Lipid Carriers Research Articles

Antioxidant and anticancer activities of hesperetin and its novel formulations in KB cells.

This study aimed to formulate the hesperetin nanostructured lipid carriers (NLCs) containing oro-mucosal gel for its activity assessment on the KB cell line. NLCs were prepared with glyceryl monostearate, oleic acid, and lecithin using a modified constant-temperature emulsification technique. The particle size analysis, in vitro drug release studies, etc., of prepared NLCs were evaluated. The formulated gels were analyzed with respect to spreadability, extrudability, swelling index, texture analysis, etc. The particle size, polydispersity index, zeta potential, and drug entrapment of nanocarriers were recorded to be 221.733 ± 61.536nm, 0.381 ± 0.091, - 51.433 ± 4.143mV, and 89.29%, respectively. The optimized NLCs in 24h released 87.14 ± 6.62% of the drug. The round shape of NLCs was noticed with scanning electron microscopy. The pH, spreadability, extrudability, swelling index, content uniformity, and drug release studies of hesperetin NLCs-containing gel (HNG) were found to be 6.81 ± 0.04, 2.49 ± 0.04cm.mg/s, 539.04 ± 32.88g/cm2, 4.27 ± 0.47, 107.98 ± 1.93%, and 90.17 ± 6.67% (in 48h), respectively. The developed formulations showed promising in vitro anticancer and antioxidant activities. HNP results authorize that the formulation may be beneficial for the treatment of oral cancer.

In vitro evaluation of lipidic nanocarriers for mebendazole delivery to improve anticancer activity

Objective Enhance the anticancer activity of the repurposed drug Mebendazole (MBZ) against A549 cell lines by developing nanostructured lipid carriers (NLCs). Significance MBZ, an anthelmintic drug, exhibits anticancer properties primarily through the inhibition of Ran GTPase and mitotic spindle assembly. Enhancing its delivery and efficacy via NLC could provide a novel and effective approach for lung cancer treatment. Methods NLCs were prepared by mixing different ratios of solid lipid (Stearic acid) and liquid lipid (Oleic acid) with surfactants and emulsifiers. The NLCs were fully characterized to ensure stability, particle size, zeta potential, and encapsulation efficiency (EE%). The stability of the NLCs was monitored over a 3-week period. The anticancer activity of MBZ-NLCs was evaluated using IC50 assays and in vitro scratch assays. Results The NLCs exhibited an average particle size of 300 ± 10 nm and a zeta potential of -27 ± 0.5 mV, indicating good stability. EE% significantly improved from 40% in conventional liposome formulations to 90.7% in NLCs. The anticancer activity of MBZ-NLCs was markedly enhanced, with an IC50 of 62 nM compared to 581 nM for free MBZ, representing a 10-fold increase in potency. Additionally, in vitro scratch assays revealed that MBZ-NLCs effectively prevented cell-cell contact, further supporting their potential for improved therapeutic efficacy. Conclusions MBZ-NLCs exhibit significantly improved stability, encapsulation efficiency, and anticancer activity compared to free MBZ. These promising results suggest that MBZ-NLCs could be a potent therapeutic approach for lung cancer treatment, warranting further in vivo studies and exploration of different administration routes.

Nanotechnological prospective for enhancing the antibacterial activity of mupirocin and cinnamon essential oil: a combination therapy

BackgroundsThe aim of the current study was to develop a distinctive nanolipid formulation, namely, nanostructured lipid carrier (NLC), which would deliver an antibacterial medication such as mupirocin (MP). Additionally, cinnamon essential oil (CEO), which is reported to exhibit antibacterial activity, was utilized in the development process in an attempt to improve the influence of MP.MethodsAs a consequence, different MP–NLC formulations were developed using the central composite design (CCD) approach. One optimized formula was selected and incorporated within the pre-formulated gel matrix, providing the MP–NLC-gel formula for efficient topical application. MP–NLC-gel was assessed for its physical characteristics to check its suitability for topical application and evaluated for its in vitro drug release over 6 h. Furthermore, it studied the formulation for its stability at different conditions; 25°C ± 2°C and at 4°C ± 3°C for 6 months. Finally, the formulation was examined for its antibacterial performance against gram-positive and -negative bacteria.ResultsThe developed topical NLC-gel formulation demonstrated pH 5.8, viscosity 14,510 cP, and spreadability 58.1 mm, which were seemed to be satisfactory properties for successful topical application. The drug was released successfully for over 6 h with 52.9%. Additionally, it was stable in both storage conditions for 6 months since it displayed non-significant variations in its evaluated characteristics compared to those of fresh preparation. Ultimately, the developed gel formulation could inhibit the growth of different bacterial strains, especially gram-negative strains.ConclusionTo sum up, these findings would demonstrate the efficiency of NLC prepared with CEO and incorporating MP to be a promising antibacterial lipid nanocarrier.

The role of lipid particle-laden interfaces in regulating the co-delivery of two hydrophobic actives from o/w emulsions

Co-delivery strategies have become an integral active delivery approach, although understanding of how the microstructural characteristics could be deployed to achieve independently regulated active co-delivery profiles, is still an area at its infancy. Herein, the capacity to provide such control was explored by utilizing Pickering emulsions stabilized by lipid particles, namely solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These dual functional species, regarding their concurrent Pickering stabilization and active carrying/delivery capabilities, were formulated with different solid lipid and surfactant types, and the effect on the release and co-release modulation of two hydrophobic actives separately encapsulated within the lipid particles themselves and within the emulsion droplets was investigated. Disparities between the release profiles from the particles in aqueous dispersions or at an emulsion interface, were related to the specific lipid matrix composition. Particles composed of lipids with higher oil phase compatibility of the emulsion droplets were shown to exert less control over their release regulation ability, as were particles in the presence of surfactant micelles in the continuous phase. Irrespective of their formulation characteristics, all particles provided a level of active release control from within the emulsion droplets, which was dependant on the permeability of the formed interfacial layer. Specifically, use of a bulkier particle surfactant or particle sintering at the droplet interface resulted in more sustained droplet release rates. Compared to sole release, the co-release performance remained unaffected by the co-existence of the two hydrophobic actives with the co-release behavior persisting over a storage period of 1 month.

Paclitaxel loaded Capmul MCM and tristearin based nanostructured lipid carriers (NLCs) for glioblastoma treatment: screening of formulation components by quality by design (QbD) approach.

Paclitaxel (PTX), a naturally occurring diterpenoid isolated from Taxus brevifolia, is a first-line drug for the treatment of glioblastoma; however, it suffers from the disadvantages of poor water solubility and nonspecific biodistribution, which cause serious side effects in the human body. The marketed formulation suffers from serious side effects, such as allergic reactions, neutropenia, and neuropathy, which require safe and effective formulations of PTX. In the present study, PTX was entrapped in a solid-liquid lipid mixture with the aid of a surfactant using a modified solvent evaporation technique. Higher entrapment of the impressive stability of the formulation was achieved by employing quality design-based strategies. Optimized levels by employing a numerical optimization technique for each factor, that is, surfactant concentration (X1), lipid concentration (X2), and amount of organic solvent (X3) were 0.3%, 0.76% & 8.3 ml respectively. The resultant formulation exhibited a particle size of 121.44 nm, entrapment efficiency of 94.27%, and zeta potential of -20.21 mV with unimodal size distribution. A reduction in the % crystalline index from 48 to 3.4% ensured the amorphous form of the entrapped drug inside the formulation, which precludes the fear of leakage and instability of the formulation. Cell line studies conducted on U87MG Cell lines also suggested that the NLC of paclitaxel are more effective than those of pure PTX. In summary, PTXNLC seem to be a superior alternative carrier system for the formulation industry to obtain higher entrapment with excellent stability.

Review on advanced drug delivery systems: innovations in formulation and delivery technologies

Advanced drug delivery systems (DDS) have transformed the pharmaceutical landscape, offering innovative solutions to enhance therapeutic outcomes and patient compliance. This review explores recent advancements in formulation technologies and delivery mechanisms, focusing on nanotechnology, polymeric systems, solid lipid nanoparticles (SLNs), and microparticle-based formulations. Nanotechnology has enabled the development of nanoparticles, liposomes, and nanocrystals that enhance drug solubility, stability, and targeted delivery. Polymeric drug delivery systems, including biodegradable polymers, offer sustained drug release, significantly improving chronic disease management and cancer therapy. SLNs and nanostructured lipid carriers (NLCs) provide stable matrices for drug encapsulation, particularly for lipophilic drugs, while microparticle-based formulations offer controlled and sustained drug release, reducing dosing frequency and enhancing patient compliance. Furthermore, novel delivery mechanisms such as transdermal systems, oral controlled release systems, targeted drug delivery, and inhalable therapies have expanded the possibilities for non-invasive, patient-friendly drug administration. Challenges in scaling up production, regulatory approval, and long-term safety remain significant, but emerging technologies like nanobots and bioengineered tissues hold promise for the future of personalized medicine. As these advanced delivery platforms continue to evolve, they are poised to revolutionize drug delivery, offering more precise, effective, and patient-centric treatments.

Rapamycin-loaded nanostructured lipid carrier modified with folic acid intended for breast cancer therapy.

Breast cancer stands as the most common form of malignancy among women globally, and it showcases commendable rates of cure when detected in early-stage and non-metastatic conditions. To overcome drug resistance and side effects observed in conventional chemotherapy, the present study aims to deliver rapamycin (RAP), a mTOR protein inhibitor, into a nanostructured lipid carrier (NLC) functionalized with folic acid for promoting active targeting to breast cancer cells. In the first step, the synthesis of 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine-N-[amino(polyethylene glycol)-2000] (ammonium salt) with folic acid (DSPE-PEG2000-FA) was successfully performed and characterized by UV spectroscopy, nuclear magnetic resonance, and infrared spectroscopy. Then, the folic acid-modified NLC loaded with RAP (FA-NLC-RAP) and the unmodified formulation (NLC-RAP) was developed and displayed a size of about 100 nm, negative surface charge, and high RAP encapsulation efficiency (94.92 % and 85.72 %, respectively). In vitro studies suggested that FA-NLC-RAP exhibited a higher degree of internalization in cancer cells (MCF-7) than in normal cells (MCF-10A), demonstrating the potential of folic acid as a ligand for promoting active targeting of RAP for breast cancer cells through folate receptors overexpressed in tumor cells FA-NLC-RAP significantly reduced tumor cell viability, similarly to that observed with the RAP solution. The release profile of the formulation was prolonged. Finally, studies in Caenorhabditis elegans evidenced the safety of FA-NLC-RAP characterized by a complete absence of toxicity in this animal model. Therefore, the findings imply that FA-NLC-RAP holds considerable promise for the treatment of breast cancer.

Dual-Ligand-Functionalized Nanostructured Lipid Carriers as a novel Dehydrocavidine delivery system for Liver fibrosis Therapy

BackgroundLiver fibrosis is a common stage of various chronic liver diseases, often developing into liver cirrhosis, and even liver cancer. Activated hepatic stellate cells (aHSCs) have been shown to promote the development of liver fibrosis. Therefore, dual-targeted combination therapy for liver may be an effective strategy for the treatment of liver fibrosis. PurposeIn this study, the novel nanostructured lipid carriers (GA&GalNH2-DC-NLCs) were prepared for Dehydrocavidine (DC), glycyrrhetinic acid (GA) and galactose-PEG2000-NH2 (GalNH2) were selected as targeted ligand-modified nanostructured lipid carriers (NLCs), which enables dual-targeting to the liver for the treatment of liver fibrosis. Study designTo study the targeting effect of GA&GalNH2-DC-NLCs on liver and its therapeutic effect on liver fibrosis, we established aHSC-T6 cell model and rat model of liver fibrosis for study. ResultsGA&GalNH2-DC-NLCs promoted drug liver targeting efficiency and apoptosis rate by upregulating the expression of Bax. It showed that compared with no and/or GA-modified NLCs and GalNH2-modified NLCs, GA&GalNH2-DC-NLCs exhibited less extracellular matrix (ECM) deposition, induced apoptosis of aHSCs, and stronger anti-fibrosis effects in vivo. This may be due the fact that GA or GalNH2-modifified NLCs simultaneously block HSCs activation and inhibit the IL-6/STAT3 pathway. ConclusionGA&GalNH2-DC-NLCs is thus a potential strategy for liver fibrosis treatment.

Nanostructured Lipid Carrier for Dermatological Application: A Comprehensive Review and Future Perspective

Abstract:: Dermatological disease states have psychological impacts that affect a patient’s life. In the management of such disorders, topical delivery has an important role. However, the conven-tional topical delivery systems suffer from various limitations, like skin irritation, a minute quan-tity of drugs reaching disease sites, and over and under medication, which leads to an adverse re-action and therapeutic failure, respectively. Therefore, researchers continuously search for an al-ternate delivery system for treating skin disease. In recent years, nanostructured lipid carriers (NLC) have emanated as promising carrier systems for topical delivery. The current review pro-vides an in-depth insight into topical administration for treating a variety of dermatological issues using NLCs as a carrier. This review highlights the suitability of NLCs as carriers for topical de-livery, their method of preparation, and their characterization. In the present review, the main emphasis has been given to the management of various dermatological problems by using NLCs as a carrier; a plethora of literature investigating NLC as the carrier for topical delivery has been included in this review. In this paper, an attempt has been made to provide a summary of the re-search carried out in this field that will encourage further research in this arena.

Improved Transdermal Delivery of Anti-hypertensive Drug Loaded Nanostructured Lipid Carriers: Statistical Design, Optimization, Depiction and Pharmacokinetic Assessment

Background: The vasoselective calcium-channel blocker lercanidipine hydrochloride (LCH) is poorly absorbed orally (only 10% bioavailability) owing to its low solubility and hepatic metabolism. Because of the LCH's poor solubility and permeability, bioavailability is low and very variable, stable aqueous liquid formulations are challenging to create, and a uniform distribution of the medication is almost impossible to produce. Objective: The purpose of this research was to see whether an approach involving the development of nanostructured lipid carriers (NLCs) might be used to create an effective, innovative oral formulation of LCH. The efficacy of several synthetic and natural liquid lipids was compared using a hot homogenization-ultrasonication strategy. Methods: Following initial improvements with hot homogenization and ultrasonication, the LCHloaded NLCs formulation was fine-tuned by Box-Behnken statistical analysis. The optimal LCHNLCs composition includes the lipid phase (2-4% w/v) of stearic acid and oleic acid, the surfactants poloxamer 188 (1%) and Tween 80(1%), and other ingredients. Results: The optimized NLCs formulation was found to have mean vesicle sizes of 128.72 ± 1.59 nm, polydispersity indices of 0.169 ± 0.06, zeta potentials of -36.81 ± 0.42 mV, and entrapment efficiencies of 79.84 ± 0.11%. The optimized NLCs formulation released much more LCH (88.74 ± 4.62) than the LCH-suspension (36.84 ± 0.37%) in in-vitro drug release experiments lasting up to 24 hours. Ex vivo studies on the ability of LCH-NLCs to pass through the gut showed that drug permeation was much better than it was with plain LCH-solution. The in vivo pharmacodynamic analysis demonstrated that, compared to conventional LCH-suspension, NLCs released LCH more slowly and steadily over a longer time period. Conclusion: These findings provide additional evidence that NLCs have great promise as a drug delivery technology for the treatment of hypertension, just as they show promise as a controlled release formulation for the treatment of LCH.

Encapsulation of Microalgae Tisochrysis lutea Extract in Nanostructured Lipid Carriers (NLCs) and Evaluation of Their Sunscreen, Wound Healing, and Skin Hydration Properties

Traditional sunscreens have relied on synthetic compounds to protect against harmful ultraviolet (UV) radiation. However, there is increasing interest in utilizing the natural photoprotective properties of microalgae extracts. This approach does not only aim to enhance the stability and efficacy of sun protection formulae but also seeks to reduce the reliance on synthetic sunscreens. This study investigates the encapsulation of Tisochrysis lutea extract (TL) in nanostructured lipid carriers (NLCs) to create a combination (NLC-TL) with enhanced physicochemical stability, antioxidant activity, SPF efficacy, wound healing capacity, and skin hydration. The particle size and ζ-potential were approximately 100 nm and −50 mV, respectively, and both formulations successfully passed the stability tests. The antioxidant activity, measured via DPPH assay, revealed that NLC-TL achieved the highest free radical scavenging activity across all tested concentrations, indicating a synergistic effect. The incorporation of TL in NLCs maintained the sun protection factor (SPF) of a 2% extract solution (1.53 ± 0.13). The wound healing assay indicated that NLC-TLs significantly enhanced wound closure compared to controls and TL alone. Additionally, skin hydration tests on healthy volunteers revealed that NLC-TLs provided superior and sustained hydration effects. These results highlight NLC-TLs’ potential as a multifunctional topical agent for cosmetic and therapeutic applications.

Optimization of docetaxel-loaded cholesterol nanostructured lipid carriers for improving cancer treatment using Taguchi experimental design

Today's diets boost breast, head, neck, ovarian, and lung cancer risk. This has prompted researchers to study active compounds against these slow killers. Docetaxel (DTX) loaded onto cholesterol nanostructured lipid carriers (NLCs) with elaidic acid appears promising. Carriers were made using solvent emulsification-diffusion. This study used Taguchi's experimental design and analysis with the L16 orthogonal array. The design was utilised to analyse NLC particle size and zeta potential data. These trials considered process factors like elaidic acid percentage (15–30 %), emulsifier concentration (1–4 %), agitation duration (2–8 min), and blending speed (800–1400 rpm). Controlled experimental design plays an important role in pharmaceutical research, as does the privilege of a comprehensive technique aimed to maximize the creation of NLCs loaded with DTX for cancer treatment. Blending speed had a substantial influence on particle size, as the lowest and maximum particle sizes were 170.54 and 190.90 nm. In the zeta potential research, values ranged from 5.88 to 30.72 mV. These data show how important blending speed is in determining particle size. This research supports the sustainable development goals of 3, 9, 12, and 17.

Silver nanoparticles in medicine and technology: Synthesis, functionality and future prospects

Nanomaterials, particularly nanoparticles (NPs), have emerged as forefront materials of the 21st century due to their unique properties and potential applications. Silver nanoparticles (AgNPs) are among the most attractive inorganic nanomaterials, widely used due to their significant antibacterial properties, broad-spectrum activity, and potential applications across various fields, including health, food storage, textiles, and environmental solutions. AgNPs exhibit a large surface-area-to-volume ratio, enabling enhanced interaction with bacterial cells, making them effective in medical and industrial applications. Despite concerns over their toxicity, AgNP-based products have been approved by multiple regulatory bodies. Nanoparticle synthesis methods are generally divided into physical, chemical, and biological approaches. Although physical and chemical methods are efficient, they involve toxic chemicals and energy-intensive processes. Biosynthesis, particularly plant-based, offers an eco-friendly alternative, reducing the environmental and health risks associated with chemical agents. The review also explores the therapeutic potential of AgNPs in drug delivery systems, especially in topical formulations like nanoemulsions, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs). These nanocarriers enhance drug stability, skin penetration, and controlled release, making them ideal for dermal and transdermal delivery. Moreover, the use of AgNPs in dentistry is highlighted for their bactericidal properties, which help prevent infections and implant failure, with the potential for enhancing therapeutic outcomes without common drawbacks like tooth staining. Overall, AgNPs exhibit promising applications in biomedical, pharmaceutical, and dental fields, and their novel functionalities continue to advance the development of nanotechnology-driven solutions.

Current Nanotechnological Strategies for Delivery of Anti-Retroviral Drugs: Overview and Future Prospects

Abstract: Globally, over forty million people are living with Human Immunodeficiency Viral (HIV) infections. Highly Active Antiretroviral Therapy (HAART) consists of two or three Antiretroviral (ARV) drugs and has been used for more than a decade to prolong the life of AIDS-diagnosed patients. The persistent use of HAART is essential for effectively suppressing HIV replication. Frequent use of multiple medications at relatively high dosages is a major reason for patient noncompliance and an obstacle to achieving efficient pharmacological treatment. Despite strict compliance with the HAART regimen, the eradication of HIV from the host remains unattainable. Anatomical and Intracellular viral reservoirs are responsible for persistent infection. Elimination of the virus from these reservoirs is critical for successful long-term therapy. Therefore, innovative approaches are required to design safe and effective therapies. Nanotechnology has revolutionized HIV drug delivery by addressing key challenges, including improving drug solubility, targeting specific cells, extending drug release, protecting drugs from degradation, overcoming biological barriers, enabling combination therapy, and enhancing vaccine delivery. Several nanocarrier systems, such as dendrimers, nanoemulsions, liposomes, solid nanoparticles (SLNs), and nanostructured lipid carriers, have been proposed to treat HIV infection. Additionally, nanosuspensions of antiretroviral drugs offer promising strategies for improving treatment outcomes. While these advancements have significantly improved HIV management strategies, challenges remain, including unexpected toxicity, avoiding harmful biological interactions, and costs associated with the large-scale production of nanopharmaceuticals.

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.

Chemosensory function of Varroa gnathosoma: transcriptomic and proteomic analyses

In this study, we evaluated the role of the gnathosoma (mouthparts) in chemosensing of the most devastating honey bee parasite, Varroa destructor mite. Through transcriptomic analysis, we compared the expression of putative chemosensory genes between the body parts containing the main chemosensory organs (the forelegs), gnathosoma and the rest of the body devoid of these two body parts. Furthermore, we checked the presence of chemosensory-related transcripts in the proteome of the gnathosoma. Our comparative transcriptomic analysis revealed the presence of 83 transcripts with known characteristic conserved domains belonging to eight chemosensory gene families in the three Varroa transcriptomes. Among these transcripts, 11 were significantly upregulated in the mite’s forelegs, compared to 8 and 10 in the gnathosoma and body devoid of both organs, respectively. Whilst the gnathosoma and the forelegs share similar expression of some putative lipid carrier proteins, membrane-bound receptors, and associated proteins, they also differ in the expression profiles of some transcripts belonging to these protein families. This suggests two functional chemosensory organs that may differ in their chemosensory function according to specific characteristics of compounds they detect. Moreover, the higher expression of some chemosensory transcripts in the body devoid of forelegs and gnathosoma compared to the gnathosoma alone, may suggest the presence of additional function of these transcripts or alternatively presence of additional external or internal chemosensory organs. Insights into the functional annotation of a highly expressed gustatory receptor present in both organs using RNA interference (RNAi) are also revealed.

Bioactive compounds delivery and bioavailability in structured edible oils systems.

The health benefits of bioactive compounds are dependent on the amount of intake as well as on the amount of these compounds that become bioavailable and bioaccessible. Various systems have been developed to deliver and increase the bioaccessibility of bioactive compounds. This review explores the impact of gelled (oleogels, bigels, emulgels, emulsions, hydrogels, and hydrogel beads), micro-(gels, particles, spheres, capsules, emulsions, and solid lipid microparticles) and nanoencapsulated systems (nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, liposomes, and nanoliposomes) on the digestibility and bioavailability of lipophilic and hydrophilic bioactives. Structurant molecules, the oil type, antioxidants, emulsifiers, and coatings in delivery systems with promising potential in food applications are critically discussed. The release and bio-accessibility of bioactive compounds in gelled systems are influenced by various factors, such as the type and concentration of gelators, the gelator-to-oil ratio, the type of antioxidant, the network of the system, and its hydrophobicity. The stability, bioaccessibility, and controlled release of bioactives were improved in structured emulsions. Several variables, including wall material, oil/water ratios, encapsulation process, and pH conditions, can affect the bioactives release in microencapsulated systems. Factors like coating type and core-to-wall ratio impact the stability and release of core components. The encapsulating material, the encapsulation technology, and the nature of the nanomaterials all have an impact on the bioaccessibility of nanoencapsulated systems. Nanoliposomes provide enhanced stability and absorption. In general, all encapsulated systems have shown great potential in improving the distribution and availability of bioactive compounds.

Protective Effects of Carotenoid-Loaded Nanostructured Lipid Carriers Against Ochratoxin-A-Induced Cytotoxicity.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceous and various Penicillium species, which are known for contaminating agricultural products and posing significant health risks, which include immunotoxicity. This study aims to evaluate the potential of nanostructured lipid carriers (NLCs) loaded with a carotenoid-enriched extract from pumpkin peel (Cucurbita maxima L.) in mitigating the toxic effects of OTA. To address the poor bioavailability and instability of carotenoids, nanoencapsulation techniques were employed to enhance their delivery and efficacy. NLCs were formulated using hydrogenated sunflower oil, pumpkin oil, and soy lecithin using hot high-pressure homogenization. The in vitro study involved co-digesting OTA-contaminated bread with an NLC formulation and assessing the impact of the encapsulated carotenoid on OTA bioaccessibility, bioavailability, and cellular toxicity using Caco-2 and Jurkat T cells. Even though no significant influence was observed on the bioaccessibility and bioavailability of OTA, carotenoid-loaded NLCs exhibited cytoprotective effects by improving cell viability and mitigating OTA-induced toxicity in both Caco-2 and Jurkat T cells. Particularly, the flow cytometry analysis highlighted the ability of carotenoids to mitigate OTA-induced cellular damage by decreasing ROS production and limiting mitochondrial mass changes. The study suggests that the encapsulation of carotenoids in NLCs represents a promising strategy to enhance their protective effects against OTA toxicity, potentially offering a novel approach to food safety and public health protection. The study underscores the potential of nanotechnology in improving the bioavailability and efficacy of natural antioxidants to mitigate mycotoxin-induced damage.

Paroxetine Loaded Nanostructured Lipid Carriers Based In-situ Gel for Brain Delivery via Nasal Route for Enhanced Anti-Depressant Effect: In Vitro Prospect and In Vivo Efficacy.

This study focused on developing a thermosensitive gel with nanostructured lipid carriers (NLCs) loaded with paroxetine (PAR) to enhance the treatment and management of depression via nasal administration. Micro emulsion technique was utilized for the PAR-NLCs preparation. The acetyl alcohol and oleic acid were used in the ratio of 76:24. In the NLCs Tween 40, Span40 and Myrj 52 were used as a surfactant. The NLCs were then added into Poloxamer mixture to get thermosensitive NLCs based gel. Characterization, in vitro and in vivo studies were performed to check the efficiency of formulation in drug delivery. The entrapment efficiency of optimized PAR-NLCs was about 90%. The particle size, zeta potential and PDI were 155 ± 1.4nm, -25.9 ± 0.5mV, and 0.12 ± 0.01 respectively. The optimized gel showed a gelling temperature of 31.50 ± 0.50°C and a gelling time of 1 ± 0.12s with a pH of 6, suitable for nasal administration. The in vitro release assay of PAR-NLC-gel showed a cumulative release of about 59% in the first 6h after comparison with PAR-NLCs which showed almost 100%release. In vivo studies included forced swim test and tail suspension tests showed significant potential for treating depression when compared to PAR-NLCs. PAR-NLCs and NLCs based gel enhanced the tissue architecture and suppressed the expression of TNF-α in brain cortex from histological and immunohistochemical analysis. PAR- NLCs gel-based delivery system can prove to be an effective delivery system for brain targeting through nose for the better management of depression.

Exploring Nanocarriers for Boosting Entacapone Bioavailability: A Journey through System Characterization and Assessment of Toxicity and Pharmacological and 2D Permeability Paybacks.

Catechol-O-methyltransferase inhibitors (iCOMT), such as entacapone, have been successfully employed to treat tremor-related symptoms of Parkinson's disease. However, iCOMT has been associated with a short half-life and poor oral bioavailability. Nanobased drug delivery systems have often been used to overcome this type of setbacks. Therefore, entacapone was encapsulated in PEGylated poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) via a nanoprecipitation process, as well as in PEGylated nanostructured lipid carriers (NLCs) using a solvent emulsification/evaporation method. Both nanoformulations presented sub-200 nm populations, with zeta-potential (ZP) values close to -30 mV, and showed stability at different pHs, while maintaining their physicochemical properties mostly intact, presenting only a change in their superficial charge (ZP values), indicating their interaction. Both nanoformulations presented interaction with mucins, which anticipates good permeation and bioavailability for oral and topical administration. No cytotoxic effects were observed for lyophilized PLGA NPs encapsulating entacapone, in which 2-hydroxypropyl-ß-cyclodextrin (HPβCD) was used as a cryoprotectant at 3% concentration (HP-PLGA@Ent), in human hepatocellular carcinoma (HepG2), human neuroblastoma (SH-SY5Y), or human epithelial colorectal adenocarcinoma (Caco-2) cell lines. Conversely, NLCs encapsulating entacapone (W-NLCs@Ent) presented cytotoxic effects on the HepG2 cell line, likely due to intracellular lipid accumulation or storage. Both nanoformulations maintained a COMT inhibition effect in HepG2 cells, using 3-BTD as the COMT probe. An increase of entacapone permeability in both monolayer and coculture models (Caco-2 and Caco-2/HT29-MTX, respectively) was observed for the developed nanoformulations. Overall, this work shows that encapsulated entacapone in different nanocarriers could be a stimulating alternative to solve entacapone setbacks, since they improve its physicochemical properties and permeability while still maintaining the COMT inhibitory activity.