Stability Of Nanostructured Lipid Carriers Research Articles

Synthesis of Nanostructured Lipid Carriers Loaded Chitosan/ Carbopol Hybrid Nanocomposite Gel for Oral Delivery of Artemether and Curcumin

Antimalarial therapy remains the utmost effective means for the management of malarial parasites in the liver and red blood cells. The application of these therapeutic agents is hampered by their improper application, hepato-toxicity caused by their continuous use, and degradation by hepatic enzymes. Recent advancements in drug delivery applications have shown potential in improving the pharmacological properties of artemether. Nanostructured lipid carriers (NLCs) loaded chitosan (CH)/Carbopol (CB) hybrid gel was prepared using glycerol monostearate (GMS) as solid lipid and clove oil as a liquid lipid for artemether (ART) and curcumin (CR) for its localized effect on the liver. The smaller particle size (~118 ± 1.0 nm) and high zeta potential (- 41.1 ± 6.46 mV) confirm the formulation and stability of NLCs. On the other hand, the shape and morphology of prepared NLCs and gel showed a spherical and wrinkled surface with a size range of 150-250 nm. The release studies of the NLC's showed a controlled release of artemether (~ 92%) and curcumin (~ 83%) for up to 30 h. Photostability data showed that, approximately, ~86.5 ± 0.3% and ~60 ± 0.9% of nanoencapsulated artemether and curcumin were still detected on exposure to sunlight, respectively. It has been found from the permeation study that 69.8% and 49.1% of the drug was permeated across the mucus membrane in 24 h with a significant increase (P < 0.05) in flux as well as permeability coefficients. The overall results showed that prepared CH/CB/NLCs hybrid gel could be a promising vehicle for the effective delivery of ART and CR for the management of malarial parasites. Lay Summary: Antimalarial therapy remains the utmost effective means for the management of malarial parasites in liver and red blood cells. Recent advancements in drug delivery applications have shown potential in improving the pharmacological properties of artemether. Application of these therapeutic agents hampered by their improper application, hepato-toxicity caused by their continuous use and degradation by hepatic enzymes. To manage the above issues, we synthesize nanostructured lipid carriers (NLC's) loaded chitosan (CH)/Carbopol (CB) hybrid gel using glycerol monostearate (GMS) as solid lipid and clove oil as liquid lipid for artemether (ATR) and curcumin (CR) for its local action in liver and the major criteria were to find a protective barrier with hepatoprotective nature of the curcumin.

Comment on "Physicochemical stimuli as tuning parameters to modulate the structure and stability of nanostructured lipid carriers and release kinetics of encapsulated antileprosy drugs" by R. Kanwar, M. Gradzielski, S. Prevost, G. Kaur, M. S. Appavou and S. K. Mehta, J. Mater. Chem. B, 2019, 7, 6539.

In a recent article [R. Kanwar et al., J. Mater. Chem. B, 2019, 7(42), 6539-6555], the authors characterized the interactions between drug-loaded nanostructured lipid carriers and bovine serum albumin using thermodynamics. They found that the interactions are spontaneous and driven by entropy. In this present paper, we report our analysis of these results in terms of equilibrium thermodynamics to show that the binding reactions exhibit enthalpy-entropy compensation. Our findings may prove useful for designing nanostructured lipid carriers.

Reply to the 'Comment on "Physicochemical stimuli as tuning parameters to modulate the structure and stability of nanostructured lipid carriers and release kinetics of encapsulated antileprosy drugs"' by J. Kang and A. M. Kang, J. Mater. Chem. B, 2020, 8, DOI.

In a recent comment [J. Kang and A. M. Kang, J. Mater. Chem. B, 2020, 8, DOI: 10.1039/D0TB01160F] on our article [R. Kanwar, M. Gradzielski, S. Prevost, G. Kaur, M. S. Appavou and S. K. Mehta, J. Mater. Chem. B., 2019, 7, 6539], the authors tried to demonstrate that the binding phenomenon between drug-loaded nanostructured lipid carriers and the protein BSA was subjected to enthalpy-entropy compensation, rather than being entropy-driven. The outcome, however, remains the same in spite of the complicated analysis attempted. While we appreciate their effort to extract more information from our data, we have a number of remarks on their process.

Effect of Combination Soy Bean Oil and Oleic Acid to Characteristic, Penetration, Physical Stability of Nanostructure Lipid Carrier Resveratrol

Resveratrol is an antioxidant that can be used as anti-aging. Topical use has several problems because solubility in water is low and unstable to light. This study aimed to evaluate the effect of the combination of soy bean oil and oleic acid liquid lipids on the characteristics, penetration, and stability of resveratrol nanostructured lipid carriers (NLC). Nanostructured lipid carriers (NLC) were made with high shear homogeneous technique. To determine the characterization of NLC, diffraction scanning calorimetry, X-ray diffraction, and Fourier transforms infrared spectrophotometry were used. Examination of the morphological form was carried out with a transmission electron microscope. The particle size and polydispersity index examination were measured by the Delsa Nano™ particle size analyzer, while the efficiency of trapping resveratrol in the NLC system was measured by the dialysis membrane method. Furthermore, the penetration depth test on the skin of mice was done by fluorescence microscope method using rhodamine B markers. Physical stability test was performed by examination of particle size and index polydispersity for 30 days. The formula with liquid soy bean oil and oleic acid liquid lipids improved the characteristics including the effectiveness of entrapment and colloidal stability. However, the formula with soy bean oil and oleic acid combination liquid lipids did not provide better penetration into the skin than the use of single liquid lipids. While the formula with soy bean oil and oleic acid liquid lipids proved to improve the physical stability for 30 days.

Comprehensive characterization of nanostructured lipid carriers using laboratory and synchrotron X-ray scattering and diffraction

The development of lipid nanoparticles requires knowledge on the crystalline structure, polymorphic transitions and lipid-drug interactions. This study aimed at introducing advanced techniques to characterize nanostructured lipid carriers (NLC) comprising palmitic acid, oleic acid, stabilizer and Domperidone. Crystallinity of single components and mixtures was investigated by laboratory Small Angle X-ray Scattering (SAXS). NLC were studied with laboratory Small and Wide Angle X-ray Scattering (SWAXS). Photon Correlation Spectroscopy and Freeze Fracture Transmission Electron Microscopy were used to monitor particle size, zeta potential and shape. Stability of NLC was investigated using synchrotron X-ray Diffraction (XRD) and SAXS and laboratory SAXS. Palmitic acid showed a lamellar structure (polymorph C), which was still present after particle preparation. Spherical 300 nm-sized particles with zeta potential values above −30 mV were obtained and Domperidone was incorporated in its amorphous form. During storage, no differences in synchrotron XRD spectra were seen. However, laboratory SAXS measurements showed a second lamellar structure, identified as polymorph B. Synchrotron SAXS temperature scans confirmed that polymorph B did not affect the morphology of the encapsulated drug or the shape of NLC. These results highlight the unique capabilities of laboratory and synchrotron X-ray Scattering and Diffraction for improved structural characterization of lipid nanoparticles.

Physicochemical stimuli as tuning parameters to modulate the structure and stability of nanostructured lipid carriers and release kinetics of encapsulated antileprosy drugs.

To unveil the effect of electrolyte concentration, pH and polymer addition on Tween 80 stabilized nanostructured lipid carriers (NLCs, based on dialkyldimethylammonium bromides DxDAB and Na oleate), an in-depth scattering analysis was performed. Dynamic and static light scattering (DLS/SLS) and small-angle neutron scattering (SANS) techniques along with zeta potential studies were exploited to understand the structural evolution and physical stability of NLCs. In these experiments, we varied the salt concentration, pH, and the admixture of Pluronic F127 in order to elucidate their effect on NLC morphologies. In most cases, two populations of different sizes are present which differ by one order of magnitude. The antileprosy drugs (ALD) Rifampicin and Dapsone were encapsulated in NLCs and the vector properties were assessed for a series of DxDAB (where x = 12, 14, 16 and 18) NLCs. The influence of composition on the entrapment and release behavior of NLCs was investigated: The size of NLCs correlates with the release rate of the incorporated drug. The interaction of drug-loaded NLCs with bovine serum albumin was studied to understand the release of ALD in the plasma.

Influence of lipid content and dilution on properties and stability of nanostructured lipid carriers (NLCs) prepared from rambutan (Nephelium lappaceum L.) kernel fat and evaluation of their β-carotene loading capacity

The effects of lipid content and dilution on the properties and stability of nanostructured lipid carriers (NLCs) prepared from rambutan (Nephelium lappaceum L.) kernel fat were investigated. The β-carotene-loading capacity of the NLCs was also evaluated. NLCs containing various lipid phase concentrations (5, 10, and 15 wt%) were prepared using Tween 80 as the emulsifier with a lipid to emulsifier weight ratio of 1:0.2. The results showed that an increase in the lipid content up to 15 wt% had no effect on the zeta-potential, particle size and polydispersity index but resulted in a higher particle density. All samples showed no phase separation during storage at 25 °C for 28 days; however, the relative recrystallization index (RRI) increased. Dilution of concentrated NLC (15 wt%) to a lower lipid content (5 and 10 wt%) produced no differences in the particle characteristics and stability during storage. NLCs loaded with β-carotene at different concentrations (0, 0.5, and 1 wt% of the lipid phase) exhibited desirable characteristics and had high encapsulation efficiency (∼97%) over 28 days of storage. These results demonstrated that NLC prepared from rambutan kernel fat can be used to entrap lipophilic bioactive components which could be used as ingredients in functional food products.

Nanostructured lipid carriers for transdermal delivery of acid labile lansoprazole

The aim of this study was to develop nanostructured lipid carriers (NLCs) for transdermal delivery of acid-labile lansoprazole (LPZ). The drug loading, particle size, zeta potential, thermal behavior and stability of NLCs were evaluated. The particle size of NLCs was in the range of 90−210nm and the zeta potential was −61.9 to +3.2mV dependent of the compositions. Stearylamine (SA) prevented lansoprazole degradation and maintained drug stable in NLCs. The anionic sodium dodecyl sulfate (SDS) adsorbed on the lipid surface and formed complex with cationic SA to prevent NLCs aggregation. The effects of type (e.g., isopropyl myristate (IPM), menthol) and concentration (e.g., 1.25, 2.50, 3.75%w/w) of enhancers on penetration of lansoprazole NLC hydrogels were investigated in vitro using Wistar rat skin. The steady-state flux of lansoprazole NLC hydrogel containing 3.75% IPM was the highest which was enhanced by 2.7 folds as compared to enhancer-free NLC hydrogel. In vivo pharmacokinetics of lansoprazole following transdermal delivery of NLC hydrogel showed that the elimination of drug was significantly reduced and the mean residence time of drug was prominently prolonged as compared to intravenous drug solution (p<0.005). The accumulation of drug in the skin and continuous penetration of drug through the skin accounted for the maintenance of drug concentration for at least 24h.

The effect of surfactant composition on the chemical and structural properties of nanostructured lipid carriers

Fine-tuning the nanoscale structure and morphology of nanostructured lipid carriers (NLCs) is central to improving drug loading and stability of the particles. The role of surfactant charge on controlling the structure, the physicochemical properties and the stability of NLCs has been investigated using three surfactant types (cationic, anionic, non-ionic), and mixed surfactants. Either one, a mixture of two, or a mixture of three surfactants were used to coat the NLCs, with these classified as one, two and three surfactant systems, respectively. The mixed (two and three) surfactant systems produced smaller NLC particles and yielded NLCs with lower crystallinity than the one surfactant system. The combined effects of the ionic and the non-ionic surfactants may play a key role in assisting the lipid-oil mixing, as well as maintaining colloidal repulsion between NLC particles. In contrast, for the three surfactant system, the lipid–oil mixture in the NLCs appeared less homogenous. This was also reflected in the results of the stability study, which indicated that NLC particle sizes in two surfactant systems appeared to be retained over longer periods than for other surfactant systems.

The effect of oil type on the aggregation stability of nanostructured lipid carriers

Second generation lipid systems for the delivery of bioactive compounds have been developed by mixing a liquid carrier oil with a solid lipid to form so-called nanostructured lipid carriers (NLCs). In this study, we investigated the effect of different liquid carrier oils on the crystallization and aggregation behavior of tristearin NLC dispersions. We found that NLC suspension stability was strongly affected by the type and amount of the carrier oil. As the oil concentration was increased, the crystallization and melting temperatures decreased, the polymorphic transformation rate increased, the particles became more spherical, and suspension stability was enhanced. These results suggest that oil trapped within the growing crystal matrix accelerated polymorphic transformation but retarded the large shape change normally associated with the transformation. We also found that considerably less surfactant was necessary to produce stable NLC suspensions than was required to stabilize solid lipid nanoparticle (SLN) suspensions without a carrier oil. Based on preliminary simulation results, we hypothesized that improved NLC suspension stability was attributable to both reduced particle shape change, which created less new surface area to be covered by surfactant, and increased mobility of surfactant molecules, which resulted in available surfactant being more efficient at covering created surface area.

The effect of polymer–surfactant emulsifying agent on the formation and stability of α-lipoic acid loaded nanostructured lipid carriers (NLC)

α-Lipoic acid loaded nanostructured lipid carriers (ALA-NLC) were developed by high pressure homogenization (HPH) technology. The effects of polymer-surfactant emulsifying agents on the formation and stability of ALA-NLC were characterized by dynamic light scattering (DLS), rheological analysis, wide angle X-ray diffraction (WAXD), and high efficiency liquid chromatography (HPLC). The particles size, viscoelastic property and stability of ALA-NLC samples were significantly influenced by polymer–surfactant emulsifying agents. Polymer is considered as a primary emulsifying agent in ALA-NLC. Surfactants, which have small and flexible hydrophilic head group, would have strong interaction with polymer, and form strong interfacial film, thus could improve the stability of ALA-NLC. These results will be productive for better understanding of the preparation and stability of NLC, and two formulations applied here may have some potential applications for α-lipoic acid dietary supplement or nutri-cosmetics.