Lecithin-chitosan Nanoparticles Research Articles

Development of famotidine-loaded lecithin-chitosan nanoparticles for prolonged and efficient anti-gastric ulcer activity

Lecithin-chitosan nanoparticles (LCNPs) represent an appealing nanocarrier for the oral delivery of hydrophobic drugs. Negatively charged lecithin and positively charged chitosan were permitted to interact to create LCNPs. Their distinctive features enable drugs to be encapsulated into the lipophilic lecithin core while improving their retention in gastric mucosa by the chitosan coat. Famotidine (FMD), a hydrophobic H2-receptor antagonist drug with a short half-life (2.5–4 h), was loaded into LCNPs to enhance its therapeutic efficacy in gastric ulcers through achieving good mucoadhesion and subsequent absorption. The optimal formula with a lecithin to chitosan ratio of 10:1 was selected and exhibited a particle size of 178.5 ± 9.5 nm, a zeta potential of 43.7 ± 2 mV, and an entrapment efficiency of 75.81 ± 2.5 %. It displayed a prolonged in vitro release profile (75.72 % over 24 h) and considerable mucoadhesive properties. FMD-LCNPs were also characterized by differential scanning calorimetry, Fourier transform-infrared (FTIR) spectroscopy, transmission electron microscopy, and stability studies. The in vivo study was performed on ethanol-induced gastric ulcer in a rat model, and the anti-gastric ulcer effects of FMD-free, FMD-marketed product, and FMD-LCNPs were determined by assessing the ulcer severity, antioxidant biomarkers, eNOS levels in addition to histopathological examination. FMD-LCNPs administration resulted in a percentage of protection from gastric severity of 96.25 % and an exceptional ameliorative effect on oxidative stress biomarkers (GSH; 162.36 % increase and MDA; 71.91 % decrease) as compared to other FMD forms. Additionally, FMD-LCNPs showed the strongest eNOS level improvement (130.34 %), which indicated the best healing impact and was confirmed by restoring the gastric mucosa to normal architecture.

Self-Assembled Lecithin-Chitosan Nanoparticles Improved Rotigotine Nose-to-Brain Delivery and Brain Targeting Efficiency

Rotigotine (RTG) is a non-ergoline dopamine agonist and an approved drug for treating Parkinson's disease. However, its clinical use is limited due to various problems, viz. poor oral bioavailability (<1%), low aqueous solubility, and extensive first-pass metabolism. In this study, rotigotine-loaded lecithin-chitosan nanoparticles (RTG-LCNP) were formulated to enhance its nose-to-brain delivery. RTG-LCNP was prepared by self-assembly of chitosan and lecithin due to ionic interactions. The optimized RTG-LCNP had an average diameter of 108 nm with 14.43 ± 2.77% drug loading. RTG-LCNP exhibited spherical morphology and good storage stability. Intranasal RTG-LCNP improved the brain availability of RTG by 7.86 fold with a 3.84-fold increase in the peak brain drug concentration (Cmax(brain)) compared to intranasal drug suspensions. Further, the intranasal RTG-LCNP significantly reduced the peak plasma drug concentration (Cmax(plasma)) compared to intranasal RTG suspensions. The direct drug transport percentage (DTP (%)) of optimized RTG-LCNP was found to be 97.3%, which shows effective direct nose-to-brain drug uptake and good targeting efficiency. In conclusion, RTG-LCNP enhanced drug brain availability, showing the potential for clinical application.

Development of a Curcumin-Loaded Lecithin/Chitosan Nanoparticle Utilizing a Box-Behnken Design of Experiment: Formulation Design and Influence of Process Parameters.

Curcumin (CUR) has impressive pharmacologic properties, including cardioprotective, neuroprotective, antimicrobial, and anticancer activity. However, the pharmaceutical application of CUR is limited due to its poor aqueous solubility and low bioavailability. The development of novel formulations has attracted considerable attention to the idea of applying nanobiotechnology to improve the therapeutic efficacy of these challenging compounds. In this study, CUR-loaded lecithin–chitosan nanoparticles (CUR/LCSNPs) were developed and optimized by the concentration of chitosan, lecithin, and stirring speed by a 3-factorial Box-Behnken statistical design, resulting in an optimal concentration of chitosan (A) and lecithin (B) with a 1200 rpm stirring speed (C), with applied constraints of minimal average particle size (Y1), optimal zeta potential (Y2), and maximum entrapment efficiency (%EE) (Y3). The mean particle size of the checkpoint formulation ranged from 136.44 ± 1.74 nm to 267.94 ± 3.72, with a zeta potential of 18.5 ± 1.39 mV to 36.8 ± 3.24 mV and %EE of 69.84 ± 1.51% to 78.50 ± 2.11%. The mean particle size, zeta potential, %EE, and % cumulative drug release from the optimized formulation were 138.43 ± 2.09 nm, +18.98 ± 0.72 mV, 77.39 ± 1.70%, and 86.18 ± 1.5%, respectively. In vitro drug release followed the Korsmeyer–Peppas model with Fickian diffusion (n < 0.45). The optimized technique has proven successful, resulting in a nanoformulation that can be used for the high loading and controlled release of lipophilic drugs.

Efficient epidermal delivery of antibiotics by self-assembled lecithin/chitosan nanoparticles for enhanced therapy on epidermal bacterial infections

The treatment for epidermal bacterial infections has become a primary healthy concern, producing a significant therapeutic challenge. Here we present a facile strategy to fabricate lecithin/chitosan nanoparticles (LCNPs) for efficient epidermal drug delivery over epidermal bacterial infections. The central rotatable composite design method was used for the optimization of the preparation, and that the optimal size (212.63 ± 1.95 nm) was obtained via analysis of variance (ANOVA). The prepared CIP-LCNPs show an average diameter of 325.9 ± 7.4 nm and a zeta potential of 26.6 ± 1.2 mV. Antibiotics can be well encapsulated in LCNPs and its release kinetics is studied with cumulative release of 93.81 ± 2.05 % for 48 h. The hemolytic activity, cytotoxicity, and skin irritation are further investigated. The zones of inhibition are 2.16 ± 0.04 cm and 2.92 ± 0.03 cm for Escherichia coli and Staphylococcus aureus, respectively. Moreover, in vitro permeation studies demonstrate that LCNPs can increase the accumulation of antibiotics in the epidermis with retention ratio 2–3 fold higher than commercial formulations. The in vivo result over epidermal-infected wound demonstrates the superior therapeutic effects of LCNPs. The developed LCNPs represent an important advance in fabricating therapeutic materials for enhanced therapy over epidermal bacterial infections.

Boosting the anti-inflammatory effect of self-assembled hybrid lecithin–chitosan nanoparticles via hybridization with gold nanoparticles for the treatment of psoriasis: elemental mapping and in vivo modeling

Gold nanoparticles are a promising drug delivery system for treatment of inflammatory skin conditions, including psoriasis, due to their small size and anti-inflammatory properties. The aim of this study was to conjugate gold nanoparticles with anti-psoriatic formulations that previously showed successful results in the treatment of psoriasis (tacrolimus-loaded chitosan nanoparticles and lecithin–chitosan nanoparticles) by virtue of their surface charges, then examine whether the hybridization with gold nanoparticles would enhance the anti-psoriatic efficacy in vivo. Successful formation of gold nanoparticles was examined by elemental mapping and selected area electron diffraction (SAED). Hybrid conjugates were examined in terms of particle size and zeta potential by dynamic light scattering (DLS). Morphological features were captured by transmission electron microscope (TEM) and X-ray diffraction (XRD) analysis was conducted, as well. All characterization was conducted for the conjugated nanoparticles and compared with their bare counterparts. The in vivo results on imiquimod (IMQ)-induced mouse model showed promising anti-psoriatic effects upon application of gold conjugated tacrolimus-loaded lecithin–chitosan hybrid nanoparticles with a significant difference from the bare hybrid nanoparticles in some of the inflammatory markers. The anti-inflammatory effect of the gold conjugate was also evident by a lower spleen to body weight ratio and a better histopathological skin condition compared to other tested formulations.

PEGylated Lecithin-Chitosan Nanoparticle-Encapsulated Alphα-Terpineol for In Vitro Anticancer Effects.

The aim of this study was to fabrication PEGylated lecithin-chitosan nanoparticles (PLC-NPs) as alphα-Terpineol's (αT-PLC-NPs) delivery system and examine its anti-cancer effects. αT-PLC-NPs were synthesized by self-assembling method; after characterization, entrapment efficiency of α-T was measured by HPLC procedure. MTT test was conducted for cytotoxicity evaluation. Chick chorioallantoic membrane (CAM) and quantitative polymerase chain reaction (qPCR) analysis were used to determine the angiogenesis properties, and qPCR, flow cytometry, and acridine orange and propidium iodide (AO/PI) staining were used to evaluate the pro-apoptotic effects of αT-PLC-NPs. Finally, the anti-inflammatory and antibacterial activity of the αT-PLC-NPs was also evaluated. αT-PLC-NPs with a size of 220.8 nm, polydispersity index (PDI) of 0.3, zeta potential of +29.03 mV, and encapsulation efficiency of 82% showed higher inhibitory effect on MCF7 cells (IC50: 750 μg/mL) compared to HFF cells (above 1000 μg/mL). Decreased angiogenesis indices and embryonic growth factors in CAM assay, decreased expression of VEGF and VEGF-R genes, and decreased cell migration showed the inhibitory effect of αT-PLC-NPs on angiogenesis. Increased expression of P53, P21, and caspase9 genes, as well as the results of AO/PI staining along with increasing the number of SubG1 phase cells in flow cytometry, confirmed the pro-apoptotic effects of αT-PLC-NPs. Also, its anti-inflammatory effects were demonstrated by inhibiting the expression of pro-inflammatory cytokines (TNF-α and IL-6). The inhibitory power of αT-PLC-NPs in suppressing gram-positive and negative bacterial strains was demonstrated by disk diffusion (DD), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) methods. PLC-NPs are a promising carrier for α-T transfer for preclinical studies.

Anti-Inflammatory Properties of Statin-Loaded Biodegradable Lecithin/Chitosan Nanoparticles: A Step Toward Nose-to-Brain Treatment of Neurodegenerative Diseases.

Nasal delivery has been indicated as one of the most interesting alternative routes for the brain delivery of neuroprotective drugs. Nanocarriers have emerged as a promising strategy for the delivery of neurotherapeutics across the nasal epithelia. In this work, hybrid lecithin/chitosan nanoparticles (LCNs) were proposed as a drug delivery platform for the nasal administration of simvastatin (SVT) for the treatment of neuroinflammatory diseases. The impact of SVT nanoencapsulation on its transport across the nasal epithelium was investigated, as well as the efficacy of SVT-LCNs in suppressing cytokines release in a cellular model of neuroinflammation. Drug release studies were performed in simulated nasal fluids to investigate SVT release from the nanoparticles under conditions mimicking the physiological environment present in the nasal cavity. It was observed that interaction of nanoparticles with a simulated nasal mucus decreased nanoparticle drug release and/or slowed drug diffusion. On the other hand, it was demonstrated that two antibacterial enzymes commonly present in the nasal secretions, lysozyme and phospholipase A2, promoted drug release from the nanocarrier. Indeed, an enzyme-triggered drug release was observed even in the presence of mucus, with a 5-fold increase in drug release from LCNs. Moreover, chitosan-coated nanoparticles enhanced SVT permeation across a human cell model of the nasal epithelium (×11). The nanoformulation pharmacological activity was assessed using an accepted model of microglia, obtained by activating the human macrophage cell line THP-1 with the Escherichia coli–derived lipopolysaccharide (LPS) as the pro-inflammatory stimulus. SVT-LCNs were demonstrated to suppress the pro-inflammatory signaling more efficiently than the simple drug solution (−75% for IL-6 and −27% for TNF-α vs. −47% and −15% at 10 µM concentration for SVT-LCNs and SVT solution, respectively). Moreover, neither cellular toxicity nor pro-inflammatory responses were evidenced for the treatment with the blank nanoparticles even after 36 h of incubation, indicating a good biocompatibility of the nanomedicine components in vitro. Due to their biocompatibility and ability to promote drug release and absorption at the biointerface, hybrid LCNs appear to be an ideal carrier for achieving nose-to-brain delivery of poorly water-soluble drugs such as SVT.

Hybrid Nanoparticles as a Novel Tool for Regulating Psychosine-Induced Neuroinflammation and Demyelination In Vitro and Ex vivo

Polymeric nanoparticles are being extensively investigated as an approach for brain delivery of drugs, especially for their controlled release and targeting capacity. Nose-to-brain administration of nanoparticles, bypassing the blood brain barrier, offers a promising strategy to deliver drugs to the central nervous system. Here, we investigated the potential of hybrid nanoparticles as a therapeutic approach for demyelinating diseases, more specifically for Krabbe’s disease. This rare leukodystrophy is characterized by the lack of enzyme galactosylceramidase, leading to the accumulation of toxic psychosine in glial cells causing neuroinflammation, extensive demyelination and death. We present evidence that lecithin/chitosan nanoparticles prevent damage associated with psychosine by sequestering the neurotoxic sphingolipid via physicochemical hydrophobic interactions. We showed how nanoparticles prevented the cytotoxicity caused by psychosine in cultured human astrocytes in vitro, and how the nanoparticle size and PDI augmented while the electrostatic charges of the surface decreased, suggesting a direct interaction between psychosine and the nanoparticles. Moreover, we studied the effects of nanoparticles ex vivo using mouse cerebellar organotypic cultures, observing that nanoparticles prevented the demyelination and axonal damage caused by psychosine, as well as a moderate prevention of the astrocytic death. Taken together, these results suggest that lecithin-chitosan nanoparticles are a potential novel delivery system for drugs for certain demyelinating conditions such as Krabbe’s disease, due to their dual effect: not only are they an efficient platform for drug delivery, but they exert a protective effect themselves in tampering the levels of psychosine accumulation.

Berberine Encapsulated Lecithin-Chitosan Nanoparticles as Innovative Wound Healing Agent in Type II Diabetes.

The aim of this research is to formulate a lecithin–chitosan based nanoparticulate system loaded with berberine (BER-LC-CTS-NPs) that could be integrated into a topically applied formulation and assessed for healing wounds in a diabetic animal model. In order to formulate BER-LC-CTS-NPs, soybean lecithin, isopropyl myristate, and berberine dispersed in ethanolic solution were added into an aqueous solution of chitosan dropwise with sonication. We assessed the influence of lecithin amount, chitosan amount, and isopropyl myristate concentration on particle diameter, zeta potential, and entrapment and employed a Box–Behnken statistical design. The resulting optimized BER-LC-CTS-NPs had a mean size of 168.4 nm, a surface charge of 33.1 mV, and entrapment of 82.3%. The optimized BER-LC-CTS-NPs showed a sustained in vitro release profile. Furthermore, the potential of the optimized BER-LC-CTS-NPs integrated into a topical gel formulation for wound healing in streptozocin-induced diabetic rats was assessed. Our findings show that combining chitosan and berberine in the nanoparticles produces a synergistic effect when it comes to wound healing. The optimized nanoparticulate system works by reducing inflammation, inducing blood vessels and fibroblast proliferation, and promoting mature collagen fibers deposition. Based on the experimental results, lecithin–chitosan nanoparticles loaded with berberine have evolved as a promising strategy for accelerating wound the healing process in diabetic patients. However, the clinical merits of the developed system need to be investigated in diabetic patients.

Structure and Fate of Nanoparticles Designed for the Nasal Delivery of Poorly Soluble Drugs

Nanoparticles are promising mediators to enable nasal systemic and brain delivery of active compounds. However, the possibility of reaching therapeutically relevant levels of exogenous molecules in the body is strongly reliant on the ability of the nanoparticles to overcome biological barriers. In this work, three paradigmatic nanoformulations vehiculating the poorly soluble model drug simvastatin were addressed: (i) hybrid lecithin/chitosan nanoparticles (LCNs), (ii) polymeric poly-ε-caprolactone nanocapsules stabilized with the nonionic surfactant polysorbate 80 (PCL_P80), and (iii) polymeric poly-ε-caprolactone nanocapsules stabilized with a polysaccharide-based surfactant, i.e., sodium caproyl hyaluronate (PCL_SCH). The three nanosystems were investigated for their physicochemical and structural properties and for their impact on the biopharmaceutical aspects critical for nasal and nose-to-brain delivery: biocompatibility, drug release, mucoadhesion, and permeation across the nasal mucosa. All three nanoformulations were highly reproducible, with small particle size (∼200 nm), narrow size distribution (polydispersity index (PI) < 0.2), and high drug encapsulation efficiency (>97%). Nanoparticle composition, surface charge, and internal structure (multilayered, core–shell or raspberry-like, as assessed by small-angle neutron scattering, SANS) were demonstrated to have an impact on both the drug-release profile and, strikingly, its behavior at the biological interface. The interaction with the mucus layer and the kinetics and extent of transport of the drug across the excised animal nasal epithelium were modulated by nanoparticle structure and surface. In fact, all of the produced nanoparticles improved simvastatin transport across the epithelial barrier of the nasal cavity as compared to a traditional formulation. Interestingly, however, the permeation enhancement was achieved via two distinct pathways: (a) enhanced mucoadhesion for hybrid LCN accompanied by fast mucosal permeation of the model drug, or (b) mucopenetration and an improved uptake and potential transport of whole PCL_P80 and PCL_SCH nanocapsules with delayed boost of permeation across the nasal mucosa. The correlation between nanoparticle structure and its biopharmaceutical properties appears to be a pivotal point for the development of novel platforms suitable for systemic and brain delivery of pharmaceutical compounds via intranasal administration.

Corrigendum to Bioactivity and cytotoxicity of quercetin-loaded lecithin-chitosan nanoparticles

Corrigendum to Bioactivity and cytotoxicity of quercetin-loaded lecithin-chitosan nanoparticles

Intranasal delivery of phenytoin-loaded nanoparticles to the brain suppresses pentylenetetrazol-induced generalized tonic clonic seizures in an epilepsy mouse model.

In this work we describe the preparation and characterization of lecithin-chitosan nanoparticles (L10Ci+), and investigate their ability to deliver the anti-epileptic drug phenytoin (PHT) to mouse brain following intranasal (IN) administration. L10Ci+ were retained in the nasal cavity compared to PHT in PEG200 solution (PHT/PEG), which suffered immediate nasal drainage. PHT was detected in the brain after 5 min of IN administration reaching a maximum of 11.84 ± 2.31 %ID g-1 after 48 hours. L10Ci+ were associated with a higher brain/plasma ratio (Cb/p) compared to the experimental control comprising free PHT injected via the intraperitoneal route (PHT-IP) across all tested time points. Additionally, L10Ci+ led to lower PHT accumulation in the liver and spleen compared to PHT-IP, which is vital for lowering the systemic side effects of PHT. The relatively high drug targeting efficiency (DTE%) of 315.46% and the drug targeting percentage (DTP%) of 68.29%, combined with the increasing anterior-to-posterior gradient of PHT in the brain confirmed the direct nose-to-brain transport of PHT from L10Ci+. Electroencephalogram (EEG) analysis was used to monitor seizure progression. L10Ci+ resulted in a complete seizure suppression after 4 hours of administration, and this inhibition persisted even with an 8-fold reduction of the encapsulated dose compared to the required PHT-IP dose to achieve a similar inhibitory effect due to systemic loss. The presented findings confirm the possibility of using L10Ci+ as a non-invasive delivery system of PHT for the management of epilepsy using reduced doses of PHT.

Bioactivity and cytotoxicity of quercetin-loaded, lecithin-chitosan nanoparticles

Quercetin is a bioactive compound with potential application as an antioxidant in food matrices. However, the use of this flavonoid becomes a challenge due to its relative degree of hydrophobicity and low bioavailability. In order to improve its dispersibility in aqueous media, protection against degradation and the bioavailability of quercetin, this study aimed to develop quercetin-loaded, lecithin-chitosan nanoparticles (NPQ) and to characterize its physical, chemical and biological properties. The nanoparticles were characterized in terms of mean size, PDI, zeta potential, morphology, encapsulation efficiency, FT-IR, transmission electron microscopy (TEM) and thermal analysis (TGA and DSC). Stability over shelf life at 4 and 30 °C, antioxidant, antimicrobial and cytotoxicity activities were also determined. Quercetin was encapsulated in lecithin-chitosan nanoparticles (NP) with an efficiency of 98.31 ± 0.01%. NPQ presented a well-defined spherical morphology with a mean size of 240.81 ± 10.82 nm and a zeta potential of +38.9 ± 1.60 mV. Stability studies showed that NPQ are relatively stable over 28 days of storage at 4 °C and 30 °C. Regarding biological activities, NPQ were able to eliminate DPPH and ABTS radicals in the same way as free quercetin and showed antimicrobial activity, without presenting cytotoxicity against normal cells (L-929 and PBMC). These results suggest that quercetin-loaded, lecithin-chitosan nanoparticles have excellent potential for application in food matrices aiming at the development of new functional foods.

Melatonin loaded lecithin-chitosan nanoparticles improved the wound healing in diabetic rats

Wound healing in diabetic patients remains a worldwide problem that can cause amputations and even lead to death. This work aimed to produce lecithin-chitosan nanoparticles loaded with melatonin (MEL-NP) incorporated in a topical formulation to be evaluated for healing in the in vivo animal model for diabetes. To produce nanoparticles, an ethanolic solution containing soybean lecithin and melatonin was added dropwise to an aqueous solution of chitosan under sonication. The nanoparticles were physicochemical characterized and evaluated in vivo for toxicity using the Galleria mellonella model and its potential for wound healing in diabetic rats. The MEL-NPs presented a particle size of 160 nm and a zeta potential of 25 mV. The melatonin entrapment efficiency was 27%. Our results indicated that treatment with MEL-NP improved wound healing demonstrated by wound closure earlier than the other treatments evaluated. A desired therapeutic effect was achieved by MEL-NP in the induction of fibroblast and angiogenic proliferation. In addition, it was accompanied by an expressive collagen deposition. Considering the observed data, the MEL-NP developed could be used as a proof of concept to develop a promising strategy for the healing of diabetic wound.

Improving antitumor outcomes for palliative intratumoral injection therapy through lecithin- chitosan nanoparticles loading paclitaxel- cholesterol complex.

BackgroundIntratumoral injection is a palliative treatment that aims at further improvement in the survival and quality of life of patients with advanced or recurrent carcinomas, or cancer patients with severe comorbidities or those with a poor performance status.MethodsIn this study, a solvent-injection method was used to prepare paclitaxel–cholesterol complex-loaded lecithin–chitosan nanoparticles (PTX-CH-loaded LCS_NPs) for intratumoral injection therapy, and the physicochemical properties of NPs were well characterized.ResultsThe particle size and zeta potential of PTX-CH-loaded LCS_NPs were 142.83±0.25 nm and 13.50±0.20 mV, respectively. Release behavior of PTX from PTX-CH-loaded LCS_NPs showed a pH-sensitive pattern. The result of cell uptake assay showed that PTX-CH-loaded LCS_NPs could effectively enter cells via the energy-dependent caveolae-mediated endocytosis and macropinocytosis in company with the Golgi apparatus. Meanwhile, PTX-CH-loaded LCS_NPs had a better ability to induce cell apoptosis than PTX solution. The in vivo antitumor results suggested that PTX-CH-loaded LCS_NPs effectively inhibited mouse mammary cancer growth and metastasis to distant organs and significantly improved the survival rate of tumor-bearing mice by intratumoral administration.ConclusionIn general, our study demonstrated that PTX-CH-loaded LCS_NPs used for palliative treatment by intratumoral injection showed improved safety and antitumor efficacy, which provided an alternative approach in the field of palliative chemotherapy.

Quercetin prevent proteoglycan destruction by inhibits matrix metalloproteinase-9, matrix metalloproteinase-13, a disintegrin and metalloproteinase with thrombospondin motifs-5 expressions on osteoarthritis model rats.

Prior study has shown that Ageratum conyzoides L. extract that containing quercetin has been proved to prevent inflammation and proteoglycan degradation by inhibiting tumor necrosis factor-alpha and matrix metalloproteinase (MMP-9) expression. Target of osteoarthritis (OA) treatment was in the synovial joint that requiring a drug delivery system. The aim of this study was to prove the efficacy of quercetin-loaded lecithin-chitosan nanoparticles on the OA model rats by observed its effect on interleukin (IL-1) β, MMP-9, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5) expressions. In this study, 70 white male Sprague Dawley rats were divided into 14 groups, 7 groups each for destabilization of medial meniscus (DMM) and monoiodoacetate (MIA)-induced OA. After 28 days from induction, SHAM and negative group received gel base topically; positive group received sodium diclofenac gel; three-dose group received each 0.84, 1.68, 3.36 mg/g quercetin-loaded nanoparticles gel; and A. conyzoides L. group received A. conyzoides L. extract gel. Each group gets treatment until day 70, and then, blood sample was collected for serum analysis; knee joint was isolated and subjected to histology samples treatment. Quercetin-loaded nanoparticle gel dose 1 (0.84 mg/g gel), dose 2 (1.68 mg/g gel), dose 3 (3.36 mg/g), and A. conyzoides L. extract gel could decreased the level of IL-1 β, MMP-9, MMP-13, ADAMTS-5, and increasing color intensity significantly on histopathological observations on DMM and MIA-induced OA.

Kaempferol loaded lecithin/chitosan nanoparticles: preparation, characterization, and their potential applications as a sustainable antifungal agent

Flavonoid compounds are strong antioxidant and antifungal agents but their applications are limited due to their poor dissolution and bioavailability. The use of nanotechnology in agriculture has received increasing attention, with the development of new formulations containing active compounds. In this study, kaempferol (KAE) was loaded into lecithin/chitosan nanoparticles (LC NPs) to determine antifungal activity compared to pure KAE against the phytopathogenic fungus Fusarium oxysporium to resolve the bioavailability problem. The influence of formulation parameters on the physicochemical properties of KAE loaded lecithin chitosan nanoparticles (KAE-LC NPs) were studied by using the electrostatic self-assembly technique. KAE-LC NPs were characterized in terms of physicochemical properties. KAE has been successfully encapsulated in LC NPs with an efficiency of 93.8 ± 4.28% and KAE-LC NPs showed good physicochemical stability. Moreover, in vitro evaluation of the KAE-LC NP system was made by the release kinetics, antioxidant and antifungal activity in a time-dependent manner against free KAE. Encapsulated KAE exhibited a significantly inhibition efficacy (67%) against Fusarium oxysporium at the end of the 60 day storage period. The results indicated that KAE-LC NP formulation could solve the problems related to the solubility and loss of KAE during use and storage. The new nanoparticle system enables the use of smaller quantities of fungicide and therefore, offers a more environmentally friendly method of controlling fungal pathogens in agriculture.

Assessment of β-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB/c mice

Patients affected by cutaneous leishmaniasis need a topical treatment which cures lesions without leaving scars. Lesions are produced not only by the parasite but also by an uncontrolled and persistent inflammatory immune response. In this study, we proposed the loading of β-lapachone (β-LP) in lecithin-chitosan nanoparticles (NP) for targeting the drug to the dermis, where infected macrophages reside, and promote wound healing. Although the loading of β-LP in NP did not influence the drug antileishmanial activity it was critical to achieve important drug accumulation in the dermis and permeation through the skin. When topically applied in Leishmania major infected BALB/c mice, β-LP NP achieved no parasite reduction but they stopped the lesion progression. Immuno-histopathological assays in CL lesions and quantitative mRNA studies in draining lymph nodes confirmed that β-LP exhibited anti-inflammatory activity leading to the down-regulation of IL-1β and COX-2 expression and a decrease of neutrophils infiltrate. From the Clinical EditorCutaneous leishmaniasis often leaves patients with unsightly scars due to the body's inflammatory response to the infection. The authors in this paper described topical treatment using β-lapachone (β- LP) loaded in lecithin-chitosan nanoparticles (NP) in an animal model. Results confirmed the reduction of inflammatory response without affecting the parasite killing efficacy. These findings would pave way for further clinical testing in the near future.

Lecithin/chitosan controlled release nanopreparations of tamoxifen citrate: Loading, enzyme-trigger release and cell uptake

Tamoxifen citrate (TAM), an anticancer drug with amphiphilic properties, was loaded in lecithin/chitosan nanoparticles (LCN) with a view to oral administration. The influence of tamoxifen loading on the physico-chemical properties of nanoparticles was studied. Size, surface charge and morphological properties of tamoxifen-loaded nanoparticles (LCN-TAM) were assessed. The increase in the tamoxifen amount in the LCN-TAM preparation up to 60mg/100ml maintained the positive zeta potential value of about +45mV. A statistically significant decrease in particle size was observed for TAM amounts between 5 and 20mg. A strong influence of loaded tamoxifen on the structure of lecithin/chitosan nanoparticles was observed, supported by the quantification of free chitosan and morphological analysis. A loading of tamoxifen in nanoparticles of around 19% was obtained. The release of the drug from the LCN-TAM colloidal dispersion was measured, showing that tamoxifen citrate was released very slowly in simulated gastro-intestinal fluids without enzymes. When enzymes able to dismantle the nanoparticle structure were added to the dissolution medium, drug release was triggered and continued in a prolonged manner. Tamoxifen-loaded nanoparticles showed cytotoxicity towards MCF-7 cells comparable to that obtained with tamoxifen citrate solution, but the rate of this toxic effect was dependent on drug release. Caco-2 cells, used as a model of the intestinal epithelium, were shown to take up the TAM loaded nanoparticles extensively.

Comparison of PLGA and lecithin/chitosan nanoparticles for dermal targeting of betamethasone valerate

Poly(lactide-co-glycolide) (PLGA) and lecithin/chitosan (LC) nanoparticles were prepared to evaluate the difference in the behavior upon administration on skin, for steroidal treatment. For this purpose, betamethasone-17-valerate (BMV)-loaded nanoparticles with a narrow size distribution and high entrapment efficiency were prepared. Permeation studies showed that both polymeric nanoparticles enhanced the amount of BMV in epidermis, which is the target site of topical steroidal treatment, when compared with commercial formulation. 1.58-Fold increase was determined in the epidermis concentration of BMV by LC nanoparticles with respect to PLGA nanoparticles. Nanoparticles were diluted in chitosan gel (10%, w/w) to prepare suitable formulation for topical application. Accumulation from both gel formulations were found significantly higher than commercial formulation in skin layers (p < 0.05). In addition, pharmacodynamic responses were also investigated as anti-inflammatory and skin-blanching parameters. Both formulations significantly improved these parameters although they contained 10 times less amount of BMV than commercial cream. Moreover, TEWL measurement exhibited no barrier function changes upon the application of nanoparticles on skin. Overall, both nanoparticles improved the localization of BMV within skin layers; but when compared with PLGA nanoparticles, the LC nanoparticles could be classified as a better candidate for topical delivery vehicle in the treatment of various dermatological inflammatory diseases.