Mucoadhesive Nanostructured Lipid Carriers Research Articles

Development and machine-learning optimization of mucoadhesive nanostructured lipid carriers loaded with fluconazole for treatment of oral candidiasis

The aim of this work was to prepare and optimize mucoadhesive nanostructured lipid carrier (NLC) impregnated with fluconazole for better management of oral candidiasis. The NLCs were fabricated using an emulsification/sonication technique. The nanoparticles consisted of stearic acid, oleic acid, Pluronic F127, and lecithin. Box–Behnken design, artificial neural networking, and variable weight desirability were employed to optimize the joint effect of drug concentration in the drug/lipid mixture, solid lipid concentration in the solid/liquid lipid mixture, and surfactant concentration in the total mixture on size and entrapment. The optimized NLCs were coated with chitosan. The nanoparticles were characterized by surface charge, spectroscopic, thermal, morphological, mucoadhesion, release, histopathological, and antifungal properties. The nanoparticles are characterized by a particle size of 335 ± 13.5 nm, entrapment efficiency of 73.1 ± 4.9%, sustained release, minor histopathological effects on rabbit oral mucosa, and higher fungal inhibition efficiency for an extended period of time compared with fluconazole solution. Coating the nanoparticles with chitosan increased its adhesion to rabbit oral buccal mucosa and improved its anti-candidiasis activity. It is concluded that mucoadhesive lipid-based nanoparticles amplify the effect of fluconazole on Candida albicans in vitro. This finding warrants pre-clinical and clinical studies in oral candidiasis disease models to corroborate in vitro findings.

Mucoadhesive nanostructured lipid carriers as a cannabidiol nasal delivery system for the treatment of neuropathic pain

The therapeutic potential of cannabidiol (CBD) has been explored to treat several pathologies, including those in which pain is prevalent. However, the oral bioavailability of CBD is low owing to its high lipophilicity and extensive first-pass metabolism. Considering the ability of the nasal route to prevent liver metabolism and increase brain bioavailability, we developed nanostructured lipid carriers (NLCs) for the nasal administration of CBD. We prepared particles with a positively charged surface, employing stearic acid, oleic acid, Span 20Ⓡ, and cetylpyridinium chloride to obtain mucoadhesive formulations. Characterisation of the CBD-NLC dispersions showed uniform nano-sized particles with diameters smaller than 200 nm, and high drug encapsulation. The mucoadhesion of cationic particles has been related to interactions with negatively charged mucin. Next, we added in-situ gelling polymers to the CBD-NLC dispersion to obtain a CBD-NLC-gel. A thermo-reversible in-situ forming gel was prepared by the addition of PluronicsⓇ. CBD-NLC-gel was characterised by its gelation temperature, rheological behaviour, and mucoadhesion. Both formulations, CBD-NLC and CBD-NLC-gel, showed high mucoadhesion, as assessed by the flow-through method and similar in vitro drug release profiles. The in vivo evaluation showed that CBD-NLC dispersion (without gel), administered intranasally, produced a more significant and lasting antinociceptive effect in animals with neuropathic pain than the oral or nasal administration of CBD solution. However, the nasal administration of CBD-NLC-gel did not lessen mechanical allodynia. These findings demonstrate that in-situ gelling hydrogels are not suitable vehicles for highly lipophilic drugs such as CBD, while cationic CBD-NLC dispersions are promising formulations for the nasal administration of CBD.

Phenylboronic acid-tethered chondroitin sulfate-based mucoadhesive nanostructured lipid carriers for the treatment of dry eye syndrome

Dry eye syndrome is a common eye disease that affects many people worldwide. It is usually treated with eye drops, which has low bioavailability owing to rapid clearance from the ocular surface and leads to poor patient compliance and side effects. For the purpose of improving the therapeutic efficacy, nanostructured lipid carrier (NLC)-loaded dexamethasone (DEX) was prepared and functionalized with (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS). As APBA has a boronic acid group, it can form a high-affinity complex with sialic acids present in the ocular mucin, which contributes to extension of corneal retention time and improvement of drug delivery. Compared with eye drops, Rhodamine B (RhB)-labeled APBA-ChS-NLC could significantly prolong the residence time on the corneal surface. Moreover, the DEX-APBA-ChS-NLC showed no irritation to the rabbit eye as indicated in irritation studies and histological images. The pharmacodynamics study indicated that DEX-APBA-ChS-NLC could relieve symptoms of dry eye disease in rabbits. These results demonstrated that the developed mucoadhesive drug carrier could improve the delivery of drugs and have promising potential to treat anterior eye diseases. Statement of SignificanceIn this research, (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS)-based nanostructured lipid carriers (NLCs) including dexamethasone (DEX) were designed and constructed. APBA-ChS, which is present on the surface of DEX-NLC and contains the boronic acid group, can form complex with sialic acids in the ocular mucin, hence leading to prolonged precorneal retention. This affinity between boronic acid and sialic acids was used to develop a mucoadhesive drug delivery system. The developed mucoadhesive drug carrier demonstrated prolonged retention time and alleviation of dry eye syndrome. APBA-ChS-based NLC may be considered a promising ocular drug delivery system for treating anterior eye diseases.

Enhanced intestinal absorption of curcumin in Caco-2 cell monolayer using mucoadhesive nanostructured lipid carriers.

This study aimed to compare the intestinal permeation of curcumin-loaded polymer coated nanostructured lipid carriers (NLCs) and uncoated NLCs using the Caco-2 cell model. The uncoated NLCs were prepared using a warm microemulsion technique, while polymer-coated NLCs were prepared with the same method but were followed by coating particle surface with polyethylene glycol (PEG) 400 or polyvinyl alcohol (PVA). After lyophilization, all formulations possessed a mean size of <400nm with a zeta potential of ∼-30mV and a high entrapment efficacy up to 90%. All NLCs formulation showed significantly improvement in curcumin water solubility, more than 60-folds as compared to curcumin dispersion. In addition, they could protect curcumin from degradation in basic pH, 90% curcumin remaining after 6h incubation in culture medium. In vitro permeation studies revealed that PEG-NLCs and PVA-NLCs provided significantly higher apparent permeation coefficient (Papp ) value than uncoated NLCs. Moreover, after 6months storage at 4 °C in the absence of sunlight, the physical, and chemical stabilities of the lyophilized curcumin-loaded polymer coated NLCs and uncoated NLCs could be maintained, i.e., the mean particle size and the amount of curcumin showed no significant changes (p>0.05) compared to those freshly prepared formulations. Considered overall, polymer coated NLCs are an important strategy to improve the oral bioavailability of curcumin. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 734-741, 2018.

Mucoadhesive nanostructured lipid carriers (NLCs) as potential carriers for improving oral delivery of curcumin

Purpose: To examine effects of polymer types on the mucoadhesive properties of polymer-coated nanostructured lipid carriers (NLCs).Experiment: Curcumin-loaded NLCs were prepared using a warm microemulsion technique followed by coating particle surface with mucoadhesive polymers: polyethylene glycol400 (PEG400), polyvinyl alcohol (PVA), and chitosan (CS). The physicochemical properties and entrapment efficacy were examined. In vitro mucoadhesive studies were assessed by wash-off test. In addition, the stability of mucoadhesive NLCs in gastrointestinal fluids and the pattern of drug release were also investigated.Findings: The obtained nanoparticles showed spherical shape with size ranging between 200 nm and 500 nm and zeta potential between −37 and −9 mV depending on the type of polymer coating. Up to 80% drug entrapment efficacy was observed. In vitro mucoadhesive studies revealed that PEG-NLCs and PVA-NLCs were adhered strongly to freshly porcine intestinal mucosa, more than 2-fold mucoadhesive compared to CS-NLCs and uncoated-NLCs. The particle size of all polymer-coated NLCs could be maintained in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) suggesting good physical stability in physiological fluid. In contrast, uncoated-NLCs showed particle aggregation in SGF. In vitro dissolution studies revealed a fast release characteristic.

Surface engineered nanostructured lipid carriers for efficient nose to brain delivery of ondansetron HCl using Delonix regia gum as a natural mucoadhesive polymer

The objective of this investigation was to fabricate ondansetron hydrochloride [OND] loaded mucoadhesive nanostructured lipid carriers [NLCs] for efficient delivery to brain through nasal route. Mucoadhesive NLCs thereby sustaining drug release for longer time in nasal cavity. NLCs were prepared by high pressure homogenization [HPH] technique using glycerol monostearate [GMS]; as solid lipid, Capryol 90; as liquid lipid, soya lecithin; as surfactant and poloxamer 188; as cosurfactant. In the fabrication of NLCs, Delonix regia gum [DRG], isolated from seeds of D. regia belonging to family fabiaceae was used as a mucoadhesive polymer. The NLCs were evaluated for particle size, morphology, drug-entrapment efficiency [%EE], mucoadhesive strength, in vitro drug release, histological examination, ex vivo permeation study, in vivo biodistribution and pharmacokinetic studies in the brain/blood following intravenous [i.v.] and intranasal [i.n.] administration. Particle size, PDI, Zeta potential was observed in the range of 92.28–135nm, 0.32–0.46, and −11.5 to −36.2 respectively. Prepared NLCs achieved thermodynamic stability, control release pattern with minor histopathological changes in sheep nasal mucosa. The significantly [P<0.05] higher values for selected batch was observed, when administered by i.n. route showed higher drug targeting efficiency [506%] and direct transport percentage [97.14%] which confirms the development of promising OND-loaded NLC for efficient nose-to-brain delivery.