feelings; PF) and their ability to conduct a full Pharmaceutical Care Plan (PCP). Students from both Jordan and the UK showed a higher satisfaction PF score toward the experiential training program compared to PCP. Being female and not having prior practice experience led to significantly lower PCP scores compared to males and having a prior practice experience, respectively.
Conclusion: The availability of a validated questionnaire will help in investigating the effectiveness of experiential training courses.
Keywords: Experiential training; Factor Analysis; Survey development; Pharmac
Bioinspired Polymerization of Quercetin to Produce a Curcumin-Loaded Nanomedicine with Potent Cytotoxicity and Cancer-Targeting Potential in Vivo
Nanomedicine has had a profound impact on the treatment of many diseases, especially cancer. However, synthesis of multifunctional nanoscale drug carriers often requires multistep coupling and purification reactions, which can pose major scale-up challenges. Here, we leveraged bioinspired oxidation-triggered polymerization of catechols to synthesize nanoparticles (NPs) from the plant polyphenol quercetin (QCT) loaded with a hydrophobic anticancer drug, curcumin, and functionalized with poly(ethylene glycol) (PEG) for steric stabilization in one reaction step. NPs were formed by base-catalyzed oxidative self-polymerization of QCT in the presence of curcumin and thiol-terminated PEG upon mixing in a universal solvent (dimethyl sulfoxide), followed by self-assembly with the gradual addition of water. Dynamic light scattering and X-ray photoelectron spectroscopy were used to confirm NP PEGylation. Drug loading was verified by UV–vis spectroscopy. Curcumin-loaded NPs were efficiently internalized by CT26 murine colon cancer cells as determined by flow cytometry and confocal microscopy. NPs also demonstrated sustained release and potent cytotoxicity in vitro. Moreover, in vivo imaging of CT26 tumor-bearing Balb/c mice following tail vein injection of DiR-labeled QCT NPs showed steady tumor accumulation of the NPs up to 24 h. This was further supported by significant tumor uptake of curcumin-loaded QCT NPs as measured by flow cytometry analysis of tumor homogenates. Our findings present a greener synthetic route for the fabrication of drug-loaded surface-functionalized NPs from poorly water-soluble plant polyphenols such as QCT as promising anticancer delivery systems
Development and characterization of k-carrageenan platforms as periodontal intra-pocket films
Purpose: To prepare emulsion-based Intrapocket polymeric films for the treatment of periodontitis.
Method: Films were fabricated by dehydration of an emulsion containing k-carrageenan (KC) in aqueous phase and Compritol® 888 ATO (Compritol® ) or Dimodan® UJ (DU® ) or different ratios of both. The resulting films were characterized by mechanical texture analyser to determine Young’s modulus and tensile strength. Glass transition temperature (Tg) of the films was evaluated by dynamic mechanical and thermal analyser while surface morphology was evaluated using scanning electron microscope. In-vitro drug release was conducted in pre-warmed phosphate buffer. Bacterial adherence was assessed after 24 h.
Results: Young’s modulus was highest for KC films to which no lipid was added (5.33 ± 0.38 GPa) and decreased following lipid incorporation. Tg was highest in KC films (106.25 ± 4.53 ° C) but decreased upon addition of lipids. The surface of KC was smooth but roughness increased with increasing Compritol® load. Drug release from KC films was complete (99.80 ± 8.43 %) after 2 h; however, upon adding lipid, the release was extended 8 h and was affected by lipid type and ratio. Microbiologic assay demonstrated noticeable reduction in viable count compared to control and was affected by lipid type and ratio. The film formulated from a combination of DU® and Compritol® in a ratio of 80:20 was strong, flexible and reduced microbial adherence. Moreover, it showed a smooth surface and extended release for over 8 h.
Conclusion: Intra-pocket films were prepared by drying emulsion-based films. Resulted films were strong, flexible, prolonged drug release over 8 h and could lower bacterial growth. The prepared film may offer efficient treatment in periodontitis patients
Exhausted Grape Seed Residues as a Valuable Source of Antioxidant Molecules for the Formulation of Biocompatible Cosmetic Scrubs
Grape seed of Obeidi, a white Lebanese autochthonous variety, was previously tested in different studies as a valuable source of bioactive molecules such as polyphenols, oils, and proteins by means of extraction procedures for the development of cosmetic and therapeutic products. However, an un-valorized, exhausted grape seed residue remains as "secondary waste" after the extraction processes. In this study, the exhausted seeds have been further exploited to produce cosmetic scrubs capable of releasing antioxidant molecules during the exfoliation process, in accordance with the principles of the circular economy and going toward a zero-waste process. The deep characterization of the exhausted seeds confirmed the presence of antioxidant phenolic molecules including gallic acid, catechins and protocatechuic acid (0.13, 0.126, and 0.089 mg/g of dry matter DM), and a high phenolic content (11.85 mg gallic acid equivalents (GAE)/g of dry matter (DM)). Moreover, these residues were shown to possess a sandy texture (Hausner ratio (HR): 1.154, Carr index (CI): 0.133, and angle of repose: 31.62 (& DEG;) degrees), similar to commercial natural exfoliants. In this respect, exhausted Obeidi grape seed residues were incorporated at increasing concentrations (0.5, 1, 1.5, and 2% w/w) in a cosmetic scrub, and stored for 5 weeks at 4, 25, and 50 & DEG;C for stability testing. All tested scrub formulations exhibited good spreadability with a spread diameter of 3.6-4.7 cm and excellent physical stability, as no phase separation or color change were observed after four cycles of heat shock at 4 and 50 & DEG;C. Finally, an in vivo skin irritation test showed that the scrub enriched with 1.5% of exhausted Obeidi grape seed residues was the most promising formulation, as it possessed a high amount of phenolic molecules (0.042 & PLUSMN; 0.001 mg GAE/mL of scrub) and good stability and could be safely applied to the skin with no irritation phenomena. Overall results underlined that exhausted grape seed residues can be transformed into promising systems for both physical and chemical exfoliation, thus confirming the importance of the effective exploitation of agro-industrial by-products for the development of high value cosmeceutics towards a more sustainable and zero-waste approach
Nature-Inspired Polymerization of Quercetin to Produce Antioxidant Nanoparticles with Controlled Size and Skin Tone-Matching Colors
Plant polyphenols have received considerable attention in recent years due to their ability to undergo oxidation-triggered self-polymerization, forming biocompatible versatile coatings and templated nanoparticles (NPs) that can be leveraged for a variety of biomedical applications. Here we show for the first time that untemplated NPs can be conveniently synthesized from the abundant plant polyphenol quercetin (QCT) simply by incubation with an oxidizing agent in a universal organic solvent, followed by self-assembly upon gradual addition of water. The process yielded NPs of around 180–200 nm in size with a range of colors that resembled light to medium-brown skin tones. The NPs were characterized by UV-Vis, FT-IR, and 1H-NMR spectroscopy and by dynamic light scattering and transmission electron microscopy to understand their physicochemical properties. Antioxidant and cell viability assays were also conducted to demonstrate the NPs’ free-radical scavenging activity and biocompatibility, altogether providing valuable insights into the structure and function of this emerging class of nanomaterials to guide future biomedical applications
Vitamin E TPGS-Poloxamer Nanoparticles Entrapping a Novel PI3Kα Inhibitor Potentiate Its Activity against Breast Cancer Cell Lines
N-(2-fluorphenyl)-6-chloro-4-hydroxy-2-quinolone-3-carboxamide (R19) is a newly synthesized phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitor with promising activity against cancer cells. The purpose of this study was to develop a polymeric nanoparticle (NP) formulation for R19 to address its poor aqueous solubility and to facilitate its future administration in preclinical and clinical settings. NPs were prepared by nanoprecipitation using two polymers: D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) and the poloxamer Pluronic P123 in different ratios. Physicochemical characterization of the NPs revealed them to be around 100 nm in size with high monodispersity, a spherical morphology, and an almost neutral surface charge. The NPs achieved ~60% drug loading efficiency and sustained release of R19 for up to 96 h, with excellent colloidal stability in serum-containing cell culture media. NPs containing TPGS enhanced R19’s potency against MCF-7 and MDA-MB-231 breast cancer cells in vitro, with half-maximal inhibitory concentrations (IC50) ranging between 1.8 and 4.3 µM compared to free R19, which had an IC50 of 14.7–17.0 µM. The NPs also demonstrated low cytotoxicity against human dermal fibroblasts and more significant induction of apoptosis compared to the free drug, which was correlated with their cellular uptake efficiency. Our findings present a biocompatible NP formulation for the delivery of a cancer-targeted PI3Kα inhibitor, R19, which can further enhance its potency for the treatment of breast cancer and potentially other cancer types
A Multi-Scale Hybrid Nanoparticle Platform with Controlled Cellular Interaction and Targeting Kinetics
Polymeric nanoparticles (NPs) and dendrimers are two major classes of nanomaterials that have demonstrated great potential for targeted drug delivery. However, they each have drawbacks such as limited tissue diffusivity/tumor penetration and rapid in vivo elimination, respectively. To address these issues, as a proof-of-concept study, we designed hybrid NPs (nanohybrids) that combined a polycationic polymer, PEI, with protective outer layers of polylactide-co-glycolide (PLGA), polyethylene glycol-b-polylactide-co-glycolide (PEG-PLGA), or PEGylated liposomes. The nanohybrids demonstrated controlled cellular interactions and cytotoxicity kinetics by controlling the release of PEI. We then investigated the ability of the nanohybrid platform to control the targeting kinetics of actively-targeted dendrimer conjugates forming the core of the nanohybrids. Folate (FA)-targeted poly(amidoamine) dendrimers were encapsulated within poly(ethylene glycol)-b-poly(D,L-lactide) NPs. The nanohybrids (~100 nm NPs encapsulating ~5 nm targeted dendrimers) maintained high selectivity to FA receptor (FR)-overexpressing KB cells (KB FR+) resembling the selectivity of free dendrimers, while displaying controlled cellular interaction kinetics due to the presence of the polymeric NP shells. Simulated penetration assays using multicellular tumor spheroids of KB FR+ cells revealed that the targeted dendrimers penetrated deep into the spheroids upon their release from the nanohybrids, whereas the NP shell did not. Biodistribution studies in healthy and tumor-bearing mice showed that by encapsulating FA-targeted dendrimers within PEGylated NPs, the larger size of the nanohybrids and the controlled release of the dendrimer conjugates delayed their renal elimination. This allowed for more efficient tumor accumulation compared to free FA-targeted dendrimers through a combination of passive and active targeting. Our results provide evidence that selective cellular interactions can be kinetically controlled by the nanohybrid design, which integrates the unique characteristics of dendrimers (effective targeting and penetration) and polymeric NPs (controlled release, suitable size for passive targeting, and long circulation). This hybrid design strategy demonstrates great potential to enhance the targeting efficacy of the individual nanocarriers
Vitamin E TPGS-Poloxamer Nanoparticles Entrapping a Novel PI3Kα Inhibitor Potentiate Its Activity against Breast Cancer Cell Lines
N-(2-fluorphenyl)-6-chloro-4-hydroxy-2-quinolone-3-carboxamide (R19) is a newly synthesized phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitor with promising activity against cancer cells. The purpose of this study was to develop a polymeric nanoparticle (NP) formulation for R19 to address its poor aqueous solubility and to facilitate its future administration in preclinical and clinical settings. NPs were prepared by nanoprecipitation using two polymers: D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) and the poloxamer Pluronic P123 in different ratios. Physicochemical characterization of the NPs revealed them to be around 100 nm in size with high monodispersity, a spherical morphology, and an almost neutral surface charge. The NPs achieved ~60% drug loading efficiency and sustained release of R19 for up to 96 h, with excellent colloidal stability in serum-containing cell culture media. NPs containing TPGS enhanced R19’s potency against MCF-7 and MDA-MB-231 breast cancer cells in vitro, with half-maximal inhibitory concentrations (IC50) ranging between 1.8 and 4.3 µM compared to free R19, which had an IC50 of 14.7–17.0 µM. The NPs also demonstrated low cytotoxicity against human dermal fibroblasts and more significant induction of apoptosis compared to the free drug, which was correlated with their cellular uptake efficiency. Our findings present a biocompatible NP formulation for the delivery of a cancer-targeted PI3Kα inhibitor, R19, which can further enhance its potency for the treatment of breast cancer and potentially other cancer types
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Facile synthesis and surface modification of bioinspired nanoparticles from quercetin for drug delivery
Nanoparticle-mediated drug delivery has demonstrated great potential to treat various diseases especially cancer. However, there is an unmet need for the scalable synthesis of multifunctional nanoparticles to meet the complex challenges of drug delivery. Here we show that we can synthesize nanoparticles from the polyphenol quercetin, which can be conveniently functionalized with ligands and drug molecules by simple mixing under ambient conditions. Nanoparticles (∼30-40 nm in diameter) were formed by oxidative self-polymerization of quercetin in alkaline buffer (pH 9). The reactivity of oxidized polyphenols was exploited to immobilize amine-terminated methoxy poly(ethylene glycol) on the nanoparticles' surface for steric stability, followed by loading with doxorubicin as a model drug. Surface modification of the nanoparticles was confirmed by X-ray Photoelectron Spectroscopy. An antioxidant assay showed that the nanoparticles retained some antioxidant activity. The nanoparticles were readily internalized by KB cells via an endo-lysosomal pathway. Doxorubicin-loaded nanoparticles showed a drug loading of 35.6 ± 4.9% w/w with a loading efficiency of 88.9 ± 12.4%, sustained drug release, and potent cytotoxicity in vitro. Our findings demonstrate a promising new application for naturally occurring polyphenols as a renewable source of drug delivery nanocarriers that can be synthesized at low cost with minimal equipment