Nanostructured Lipid Carriers For Delivery Research Articles

Engineering of VCAM-1-targeted nanostructured lipid carriers for delivery of melatonin against acute lung injury through SIRT1/NLRP3 mediated pyroptosis signaling pathway

Acute lung injury (ALI) is a prevalent and critical condition in clinical practice. Although certain pharmacological interventions have demonstrated benefits in preclinical studies, none have been proven entirely effective thus far. Therefore, the development of more efficient treatment strategies for ALI is imperative. In this study, we prepared nanostructured lipid carriers (NLCs) conjugated with anti-VCAM-1 antibodies to encapsulate melatonin (MLT), resulting in VCAM/MLT NLCs. This approach aimed to enhance the distribution of melatonin in lung vascular endothelial cells. The VCAM/MLT NLCs had an average diameter of 364 nm, high drug loading content, and a sustained drug release profile. Notably, the NLCs conjugated with anti-VCAM-1 antibodies demonstrated more specific cellular delivery mediated by the VCAM-1 receptors, increased cellular internalization, and enhanced accumulation in lung tissues. Treatment with VCAM/MLT NLCs effectively alleviated pulmonary inflammation by activating NLRP3 inflammasome-dependent pyroptosis through up-regulation of Sirtuin 1. Our findings suggest that VCAM/MLT NLCs demonstrate remarkable therapeutic effects on ALI in both in vitro and in vivo settings, making them a promising and efficient treatment strategy for ALI.

Development of α-Tocopherol Succinate-Based Nanostructured Lipid Carriers for Delivery of Paclitaxel.

The management of retinoblastoma (RB) involves the use of invasive treatment regimens. Paclitaxel (PTX), an effective antineoplastic compound used in the treatment of a wide range of malignant tumors, poses treatment challenges due to systemic toxicity, rapid elimination, and development of resistance. The goal of this work was to develop PTX-loaded, α-tocopherol succinate (αTS)-based, nanostructured lipid carrier (NLCs; αTS-PTX-NLC) and PEGylated αTS-PTX-NLC (αTS-PTX-PEG-NLC) to improve ocular bioavailability. The hot homogenization method was used to prepare the NLCs, and repeated measures ANOVA analysis was used for formulation optimization. αTS-PTX-NLC and αTS-PTX-PEG-NLC had a mean particle size, polydispersity index and zeta potential of 186.2 ± 3.9 nm, 0.17 ± 0.03, −33.2 ± 1.3 mV and 96.2 ± 3.9 nm, 0.27 ± 0.03, −39.15 ± 3.2 mV, respectively. The assay and entrapment efficiency of both formulations was >95.0%. The NLC exhibited a spherical shape, as seen from TEM images. Sterilized (autoclaved) formulations were stable for up to 60 days (last time point checked) under refrigerated conditions. PTX-NLC formulations exhibited an initial burst release and 40% drug release, overall, in 48 h. The formulations exhibited desirable physicochemical properties and could lead to an effective therapeutic option in the management of RB.

Intramuscular Delivery of Replicon RNA Encoding ZIKV-117 Human Monoclonal Antibody Protects against Zika Virus Infection

Monoclonal antibody (mAb) therapeutics are an effective modality for the treatment of infectious, autoimmune, and cancer-related diseases. However, the discovery, development, and manufacturing processes are complex, resource-consuming activities that preclude the rapid deployment of mAbs in outbreaks of emerging infectious diseases. Given recent advances in nucleic acid delivery technology, it is now possible to deliver exogenous mRNA encoding mAbs for in situ expression following intravenous (i.v.) infusion of lipid nanoparticle-encapsulated mRNA. However, the requirement for i.v. administration limits the application to settings where infusion is an option, increasing the cost of treatment. As an alternative strategy, and to enable intramuscular (IM) administration of mRNA-encoded mAbs, we describe a nanostructured lipid carrier for delivery of an alphavirus replicon encoding a previously described highly neutralizing human mAb, ZIKV-117. Using a lethal Zika virus challenge model in mice, our studies show robust protection following alphavirus-driven expression of ZIKV-117 mRNA when given by IM administration as pre-exposure prophylaxis or post-exposure therapy.

Pulmonary delivery of nanostructured lipid carriers for effective repurposing of salinomycin as an antiviral agent

Coronavirus disease outbreak caused a severe public health burden all over the world. Salinomycin (SAL) is a broad-spectrum antibiotic that had drawn attention in selective targeting of cancer and viral infections. Recent drug screen identified SAL as a potent antiviral agent against SARS-CoV-2. In this hypothesis, we discuss the potential of pulmonary delivery of SAL using nanostructured lipid carriers (NLCs) against SARS-CoV-2.

Design, Optimization and Characterization of Nanostructured Lipid Carriers of Raloxifene Hydrochloride for Transdermal Delivery

Introduction: Raloxifene Hydrochloride (RXL), a BCS class II drug, is used for the treatment of invasive breast cancer and osteoporosis in post menopausal women. Even though the drug is highly efficient, it shows poor bioavailability of 2% when administered orally. The aim of the study was to develop, statistically optimize, and characterize Raloxifene Hydrochloride loaded Nanostructured Lipid Carriers (NLC) for transdermal delivery to overcome the bioavailability issue. Methods: The RXL-NLC’s were developed using glyceryl behenate (Compritol® 888 ATO), glyceryl monostearate (GMS), and capric triglyceride (Miglyol® 810) as solid and liquid lipids, and Polysorbate 80 (Tween 80) and cremophor EL were used as surfactants and co-surfactant. A response surface methodology was applied for the optimization of NLC, using Box-Behnken experimental design. Amount of the drug, tween 80 and polyethoxylated castor oil (cremophor EL), each at three levels, were selected as independent variables, while particle size and polydispersity index were identified as dependent variables. The optimized batch was characterized for Particle size (79.8 nm±3), Polydispersity index (0.229±0.05), Zeta potential (-12.3±5) and Entrapment efficiency (79.14%±5). Surface morphology of the NLC’s were studied using Transmission Electron microscopy (TEM) and the shift in the endotherm of Differential scanning calorimetry confirmed the entrapment of the drug within NLC. In vitro drug release studies were performed using dialysis bag (12000-14000 Da) method. The optimized NLC dispersion was then incorporated into gel and characterized for gel uniformity, spreadability, pH, viscosity and drug content. Results: In vivo skin penetration study was carried out by tape stripping method, which showed increase in penetration when incorporated into nanogel as compared to plain drug gel. Conclusion: Based on the above result it can be concluded that transdermal delivery of NLC’s can be a superior alternative for orally low bioavailable drugs such as RXL which undergoes rapid first pass metabolism.

Development and Characterization of Ofloxacin & Prednisolone Loaded Nanostructured Lipid Carriers (Nlc) for Topical Route

Aim: The present study was designed to develop and characterize nanostructured lipid carriers (NLC) of Ofloxacin and Prednisolone for topical use in case of infections associated with inflammation. Materials and Methods: Ofloxacin was obtained as gift sample from Mankind Pharma Ltd, VillKyarta, P.O. Misserwal, Poonta Sahib, Sir Mour. H.P. Whereas Prednisolone was purchased from Yarrow chem., Mumbai. It was evaluated for its pre-formulation studies (organoleptic properties, melting point, solubility, compatibility, max. wavelength of absorption). NLCs were prepared through melt-emulsification followed by ultra-sonication technique. Further optimized batch of NLCs was incorporated into Gel. Formulated NLCs were evaluated in terms of morphological characteristics, particle size (Polydispersity Index), drug content, In-vitro drug release (using egg membrane), drug release kinetics (Ritger-Peppas diffusion method). Finally, gel containing NLCs was studied by physical characteristics, pH, viscosity, spreadability, drug content, In-vitro drug release and its kinetics. Results and Discussion: In pre-formulation study, drugs were found having the similar properties as described in Indian Pharmacopoeia (IP) and United States Pharmacopoeia (USP). SEM photomicrograph revealed that NLCs were spherical with more or less smooth surface; particle size 512.3-1703 nm and PDI- 0.399-0.742 (ofloxacin) and particle size 539.3-1736.7 nm and PDI- 0.335 - 0.711 (prednisolone);drug content was found in range of 56.7 - 75.6% for ofloxacin and 65.9 – 81.8% for prednisolone. NLC1 demonstrated maximum release rate with 83.37±1.70% and NLC8 73.96±0.53%.NLC6 was best fitted in Korsmeyer - peppas model as the regression coefficients were 0.960, 0.964, 0.977, 0.950, 0.980 & 0.987 respectively and prednisolone NLC 9 (0.953) and they were close to 1. Conclusion: In conclusion, the prepared NLCs had prolonged release effects with good potential for topical delivery of NLC based gel formulation of ofloxacin& prednisolone.

Propolis wax nanostructured lipid carrier for delivery of β sitosterol: Effect of formulation variables on physicochemical properties

Preparation and characterization of novel functional nanostructured lipid carriers containing β sitosterol has been studied. The nanostructured lipid carrires (NLCs) were formulated with propolis wax (PW) alone or in mixture (1:1 w/w) with glyceryl behenate (GB), and pomegranate seed oil (PSO) and produced by a hot melt emulsification method. Response surface methodology was used to optimize formulations with respect to β sitosterol concentration, liquid lipid content and solid lipid composition. The NLCs formulated with less oil and higher drug content showed higher size and lower encapsulation efficiency. Solid state analysis exhibited lower crystallinity of optimal formulations compared to raw lipids and a drug amorphization into the NLC matrix. The compatibility between drug and encapsulating materials was confirmed by Fourier transform infrared spectroscopy. Transmission electron microscopy showed spherical particles ranged around 100 nm confirming the applicability of such formulations for the production of functional foods.

Microneedle-mediated transdermal delivery of nanostructured lipid carriers for alkaloids from Aconitum sinomontanum

A combination method using microneedle (MN) pretreatment and nanostructured lipid carriers (NLCs) was developed to improve the transdermal delivery of therapeutics. The MN treatment of the skin and co-administration of NLCs loaded with total alkaloids isolated from Aconitum sinomontanum (AAS–NLCs) significantly increased the skin permeation of the drugs. Fluorescence imaging confirmed that MNs could provide microchannels penetrating the stratum corneum, and delivery of NLCs through the channels led to their deeper permeation. In vivo studies showed that combination of AAS–NLCs with MNs (AAS–NLCs–MN) in transdermal delivery could improve the bioavailability and maintain stable drug concentrations in the blood. Moreover, AAS–NLCs–MN showed benefits in eliminating paw swelling, decreasing inflammation and pain, and regulating immune function in adjuvant arthritis rats. After administration of AAS–NLCs–MN, no skin irritation was observed in rabbits, and electrocardiograms of rats showed improved arrhythmia. These results indicated that the dual approach combining MN insertion and NLCs has the potential to provide safe transdermal delivery and to improve the therapeutic efficacy through sustained release of AAS.

Effect of surface charge on the brain delivery of nanostructured lipid carriers in situ gels via the nasal route

The aim of this study was to investigate the influence of the nanocarrier surface charge on brain delivery of a model hydrophilic drug via the nasal route. Anionic and cationic nanostructured lipid carriers (NLCs) were prepared and optimized for their particle size and zeta potential. The optimum particles were incorporated in poloxamer in situ gels and their in vivo behavior was studied in the plasma and brain after administration to rats. Optimum anionic and cationic NLCs of size <200nm and absolute zeta potential value of ≈34mV were obtained. Toxicity study revealed mild to moderate reversible inflammation of the nasal epithelium in rats treated with the anionic NLCs (A7), and destruction of the lining mucosal nasal epithelium in rats treated with the cationic NLCs (C7L). The absolute bioavailability of both drug loaded anionic and cationic NLCs in situ gels was enhanced compared to that of the intranasal solution (IN) of the drug with values of 44% and 77.3%, respectively. Cationic NLCs in situ gel showed a non significant higher Cmax (maximum concentration) in the brain compared to the anionic NLCs in situ gel. Anionic NLCs in situ gel gave highest drug targeting efficiency in the brain (DTE%) with a value of 158.5 which is nearly 1.2 times that of the cationic NLCs in situ gel.

Transparent Dispersions of Milk-Fat-Based Nanostructured Lipid Carriers for Delivery of β-Carotene

Nanostructured lipid carriers (NLCs) are possible vehicles to incorporate lipophilic bioactive compounds in transparent functional beverages. In this work, anhydrous milk fat (AMF) and Tween 80 were used to prepare NLCs using a phase-inversion temperature method, and β-carotene was used as a model lipophilic bioactive compound. The phase-inversion temperature decreased from >95 to 73 °C, when NaCl increased from 0 to 1.0 M in the aqueous phase. At 0.8 M NaCl and phase inversion by heating at 90 °C for 30 min, transparent NLC dispersions were observed at AMF levels higher than 10% (w/w), corresponding to particles smaller than ~25 nm. The NLC dispersions were dilution- and dialysis-stable and maintained turbidity and particle size during 90 days of storage at room temperature. The degradation of β-carotene encapsulated in NLCs was much reduced when compared to its encapsulation in the soybean-oil-based nanoemulsion.

Galactosylated nanostructured lipid carriers for delivery of 5-FU to hepatocellular carcinoma

The aim of the present study was to design a targeted delivery system of 5-fluorouracil (5-FU) for hepatocellular carcinoma (HCC). Lactobionic acid (LB) was conjugated to stearyl amine (SA) by a chemical reaction. The nanostructured lipid carriers (NLCs), containing LB conjugate, lecithin, glyceryl monostearate, oil [oleic acid (OA) or Labrafac 5 or 10%], and 5-FU, were dissolved in alcohol/acetone, the oil phase was added to the aqueous phase containing Tween 80 or Solutol® HS15 (0.25 or 0.5%), and NLCs were prepared by an emulsification-solvent diffusion method. Physical properties and drug release were studied in NLCs. The thiazolyl blue tetrazolium bromide assay was used to study the cytotoxicity of NLCs on HepG2 cells, and the cellular uptake of NLCs was determined by flow cytometry. Fourier transform infrared spectroscopy and 1H-NMR spectra confirmed the successful conjugation of LB and SA. The optimized NLCs consisted of 0.5% Solutol HS15 and 10% OA oil. The particle size of these nanoparticles was 139.2 nm, with a zeta potential of –18 mV, loading efficiency of 34.2%, release efficiency after 2 hours of the release test was 72.6%, and crystallinity was 0.63%. The galactosylated NLCs of 5-FU were cytotoxic on the HepG2 cell line in a half concentration of 5-FU and seems promising in reducing 5-FU dose in HCC.