Nanostructured Lipid Carriers Research Articles

How do various encapsulation techniques improve the oral delivery of food protein hydrolysates?

AbstractThe development of bioformulations based on food protein hydrolysates (FPHs) has gained significant traction in the food and pharmaceutical sectors due to their biophysical and biochemical properties, including health‐promoting effects, biocompatibility, and biodegradability. However, the oral delivery of FPHs presents notable technical challenges, largely due to their inherent limitations such as (bio)stability, permeability, bioavailability, and molecular size. This review provides a comprehensive overview of FPHs, including their structural characteristics, origins, methods of preparation, and associated health benefits. Additionally, it highlights the challenges related to their oral delivery. Recent advancements in the formulation and delivery of FPHs through biopolymeric controlled release systems—such as micro‐ and nanoparticles, hydrogels, biofunctional films and composites, and electrospun fibers—are discussed. We also explore lipid‐based delivery platforms, including liposomes, chitosomes, emulsions, Pickering emulsions, nanostructured lipid carriers, solid lipid nanoparticles, and surfactant‐based carriers. Furthermore, this article emphasizes the importance of controlled delivery and targeted release of FPHs following oral administration. The challenges in designing effective lipid/biopolymer‐based carriers for FPHs, along with future prospects and opportunities in this growing field, are also thoroughly examined.

Emerging therapies and innovations in vitiligo management: a comprehensive review.

Vitiligo is a common skin disorder where melanocytes, the cells that produce skin pigment, are destroyed by the immune system, leading to white patches on the skin and mucous membranes. This condition affects 0.4% to 2.0% of the global population, with a higher prevalence in females and often beginning in childhood. In India, about 1% of the population is affected, particularly in northern regions, with a higher incidence in females and links to other autoimmune diseases. This review examines recent progress in understanding vitiligo and its treatment. It focuses on the genetic, autoimmune, and environmental factors involved in the disease and highlights new therapies, such as targeted molecular treatments and advanced repigmentation methods. Current research shows that oxidative stress and genetic predispositions contribute to the autoimmune destruction of melanocytes. Novel drug delivery systems, including liposomes, nanoemulsions, and nanostructured lipid carriers, have improved treatment effectiveness. Clinical trials are exploring new treatments like Ruxolitinib cream and melanocyte transplantation, while teledermatology is becoming useful for managing patients. Vitiligo also poses a significant economic burden due to its impact on patients' quality of life. Continued research is essential to develop better, more accessible treatments and reduce the economic impact of vitiligo.

Enhancing Acute Migraine Treatment: Exploring Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for the Nose-to-Brain Route.

Migraine has a high prevalence worldwide and is one of the main disabling neurological diseases in individuals under the age of 50. In general, treatment includes the use of oral analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) for mild attacks, and, for moderate or severe attacks, triptans or 5-HT1B/1D receptor agonists. However, the administration of antimigraine drugs in conventional oral pharmaceutical dosage forms is a challenge, since many molecules have difficulty crossing the blood-brain barrier (BBB) to reach the brain, which leads to bioavailability problems. Efforts have been made to find alternative delivery systems and/or routes for antimigraine drugs. In vivo studies have shown that it is possible to administer drugs directly into the brain via the intranasal (IN) or the nose-to-brain route, thus avoiding the need for the molecules to cross the BBB. In this field, the use of lipid nanoparticles, in particular solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has shown promising results, since they have several advantages for drugs administered via the IN route, including increased absorption and reduced enzymatic degradation, improving bioavailability. Furthermore, SLN and NLC are capable of co-encapsulating drugs, promoting their simultaneous delivery to the site of therapeutic action, which can be a promising approach for the acute migraine treatment. This review highlights the potential of using SLN and NLC to improve the treatment of acute migraine via the nose-to-brain route. First sections describe the pathophysiology and the currently available pharmacological treatment for acute migraine, followed by an outline of the mechanisms underlying the nose-to-brain route. Afterwards, the main features of SLN and NLC and the most recent in vivo studies investigating the use of these nanoparticles for the treatment of acute migraine are presented.

Novel natural lipids based NLC containing finasteride improved androgenetic alopecia treatment in rats

Androgenetic alopecia (AGA) is the most common hair loss disorder, affecting millions of men and women worldwide. Current formulations used to treat this condition often lead to a wide variety of side effects, ranging from allergies to sexual disfunction, especially when those drugs are administered orally. In this study, we developed and tested unique formulations containing nanostructured lipid carriers (NLC) composed of lipids extracted from fruit seeds, carrying finasteride to enhance efficacy of AGA treatment. By stabilizing the hydrophobic compounds in the solid matrix, three formulations of NLC were engineered and successfully prepared. Further an in vivo model of AGA was induced in rats by the administration of testosterone, as a platform to evaluate the efficiency of the formulations. The chosen formulation exhibited high bioavailability, medium size of 124.5 nm and PdI of 0.143, without systemic absorption. In addition, it promoted efficient and significant follicle restoration in AGA induced rats by increasing number of active bulbs and showed to be a safe formulation for topical application. The results of this research indicate that the presented formulation has significant potential to yield improved outcomes in AGA treatment.

Enhancement of Solubility and Dissolution Rate of Poorly Soluble Anticancer Drug Using Nanostructured Lipid Carrier Based Drug Delivery System

Enhancement of Solubility and Dissolution Rate of Poorly Soluble Anticancer Drug Using Nanostructured Lipid Carrier Based Drug Delivery System

Doxorubicin and 4-nitrochalcone loaded in beeswax-based nanostructured lipid carriers: In vitro antitumoral screening and evaluation of synergistic effect on HepG-2 cells

Cancer is the second most deadly disease worldwide, and the most traditional approaches such as chemotherapy still face limitations associated to drug dosage and off-target side effects. To address these issues, we propose the simultaneous administration of 4-Nitrochalcone (4NC) and Doxorubicin (DOX) using beeswax based nanostructured lipid carriers (NLCs). The co-encapsulation of 4NC and DOX in the beeswax based NLCs was performed using the water/oil/water double emulsion technique in association with the melt dispersion approach. The system composed by semi-spherical NLCs with an average diameter around 200 nm and narrow size distribution, displayed colloidal stability before and after redispersion, keeping the zeta potential below −30 mV. The antitumor activity of the nanoparticles was screened on different tumor cell lines, and the induced cellular death and internal ROS levels were analyzed on hepatocarcinoma cells, which were found to be more affected by the combination of 4NC and DOX. The results indicated that 4NC + DOX-NCLs could promote cytotoxicity and oxidative damage-mediated apoptosis in a HepG-2 cell line.

Quality by Design Approach for the Development of Cariprazine Hydrochloride Loaded Lipid-Based Formulation for Brain Delivery via Intranasal Route.

Cariprazine (CPZ) is a third-generation antipsychotic medication that has been approved for treating schizophrenia. This study aimed to develop a cariprazine-loaded nanostructured lipid carrier (CPZ-NLCs) to prevent first-pass metabolism and improve bioavailability and site-specific delivery from the nose to the brain. The CPZ-NLCs were prepared using melt emulsification. The formulation was optimized using the Box-Behnken design (BBD); where the influence of independent variables on critical quality attributes, such as particle size and entrapment efficiency, was studied. The optimized batch (F6) had a particle size of 173.3 ± 0.6 nm and an entrapment efficiency of 96.1 ± 0.57%, respectively. The in vitro release showed >96% release of CPZ from NLC within 30 min. The optimized formulation's ex vivo studies revealed significantly increased CPZ permeability (>75%) in sheep nasal mucosa compared to the CPZ suspension (~26%). The ciliotoxicity study of the nasal mucosa revealed that the CPZ-NLC formulation did not affect the nasal epithelium. The intranasal administration of the formulation achieved 76.14±6.23 μg/ml concentration in the brain which was significantly higher than the oral CPZ suspension administration (30.46±7.24 μg/ml). The developed formulation was stable for 3 months. The study concluded that the developed CPZ-NLC could significantly improve the bioavailability with quick delivery to the brain.

Design and Development of Gastro-retentive Gel Forming System Comprising Curcumin Loaded Nanostructured Lipid Carrier for Stomach Specific Delivery

Design and Development of Gastro-retentive Gel Forming System Comprising Curcumin Loaded Nanostructured Lipid Carrier for Stomach Specific Delivery

Are Nanostructured Lipid Carriers (NLC) better than Solid Lipid Nanoparticles (SLN) for delivering abiraterone acetate through the gastrointestinal tract?

Abiraterone acetate (AbA) is a progesterone derivative indicated for the treatment of metastatic prostate cancer. This BCS (Biopharmaceutics Classification System) Class IV molecule has an extremely poor oral bioavailability (<10 %), notably due to its very low water solubility and intestinal permeability. Among the few existing galenic strategies to improve AbA’s oral bioavailability, lipid nanoparticles such as Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are relevant nanovectors. The objective of this study is to develop and compare SLN and NLC for oral delivery of abiraterone acetate. Both SLN and NLC are biocompatible, biodegradable and produced by high pressure homogenization (HPH), an ecological-friendly manufacturing process, organic solvent-free and easily scalable. The HPH process allowed the formation of AbA-loaded SLN and NLC with particle size lower than 160 nm and high encapsulation efficiencies. The addition of a liquid lipid significantly reduced the mean diameter of the nanoparticles, reflecting the greater benefit of the NLC formulation compared to SLN. Both SLN and NLC formulations offered an important protection of AbA in intestinal media, with a better stability for NLC. When encapsulated in SLN or NLC, the AbA is strongly retained by the nanoparticles, whatever the dissolution medium, which means that both formulas are able to protect and retain the drug in the intestinal tract, right up to its delivery to the enterocytes surface. High concentrations of nanoparticles were administered without cytotoxicity, especially for the NLC, which provides a real added value in terms of biocompatibility with Caco-2 cells. Finally, the nanoparticles were able to penetrate into enterocytes by the transcellular route, demonstrating an intense cellular internalization.

Applicability of QbD-assisted Analytical Method for Simultaneous Detection of Tetrahydrocurcumin and Folic Acid in Developed Nanostructured Lipid Carriers

Aims: Applicability of QbD-assisted analytical method for simultaneous detection of tetrahydrocurcumin and folic acid in developed nanostructured. Background: Diabetic foot ulcer (DFU) is a multifactorial disorder that involves chronic inflammation, oxidative stress and neuropathy. Current treatment therapies involving the use of growth factors and skin substitutes being costly, are out of reach for the majority of patients. The present research explored the usefulness of (5929IN008, application number 202211045937), a combination of tetrahydrocurcumin and folic acid-loaded nanostructured lipidic carriers. Objectives: To develop and validate a QbD-assisted method for simultaneous analysis of tetrahydrocurcumin (THC) and folic acid (FA). Applicability of the above method to determine total drug content (TDC) and entrapment efficiency (EE) of nanostructured lipid carriers (NLCs) loaded THC and FA. Methods: A high-performance liquid chromatographic (HPLC) method was developed, optimized and validated using Box-Behnken design for improved method performance. Chromatographic separation was conducted on a Supelco 250 x 4.6 mm (5 μm) column with optimized mobile phase composition containing tetrahydrofuran: citric acid buffer pH 3.5 (50:50) at a flow rate of 0.4 mL.min-1 and diode array detection between 210 and 360 nm. Results: The method developed in a concentration range of 1 to 100 μg.mL-1 was found to be linear (R2 0.999, p≤0.001), accurate (99.10-101.70%) and precise with high recovery values in intra and inter-day results. The system adaptability and robustness evaluation revealed that the percent recovery ranged from 96.90 to 102.80%, and the percent relative standard deviation (%RSD) values were less than 2%. Moreover, the method was further applied for the determination of TDC (86±6% and 96±8%) and drug EE (81±21% and 73±13%) for THC and FA, respectively. Conclusion: The investigation indicated the applicability of the developed and validated method for the estimation of THC and FA in the developed nanostructured lipidic carriers.

Nanostructured lipid carriers decorated with polyphosphate coated linear and loop cell-penetrating peptides

AimThis study aimed to evaluate the cellular uptake of nanostructured lipid carriers (NLCs) decorated with polyphosphate coated linear and loop cell-penetrating peptides (CPPs). MethodsLinear-CPPs and loop-CPPs were synthesized via ring-opening polymerization and anchored on the surface NLCs, followed by coating with polyphosphate (PP). These nanocarriers (NCs) were characterized in terms of particle size, polydispersity index (PDI), and zeta potential. Cell viability and hemolysis, as well as enzyme-induced charge conversion via phosphate cleavage by free and membrane-bound intestinal alkaline phosphatase (IAP) were investigated. Cellular uptake studies by Caco-2 and HEK cells were quantitatively analyzed by flow cytometry and visualized by confocal microscopy. ResultsA shift in charge from positive to negative was obtained for both linear- and loop-CPPs-NLCs by coating with PP. PP-linear-CPPs-NLCs and PP-loop-CPPs-NLCs exhibited a particle size < 270 nm and a PDI of approximately 0.3. They had a minor effect on cell viability and caused in a concentration of 0.1 % (m/v) around 10 % hemolysis within 24 h. IAP triggered the cleavage and release of monophosphate from the surface of NLCs causing charge conversion from –22.2 mV to + 5.3 mV (Δ27.5 mV) for PP-linear-CPPs-NLCs and from −19.2 mV to + 11.9 mV (Δ31.1 mV) for PP-loop-CPPs-NLCs. Inhibition of alkaline phosphatase activity on Caco-2 and HEK cells confirmed the involvement of this enzyme in charge conversion. PP-linear-CPPs-NLCs showed on Caco-2 cells a higher uptake than PP-loop-CPPs-NLCs, whereas on HEK cells uptake of both types of NLCs was on the same level. The results of cellular uptake were confirmed visually by confocal microscopy. ConclusionCPPs-NLCs coated with polyphosphate are a promising approach to overcome the polycationic dilemma and to enhance cellular uptake.

Simvastatin and adenosine-co-loaded nanostructured lipid carriers for wound healing: Development, characterization and cell-based investigation

Chronic wounds represent a significant global health burden, characterized by delayed skin healing and associated comorbidities. The present study aimed to develop nanostructured lipid carriers (NLCs) as a topical delivery system for the co-administration of simvastatin and adenosine to address chronic wound management. The rationale behind the co-delivery approach was to mitigate the cytotoxicity associated with high-dose simvastatin, while preserving its therapeutic benefits through a potential synergistic or additive effect. A significant challenge in the development of these NLCs was the encapsulation of the highly hydrophilic adenosine within the hydrophobic lipid matrix. The NLCs were prepared using a hot homogenization-sonication method with a double emulsion technique and optimized through a series of formulation trials, employing various surfactants, solid and liquid lipids, to achieve efficient drug encapsulation, particularly for the hydrophilic adenosine. Optimized formulations F5- and F10-S/A 0.6 %/2 % (containing 0.6 % simvastatin and 2 % adenosine), exhibited promising physicochemical properties. The main difference was the liquid lipid used: F5 containing Miglyol 810 N, while F10 Capmul MCM C-8. Both formulations displayed a mean particle size below 230 nm, a polydispersity index (PDI) of approximately 0.2, and a zeta potential of around –22 mV. While simvastatin association efficiency (AE) was nearly 100 %, adenosine AE was higher for F10 (24 %), compared to F5 (13.5 %). F5 demonstrated superior stability compared to F10, maintaining consistent particle size and PDI over a 60-day period. Formulation F5 also demonstrated superior cell-based in vitro performance compared to F10, with higher cell viability (MTT assay), greater cell proliferation induction (SRB assay), and enhanced cell proliferation and migration in the wound-scratch assay. While F10 displayed higher adenosine AE, F5 excelled in terms of stability and biological activity. The slightly increase in intracellular reactive oxygen species levels observed with F5 may contribute to its enhanced proliferative effects. In-depth characterization revealed that F5 comprised spherical nanoparticles, and thermal analysis indicated no significant changes in the nanocarrier structure upon drug encapsulation. Additionally, ex vivo permeability study demonstrated superior skin retention of both simvastatin and adenosine for F5 compared to an emulsion control. Overall, the F5 nanocarrier demonstrated suitable physicochemical properties, cellular biocompatibility, induction of cell proliferation and migration events, and drug retention capacity in the skin layers, indicating its potential as a promising topical treatment for difficult-to-heal wounds.

Establishment of a semi-continuous nano-production line using the Microfluidizer® technology for the fabrication of lipid-based nanoparticles part 1: Screening of critical parameters and Design of Experiment optimization studies

A variety of strategies for producing high-quality nanoparticles have been reported in recent years. Batch-based bottom-up and top-down technologies are generally the most efficient methods, but present a number of challenges, particularly in terms of variability, safety, sustainability and large-scale production. In this study, a scalable, semi-continuous production line was built by connecting individual processing units, including a high shear mixing device, the Microfluidizer® technology and a cooling system. Each unit was equipped with an adequate temperature control to allow solvent-free production of solid lipid nanoparticles (consisting of Precirol® ATO 5 or Gelucire® 43/01) and nanostructured lipid carriers (additionally comprising Labrafac™ lipophile WL 1349). Subsequently, critical formulation parameters and critical process parameters (CPPs) of the individual processing units and their effects on particle size (i.e., critical quality attribute (CQA)) were investigated to identify appropriate input parameters for the subsequent Design of Experiment (DoE) studies conducted after linking the process units to a semi-continuous production line. For particle size monitoring, spatially resolved dynamic light scattering (SR-DLS) measurements were conducted and compared to standard DLS measurements to evaluate the applicability of SR-DLS as an inline monitoring tool. It was found that matrix composition, emulsifier concentration, pressure and number of cycles when processing through Microfluidizer® processor were the most influencing parameters. By optimizing these parameters, five-times higher throughputs could be achieved by the semi-continuous manufacturing line. In addition, the particle size measurements with SR-DLS confirmed the feasibility of implementing this technology for real-time particle size monitoring as an important safety factor in quality control.

Clinical Trials of Intratesticular Administration of Nanostructured Lipid Carriers Encapsulated Alpha-Mangostin: Safety and Efficacy on Feline Reproductive Health

Surgical castration is a primary method for controlling male fertility, but it is impractical for large-scale population control of stray animals. Developing nanoparticle-mediated sterilants that induce cell apoptosis rather than necrosis is a complex and promising area of research. This study aimed to investigate the impact of intratesticular administration of alpha-mangostin encapsulated in nanostructured lipid carriers (AM-NLC) on testicular changes and any associated adverse effects over a 168-day observation period. Thirty-two healthy mature tomcats were enrolled. None of the cats treated with either AM-NLC (n=28) or blank NLC (n=4) exhibited noticeable complications related to pain or stress throughout the study, as assessed by clinical examination, blood profiles, and serum amyloid A levels. Histopathological analysis of AM-NLC treated cats revealed seminiferous epithelium degeneration, leading to defective tubules. Key findings included germ cell depletion, disorganized spermatogenic cells without spermatids in certain areas, apoptotic bodies, and intracytoplasmic vacuolization. The intertubular compartment showed no signs of inflammation, hyalinization, fibrosis, or necrosis. Despite widespread degeneration, some normal tubules were present in focal areas. The severity score of seminiferous tubule degeneration significantly increased from day 56 onwards (P<0.05), suggesting a gradual and progressive compromise of the seminiferous epithelium. In contrast, testes from the blank-NLC group exhibited normal spermatogenesis. Overall, there were no significant changes in the volume of dissected testes, serum testosterone levels, or apoptotic index in AM-NLC-treated cats (P>0.05). In conclusion, this study represents the first in vivo investigation of apoptotic-inducing agents as a novel nanomedicine-based antifertility compound for non-surgical castration in male animals. While the AM-NLC formulation proved safe for intratesticular administration, it failed to induce infertility in cats, as epididymal spermatozoa persisted throughout the study. Further research into alternative apoptosis-inducing nanomedicine sterilants remains both essential and challenging.

Effects of thermal processing and pH on the physicochemical properties, stability, and structure of taxifolin-loaded nanostructured lipid carriers

In the present study the potential of nanolipid carriers (transfersomes) for improving the oral delivery of taxifolin, a poorly water-soluble bioactive compound with high antioxidant and anti-inflammatory activity was evaluated. Two transfersome formulations were prepared using lecithin, Span®60, and Tween®80, with cholesterol as a stabilizer (FA) and without cholesterol (FB), by the Ethanol Injection Method (EIM). The influences of thermal treatment (60-90°C) and pH (2, 4, 6, and 8) on physical stability, structure, and taxifolin degradation were evaluated. The transfersomes were physically and chemically stable during heating at lower temperatures (≤70°C), while thermal treatment at 80–90°C led to an increase in particle size (an increase of around 200 nm) and a decrease in taxifolin encapsulation. Moreover, there was no significant difference in particle size or polydispersity index (PDI) at high temperatures. The particle sizes of transfersomes FA and FB increased from 128 and 182 nm at pH 7 to 224 and 331 nm at pH 2, respectively. Both transfersome preparations remained relatively stable, with consistent antioxidant activity (IC50 = 0.64 mg/ml) over four weeks of storage at different temperatures (4, 25, and 40°C), showing higher stability at lower temperatures. The in vitro digestion experiment indicated physical stability after exposure to the simulated stomach stage. However, the reduction in the nanovesicles' surface charge after incubation with gastric juice, increased particle size. Based on these results, taxifolin-loaded transfersomes can be pasteurized at low temperatures, for incorporation into enriched food and beverage products.

NANOSTRUCTURE LIPID CARRIER TECHNOLOGY IN DRUG DELIVERY: ROUTE OF ADMINISTRATION, PREPARATION METHOD, CHARACTERIZATION, AND APPLICATION FOR ANTI-AGING

The new method, known as nanostructured lipid carrier (NLC) in drug delivery systems, has the potential to increase therapeutic efficacy, stability, and bioavailability. This systematic literature review aimed to provide a detailed summary of NLC technology in drug delivery systems, including routes of administration, preparation methods, characterization, and utilization for the delivery of anti-aging active ingredients in cosmetics. To collect scholarly articles on NLCs, we employed a systematic search method using Google Scholar and PubMed. After the screening process, 53 pertinent papers out of 102 articles were chosen for descriptive analysis. NLC exhibit significant promise in many drug delivery applications, including oral, topical, parenteral, and transmucosal routes, with many benefits, including improved bioavailability, stability, and drug penetration through the skin, cornea, and brain. Moreover, NLC technology has been effectively applied for the administration of drugs, including anti-aging drugs. Topical anti-aging preparations generally use synthetic or natural active ingredients. However, synthetic ingredients are often less stable and can irritate skin. NLC can protect and control the release of active ingredients, thereby reducing the risk of irritation. NLC can also improve the penetration of active ingredients into the deeper layers of the skin, allowing it to reach the dermis layer, which is responsible for most skin aging. The efficient absorption capacity of NLC technology in topical preparations presents new opportunities for anti-aging cosmetic product development owing to its effectiveness in skin penetration. Keywords: Nanostructured Lipid Carrier (NLC), drug delivery system, drug penetration, anti-aging

Development of Nanostructured Lipid Carriers for Donepezil Hydrochloride Effective Nose to Brain Delivery

ABSTRACT: This study focuses on the development and evaluation of nanostructured lipid carriers (NLCs) for the efficient intranasal delivery of donepezil hydrochloride. The NLCs were prepared using the microemulsion technique. Each excipient used in the formulation was thoroughly evaluated for stability, assessing factors such as color change, phase separation, precipitation, and texture. Characterization of the NLCs included the construction of a pure calibration curve, differential scanning calorimetry (DSC), infrared spectroscopy (IR), and the IR analysis of physical mixtures. The donepezil hydrochloride-loaded NLCs were then incorporated into a thermosensitive gel using Pluronic F127, which was also prepared using the microemulsion technique. The NLCs were further characterized by evaluating their zeta potential, entrapment efficiency, and particle size. The thermosensitive gel's properties were assessed by measuring the gelation temperature and viscosity. Drug release studies were conducted using a dialysis membrane to compare the release profiles of the pure drug, donepezil-HCl-loaded NLCs, and the NLC-loaded thermosensitive gel, focusing on their potential for controlled drug release.

Approach of nanostructured lipid carriers (NLCS): tool as a new targeted drug delivery system: A review

The most significant advancement in the creation of more efficient medicine delivery systems has come from nanotechnology. The target drug delivery system is now incredibly simple and efficient thanks to cutting-edge nanotechnology. A target drug delivery system is a technique for getting the medication's active ingredient to the body's injured area. Nanostructured lipid carriers (NLC) are an exceptional and unique development in the field of nanotechnology. Site-specific drug delivery systems can be constructed using NLCs, a novel form of second generation emulsion system that combines spatially incompatible liquid lipids with a mixture of solid lipids. This potential delivery mechanism provides longer stability than SLNs. Because of the potential advantages of drug design at the nanoscale, such as the capacity to increase immunogenicity and bioavailability, which can lead to the development of more convenient administration routes, fewer side effects, improved biodistribution, and an extended drug life cycle, the application of nanostructured and nanophases is seen to bridge the gap between biological and physical sciences.

Chlorin e6-Loaded Nanostructured Lipid Carriers Targeted by Angiopep-2: Advancing Photodynamic Therapy in Glioblastoma.

Glioblastoma (GBM) is a highly aggressive brain tumor known for its resistance to standard treatments. Despite surgery being a primary option, it often leads to incomplete removal and high recurrence rates. Photodynamic therapy (PDT) holds promise as an adjunctive treatment, but safety concerns and the need for high-power lasers have limited its widespread use. This research addresses these challenges by introducing a novel PDT approach, using chlorin e6 (Ce6) enclosed in nanostructured lipid carriers (Ang-Ce6-NLCs) and targeted to GBM with the angiopep-2 peptide. Remarkably, a single 5-min irradiation session with LEDs at 660nm and low power density (10mW cm- 2) proves effective against GBM, while reducing safety risks associated with high-power lasers. Encapsulation improves Ce6 stability and performance in physiological environments, while angiopep-2 targeting enhances delivery to GBM cells, maximizing treatment efficacy and minimizing off-target effects. The findings demonstrate that Ang-Ce6-NLCs-mediated PDT brings about a significant reduction in GBM cell viability, increases oxidative stress, reduces tumor migration, and enhances apoptosis. Overall, such treatment holds potential as a safe and efficient intraoperative removal of GBM infiltrating cells that cannot be reached by surgery, using low-power LED light to minimize harm to surrounding healthy tissue while maximizing tumor treatment.

Agomelatine-loaded nanostructured lipid carriers alleviate neuropathic pain in rats by Nrf2/HO-1 signalling pathway.

Neuropathic pain arises from impairments or malfunctions within the nervous system, resulting in atypical transmission and interpretation of pain signals. In the present study, we examined the neuroprotective effects of agomelatine (AGM) and agomelatine-loaded nanostructured lipid carriers (AGM-NLCs) in neuropathic animal models induced by chronic constriction injury (CCI) of the sciatic nerve. Male Sprague Dawley rats were divided into seven experimental groups to compare the effects of AGM and AGM-NLCs, which were administered at 20 mg/kg for 14 consecutive days after CCI. Our finding demonstrated that CCI triggered the onset of analgesia in these animals, corroborated by mechanical allodynia and thermal hyperalgesia. Furthermore, CCI induced an elevation in inflammatory mediators such as interleukin (IL)-1β and inducible nitric oxide synthase (iNOS), and downregulated heme oxygenase-1 (HO-1) and nuclear factor E2-related factor (Nrf2). Treatment with AGM and AGM-NLCs reversed inflammatory cascades and elevated antioxidant enzyme levels, leading to a reduction in paw withdrawal latency and threshold in rats. To further investigate the effect of AGM and AGM-NLCs, all-trans retinoic acid (ATRA) was administered, which antagonizes Nrf2. ATRA substantially downregulated Nrf2 expression and exacerbated thermal hyperalgesia, whereas Nrf2 and HO-1 expressions were significantly upregulated after AGM-NLCs administration. Overall, the results demonstrated that AGM-NLCs offer promising antinociceptive and anti-inflammatory properties in alleviating neuropathic pain symptoms, which can be attributed to improved drug delivery and therapeutic outcomes compared with AGM alone.