Impact of liquid lipid on development and stability of trimyristin nanostructured lipid carriers for oral delivery of resveratrol

Houacine, Chahinez; Adams, David R.; Singh, Kamalinder K.

doi:10.1016/j.molliq.2020.113734

Cited by 50 publications

(26 citation statements)

References 59 publications

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“…However, the work of Pinto et al observed both an increase and a decrease, depending on the ratio of solid to liquid lipid and they highlight the importance of the ratio of saturated to unsaturated fatty acids [ 39 ]. Such differing results between experimental reports demonstrate the importance of careful design when specific properties are required but that varying the lipids, the ratios and the surfactant will all have an effect that can best be determined by a carefully executed DOE [ 32 , 40 , 41 ].…”

Section: Resultsmentioning

confidence: 99%

Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

et al. 2021

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Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED.

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Section: Resultsmentioning

confidence: 99%

Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

et al. 2021

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“…The zeta potential of −25.6 signifies good stability of RV-NLCs due to electric repulsion. Our previous report has demonstrated good shelf-life stability of RV-NLCs [ 27 ]. In the presence of physiological media PSS, NLCs showed no disintegration or aggregation with zeta potential in the range of −9 mV due to the presence of an ionic layer on the surface of NLCs.…”

Section: Discussionmentioning

confidence: 99%

“…Blank (non-loaded), RV and RV–dye-loaded trimyristin–triolein NLCs were prepared using a hot melt emulsification technique [ 27 ]. The water phase containing surfactants, sodium cholate (0.25%) and Tween-80 (1%) was heated to 70 °C prior to amalgamation with the melted lipid phase comprising trimyristin (1.5%), triolein (0.5%), phosphatidylcholines (0.5%), Span-80 and RV (1 mg/mL).…”

Section: Methodsmentioning

confidence: 99%

“…RV-NLC stability was assessed in physiological salt solution (PSS), in which ex vivo coronary artery experiments were conducted. RV-NLCs were incubated in PSS, and samples were withdrawn at predetermined time points and assessed for particle size, polydispersity index and zeta potential using a Zetasizer Nano ZS system (Malvern Instruments, Malvern, UK) [ 27 ]. To determine the release rate of RV from NLCs, a dialysis tubing diffusion method was employed.…”

Section: Methodsmentioning

confidence: 99%

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Nanostructured Lipid Carriers Deliver Resveratrol, Restoring Attenuated Dilation in Small Coronary Arteries, via the AMPK Pathway

et al. 2021

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Nanostructured lipid carriers (NLCs) are an emerging drug delivery platform for improved drug stability and the bioavailability of antihypertensive drugs and vasoprotective nutraceutical compounds, such as resveratrol (RV). The objective of this study was to ascertain NLCs’ potential to deliver RV and restore attenuated dilator function, using an ex vivo model of acute hypertension. Trimyristin–triolein NLCs were synthesized and loaded with RV. The uptake of RV-NLCs by human coronary artery endothelial cells (HCAECs) maintained their viability and reduced both mitochondrial and cytosolic superoxide levels. Acute pressure elevation in isolated coronary arteries significantly attenuated endothelial-dependent dilator responses, which were reversed following incubation in RV-NLCs, superoxide dismutase or apocynin (p < 0.0001). RV-NLCs demonstrated a five-fold increase in potency in comparison to RV solution. At elevated pressure, in the presence of RV-NLCs, incubation with Nω-nitro-l-arginine (L-NNA) or indomethacin resulted in a significant reduction in the restored dilator component (p < 0.0001), whereas apamin and TRAM-34 had no overall effect. Incubation with the adenosine monophosphate-activated protein kinase (AMPK) inhibitor dorsomorphin significantly attenuated dilator responses (p < 0.001), whereas the SIRT-1 inhibitor EX-527 had no effect. RV-NLCs improved the impaired endothelial-dependent dilation of small coronary arteries, following acute pressure elevation, via NO and downstream COX elements, mediated by AMPK. We suggest that RV-NLCs are an effective delivery modality for improved potency and sustained drug release into the vasculature. Our findings have important implications for the future design and implementation of antihypertensive treatment strategies.

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“…LPH NPs (1 mL) were taken and centrifuged at 20,000 g for 2 h at 10 °C. For indirect method, supernatant was removed and was analyzed for free VRC content, employing a previously validated high-performance liquid chromatography (HPLC) method on a chromatograph (M/s Waters, USA) with acetonitrile and acetic acid solution (50:50) as mobile phase, at flow rate of 1 mL.minute −1 [ 32 , 33 ]. Further, the direct method involved the washing of pellet, thrice with water, and then dissolving it in 2% acetic acid solution and methanol, followed by probe sonication for 15 min and filtration through 0.4-micron syringe filter.…”

Section: Methodsmentioning

confidence: 99%

Nebulised surface-active hybrid nanoparticles of voriconazole for pulmonary Aspergillosis demonstrate clathrin-mediated cellular uptake, improved antifungal efficacy and lung retention

et al. 2021

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Background Incidence of pulmonary aspergillosis is rising worldwide, owing to an increased population of immunocompromised patients. Notable potential of the pulmonary route has been witnessed in antifungal delivery due to distinct advantages of direct lung targeting and first-pass evasion. The current research reports biomimetic surface-active lipid-polymer hybrid (LPH) nanoparticles (NPs) of voriconazole, employing lung-specific lipid, i.e., dipalmitoylphosphatidylcholine and natural biodegradable polymer, i.e., chitosan, to augment its pulmonary deposition and retention, following nebulization. Results The developed nanosystem exhibited a particle size in the range of 228–255 nm and drug entrapment of 45–54.8%. Nebulized microdroplet characterization of NPs dispersion revealed a mean diameter of ≤ 5 μm, corroborating its deep lung deposition potential as determined by next-generation impactor studies. Biophysical interaction of LPH NPs with lipid-monolayers indicated their surface-active potential and ease of intercalation into the pulmonary surfactant membrane at the air-lung interface. Cellular viability and uptake studies demonstrated their cytocompatibility and time-and concentration-dependent uptake in lung-epithelial A549 and Calu-3 cells with clathrin-mediated internalization. Transepithelial electrical resistance experiments established their ability to penetrate tight airway Calu-3 monolayers. Antifungal studies on laboratory strains and clinical isolates depicted their superior efficacy against Aspergillus species. Pharmacokinetic studies revealed nearly 5-, 4- and threefolds enhancement in lung AUC, Tmax, and MRT values, construing significant drug access and retention in lungs. Conclusions Nebulized LPH NPs were observed as a promising solution to provide effective and safe therapy for the management of pulmonary aspergillosis infection with improved patient compliance and avoidance of systemic side-effects.

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Impact of liquid lipid on development and stability of trimyristin nanostructured lipid carriers for oral delivery of resveratrol

Abstract: liquid lipids and future strategy for rational design of stable NLC systems for delivery of various bio-actives for drug delivery applications.

Cited by 50 publications

References 59 publications

Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

Nanostructured Lipid Carriers Deliver Resveratrol, Restoring Attenuated Dilation in Small Coronary Arteries, via the AMPK Pathway

Nebulised surface-active hybrid nanoparticles of voriconazole for pulmonary Aspergillosis demonstrate clathrin-mediated cellular uptake, improved antifungal efficacy and lung retention

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