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Aim: Breast cancer and its metastases involve high mortality even with advances in chemotherapy. Solid lipid nanoparticles provide a platform for drug delivery, reducing side effects and treatment-induced bone loss. A solid nanoparticle containing doxorubicin was evaluated for its ability to prevent bone loss in a pre-clinical breast cancer model.Methods: We investigated the effects of SLNDox in an aggressive metastatic stage IV breast cancer model, which has some important features that are interesting for bone loss investigation. This study evaluates bone loss prevention potential from solid lipid nanoparticles containing doxorubicin breast cancer treatment, an evaluation of the attenuation of morphological changes in bone tissue caused by the treatment and the disease and an assessment of bone loss imaging using computed tomography and electron microscopy.Results: Chemotherapy-induced bone loss was also observed in tumor-free animals; a solid lipid nanoparticle containing doxorubicin prevented damage to the growth plate and to compact and cancellous bones in the femur of tumor-bearing and healthy animals.Conclusion: The association of solid lipid nanoparticles with chemotherapeutic drugs with proven efficacy promotes the prevention of serious consequences of chemotherapy, reducing tumor progression, increasing quality of life and improving prognosis and survival.

[Box: see text].

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This study introduces the nanobromhexine lipid particle (NBL) platform designed for effective pulmonary drug delivery. Inspired by respiratory virus transport mechanisms, NBL address challenges associated with mucus permeation and inflammation in pulmonary diseases. Composed of low molecular weight polyethylene glycol-coated lipid nanoparticles with bromhexine hydrochloride, NBL exhibit a size of 118 ± 24 nm, a neutral zeta potential, osmolarity of 358 ± 28 mOsmol/kg, and a pH of 6.5. Nebulizing without leakage and showing no toxicity to epithelial cells, NBL display mucoadhesive properties with a 60% mucin-binding efficiency. They effectively traverse the dense mucus layer of Calu-3 cultures in an air-liquid interface, as supported by a 55% decrease in MUC5AC density and a 29% increase in nanoparticles internalization compared to non-exposed cells. In assessing immunomodulatory effects, NBL treatment in SARS-CoV-2-infected lung cells leads to a 40-fold increase in anti-inflammatory MUC1 gene expression, a proportional reduction in pro-inflammatory IL-6 expression, and elevated anti-inflammatory IL-10 expression. These findings suggest a potential mechanism to regulate the excessive IL-6 expression triggered by virus infection. Therefore, the NBL platform demonstrates promising potential for efficient pulmonary drug delivery and immunomodulation, offering a novel approach to addressing mucus permeation and inflammation in pulmonary diseases.

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Solid lipid nanoparticles (SLNs) represent promising nanostructures for drug delivery systems. This study successfully synthesized SLNs containing different proportions of babassu oil (BBS) and copaiba oleoresin (COPA) via the emulsification-ultrasonication method. Before SLN synthesis, the identification and quantification of methyl esters, such as lauric acid and ß-caryophyllene, were performed via GC-MS analysis. These methyl esters were used as chemical markers and assisted in encapsulation efficiency experiments. A 22 factorial design with a center point was employed to assess the impact of stearic acid and Tween 80 on particle hydrodynamic diameter (HD) and polydispersity index (PDI). Additionally, the effects of temperature (8 ± 0.5 °C and 25 ± 1.0 °C) and time (0, 7, 15, 30, 40, and 60 days) on HD and PDI values were investigated. Zeta potential (ZP) measurements were utilized to evaluate nanoparticle stability, while transmission electron microscopy provided insights into the morphology and nanometric dimensions of the SLNs. The in vitro cytotoxic activity of the SLNs (10 µg/mL, 30 µg/mL, 40 µg/mL, and 80 µg/mL) was evaluated using the MTT assay with PC-3 and DU-145 prostate cancer cell lines. Results demonstrated that SLNs containing BBS and COPA in a 1:1 ratio exhibited a promising cytotoxic effect against prostate cancer cells, with a percentage of viable cells of 68.5% for PC-3 at a concentration of 30 µg/mL and 48% for DU-145 at a concentration of 80 µg/mL. These findings underscore the potential therapeutic applications of SLNs loaded with BBS and COPA for prostate cancer treatment.

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Silybin (SIB) is a hepatoprotective drug known for its poor oral bioavailability, attributed to its classification as a class IV drug with significant metabolism during the first-pass effect. This study explored the potential of solid lipid nanoparticles with (SLN-SIB-U) or without (SLN-SIB) ursodeoxycholic acid and polymeric nanoparticles (PN-SIB) as delivery systems for SIB. The efficacy of these nanosystems was assessed through in vitro studies using the GRX and Caco-2 cell lines for permeability and proliferation assays, respectively, as well as in vivo experiments employing a murine model of Schistosomiasis mansoni infection in BALB/c mice. The mean diameter and encapsulation efficiency of the nanosystems were as follows: SLN-SIB (252.8 ± 4.4 nm, 90.28 ± 2.2%), SLN-SIB-U (252.9 ± 14.4 nm, 77.05 ± 2.8%), and PN-SIB (241.8 ± 4.1 nm, 98.0 ± 0.2%). In the proliferation assay with the GRX cell line, SLN-SIB and SLN-SIB-U exhibited inhibitory effects of 43.09 ± 5.74% and 38.78 ± 3.78%, respectively, compared to PN-SIB, which showed no inhibitory effect. Moreover, SLN-SIB-U demonstrated a greater apparent permeability coefficient (25.82 ± 2.2) than PN-SIB (20.76 ± 0.1), which was twice as high as that of SLN-SIB (11.32 ± 4.6) and pure SIB (11.28 ± 0.2). These findings suggest that solid lipid nanosystems hold promise for further in vivo investigations. In the murine model of acute-phase Schistosomiasis mansoni infection, both SLN-SIB and SLN-SIB-U displayed hepatoprotective effects, as evidenced by lower alanine amino transferase values (22.89 ± 1.6 and 23.93 ± 2.4 U/L, respectively) than those in control groups I (29.55 ± 0.7 U/L) and I+SIB (34.29 ± 0.3 U/L). Among the prepared nanosystems, SLN-SIB-U emerges as a promising candidate for enhancing the pharmacokinetic properties of SIB.

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A better understanding of how emulsifier type could differently influence the behavior of nanostructured lipid carriers (NLC) under the gastrointestinal digestion process, as well as at the cellular level, is of utmost importance for the NLC-based formulations' optimization and risk assessment in the food field. In this study, NLC composed by fully hydrogenated soybean and high-oleic sunflower oils were prepared using soy lecithin (NLC Lß) or Tween 80 (NLC Tß) as an emulsifier. ß-Carotene was entrapped within NLC developed as a promising strategy to overcome ß-carotene's low bioavailability and stability. The effect of emulsifier type on the digestibility of ß-carotene-loaded NLC was evaluated using an in vitro dynamic digestion model mimicking peristalsis motion. The influence of ß-carotene-loaded NLC on cell viability was assessed using Caco-2 cells in vitro. NLC Tß remained stable in the gastric compartment, presenting particle size (PS) similar to the initial NLC (PS: 245.68 and 218.18 nm, respectively), while NLC Lß showed lower stability (PS > 1000 nm) in stomach and duodenum phases. NLC Tß also provided high ß-carotene protection and delivery capacity (i.e., ß-carotene bioaccessibility increased 10-fold). Based on the results of digestion studies, NLC Tß has shown better physical stability during the passage through the in vitro dynamic gastrointestinal system than NLC Lß. Moreover, the developed NLC did not compromise cell viability up to 25 µg/mL of ß-carotene. Thus, the NLC developed proved to be a biocompatible structure and able to incorporate and protect ß-carotene for further food applications. PRACTICAL APPLICATION: The findings of this study hold significant implications for industrial applications in terms of developing nanostructured lipid carriers from natural raw materials widely available and used to produce other lipid-based products in the food industry, as an alternative to synthetic ones. In this respect, the ß-carotene-loaded NLC developed in this study would find a great industrial application in the food industry, which is in constant search to develop functional foods capable of increasing the bioavailability of bioactive compounds.

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This study focused on developing electrically stimulable hyaluronic acid (HA) films incorporating lipid nanoparticles (NPs) designed for the topical administration of lipophilic drugs and macromolecules. Based on beeswax and medium-chain triglycerides, NPs were successfully integrated into silk fibroin/chitosan films containing HA (NP-HA films) at a density of approximately 1011 NP/cm2, ensuring a uniform distribution. This integration resulted in a 40% increase in film roughness, a twofold decrease in Young's modulus, and enhanced film flexibility and bioadhesion work. The NP-HA films, featuring Ag/AgCl electrodes, demonstrated the capability to conduct a constant electrical current of 0.2 mA/cm2 without inducing toxicity in keratinocytes and fibroblasts during a 15-min application. Moreover, the NPs facilitated the homogeneous distribution of lipophilic drugs within the film, effectively transporting them to the skin and uniformly distributing them in the stratum corneum upon film administration. The sustained release of HA from the films, following Higuchi kinetics, did not alter the macroscopic characteristics of the film. Although anodic iontophoresis did not noticeably affect the release of HA, it did enhance its penetration into the skin. This enhancement facilitated the permeation of HA with a molecular weight (MW) of up to 2 × 105 through intercellular and transcellular routes. Confocal Raman spectroscopy provided evidence of an approximate 100% increase in the presence of HA with a MW in the range of 1.5-1.8 × 106 in the viable epidermis of human skin after only 15 min of iontophoresis applied to the films. Combining iontophoresis with NP-HA films exhibits substantial potential for noninvasive treatments focused on skin rejuvenation and wound healing.

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In this study, nanostructured lipid carriers (NLC) were developed and employed to obtain in situ thermosensitive formulations for the ductal administration and prolonged retention of drugs as a new strategy for breast cancer local treatment. NLC size was influenced by the type and concentration of the oil phase, surfactants, and drug incorporation, ranging from 221.6 to 467.5 nm. The type of liquid lipid influenced paclitaxel and 5-fluorouracil cytotoxicity, with tributyrin-containing NLC reducing IC50 values by 2.0-7.0-fold compared to tricaprylin NLC in MCF-7, T-47D and MDA-MB-231 cells. In spheroids, the NLCs reduced IC50 compared to either drug solution (3.2-6.2-fold). Although a significant reduction (1.26 points, p < 0.001) on the health index of Galleria mellonella larvae was observed 5 days after NLC administration, survival was not significantly reduced. To produce thermosensitive gels, the NLCs were incorporated in a poloxamer (11 %, w/w) dispersion, which gained viscosity (2-fold) at 37 °C. After 24 h, ∼53 % of paclitaxel and 83 % of 5-fluorouracil were released from the NLC; incorporation in the poloxamer gel further prolonged release. Intraductal administration of NLC-loaded gel increased the permanence of hydrophilic (2.2-3.0-fold) and lipophilic (2.1-2.3-fold) fluorescent markers in the mammary tissue compared to the NLC (as dispersion) and the markers solutions. In conclusion, these results contribute to improving our understanding of nanocarrier design with increased cytotoxicity and prolonged retention for the intraductal route. Tributyrin incorporation increased the cytotoxicity of paclitaxel and 5-fluorouracil in monolayer and spheroids, while NLC incorporation in thermosensitive gels prolonged tissue retention of both hydrophilic and hydrophobic compounds.

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OBJECTIVE: Previously, lipid nanoparticles (LDE) injected in women with endometriosis were shown to concentrate in the lesions. Here, the safety and feasibility of LDE carrying methotrexate (MTX) to treat deep infiltrating endometriosis was tested. DESIGN: Prospective pilot study. SETTING: Perola Byington Hospital Reference for Women's Health. SUBJECTS: Eleven volunteers (aged 30-47 years, BMI 26.15 ± 6.50 kg/m2) with endometriosis with visual analog scale pelvic pain scores (VAS) > 7 and rectosigmoid lesions were enrolled in the study. INTERVENTION: Three patients were treated with LDE-MTX at single intravenous 25 mg/m2 dose of MTX and eight patients with two 25 mg/m2 doses with 1-week interval. MAIN OUTCOME MEASURES: Clinical complaints, blood count, and biochemistry were analyzed before treatment and on days 90, 120, and 180 after LDE-MTX administration. Endometriotic lesions were evaluated by pelvic and transvaginal ultrasound (TVUS) before treatment and on days 30 and 180 after LDE-MTX administration. RESULTS: No clinical complaints related with LDE-MTX treatment were reported by the patients, and no hematologic, renal, or hepatic toxicities were observed in the laboratorial exams. FSH, LH, TSH, free T4, anti-Müllerian hormone, and prolactin levels were also within normal ranges during the observation period. Scores for deep dyspareunia (p < 0.001), chronic pelvic pain (p = 0.008), and dyschezia (p = 0.025) were improved over the 180-day observation period. There was a non-significant trend for reduction of VAS scores for dysmenorrhea. Bowel lesions by TVUS were unchanged. No clear differences between the two dose levels in therapeutic responses were observed. CONCLUSION: Results support the safety and feasibility of using LDE-MTX in women with deep infiltrating endometriosis as a novel and promising therapy for the disease. More prolonged treatment schemes should be tested in future placebo-controlled studies aiming to establish the usefulness of this novel nanomedicine approach.

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OBJECTIVE: This study aimed to develop a holobiont tablet with rapid dispersibility to provide regulation of the microbiota, virucidal activity, and skin barrier protection. METHODS: A 23 factorial experiment was planned to define the best formulation for the development of the base tablet, using average weight, hardness, dimensions, swelling rate, and disintegration time as parameters to be analyzed. To produce holobiont tablets, the chosen base formulation was fabricated by direct compression of prebiotics, postbiotics, and excipients. The tablets also incorporated solid lipid nanoparticles containing postbiotics that were obtained by high-pressure homogenization and freeze-drying. The in vitro virucidal activity against alpha-coronavirus particles (CCoV-VR809) was determined in VERO cell culture. In vitro analysis, using monolayer cells and human equivalent skin, was performed by rRTq-PCR to determine the expression of interleukins 1, 6, 8, and 17, aquaporin-3, involucrin, filaggrin, FoxO3, and SIRT-1. Antioxidant activity and collagen-1 synthesis were also performed in fibroblast cells. Metagenomic analysis of the skin microbiome was determined in vivo before and after application of the holobiont tablet, during one week of continuous use, and compared to the use of alcohol gel. Samples were analyzed by sequencing the V3-V4 region of the 16S rRNA gene. RESULTS: A handrub tablet with rapid dispersibility was developed for topical use and rinse off. After being defined as safe, the virucidal activity was found to be equal to or greater than that of 70% alcohol, with a reduction in interleukins and maintenance or improvement of skin barrier gene markers, in addition to the reestablishment of the skin microbiota after use. CONCLUSIONS: The holobiont tablets were able to improve the genetic markers related to the skin barrier and also its microbiota, thereby being more favorable for use as a hand sanitizer than 70% alcohol.

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The present study thus aimed at the development and physicochemical characterization of solid lipid nanoparticles loaded with crude extract of Piper corcovadensis roots (SLN - CEPc) and chitosan - coated solid lipid nanoparticles loaded with crude extract of P. corcovadensis roots (C - SLN - CEPc), as well as the determination of its antimycobacterial activity against Mycobacterium tuberculosis H37Rv, its cytotoxicity against the Vero cell line and evaluation in the hemolysis assay. Both formulat ions containing the encapsulated extract showed high encapsulation efficiency, formed by a monodispersed system with small and spherical particles, and there was no aggregation of particles. In the biological assays, SLN - CEPc and C - SLN - CEPc showed promisin g anti - M. tuberculosis activity with a minimum inhibitory concentration (MIC) of 12.5 µg/mL, whereas the cytotoxic concentrations obtained at 50% (CC 50 ) in Vero cells were 60.0 and 70.0 µg/mL, respectively. Therefore, nanoencapsulation showed satisfactory results, justifying its usage in the development of new products.

El presente estudio apuntó al desarrollo y caracterización fisicoquímica de na nopartículas lípidas en estado sólido, cargadas con extracto crudo de raíz de Piper c orcovadensis (SLN - CEPc) y nanopartículas lípidas en estado sólido cubiertas con quitosano cargadas co n extracto crudo de raíz de P. corcovadensis (C - SLN - CEPc), así como la determinación de su actividad antimico bacterial contra Mycobacterium tuberculosis H37Rv, su citotoxicidad contra la línea celular Vero y su evaluación en ensayo de hemólisis. Ambas formulaciones que contenían el extracto encapsulado mostraron alta eficien cia de encapsulación, formado por un sistema monodispersado con pequeñas partículas esféricas, y no hubo agregación de partículas. En los ensayos biológicos, SLN - CEPc y C - SLN - CEPc mostraron un a prometedora actividad anti - M. tuberculosis con una mínima conc entración inhibitoria (MIC) de 12,5 µg/mL, mientras que las concentraciones citotóxicas obtenidas al 50% (CC 50 ) en células Vero estuvo en 60,0 y 70,0 µg/mL, respectivamente. Por lo tanto, la nanoencapsulación mostró resultados satisfactorios, justificando su uso en el desarrollo de nuevos productos.

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Introduction: Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results in the treatment of hematological tumors. However, current approved methods to engineer T cells to express CAR use viral vectors, which are integrative and have been associated with severe adverse effects due to constitutive expression of CAR. In this context, non-viral vectors such as ionizable lipid nanoparticles (LNPs) arise as an alternative to engineer CAR T cells with transient expression of CAR. Methods: Here, we formulated a mini-library of LNPs to deliver pDNA to T cells by varying the molar ratios of excipient lipids in each formulation. LNPs were characterized and screened in vitro using a T cell line (Jurkat). The optimized formulation was used ex vivo to engineer T cells derived from human peripheral blood mononuclear cells (PBMCs) for the expression of an anti-CD19 CAR (CAR-CD19BBz). The effectiveness of these CAR T cells was assessed in vitro against Raji (CD19+) cells. Results: LNPs formulated with different molar ratios of excipient lipids efficiently delivered pDNA to Jurkat cells with low cytotoxicity compared to conventional transfection methods, such as electroporation and lipofectamine. We show that CAR-CD19BBz expression in T cells was transient after transfection with LNPs. Jurkat cells transfected with our top-performing LNPs underwent activation when exposed to CD19+ target cells. Using our top-performing LNP-9-CAR, we were able to engineer human primary T cells to express CAR-CD19BBz, which elicited significant specific killing of CD19+ target cells in vitro. Conclusion: Collectively, our results show that LNP-mediated delivery of pDNA is a suitable method to engineer human T cells to express CAR, which holds promise for improving the production methods and broader application of this therapy in the future.

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2-Ketones are signal molecules reported as plant growth stimulators, but their applications in vegetables have yet to be achieved. Solid lipid nanoparticles (SLNs) emerge as a relevant nanocarrier to develop formulations for the controlled release of 2-ketones. In this sense, seedlings of Lactuca sativa exposed to 125, 375, and 500 µL L-1 of encapsulated 2-nonanone and 2-tridecanone into SLNs were evaluated under controlled conditions. SLNs evidenced a spherical shape with a size of 230 nm. A controlled release of encapsulated doses of 2-nonanone and 2-tridecanone was observed, where a greater release was observed as the encapsulated dose of the compound increased. Root development was strongly stimulated mainly by 2-tridecanone and leaf area (25-32%) by 2-nonanone. Chlorophyll content increased by 15.8% with exposure to 500 µL L-1 of 2-nonanone, and carotenoid concentration was maintained with 2-nonanone. Antioxidant capacity decreased (13-62.7%) in L. sativa treated with 2-ketones, but the total phenol concentration strongly increased in seedlings exposed to some doses of 2-ketones. 2-Tridecanone strongly modulates the enzymatic activities associated with the scavenging of H2O2 at intra- and extracellular levels. In conclusion, 2-ketones released from SLNs modulated the growth and the antioxidant system of L. sativa, depending on the dose released.

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Plant and herbal essential oils (EOs) offer a wide range of pharmacological actions that include anticancer effects. Here, we evaluated the cytotoxic activity of EO from Lippia alba (chemotype linalool), L. alba (chemotype dihydrocarvone, LaDEO), Clinopodium nepeta (L.) Kuntze (CnEO), Eucalyptus globulus, Origanum × paniculatum, Mentha × piperita, Mentha arvensis L., and Rosmarinus officinalis L. against human lung (A549) and colon (HCT-116) cancer cells. The cells were treated with increasing EO concentrations (0-500 µL/L) for 24 h, and cytotoxic activity was assessed. LaDEO and CnEO were the most potent EOs evaluated (IC50 range, 145-275 µL/L). The gas chromatography-mass spectrometry method was used to determine their composition. Considering EO limitations as therapeutic agents (poor water solubility, volatilization, and oxidation), we evaluated whether LaDEO and CnEO encapsulation into solid lipid nanoparticles (SLN/EO) enhanced their anticancer activity. Highly stable spherical SLN/LaDEO and SLN/CnEO SLN/EO were obtained, with a mean diameter of 140-150 nm, narrow size dispersion, and Z potential around -5mV. EO encapsulation strongly increased their anticancer activity, particularly in A549 cells exposed to SLN/CnEO (IC50 = 66 µL/L CnEO). The physicochemical characterization, biosafety, and anticancer mechanisms of SLN/CnEO were also evaluated in A549 cells. SLN/CnEO containing 97 ± 1% CnEO was highly stable for up to 6 months. An increased in vitro CnEO release from SLN at an acidic pH (endolysosomal compartment) was observed. SLN/CnEO proved to be safe against blood components and non-toxic for normal WI-38 cells at therapeutic concentrations. SLN/CnEO substantially enhanced A549 cell death and cell migration inhibition compared with free CnEO.

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The coenzyme Q10 is a compound widely used in pharmaceutical and cosmetic formulations because it is a potent eliminator of free radicals, giving it antioxidant and anti-aging properties. It is naturally synthesized by the human body, but its production wanes with age, leading to the formation of wrinkles. The efficacy of topical application of the coenzyme to counteract this process is subject to several difficulties, due to its instability in the presence of light, low solubility in water and high lipophilicity. Because of these drawbacks, many studies have been conducted of release systems. Lipid nanoparticles stand out in this sense due to the advantages of skin compatibility, protection of the active ingredient against degradation in the external medium, capacity to increase penetration of that ingredient in the skin, and its controlled and prolonged release. In this context, this article presents a review of the main studies of the coenzyme Q10 encapsulated in lipid nanoparticles for topical use, focusing on the analytic methods used to characterize the systems regarding morphology, zeta potential, release profile, Q10 content, encapsulation efficiency, crystalline organization and structure of the lipid matrix, rheology, antioxidant activity, skin penetration and efficacy, among other aspects. We also describe the main results of the different studies and discuss the critical aspects - the simplest, most reproducible, best, and most relevant - that characterize lipid nanoparticles with encapsulated Q10 for topical use.

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Perillyl alcohol (POH), a bioactive monoterpenoid derived from limonene, shows promise as an antitumor agent for brain tumor treatment. However, its limited oral bioavailability and inadequate brain distribution hinder its efficacy. To address these challenges, this study developed nanostructured lipid carriers (NLCs) loaded with POH to improve its brain biodistribution. The NLCs prepared using hot homogenization exhibited an average diameter of 287 nm and a spherical morphology with a polydispersity index of 0.143. High encapsulation efficiency of 99.68% was achieved. X-ray diffraction analyses confirmed the semicrystalline state of POH-loaded NLCs. In vitro release studies demonstrated a biphasic release profile. Stability studies in simulated gastric and intestinal fluids confirmed their ability to withstand pH variations and digestive enzymes. In vivo pharmacokinetic studies in rats revealed significantly enhanced oral bioavailability of POH when encapsulated in the NLCs. Biodistribution studies showed increased POH concentration in brain tissue with NLCs compared with free POH, which was distributed more in non-target tissues such as the liver, lungs, kidneys, and spleen. These findings underscore the potential of NLCs as effective delivery systems for enhancing oral bioavailability and brain biodistribution of POH, providing a potential therapeutic strategy for brain tumor treatment.

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This study aimed to evaluate Attalea funifera seed oil with or without resveratrol entrapped in organogel nanoparticles in vitro against A375 human melanoma tumor cells. Organogel nanoparticles with seed oil (SON) or with resveratrol entrapped in the seed oil (RSON) formed functional organogel nanoparticles that showed a particle size <100 nm, polydispersity index <0.3, negative zeta potential, and maintenance of electrical conductivity. The resveratrol entrapment efficiency in RSON was 99 ± 1%. The seed oil and SON showed no cytotoxicity against human non-tumor cells or tumor cells. Resveratrol at 50 µg/mL was cytotoxic for non-tumor cells, and was cytotoxic for tumor cells at 25 µg/mL. Resveratrol entrapped in RSON showed a decrease in cytotoxicity against non-tumor cells and cytotoxic against tumor cells at 50 µg/mL. Thus, SON is a potential new platform for the delivery of resveratrol with selective cytotoxic activity in the treatment of melanoma.

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In view of the strong anti-inflammatory activity of glucocorticoids (GC) they are used in the treatment of almost all inflammatory lung diseases. In particular, inhaled GC (IGC) allow high drug concentrations to be deposited in the lung and may reduce the incidence of adverse effects associated with systemic administration. However, rapid absorption through the highly absorbent surface of the lung epithelium may limit the success of localized therapy. Therefore, inhalation of GC incorporated into nanocarriers is a possible approach to overcome this drawback. In particular, lipid nanocarriers, which showed high pulmonary biocompatibility and are well known in the pharmaceutical industry, have the best prospects for pulmonary delivery of GC by inhalation. This review provides an overview of the pre-clinical applications of inhaled GC-lipid nanocarriers based on several key factors that will determine the efficiency of local pulmonary GC delivery: 1) stability to nebulization, 2) deposition profile in the lungs, 3) mucociliary clearance, 4) selective accumulation in target cells, 5) residence time in the lung and systemic absorption and 6) biocompatibility. Finally, novel preclinical pulmonary models for inflammatory lung diseases are also discussed.

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Many pharmaceutically active molecules are highly lipophilic, which renders their administration and adsorption in patients extremely challenging. Among the countless strategies to overcome this problem, synthetic nanocarriers have demonstrated superb efficiency as drug delivery systems, since encapsulation can effectively prevent a molecules' degradation, thus ensuring increased biodistribution. However, metallic and polymeric nanoparticles have been frequently associated with possible cytotoxic side effects. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which are prepared with physiologically inert lipids, therefore emerged as an ideal strategy to bypass toxicities issues and avoid the use of organic solvents in their formulations. Different approaches to preparation, using only moderate amounts of external energy to facilitate a homogeneous formation, have been proposed. Greener synthesis strategies have the potential to provide faster reactions, more efficient nucleation, better particle size distribution, lower polydispersities, and furnish products with higher solubility. Particularly microwave-assisted synthesis (MAS) and ultrasound-assisted synthesis (UAS) have been utilized in the manufacturing of nanocarrier systems. This narrative review addresses the chemical aspects of those synthesis strategies and their positive influence on the characteristics of SLNs and NLCs. Furthermore, we discuss the limitations and future challenges for the manufacturing processes of both types of nanoparticles.