Fabrication and Characterization of Pectin Films Containing Solid Lipid Nanoparticles for Buccal Delivery of Fluconazole.

Fluconazole (FZ) is a potential antifungal compound for treating superficial and systemic candidiasis. However, the use of conventional oral drug products has some limitations. The development of buccal film may be a potential alternative to oral formulations for FZ delivery. The present study involved the development of novel FZ-loaded solid lipid nanoparticles (FZ-SLNs) in pectin solutions and the investigation of their particle characteristics. The particle sizes of the obtained FZ-SLNs were in the nanoscale range. To produce pectin films with FZ-SLNs, four formulations were selected based on the small particle size of FZ-SLNs and their suitable polydispersity index. The mean particle sizes of all chosen FZ-SLNs formulations did not exceed 131.7 nm, and the mean polydispersity index of each formulation was less than 0.5. The properties of films containing FZ-SLNs were then assessed. The preparation of all FZ-SLN-loaded pectin films provided the mucoadhesive matrices. The evaluation of mechanical properties unveiled the influence of particle size variation in FZ-SLNs on the integrity of the film. The Fourier-transform infrared spectra indicated that hydrogen bonds could potentially form between the pectin-based matrix and the constituents of FZ-SLNs. The differential scanning calorimetry thermogram of each pectin film with FZ-SLNs revealed that the formulation was thermally stable and behaved in a solid state at 37 °C. According to a drug release study, a sustained drug release pattern with a burst in the initial stage for all films may be advantageous for reducing the lag period of drug release. All prepared films with FZ-SLNs provided a sustained release of FZ over 6 h. The films containing FZ-SLNs with a small particle size provided good permeability across the porcine mucosa. All film samples demonstrated antifungal properties. These results suggest the potential utility of pectin films incorporating FZ-SLNs for buccal administration.

Advanced Drug Carriers: A Review of Selected Protein, Polysaccharide, and Lipid Drug Delivery Platforms.

Studies on bionanocomposite drug carriers are a key area in the field of active substance delivery, introducing innovative approaches to improve drug therapy. Such drug carriers play a crucial role in enhancing the bioavailability of active substances, affecting therapy efficiency and precision. The targeted delivery of drugs to the targeted sites of action and minimization of toxicity to the body is becoming possible through the use of these advanced carriers. Recent research has focused on bionanocomposite structures based on biopolymers, including lipids, polysaccharides, and proteins. This review paper is focused on the description of lipid-containing nanocomposite carriers (including liposomes, lipid emulsions, lipid nanoparticles, solid lipid nanoparticles, and nanostructured lipid carriers), polysaccharide-containing nanocomposite carriers (including alginate and cellulose), and protein-containing nanocomposite carriers (e.g., gelatin and albumin). It was demonstrated in many investigations that such carriers show the ability to load therapeutic substances efficiently and precisely control drug release. They also demonstrated desirable biocompatibility, which is a promising sign for their potential application in drug therapy. The development of bionanocomposite drug carriers indicates a novel approach to improving drug delivery processes, which has the potential to contribute to significant advances in the field of pharmacology, improving therapeutic efficacy while minimizing side effects.

Solid Lipid Nanoparticles Encapsulating a Benzoxanthene Derivative in a Model of the Human Blood-Brain Barrier: Modulation of Angiogenic Parameters and Inflammation in Vascular Endothelial Growth Factor-Stimulated Angiogenesis.

Lignans, a class of secondary metabolites found in plants, along with their derivatives, exhibit diverse pharmacological activities, including antioxidant, antimicrobial, anti-inflammatory, and antiangiogenic ones. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a crucial process for cancer growth and development. Several studies have elucidated the synergistic relationship between angiogenesis and inflammation in various inflammatory diseases, highlighting a correlation between inflammation and vascular endothelial growth factor (VEGF)-induced angiogenesis. Thus, the identification of novel molecules capable of modulating VEGF effects presents promising prospects for developing therapies aimed at stabilizing, reversing, or even arresting disease progression. Lignans often suffer from low aqueous solubility and, for their use, encapsulation in a delivery system is needed. In this research, a bioinspired benzoxantene has been encapsulated in solid lipid nanoparticles that have been characterized for their pharmacotechnical properties and their thermotropic behavior. The effects of these encapsulated nanoparticles on angiogenic parameters and inflammation in VEGF-induced angiogenesis were evaluated using human brain microvascular endothelial cells (HBMECs) as a human blood-brain barrier model.

Thermosensitive and mucoadhesive gels containing solid lipid nanoparticles loaded with fluconazole and niosomes loaded with clindamycin for the treatment of periodontal diseases: a laboratory experiment.

BACKGROUND: Periodontal diseases may benefit more from topical treatments with nanoparticles rather than systemic treatments due to advantages such as higher stability and controlled release profile. This study investigated the preparation and characterization of thermosensitive gel formulations containing clindamycin-loaded niosomes and solid lipid nanoparticles (SLNs) loaded with fluconazole (FLZ), as well as their in vitro antibacterial and antifungal effects in the treatment of common microorganisms that cause periodontal diseases. METHODS: This study loaded niosomes and SLNs with clindamycin and FLZ, respectively, and assessed their loading efficiency, particle size, and zeta potential. The particles were characterized using a variety of methods such as differential scanning calorimetry (DSC), dynamic light scattering (DLS), and Transmission Electron Microscopy (TEM). Thermosensitive gels were formulated by combining these particles and their viscosity, gelation temperature, in-vitro release profile, as well as antibacterial and antifungal effects were evaluated. RESULTS: Both types of these nanoparticles were found to be spherical (TEM) with a mean particle size of 243.03 nm in niosomes and 171.97 nm in SLNs (DLS), and respective zeta potentials of -23.3 and -15. The loading rate was 98% in niosomes and 51% in SLNs. The release profiles of niosomal formulations were slower than those of the SLNs. Both formulations allowed the release of the drug by first-order kinetic. Additionally, the gel formulation presented a slower release of both drugs compared to niosomes and SLNs suspensions. CONCLUSION: Thermosensitive gels containing clindamycin-loaded niosomes and/or FLZ-SLNs were found to effectively fight the periodontitis-causing bacteria and fungi.

Enhanced cardioprotective activity of ferulic acid-loaded solid lipid nanoparticle in an animal model of myocardial injury.

Myocardial infarction results in an increased inflammatory and oxidative stress response in the heart, and reducing inflammation and oxidative stress after MI may offer protective effects to the heart. In the present study, we examined the cardioprotective effects of ferulic acid (FA) and ferulic acid nanostructured solid lipid nanoparticles (FA-SLNs) in an isoproterenol (ISO) induced MI model. Male Sprague Dawley rats were divided into five experimental groups to compare the effects of FA and FA-SLNs. The findings revealed that ISO led to extensive cardiomyopathy, characterized by increased infarction area, edema formation, pressure load, and energy deprivation. Additionally, ISO increased the levels of inflammatory markers (COX-2, NLRP3, and NF-кB) and apoptotic mediators such as p-JNK. However, treatment with FA and FA-SLNs mitigated the severity of the ISO-induced response, and elevated the levels of antioxidant enzymes while downregulating inflammatory pathways, along with upregulation of the mitochondrial bioenergetic factor PPAR-γ. Furthermore, virtual docking analysis of FA with various protein targets supported the in vivo results, confirming drug-protein interactions. Overall, the results demonstrated that FA-SLNs offer a promising strategy for protecting the heart from further injury following MI. This is attributed to the improved drug delivery and therapeutic outcomes compared to FA alone.

Indocyanine green combined with methylene blue versus methylene blue alone for sentinel lymph node biopsy in breast cancer: a retrospective study.

BACKGROUND: Recent studies have shown that near-infrared (NIR) fluorescence imaging using Indocyanine green (ICG) may improve the efficiency of sentinel lymph node biopsy (SLNB). This study aimed to assess the effectiveness of the combination of ICG and methylene blue (MB) in breast cancer patients undergoing SLNB. PATIENTS AND METHOD: We evaluated ICG plus MB (ICG + MB) identification effectiveness with MB alone using retrospective analysis. From 2016 to 2020, we collected data on 300 eligible breast cancer patients who got SLNB treatment in our institution by ICG + MB or MB alone. By comparing the distribution of clinicopathological characteristics, the detection rate of sentinel lymph nodes (SLNs) and metastatic SLNs, as well as the total number of SLNs in the two groups, we were able to assess the imaging efficiency. RESULTS: Fluorescence imaging allowed 131 out of 136 patients in the ICG + MB group to find SLNs. ICG + MB group and MB group had detection rates of 98.5% and 91.5% (P = 0.007, χ2 = 7.352), respectively. Besides, the ICG + MB approach was able to produce improved recognition outcomes. What's more, compared with the MB group, the ICG + MB group can identify more lymph nodes (LNs) (3.1 to 2.6, P = 0.000, t = 4.447). Additionally, in the ICG + MB group, ICG could identify more LNs than MB (3.1 vs 2.6, P = 0.004, t = 2.884). CONCLUSION: ICG has high detection effectiveness for SLNs, and when paired with MB, the detection efficiency can be increased even further. Furthermore, the ICG + MB tracing mode does not involve radioisotopes, which has a lot of promise for clinical use and can take the place of conventional standard detection methods.

Development of Computational In Silico Model for Nano Lipid Carrier Formulation of Curcumin.

The oral delivery system is very important and plays a significant role in increasing the solubility of drugs, which eventually will increase their absorption by the digestive system and enhance the drug bioactivity. This study was conducted to synthesize a novel curcumin nano lipid carrier (NLC) and use it as a drug carrier with the help of computational molecular docking to investigate its solubility in different solid and liquid lipids to choose the optimum lipids candidate for the NLCs formulation and avoid the ordinary methods that consume more time, materials, cost, and efforts during laboratory experiments. The antiviral activity of the formed curcumin-NLC against SARS-CoV-2 (COVID-19) was assessed through a molecular docking study of curcumin's affinity towards the host cell receptors. The novel curcumin drug carrier was synthesized as NLC using a hot and high-pressure homogenization method. Twenty different compositions of the drug carrier (curcumin nano lipid) were synthesized and characterized using different physicochemical techniques such as UV-Vis, FTIR, DSC, XRD, particle size, the zeta potential, and AFM. The in vitro and ex vivo studies were also conducted to test the solubility and the permeability of the 20 curcumin-NLC formulations. The NLC as a drug carrier shows an enormous enhancement in the solubility and permeability of the drug.

Rivaroxaban-loaded SLNs with treatment potential of deep vein thrombosis: in-vitro, in-vivo, and toxicity evaluation.

OBJECTIVES: Rivaroxaban (RXB), a novel Xa inhibitor having groundbreaking therapeutic potential. However, this drug is associated with few limitations, including its pharmacokinetics related toxicities. Here, we developed RXB-loaded SLNs (RXB-SLNs) to improve its biopharmaceutical profile. Methods: High pressure homogenizer was used to prepare RXB-SLNs, followed by their particle characterization, Transmission electron microscopy (TEM), Dynamic light scattering (DSC), and Powder X-ray diffraction (PXRD) analysis. Beside this, in-vitro, ex-vivo, and in-vivo evaluation, prothrombin time assessment and toxicity was investigated. RESULTS: RXB-SLNs had their particle size in nano range (99.1 ± 5.50 nm) with excellent morphology and low polydispersity index (0.402 ± 0.02) and suitable zeta potential (-25.9 ± 1.4 mV). The incorporation efficiency was observed around 95.9 ± 3.9%. In-vitro release profiles of the RXB-SLNs exhibited enhanced dissolution (89 ± 9.91%) as compared to pure drug (11 ± 1.43%) after 24 h of the study. PK study demonstrated a seven times enhanced bioavailability of RXB-SLNs when compared with pure drug. Furthermore, RXB-SLNs exhibited an expressive anti-coagulant behavior in human and rat blood plasma. Also, the final formulation exhibited no toxicity after oral administration of the SLNs. CONCLUSIONS: All together, these studies revealed the capability of the SLNs for carrying the RXB with enhanced therapeutic efficacy and no toxicity, most importantly for the treatment of deep vein thrombosis.

HSPiP and QbD Program-Based Analytical Method Development and Validation to Quantify Ketoconazole in Dermatokinetic Study.

Ketoconazole (KTZ) is the most potential azole anti-mycotic drug. The quantification of KTZ from various layers of the skin after topical application of lipidic nanocarriers is critical. We addressed a sensitive, specific, simple, rapid, reproducible, and economic analytical method to quantify KTZ from the treated skin homogenate using the Hansen solubility parameter (HSP, HSPiP software)-based modeling and experimental design. The software provided various HSP values for KTZ and solvents to compose the mobile phase. The Taguchi model identified the significant sets of factors to develop a robust bioanalytical method with reduced variability. In the optimization, acetonitrile (ACN) concentration (X1 as A) and the pH of mobile phase (X2 as B) were two factors against two responses (Y1: peak area and Y2: retention time). The HPLC (high-performance liquid chromatography) method validation was carried out based on US-FDA guidelines for the developed KTZ formulations (suspension, solid nanoparticles, and commercial product) extracted from the treated rat skin. The experimental solubility of KTZ was found to be maximum in the two solvents (ACN and ethyl acetate), based on HSP values. Surface response methodology (SRM) identified remarkable impact of ACN concentration and the mobile phase pH on the peak area and retention time. Analytical limits (0.17 and 0.50 µg/mL) were established for KTZ-SLNs (extracted from the skin). The method was implemented with high reproducibility, accuracy, and selectivity to quantify KTZ from the treated rat skin.

Evaluation of the hepatoprotective effect of curcumin-loaded solid lipid nanoparticles against paracetamol overdose toxicity: Role of inducible nitric oxide synthase.

Curcumin (Cur) is a natural compound that exhibited therapeutic effects against various liver injuries however Cur showed poor water solubility and bioavailability. This study aimed to design Cur-loaded solid lipid nanoparticles (SLNs) and to evaluate the hepatoprotective and antioxidant effects in a model of acute hepatotoxicity induced by paracetamol (PCM) overdose compared to the raw Cur and N-acetylcysteine (NAC). SLNs were prepared by emulsion/solvent evaporation method and 32 factorial design was employed. Wistar rats were divided into Control, PCM, PCM + NAC, PCM + raw Cur, and PCM + Cur-SLNs groups and treated orally for 14 days before receiving a single PCM dose. The Cur-loaded SLNs showed high entrapment efficiency % ranging between 69.1 and 92.1%, particle size (PS) between 217 and 506 nm, and zeta potential values between -17.9 and -25.5 mV. The in vivo results revealed that the PCM group exhibited deterioration of liver functions, pathological lesions on the liver tissues, severe oxidative stress, and increases in both the serum and hepatic iNOS levels. Remarkably, the PCM + Cur-SLNs group showed significantly better liver functions and tissue integrity compared to the PCM group. Furthermore, higher reduced glutathione and catalase but lower malondialdehyde and iNOS levels were observed. In conclusion, Cur-loaded SLNs effectively prevented the liver damage induced by PCM overdose through alleviating the oxidative stress and inhibiting the serum and hepatic iNOS expression in an effect comparable to NAC and better than raw Cur.

Sentinel Lymph Node Removal After Neoadjuvant Chemotherapy in Clinically Node-Negative Patients: When to Stop?

BACKGROUND: The maximum number of sentinel lymph nodes (SLN) to be resected to accurately stage the axilla in patients undergoing neoadjuvant chemotherapy (NAC) for the treatment of clinically node-negative (cN0) breast cancer has not been determined. We sought to determine the sequence of removal of the positive SLNs in this patient population. METHODS: All patients aged ≥ 18 years diagnosed with cN0 invasive breast cancer who received NAC and underwent SLN surgery at Mayo Clinic Rochester between September 2008 and September 2018 were identified. Univariate analysis was performed to compare factors associated with positive nodes and where the first positive node was in the sequence of removal of the SLNs. RESULTS: We identified 446 cancers among 440 patients with a median age of 51 (IQR: 43, 61) years. At surgery, 381 (85.4%) cancers were pathologically node (ypN) negative and 65 (14.6%) were pN + . The number of nodes removed was similar for both patients with ypN0 and ypN + disease, with a median number of SLNs removed of 2.0 (IQR: 2.0, 3.0). Of all patients with a positive node, the first positive node was most commonly the 1st node removed (75.4%), and was identified by the 3rd SLN removed in all cases. CONCLUSIONS: Among cN0 patients treated with NAC, if a positive SLN is present, it is most commonly identified as the 1st sentinel node removed by the surgeon, and was identified by the 3rd sentinel node in our series. This suggests that once 3 SLNs have been resected, removal of additional sentinel lymph nodes does not add diagnostic value.

Application of preoperative computed tomographic lymphography for precise sentinel lymph node biopsy in breast cancer patients.

BACKGROUND: In light of the extensive application of sentinel lymph node biopsy (SLNB) in clinically node-negative breast cancer patients and the recently investigated failure of SLNB after lumpectomy, it has become important to explore methods for preoperative mapping of sentinel lymph nodes (SLNs) and their lymphatics to direct precise SLNB and improve the identification rate of SLNs. METHODS: Twenty-seven patients with suspected breast cancer based on the results of the clinical examination and imaging were enrolled in the study. Computed tomographic lymphography (CTLG) followed by CT three-dimensional reconstruction was performed to determine the localization of SLNs and lymphatics on the body surface preoperatively. Intraoperatively combined staining with methylene blue and indocyanine green was used to evaluate the accuracy and feasibility of CTLG. RESULTS: SLNs and lymphatics from the breast were identified using CTLG in all patients, and preoperative SLNs and lymphatics localization on the body surface showed a significant role in the selection of operative incision and injection points. The accuracy rate of SLN and lymphatic detection by CTLG was 92.6% compared with intraoperatively combined staining. Moreover, preoperative CTLG performed well in SLN number detection, and the accuracy rate was 95.2%. CONCLUSION: We evaluate the procedure and application of preoperative CTLG in the superficial localization of SLNs and lymphatics, which may lead to a decreased incidence of cutting off the lymphatics of SLNs and consequently more rapid and accurate SLN detection. This method promotes personalized SLN mapping, providing detailed information about the number and anatomical location of SLNs and lymphatics for adequate surgical planning for breast cancer patients.

Effect of Different Nail Penetration Enhancers in Solid Lipid Nanoparticles Containing Terbinafine Hydrochloride for Treatment of Onychomycosis.

Onychomycosis is considered a stubborn nail fungal infection that does not respond to conventional topical antifungal treatments. This study aimed to develop and characterize novel solid lipid nanoparticles (SLNs) formulae containing terbinafine HCl (TFH) and loaded with different nail penetration enhancers (nPEs). Three (nPEs) N-acetyl-L-cysteine, thioglycolic acid, and thiourea were used. Characterization of the prepared formulae was done regarding particle size, zeta potential, polydispersity index (PDI), entrapment efficiency (EE%), physical stability, in vitro release study, infrared (FT-IR), and their morphological structures. The selected formulae and the marketed cream Lamifen® were compared in terms of their antifungal activity against Trichophyton rubrum as well as their nail hydration and their drug uptake by the nail clippers. Thiourea was the nPE of choice; formulae (N2 and N8), with thiourea, were considered the optimum TFH SLNs containing nPEs. They were selected for their optimum particle size of 426.3 ± 10.18 and 450.8 ± 11.45 nm as well as their highest EE% of 89.76 ± 1.25 and 90.35 ± 1.33, respectively. The in vitro microbiological screening of the antifungal activity of these two formulae showed significantly larger zones of inhibition in comparison with the marketed product. The ex vivo screening of the drug uptake of the two selected formulae was significantly higher than that of the marketed product. The nPE formulae present a very promising option as they showed optimum physicochemical characterization with high antifungal activity and high drug uptake as well as good nail hydration effect.

Talazoparib nanoparticles for overcoming multidrug resistance in triple-negative breast cancer.

Herein, we investigated efflux pumps-mediated talazoparib-resistance in the treatment of triple-negative breast cancer (TNBC). Furthermore, we produced a novel talazoparib-solid lipid nanoparticles (SLNs) and then explored in vitro therapeutic efficacy of talazoparib-SLNs to overcome talazoparib-resistance in TNBC cells. Talazoparib-SLNs formulation was produced and then characterized. Calcein and Rho-123 were used to analyze the functional activity of drug efflux pumps in these cells. Additionally, RT-PCR, western blot and immunofluorescence analysis were used to detect the messenger RNA, and protein expression level, and cellular localization of the multidrug resistance (MDR1), breast cancer resistance protein (BCRP), and MRP1. We found that talazoparib efflux was mediated by BCRP and MRP1 pumps in TNBC cells. Talazoparib-SLNs could significantly enhance therapeutic efficacy of talazoparib. Furthermore, talazoparib-SLNs were more effective in the suppression of MDR1, BCRP, and MRP1 gene and protein expression levels than talazoparib. Consequently, this study suggests that talazoparib-SLNs formulation represents a promising therapeutic carrier to reverse MDR-mediated resistance in TNBC.

Preparation, optimization, and in-vitro characterization of α-tocopherol-loaded solid lipid nanoparticles (SLNs).

Objective: The main scope of present investigation was preparation and physicochemical characterization of solid lipid nanoparticles (SLNs) loaded by α-tocopherol acetate (ATA).Methods: ATA-loaded nanoparticles were prepared by solvent injection-homogenization technique using stearic acid as the solid lipid, phosphatidylcholine as the stabilizer and finally coated by chitosan with the aim of increasing z-potential and also having a more stable nano-formulation. Then, characterization of SLNs has been conducted using dynamic light scattering (DLS), zeta potential measurement, Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC).Results: Nanoparticles with average sizes of 175 ± 15 nm and zeta potential of +35 ± 2.5 mV were obtained. An excellent drug entrapment efficiency of 90.58 ± 1.38% was obtained with a no-burst slow release up to about 10 days tested. The final plateau of release of ATA from nanoparticulate system within 216 h was 61.13 ± 0.13% which was approached in about 150 h. Physical stability studies showed that the ATA nano-formulation remained stable with slight increase in mean particle size and polydispersity index over a 3-month period in refrigerated temperature. Considering both FTIR and DSC analysis, it can be concluded that there is no new band formation between materials and ATA in our nano-formulation. Particle sizes obtained using AFM images are in a good agreement to those established from the DLS analysis.Conclusion: These data showed a promising delivery system for vitamin E based on SLN platform.

Preparation, statistical optimization, in vitro characterization, and in vivo pharmacological evaluation of solid lipid nanoparticles encapsulating propolis flavonoids: a novel treatment for skin edema.

Propolis is a natural resinous product and exerts anti-inflammatory properties. The aim of this study is formulation and characterization of solid lipid nanoparticles (SLNs) encapsulating propolis flavonoids (PFs), intended for topical treatment of skin edema. The nanoparticles were prepared and statistically optimized using Box-Behnken response surface methodology. The in vitro release profile of the optimized nanoparticles was investigated. Cytotoxicity of nanoparticles on HSF-PI 18 cell line was determined. Permeation and penetration of nanoparticles across the incised skin were measured. Finally, the nanoparticles were incorporated into a pharmaceutical hydrogel formulation and the in vivo efficacy in reduction of skin edema was determined. The size, PdI, zeta potential, entrapment efficiency (EE%) and loading efficiency (LE %) of the optimized nanoparticles were 111.3 ± 19.35 nm, 0.34 ± 0.005, -24.17 ± 3.3 mV, 73.5 ± 0.86%, and 3.2 ± 0.27%, respectively. Data obtained through in vitro release study suggested a burst release followed by a prolonged release behavior up to 24 h post incubation time interval. The prepared SLNs exhibited no cytotoxicity on HSF-PI 18 cell line. Ex vivo permeation and penetration study of nanoparticles across the incised skin showed approximately a 2.5-fold and a 3-fold increase in cumulative amount of transport and cumulative amount of skin penetration, respectively. Finally, in vivo studies in rat models, showed a threefold reduction in volume of the edema in animals treated with SLNs. The obtained data revealed that the prepared SNs entrapping PFs, exert high skin targeting effects, prolonged anti-inflammatory properties and therefore high efficiency in treatment of skin edema.

In Vivo Effect of Resveratrol-Loaded Solid Lipid Nanoparticles to Relieve Physical Fatigue for Sports Nutrition Supplements.

Resveratrol (RSV) is a natural flavonoid polyphenol compound extracted from the plants which shows various biological activities. However, the clinical application of RSV is limited by its poor aqueous solubility, rapid metabolism and poor bioavailability. In this study, resveratrol-loaded solid lipid nanoparticles (RSV- SLNs) was design as a nano-antioxidant against the physical fatigue. The resultant RSV-SLNs were characterized by photon correlation spectroscopy (PCS), transmission electron micrographs (TEM), zeta potential, differential scanning calorimetry (DSC) and Raman spectroscopy pattern. Furthermore, the in vivo anti-fatigue effect assays showed that RSV-SLNs prolonged the mice exhausted time and running distance. The biochemical parameters of blood related to fatigue suggested that RSV-SLNs have potential applications to improve the antioxidant defense of the mice after extensive exercise and confer anti-fatigue capability. Furthermore, the molecular mechanisms of antioxidant by RSV-SLNs supplementation was investigated through the analysis of silent information regulator 2 homolog 1 (SIRT1) protein expression, which demonstrated that it could downregulate the expression of SIRT1 and increase autophagy markers, microtubule-associated protein 1 light chain 3-II (LC3-II) and sequestosome-1 (SQSTM1/p62). These results reveal that the RSV-SLNs may have great potential used as a novel anti-fatigue sports nutritional supplement.

The potential role of sesquiterpene lactones isolated from medicinal plants in the treatment of the metabolic syndrome - A review.

Metabolic syndrome comprises a cluster of metabolic disorders related to the development of cardiovascular disease and type 2 diabetes mellitus. In latter years, plant secondary metabolites have become of special interest because of their potential role in preventing and managing metabolic syndrome. Sesquiterpene lactones constitute a large and diverse group of biologically active compounds widely distributed in several medicinal plants used for the treatment of metabolic disorders. The structural diversity and the broad spectrum of biological activities of these compounds drew significant interests in the pharmacological applications. This review describes selected sesquiterpene lactones that have been experimentally validated for their biological activities related to risk factors of metabolic syndrome, together with their mechanisms of action. The potential beneficial effects of sesquiterpene lactones discussed in this review demonstrate that these substances represent remarkable compounds with a diversity of molecular structure and high biological activity, providing new insights into the possible role in metabolic syndrome management.

Antibiofilm Potential of Silver Sulfadiazine-Loaded Nanoparticle Formulations: A Study on the Effect of DNase-I on Microbial Biofilm and Wound Healing Activity.

Biofilm resistance is one of the severe complications associated with chronic wound infections, which impose extreme microbial tolerance against antibiotic therapy. Interestingly, deoxyribonuclease-I (DNase-I) has been empirically proved to be efficacious in improving the antibiotic susceptibility against biofilm-associated infections. DNase-I hydrolyzes the extracellular DNA, a key component of the biofilm responsible for the cell adhesion and strength. Moreover, silver sulfadiazine, a frontline therapy in burn wound infections, exhibits delayed wound healing due to fibroblast toxicity. In this study, a chitosan gel loaded with solid lipid nanoparticles of silver sulfadiazine (SSD-SLNs) and supplemented with DNase-I has been developed to reduce the fibroblast cytotoxicity and overcome the biofilm-imposed resistance. The extensive optimization using the Box-Behnken design (BBD) resulted in the formation of SSD-SLNs with a smooth surface as confirmed by scanning electron microscopy and controlled release (83%) for up to 24 h. The compatibility between the SSD and other formulation excipients was confirmed by Fourier transform infrared, differential scanning calorimetry, and powder X-ray diffraction studies. Developed SSD-SLNs in combination with DNase-I inhibited around 96.8% of biofilm of Pseudomonas aeruginosa as compared to SSD with DNase-I (82.9%). In line with our hypothesis, SSD-SLNs were found to be less toxic (cell viability 90.3 ± 3.8% at 100 µg/mL) in comparison with SSD (Cell viability 76.9 ± 4.2%) against human dermal fibroblast cell line. Eventually, the results of the in vivo wound healing study showed complete wound healing after 21 days' treatment with SSD-SLNs along with DNase-I, whereas marketed formulations SSD and SSD-LSNs showed incomplete healing after 21 days. Data in hand suggest that the combination of SSD-SLNs with DNase-I is an effective treatment strategy against the biofilm-associated wound infections and accelerates wound healing.

Solid lipid nanoparticles of Annona muricata fruit extract: formulation, optimization and in vitro cytotoxicity studies.

The present study was aimed to develop Annona muricata fruit extract loaded solid lipid nanoparticles (SLNs) and explore its cytotoxic potential in vitro model of breast cancers. Extract loaded SLNs were successfully prepared by high-pressure homogenization followed by ultrasonication method and optimized using 23 full factorial design. The extract loaded SLNs were characterized using different parameters such as particle size (PS), % entrapment efficiency (EE), zeta potential (ZP) and % cumulative drug release (CDR). The SLNs formulation was optimized on the basis of software analysis with an overall desirability factor. The PS and %EE of the optimized formulation were found to be 134.8 nm and 83.26%, respectively. The optimized formulation showed a CDR of 79.83% up to 48 h. In vitro cytotoxicity efficacy of extract loaded SLNs was determined using MTT and Apoptosis assay and compared to that of a free extract. The SLNs showed a notable apoptotic effect and better efficacy to kill MCF7 cancer cells as compared to free extract. Thus, extract loaded SLNs could be an alternative dosage form which possibly controls therapeutic action with reducing side effect.