Stable Nanostructured Lipid Carriers Research Articles

Integrating Natural Deep Eutectic Solvents into Nanostructured Lipid Carriers: An Industrial Look.

The industries are searching for greener alternatives for their productions due to the rising concern about the environment and creation of waste and by-products without industrial utility for that specific line of products. This investigation describes the development of two stable nanostructured lipid carriers (NLCs): one is the formulation of a standard NLC, and the other one is the same NLC formulation associated with a natural deep eutectic solvent (NaDES). The research presents the formulation paths of the NLCs through completeness, which encompass dynamic light scattering (DLS), zeta potential tests, and pH. Transmission electron microscopy (TEM) and confocal microscopy were performed to clarify the morphology. Cytotoxicity tests with zebrafish were realized, and the results are complementary to the in vitro outcomes reached with fibroblast L132 tests by the MTT technique and the zymography test. Infrared spectroscopy and X-ray diffractometry tests elucidated the link between the physicochemical characteristics of the formulation and its behavior and properties. Different cooling techniques were explored to prove the tailorable properties of the NLCs for any industrial applications. In conclusion, the compiled results show the successful formulation of new nanocarriers based on a sustainable, eco-friendly, and highly tailorable technology, which presents low cytotoxic potential.

Development of a Versatile Nanostructured Lipid Carrier (NLC) Using Design of Experiments (DoE)-Part II: Incorporation and Stability of Butamben with Different Surfactants.

Nanostructured lipid carriers (NLCs) are typically composed of liquid lipids, solid lipids, and surfactants, enabling the encapsulation of lipophilic drugs. Butamben is a Class II anesthetic drug, according to the Biopharmaceutical Classification System (BCS); it has a log P of 2.87 and is considered a 'brick dust' (poorly water-soluble and poorly lipid-soluble) drug. This characteristic poses a challenge for the development of NLCs, as they are not soluble in the liquid lipid present in the NLC core. In a previous study, we developed an NLC core consisting of a solid lipid (CrodamolTM CP), a lipophilic liquid with medium polarity (SRTM Lauryl lactate), and a hydrophilic excipient (SRTM DMI) that allowed the solubilization of 'brick dust' types of drugs, including butamben. In this study, starting from the NLC core formulation previously developed we carried out an optimization of the surfactant system and evaluated their performance in aqueous medium. Three different surfactants (CrodasolTM HS HP, SynperonicTM PE/F68, and CroduretTM 40) were studied and, for each of them, a 23 factorial design was stablished, with total lipids, % surfactant, and sonication time (min) as the input variables and particle size (nm), polydispersity index (PDI), and zeta potential (mV) as the response variables. Stable NLCs were obtained using CrodasolTM HS HP and SynperonicTM PE/F68 as surfactants. Through a comparison between NLCs developed with and without SRTM DMI, it was observed that besides helping the solubilization of butamben in the NLC core, this excipient helped in stabilizing the system and decreasing particle size. NLCs containing CrodasolTM HS HP and SynperonicTM PE/F68 presented particle size values in the nanometric scale, PDI values lower than 0.3, and zeta potentials above |10|mV. Concerning NLCs' stability, SBTB-NLC with SynperonicTM PE/F68 and butamben demonstrated stability over a 3-month period in aqueous medium. The remaining NLCs showed phase separation or precipitation during the 3-month analysis. Nevertheless, these formulations could be freeze-dried after preparation, which would avoid precipitation in an aqueous medium.

Improvement of lidocaine skin permeation by using passive and active enhancer methods

Lidocaine is generally recognized and preferred for local anaesthesia, but in addition, studies have described additional benefits of lidocaine in cancer therapy, inflammation reduction, and wound healing. These properties contribute to its increasing importance in dermatological applications, and not only in pain relief but also in other potential therapeutic outcomes. Therefore, the purpose of our study was to enhance lidocaine delivery through the skin. A stable nanostructured lipid carrier (NLC), as a passive permeation enhancer, was developed using a 23 full factorial design. The nanosystems were characterized by crystallinity behaviour, particle size, zeta potential, encapsulation efficiency measurements, and one of them was selected for further investigation. Then, NLC gel was formulated for dermal application and compared to a traditional dermal ointment in terms of physicochemical (rheological behaviour) and biopharmaceutical (qualitative Franz diffusion and quantitative Raman investigations) properties. The study also examined the use of 3D printed solid microneedles as active permeation enhancers for these systems, offering a minimally invasive approach to enhance transdermal drug delivery. By actively facilitating drug permeation through the skin, microneedles can complement the passive transport achieved by NLCs, thereby providing an innovative and synergistic approach to improving lidocaine delivery.

When it is too much: Identifying butamben excess on the surface of pharmaceutical preformulation samples by Raman mapping

Butamben is a topical local anesthetic which formulation in lipid-based drug delivery systems (DDS) is challenging due to its affinity for hydrophilic excipients. This means that a medium polarity excipient is preferred for the development of a stable nanostructured lipid carrier (NLC) formulation. In turn, in NLC, the type and number of excipients will determine the active pharmaceutical ingredient (API) solubility and the maximum drug upload. To solve this dilemma and get the best formulation, a throughout screening study to evaluate API solubilization in different excipients was carried out. Subsequently, excipients with different solubilization capacities were selected for microscopic evaluation by Raman mapping, and in turn analysis of the distributional homogeneity index (DHI) and standard deviation of the histograms allowed solving the posed question. Design of experiments (DoE) was employed to understand better the interactions between the excipients; linear and higher-order models were obtained with R2 above of 0.8824. Even though DHI is a good parameter to be used as response, an API concentration higher than 30% (w/w) provided a homogeneous surface in case of good miscibility and, in this case, this parameter needs to be employed with an inspection and/or evaluation of other parameters. A curve of concentration vs. mean scores of images proved to be an alternative to identify the saturation/limit of linear range.

Highly stable nanostructured lipid carriers containing candelilla wax for d-limonene encapsulation: Preparation, characterization and antifungal activity

The objective of this work was to develop nanostructured lipid carriers (NLCs) with preservation effect by using pea protein isolate (PPI) nanoparticles as emulsifiers, candelilla wax (CW) as organo-gelator and d-limonene (DL) as antifungal agent. The optimal formulation parameters of NLCs were firstly determined based on results of particle size, poly-dispersity index and zeta potential, and then NLCs prepared by optimal formulation were further characterized. The results showed that DL was successfully encapsulated inside NLCs. Moreover, the encapsulation of amorphous DL led to more disordered crystalline state of NLCs. In addition, in comparing the properties of NLCs and nanoemulsions (NEs) without CW, it was found that the addition of CW seemed to have several beneficial effects on NLCs: 1) NLC droplets were well dispersed, whereas NE droplets exhibited coalescence and flocculation; 2) compared with NEs, NLCs displayed excellent storage stability and inhibition ability of DL release. Furthermore, antifungal activity of NLCs was observed by in vitro and in vivo study. The acquired information in current research can provide novel insight into development of stable and antifungal nanocarriers that own a promising application in tomato preservation.

NANOSTRUCTURED LIPID CARRIERS AS A PROMISING DERMAL DELIVERY PLATFORM FOR ST. JOHN'S WORT EXTRACT: PRELIMINARY STUDIES

urpose: Nanostructured lipid carriers (NLC) can improve the stability of various phytochemicals, so this research aimed to develop and employ such delivery systems for Hypericum perforatum extract containing the light- and oxygen-sensitive phloroglucinol hyperforin. Materials and methods: By varying the processing parameters and the solid and liquid lipids used, different NLC models were obtained via emulsification, followed by high-shear homogenization and ultrasonication. After characterization of the elaborated nanocarriers, those that exhibited optimal properties were loaded with St. John's wort extract by incorporating it in the lipid phase before emulsification and also studied. Results: The NLC models developed by prolonged ultrasonication demonstrated favorable characteristics regarding particle size, polydispersity index (PDI), and zeta potential (ZP). The physically stable during long-term storage nanosystems, which also showed a reduced degree of crystallinity of the solid lipid included, were loaded with St. John's wort extract. Of the carriers so-obtained, those developed by ultrasonication at ambient temperatures can be described as acceptably uniform systems (PDI from 0.23±0.01 to 0.27±0.01), comprising particles with dimensions below 200 nm, favorable ZP values (ζ > |30 mV|), and superior entrapment efficacy (EE) greater than 85%. Conclusion: In this research, different stable NLC dispersions were successfully developed. After the inclusion of the St. John's wort extract, the model possessing the highest EE (87.77±0.64%) was chosen as a carrier to conduct further studies evaluating its wound-healing potential.

Development of nanostructured lipid carriers as a promising tool for methotrexate delivery: physicochemical and in vitro evaluation

The aim of the present study is to fabricate the stable nanostructured lipid carriers (NLCs) using biocompatible excipients for the encapsulation of Methotrexate (MTX), a chemotherapeutic agent for breast cancer treatment. MTX has restricted clinical applications owing to its low solubility, non-specific targeting and adverse side effects. Glyceryl Monostearate (GMS) and Miglyol 812 (MI1) were chosen as solid and liquid lipids, respectively, for the fabrication of NLCs, and the influence of variation of solid and liquid composition was investigated. The prepared NLCs exhibited long-term stability and spherical shape morphology as characterized by electron microscopy. The internal structure of fabricated NLCs was arranged into cubic crystalline as confirmed by small-angle X-ray scattering (SAXS) analysis. MTX's encapsulation efficiency of ∼85 ± 0.9%. and sustained in vitro release of MTX ∼ 52% ± 3.0 in 24 h was achieved. Classical molecular dynamics (MD) simulations were performed to study the structural stability of the MTX encapsulated NLCs. Hemolysis carried out on the NLCs showcased the biosafety of the formulation under the tolerance limit (<10%). Further, the MTT assay demonstrates that MTX-loaded NLCs exhibited toxicity against HeLa and MCF-7 cell lines as compared to blank NLCs. The finding demonstrates NLCs as promising vehicles for MTX delivery to address cancer. Communicated by Ramaswamy H. Sarma

Development, formulation, and cellular mechanism of a lipophilic copper chelator for the treatment of Wilson’s disease

Copper homeostasis is finely regulated in human to avoid any detrimental impact of free intracellular copper ions. Upon copper accumulation, biliary excretion is triggered in liver thanks to trafficking of the ATP7B copper transporter to bile canaliculi. However, in Wilson’s disease this protein is mutated leading to copper accumulation. Current therapy uses Cu chelators acting extracellularly and requiring a life-long treatment with side effects. Herein, a new Cu(I) pro-chelator was encapsulated in long-term stable nanostructured lipid carriers. Cellular assays revealed that the pro-chelator protects hepatocytes against Cu-induced cell death. Besides, the cellular stresses induced by moderate copper concentrations, including protein unfolding, are counteracted by the pro-chelator. These data showed the pro-chelator efficiency to deliver intracellularly an active chelator that copes with copper stress and surpasses current and under development chelators. Although its biological activity is more mitigated, the pro-chelator nanolipid formulation led to promising results. This innovative approach is of outmost importance in the quest of better treatments for Wilson’s disease.

Live-attenuated RNA hybrid vaccine technology provides single-dose protection against Chikungunya virus

We present a live-attenuated RNA hybrid vaccine technology that uses an RNA vaccine delivery vehicle to deliver invitro-transcribed, full-length, live-attenuated viral genomes to the site of vaccination. This technology allows ready manufacturing in a cell-free environment, regardless of viral attenuation level, and it promises to avoid many safety and manufacturing challenges of traditional live-attenuated vaccines. We demonstrate this technology through development and testing of a live-attenuated RNA hybrid vaccine against Chikungunya virus (CHIKV), comprised of an invitro-transcribed, highly attenuated CHIKV genome delivered by a highly stable nanostructured lipid carrier (NLC) formulation as an intramuscular injection. We demonstrate that single-dose immunization of immunocompetent C57BL/6 mice results in induction of high CHIKV-neutralizing antibody titers and protection against mortality and footpad swelling after lethal CHIKV challenge.

Raman Imaging and Chemometrics Evaluation of Natural and Synthetic Beeswaxes as Matrices for Nanostructured Lipid Carriers Development

Beeswaxes are interesting solid lipids for the development of nanostructured lipid carriers (NLC), and their origin can be either natural or synthetic. Due to this difference, their performance should be distinct and unstable formulations can be generated. The objective of this work was to investigate miscibility and structural changes (polymorphism) in pre-formulations (blends of solid and liquid lipids) using synthetic and natural beeswaxes in combination with copaiba oil (a natural liquid lipid), in the concentration range of 5.0 to 50.0% (w/w). Raman spectra were acquired over a region of 4 mm2 (mapping mode), dead pixels were removed using Independent Components Analysis (ICA) and Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS) was then used to generate the images. Samples were analyzed at the initial time and after 3 months, using the Distributional Homogeneity Index (DHI) and standard deviation of the histograms. The pre-formulation containing synthetic beeswax showed different structural forms before and after melting, and structural changes over time, depending on the amount of the liquid lipid incorporated. These results demonstrate how spectroscopic imaging techniques can be valuable in pharmaceutical development, as well as the importance of choosing the type and proportion of solid lipid to achieve stable NLC formulations.

Proficiency of nanostructured lipid carriers for the formulation of amphiphilic bile acid oligomers

Biocompatible nanostructured lipid carriers (NLCs) are promising drug delivery vehicles for the formulation of hydrophobic drugs. These nanocarriers comprising liquid lipid inside solid core provide improved drug loading capacity compared to other existing lipid-based nanocarriers such as solid lipid nanoparticles or liquid emulsions. In the present report, we successfully employed D12DAB based NLCs for the formulation of bile acid-derived amphipathic oligomers. The prepared nano-formulation rendered adequate aqueous solubility to these bioactive bile acid oligomers. Hydrodynamic diameter, viscosity, surface tension, conductivity and zeta potential of the prepared NLCs were determined by dynamic light scattering, viscometer, tensiometer, conductivity meter, and zeta analyzer and was found to be in the range of 122−147 nm, 2.07–2.15 mPa.s, 29.7–30.2 mN/m, 540−550 mS/m, and 15.7−16 mV, respectively. In addition, Field Emission Scanning Electron Microscopy and Transmission Electron Microscopy analysis were performed to understand the external morphology and internal structure of synthesized NLCs. The applications of the synthesized NLCs to encapsulate dapsone and its release kinetics were studied in detail. The results conferred the formation of bile acid-enriched stable NLCs which could be a promising system to formulate and/or deliver several combinations of antibiotics or other bioactive agents to treat undesired physiological conditions.

Tucumã (Astrocaryum vulgare) fat: an Amazonian material as a pharmaceutical input for lipid nanoparticle production

Native Amazon palm trees have been target of research and product development especially because of their oil and fat. Tucuma-do-Para (Astrocaryum vulgare) is a palm tree from which is possible to extract fruit seed fat. This article studied its physico-chemical characterization and analyzed its feasibility of use as raw material for nanostructured lipid nanoparticle (NLC) in pharmaceuticals. Through acidity, refraction and iodine indexes it was possible to determine that the fat has good quality and is in accordance with the literature. Ultraviolet spectrum scanning did not show peaks in region of dienes and trienes, compounds which appear when fat is decomposing. Infrared spectra and nuclear magnetic resonance determined spectral identity of the fat, confirming it is composed mainly by saturated groups. Fatty acid profile by gas chromatography coupled to mass spectrometer evidenced components in greater quantity: lauric and myristic acids in saturated part and oleic acid in unsaturated part. These acids have pharmacotechnical importance as permeation agents of active substances. Tucuma fat has thermal stability up to 350 °C and melting point of 35 °C. To reach nanostructured lipid carriers preparation it was necessary to increase its melting point by mixing it with carnauba wax. Through X-ray diffraction in crystallized tucuma fat/carnauba wax mixture it was possible to identify stable β′-form which is the ideal form for production of stable nanostructured lipid carriers. From this lipidic mixture of tucuma fat/carnauba wax in 1:1 ratio, 9 formulations of nanostructures lipid carriers were prepared, from which 3 formulations were distinguished by their excelente particle size and polydispersity index values.

Lectin recognition and hepatocyte endocytosis of GalNAc-decorated nanostructured lipid carriers

Liver is the main organ for metabolism but is also subject to various pathologies, from viral, genetic, cancer or metabolic origin. There is thus a crucial need to develop efficient liver-targeted drug delivery strategies. Asialoglycoprotein receptor (ASGPR) is a C-type lectin expressed in the hepatocyte plasma membrane that efficiently endocytoses glycoproteins exposing galactose (Gal) or N-acetylgalactosamine (GalNAc). Its targeting has been successfully used to drive the uptake of small molecules decorated with three or four GalNAc, thanks to an optimisation of their spatial arrangement. Herein, we assessed the biological properties of highly stable nanostructured lipid carriers (NLC) made of FDA-approved ingredients and formulated with increasing amounts of GalNAc. Cellular studies showed that a high density of GalNAc was required to favour hepatocyte internalisation via the ASGPR pathway. Interaction studies using surface plasmon resonance and the macrophage galactose-lectin as GalNAc-recognising lectin confirmed the need of high GalNAc density for specific recognition of these NLC. This work is the first step for the development of efficient nanocarriers for prolonged liver delivery of active compounds.

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

Nanostructured lipid carriers (NLCs) have emerged as versatile carriers to improve oral bioavailability of poorly water-soluble drugs as well as to protect labile drugs from degradation and metabolism. Prepared by blending solid and liquid lipids, the choice of liquid lipid can have a great influence on their physicochemical characteristics and stability. The present work investigated the impact of six different liquid lipids with diverse chemical structures and hydrophilic and lipophilic balance (HLBs) on the critical quality attributes (CQAs) and storage stability of NLCs with trimyristin as solid lipid. Resveratrol (RES) was used as model drug as its low water solubility, poor bioavailability, rapid metabolism and clearance from systemic circulation restricts its clinical use despite its wide spectrum of biological activities. Liquid lipids investigated included, two triglycerides, one medium chain (C8) glycerol tricaprylate (GTC) and second, long chain (C18) glyceryl trioleate (GTO); two propylene glycol fatty acid esters, propylene glycol monocaprylate (PGMC) and propylene glycol monolaurate (PGML); fatty acid ester decyl oleate (DO) and a PEGylated lipid polyethylene glycol-8 caprylic/capric glycerides (PCG). Box–Behnken experimental design was employed to ascertain the effect of four independent factors viz. type of liquid lipid, amount of liquid lipid, amount of drug and surfactant concentration and interactions between these factors on the CQAs of NLCs as response variables viz. particle size (PS), polydispersity index (PDI), zeta potential (ZP), drug encapsulation efficiency (EE), and drug loading (DL). The relationship between various factors and responses was established by response surface methodology (RSM). The oils with higher lipophilicity C18 triglycerides (GTO) and C18 fatty acid ester DO yielded NLCs with lower PS as compared to the oils with lower lipophilicity (PGC, PGMC and PGML). Although increasing the concentration of liquid lipids had an upward trend on the PS of NLCs, its PDI was more predominantly influenced by the nature of liquid lipid. The characteristic of the liquid lipid influenced the DL remarkably which varied from 2.94 to 7.56%. The ZP of nanoparticles varied from −21.3 to −39.9 mV with liquid lipids with free hydroxyl groups and higher HLB playing a more prominent role contributing to the increase in the negative surface charge. The characteristics of liquid lipid influenced the depression of melting point of RES with maximum distortion of the crystal lattice was caused by PGMC and least by GTO. The two, long chain oleates, DO and GTO exhibited a shift of lipid peak in NLCs to higher melting points (116 and 111 °C) than the less lipophilic liquid lipids (103–104 °C). The attributes of liquid lipid also discriminate whether the particle growth during storage followed Oswald's ripening or coalescence. NLC containing GTO exhibited the highest stability in terms of maintenance of the PS and particle size distribution at 20 °C. This study provides vital insight on impact of liquid lipids and future strategy for rational design of stable NLC systems for delivery of various bio-actives for drug delivery applications.

Formulation and Characterization of Novel Nanostructured Lipid Carriers with Photoprotective Properties Made from Carnauba Wax, Beeswax, Pumpkin Seed Oil, and UV Filters

AbstractPumpkin seed oil (PSO) with carnauba wax and beeswax was used to develop nanostructured lipid carriers (NLC) loaded with a UV filter, Uvinul® A Plus B. The aims of the study were to optimize the concentration of PSO to develop a stable NLC formulation, determine storage stability of the NLC with and without PSO, and the synergistic effect of PSO‐NLC with UV filter for photoprotective properties. The physical properties of NLC were optimized based on the mean particle size, polydispersity index, and storage stability. The optimized NLC consisted 10% lipid phase (3.5% carnauba wax, 3.5% beeswax, and 3.0% PSO) and 90% aqueous phase. After optimization, Uvinul® A Plus B was added in the optimized PSO‐NLC to produce a photoprotective formulation. Uvinul® A Plus B consisted of both UVA (Diethylamino Hydroxybenzoyl Hexyl Benzoate) and UVB (Ethylhexyl Methoxycinnamate) filters. The NLC produced with PSO and Uvinul® A Plus B had mean particle size of 135 ± 2 nm and showed good physical stability under storage time. Besides that, the NLC produced also proven to have positive effect in enhancing the entrapment efficiency and drug loading, which were 82.86 ± 0.15% and 55.41 ± 0.04%, respectively, and showed sun protection factor value of 16.61 ± 3.45. The results indicated the presence of synergistic effect among the PSO‐NLC with Uvinul® A Plus B.

Ocular Formulation Based on Palmitoylethanolamide-Loaded Nanostructured Lipid Carriers: Technological and Pharmacological Profile.

The present work was aimed for the preparation of a stable nanostructured lipid carrier (NLC) system for the delivery of N-palmitoylethanolamide (PEA) to the back of the eye. PEA is an interesting natural compound showing anti-inflammatory and neuroprotective activities. The limits of PEA (poor solubility and high instability) justify its nanoencapsulation into drug delivery systems. Two different well-known techniques were compared to formulate NLC: the high shear homogenization technique (HSH) and the method based on a combination of HSH technique and ultrasonication (HSH/US). Nanoparticles were evaluated in relation to mean size, homogeneity, surface charge, and physical stability by Turbiscan technology. Retinal distribution of PEA was carried out in a rat eye after single instillation of PEA-NLC ophthalmic formulation. The novel formulation delivered remarkable levels of PEA to the retina. Lastly, topical administration of PEA-NLC ophthalmic formulation was able to significantly inhibits retinal tumor necrosis factor-α (TNF-α) levels in streptozotocin-induced diabetic rats. The present findings suggest that the novel ophthalmic formulation may be useful for the treatment of retinal diseases such as diabetic retinopathy. Clinical studies are in progress to evaluate this possibility.

Development of Nanostructured Lipid Carriers (NLCs) Using Pumpkin and Kenaf Seed Oils with Potential Photoprotective and Antioxidative Properties

Both pumpkin and kenaf seed oil with carnauba wax (CW) and beeswax (BW) are used to develop nanostructured lipid carriers (NLCs) loaded with Uvinul T150 and Uvinul A Plus Granular for a UV protection formulation. The study aims to optimize the concentration and the type of seed oil in order to develop a stable NLC formulation with high entrapment efficiency, drug loading, antioxidant activities, and UV absorbing properties. The physical properties of the NLCs are analyzed based on the mean particle size, polydispersity index (PDI), long‐term storage stability, Fourier‐transform infrared spectroscopy (FT‐IR), and differential scanning calorimetry (DSC). They are also compared for their entrapment efficiency, drug loading, in vitro antioxidant activities, and in vitro UV absorbing properties. The optimized NLC consists of 10% lipid phase and 1% Uvinul T150 and Uvinul A Plus Granular, respectively. It has mean particle size of 238.20 ± 3.61 nm and remains physically stable on storage at both 25 ± 2 and 40 ± 2 °C. Spherical amorphous NLC structure with encapsulated UV filters is observed by transmission electron microscopy (TEM). Besides, it shows high entrapment efficiency (≥95%) for both Uvinul T150 and Uvinul A Plus Granular in addition to its antioxidant activities as indicated by both DPPH and ABTS radical scavenging activities. In addition, the formulation had high UV absorbing properties, showing its potential to be utilized in the formation of sunscreen prototype.Practical Application: The preliminary study on pumpkin and kenaf seed oil shows bioactive potential with high antioxidant activities. The finding of kenaf seed oil‐NLC can be applied in the cosmetic industry to produce a wide variety of environmental‐friendly products with improved stability and beneficial properties. Also, the application of technology by forming NLCs can be used to develop lotions, creams, etc., with multifunctional properties. Besides, NLCs as carriers for UV filters is proven in the present study to exhibit high entrapment efficiency and drug loading properties. This is beneficial in developing advanced cosmetic prototypes that possess broad spectrum effectiveness with fewer side effects.Nanostructure lipid carriers (NLCs) are applied to encapsulate UV filters with pumpkin and kenaf seed oils. Kenaf seed oil‐NLC (F7) is selected as the best formulation for UV filters encapsulation. With spherical amorphous NLC structure, it shows high entrapment efficiency for the UV filters and antioxidant activities. Results indicate that F7 with high UV absorbing properties remains physically stable upon 12 weeks of storage period.

Delimiting the knowledge space and the design space of nanostructured lipid carriers through Artificial Intelligence tools

Nanostructured lipid carriers (NLC) are biocompatible and biodegradable nanoscale systems with extensive application for controlled drug release. However, the development of optimal nanosystems along with a reproducible manufacturing process is still challenging. In this study, a two-step experimental design was performed and databases were successfully modelled using Artificial Intelligence techniques as an innovative method to get optimal, reproducible and stable NLC. The initial approach, including a wide range of values for the different variables, was followed by a second set of experiments with variable values in a narrower range, more suited to the characteristics of the system. NLC loaded with rifabutin, a hydrophobic drug model, were produced by hot homogenization and fully characterized in terms of particle size, size distribution, zeta potential, encapsulation efficiency and drug loading. The use of Artificial Intelligence tools has allowed to elucidate the key parameters that modulate each formulation property. Stable nanoparticles with low sizes and polydispersions, negative zeta potentials and high drug loadings were obtained when the proportion of lipid components, drug, surfactants and stirring speed were optimized by FormRules® and INForm®. The successful application of Artificial Intelligence tools on NLC formulation optimization constitutes a pioneer approach in the field of lipid nanoparticles.

A Nanostructured Lipid Carrier for Delivery of a Replicating Viral RNA Provides Single, Low-Dose Protection against Zika

Since the first demonstration of invivo gene expression from an injected RNA molecule almost two decades ago,1 the field of RNA-based therapeutics is now taking significant strides, with many cancer and infectious disease targets entering clinical trials.2 Critical to this success has been advances in the knowledge and application of delivery formulations. Currently, various lipid nanoparticle (LNP) platforms are at the forefront,3 but the encapsulation approach underpinning LNP formulations offsets the synthetic and rapid-response nature of RNA vaccines.4 Second, limited stability of LNP formulated RNA precludes stockpiling for pandemic readiness.5 Here, we show the development of a two-vialed approach wherein the delivery formulation, a highly stable nanostructured lipid carrier (NLC), can be manufactured and stockpiled separate from the target RNA, which is admixed prior to administration. Furthermore, specific physicochemical modifications to the NLC modulate immune responses, either enhancing or diminishing neutralizing antibody responses. We have combined this approach with a replicating viral RNA (rvRNA) encoding Zika virus (ZIKV) antigens and demonstrated a single dose as low as 10ng can completely protect mice against a lethal ZIKV challenge, representing what might be the most potent approach to date of any Zika vaccine.

DESIGN AND PHYSICOCHEMICAL EVALUATION OF NANOSTRUCTURED LIPID CARRIER ENCAPSULATED ZINGIBER ZERUMBET OIL BY D-OPTIMAL MIXTURE DESIGN

The D-optimal mixture design was employed to evaluate the effect of different composition variables on particle size, polydispersity index, zeta potential and encapsulation efficiency for optimization of Zingiber zerumbet oil loaded nanostructured lipid carrier (NLC). The glyceryl monostearate were used as solid lipid, virgin coconut oil as liquid lipid, and Tween 80 as well as soy lecithin were used as surfactant to achieve stable NLC formulation. The hot homogenization and ultrasonication techniques were employed in preparation of NLC. The statistical evaluations by ANOVA revealed that optimum NLC formulation generated as 3.7% Zingiber zerumbet oil, 5% liquid lipid and 1.3% solid lipid. The optimal NLC formulation had an average diameter of 91.002 nm, PDI of 0.172, zeta-potential of -40.88 mV, and encapsulation efficiency of 94.45%. The transmission electron microscopy (TEM) observations exhibited spherical morphology of Zingiber zerumbet oil loaded NLC. Penetration through Strat-M® membrane shown an excellent diffusion coefficient of NLC-Zingiber zerumbet oil. Therefore, D-optimal mixture design has succeeded in generating optimum NLC formulation for encapsulation of Zingiber zerumbet oil. The stable formulation of NLC for encapsulating essential oil give promising future in various applications such as drug delivery, food, textile and cosmetics.