Effects of solid lipid nanocarrier containing methyl urolithin A by coating folate-bound chitosan and evaluation of its anti-cancer activity.

BACKGROUND: Nanotechnology-based drug delivery systems have received much attention over the past decade. In the present study, we synthesized Methyl Urolithin A-loaded solid lipid nanoparticles decorated with the folic acid-linked chitosan layer called MuSCF-NPs and investigated their effects on cancer cells. METHODS: MuSCF-NPs were prepared using a high-pressure homogenization method and characterized using FTIR, FESEM, DLS, and zeta potential methods. Drug encapsulation was assessed by spectrophotometry and its cytotoxic effect on various cancer cells (MDA-MB231, MCF-7, PANC, AGS, and HepG2) by the MTT method. Antioxidant activity was assessed by the ABTS and DPPH methods, followed by expression of genes involved in oxidative stress and apoptosis by qPCR and flow cytometry. RESULTS: The results showed the formation of monodisperse and stable round nanoparticles with a size of 84.8 nm. The drug loading efficiency in MuSCF-NPs was reported to be 88.6%. MuSCF-NPs exhibited selective cytotoxicity against MDA-MB231 cells (IC50 = 40 µg/mL). Molecular analysis showed a significant increase in the expression of Caspases 3, 8, and 9, indicating that apoptosis was occurring in the treated cells. Moreover, flow cytometry results showed that the treated cells were arrested in his SubG1 phase, confirming the pro-apoptotic effect of the nanoparticles. The results indicate a high antioxidant effect of the nanoparticles with IC50 values ​​of 45 µg/mL and 1500 µg/mL against ABTS and DPPH, respectively. The reduction of catalase gene expression confirmed the pro-oxidant effect of nanoparticles in cancer cells treated at concentrations of 20 and 40 µg/mL. CONCLUSIONS: Therefore, our findings suggest that the MuSCF-NPs are suitable candidates, especially for breast cancer preclinical studies.

Liposomes to Cubosomes: The Evolution of Lipidic Nanocarriers and Their Cutting-Edge Biomedical Applications.

Lipidic nanoparticles have undergone extensive research toward the exploration of their diverse therapeutic applications. Although several liposomal formulations are in the clinic (e.g., DOXIL) for cancer therapy, there are many challenges associated with traditional liposomes. To address these issues, modifications in liposomal structure and further functionalization are desirable, leading to the emergence of solid lipid nanoparticles and the more recent liquid lipid nanoparticles. In this context, "cubosomes", third-generation lipidic nanocarriers, have attracted significant attention due to their numerous advantages, including their porous structure, structural adaptability, high encapsulation efficiency resulting from their extensive internal surface area, enhanced stability, and biocompatibility. Cubosomes offer the potential for both enhanced cellular uptake and controlled release of encapsulated payloads. Beyond cancer therapy, cubosomes have demonstrated effectiveness in wound healing, antibacterial treatments, and various dermatological applications. In this review, the authors provide an overview of the evolution of lipidic nanocarriers, spanning from conventional liposomes to solid lipid nanoparticles, with a special emphasis on the development and application of cubosomes. Additionally, it delves into recent applications and preclinical trials associated with cubosome formulations, which could be of significant interest to readers from backgrounds in nanomedicine and clinicians.

Co-encapsulation of omega-3 and vitamin D3 in beeswax solid lipid nanoparticles to evaluate physicochemical and in vitro release properties.

In recent years, lipophilic bioactive compounds have gained much attention due to their wide range of health-benefiting effects. However, their low solubility and susceptibility to harsh conditions such as high temperatures and oxidation stress have limited their potential application for the development of functional foods and nutraceutical products in the food industry. Nanoencapsulation can help to improve the stability of hydrophobic bioactive compounds and protect these sensitive compounds during food processing conditions, thus overcoming the limitation of their pure use in food products. The objective of this work was to co-entrap vitamin D3 (VD3) and omega 3 (ω3) as hydrophobic bioactive compounds providing significant health benefits in beeswax solid lipid nanoparticles (BW. SLNs) for the first time and to investigate the effect of different concentrations of VD3 (5 and 10 mg/mL) and ω3 (8 and 10 mg) on encapsulation efficiency (EE). Our findings revealed that the highest EE was obtained for VD3 and ω3 at concentrations of 5 mg/mL and 10 mg, respectively. VD3/ω3 loaded BW. SLNs (VD3/ω3-BW. SLNs) were prepared with zeta potential and size of-32 mV and 63.5 nm, respectively. Results obtained by in-vitro release study indicated that VD3 release was lower compared to ω3 in the buffer solution. VD3 and ω3 incorporated in BW. SLNs demonstrated excellent stability under alkaline and acidic conditions. At highly oxidizing conditions, 96.2 and 90.4% of entrapped VD3 and ω3 remained stable in nanoparticles. Moreover, nanoparticles were stable during 1 month of storage, and no aggregation was observed. In conclusion, co-loaded VD3 and ω3 in BW. SLNs have the great potential to be used as bioactive compounds in food fortification and production of functional foods.

Lipid-Based Nanoparticles as Oral Drug Delivery Systems: Overcoming Poor Gastrointestinal Absorption and Enhancing Bioavailability of Peptide and Protein Therapeutics.

Delivery and formulation of oral peptide and protein therapeutics have always been a challenge for the pharmaceutical industry. The oral bioavailability of peptide and protein therapeutics mainly relies on their gastrointestinal solubility and permeability which are affected by their poor membrane penetration, high molecular weight and proteolytic (chemical and enzymatic) degradation resulting in limited delivery and therapeutic efficacy. The present review article highlights the challenges and limitations of oral delivery of peptide and protein therapeutics focusing on the application, potential and importance of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as lipid-based drug delivery systems (LBDDSs) and their advantages and drawbacks. LBDDSs, due to their lipid-based matrix can encapsulate both lipophilic and hydrophilic drugs, and by reducing the first-pass effect and avoiding proteolytic degradation offer improved drug stability, dissolution rate, absorption, bioavailability and controlled drug release. Furthermore, their small size, high surface area and surface modification increase their mucosal adhesion, tissue-targeted distribution, physiological function and half-life. Properties such as simple preparation, high-scale manufacturing, biodegradability, biocompatibility, prolonged half-life, lower toxicity, lower adverse effects, lipid-based structure, higher drug encapsulation rate and various drug release profile compared to other similar carrier systems makes LBDDSs a promising drug delivery system (DDS). Nevertheless, undesired physicochemical features of peptide and protein drug development and discovery such as plasma stability, membrane permeability and circulation half-life remain a serious challenge which should be addressed in future.

A Comprehensive Review on Novel Lipid-Based Nano Drug Delivery.

Novel drug delivery system opens the doors towards nano/micro formulation strategies to overcome the challenges associated with the poorly soluble and permeable drugs. Lipid based nanoparticles are widely accepted that includes liposomes, niosomes and micelles which are FDA approved. Such lipid based drug delivery allows delivery for natural phytoconstituents, biopharmaceutical classification system (BCS) class II and class IV drugs are effectively delivered to improve its solubility, permeability and bioavailability. The article provides the recent advances and application of lipid based dosage form for improvement of therapeutic efficacy.

Enhanced efficacy of ß-carotene loaded solid lipid nanoparticles optimized and developed via central composite design on breast cancer cell lines.

ß-carotene is obtained from both plants and animals and has been the subject of intense research because of its provitamin-A, antioxidant, and anticancer effects. Its limited absorption and oxidative degradation significantly reduce its antitumor efficacy when taken orally. In our study, we utilize a central composite design to develop "bio-safe and highly bio-compatible" solid lipid nanoparticles (SLNs) by using only the combination of palmitic acid and poloxamer-407, a block co-polymer as a surfactant. The current research aim to develop and characterize SLNs loaded with ß-carotene to improve their bioavailability and therapeutic efficacy. In addition, the improved cytotoxicity of solid lipid nanoparticles loaded with ß-carotene was screened in-vitro in human breast cancer cell lines (MCF-7). The nanoparticles exhibits good stability, as indicated by their mean zeta potential of -26.3 ± 1.3 mV. The particles demonstrated high drug loading and entrapment capabilities. The fabricated nanoparticle's prolonged release potential was shown by the in-vitro release kinetics, which showed a first-order release pattern that adhered to the Higuchi model and showed a slow, linear, and steady release over 48 h. Moreover, a diffusion-type release mechanism was used to liberate ß-carotene from the nanoparticles. For six months, the nanoparticles also showed a notable degree of physical stability. Lastly, using the MTT assay, the anti-cancer properties of ß-carotene-loaded solid lipid nanoparticles were compared with intact ß-carotene on MCF-7 cell lines. The cytotoxicity tests have shown that the encapsulation of ß-carotene in the lipid bilayers of the optimized formulation does not interfere with the anti-cancer activity of the drug. When compared to standard ß-carotene, ß-carotene loaded SLNs showed enhanced anticancer efficacy and it is a plausible therapeutic candidate for enhancing the solubility of water-insoluble and degradation-sensitive biotherapeutics like ß-carotene.

Compritol®-based solid lipid nanoparticles of desvenlafaxine prepared by ultrasonication-assisted hot-melt encapsulation to modify its release.

Aims: Desvenlafaxine (DES) in conventional dosage forms shows initial burst release after oral administration, leading to exaggeration of its side effects. These side effects can be overcome by a sustained-release dosage form using the chemically inert, low-melting-point lipid Compritol® 888 ATO, as it reduces initial burst release. Materials & methods: The potential of DES-loaded solid lipid nanoparticles (DES-SLNs) synthesized by ultrasonication-assisted hot-melt encapsulation to modify the release of DES was investigated. Results: The entrapment efficiency of DES-SLNs was 65.90% with the in vitro release profile showing a sustained-release behavior achieving 81% cumulative release within 16 h without initial burst release. Conclusion: DES-SLNs are a potential carrier for sustained release of water-soluble antidepressant drugs such as DES.

Construction of various lipid carriers to study the transdermal penetration mechanism of sinomenine hydrochloride.

OBJECTIVE: To investigate the transdermal mechanisms and compare the differences in transdermal delivery of Sinomenine hydrochloride (SN) between solid lipid nanoparticles (SLN), liposomes (LS), and nanoemulsions (NE). METHODS: SN-SLN, SN-LS and SN-NE were prepared by ultrasound, ethanol injection and spontaneous emulsification, respectively. FTIR, DSC, in vitro skin penetration, activation energy (Ea) analysis were used to explore the mechanism of drug penetration across the skin. RESULTS: The particle size and encapsulation efficiency were 126.60 nm, 43.23 ± 0.48%(w/w) for SN-SLN, 224.90 nm, 78.31 ± 0.75%(w/w) for SN-LS, and 83.22 nm, 89.01 ± 2.16%(w/w) for SN-LS. FTIR and DSC showed the preparations had various levels of impacts on the stratum corneum's lipid structure which was in the order of SLN > NE > LS. Ea values of SN-SLN, SN-LS, and SN-NE crossing the skin were 2.504, 1.161, and 2.510 kcal/mol, respectively. CONCLUSION: SLN had a greater degree of alteration on the skin cuticle, which allows SN to permeate skin more effectively.

Curcumin/TGF-ß1 siRNA loaded solid lipid nanoparticles alleviate cerebral injury after intracerebral hemorrhage by transnasal brain targeting.

Intracerebral hemorrhage (ICH) is a prevalent cerebrovascular disorder. The inflammation induced by cerebral hemorrhage plays a crucial role in the secondary injury of ICH and often accompanied by a poor prognosis, leading to disease exacerbation. However, blood-brain barrier (BBB) limiting the penetration of therapeutic drugs to the brain. In this paper, our primary objective is to develop an innovative, non-invasive, safe, and targeted formulation. This novel approach aims to synergistically harness the combined therapeutic effects of drugs to intervene in inflammation via a non-injectable route, thereby significantly mitigating the secondary damage precipitated by inflammation following ICH. Thus, a novel "anti-inflammatory" cationic solid lipid nanoparticles (SLN) with targeting ability were constructed, which can enhance the stability of curcumin(CUR) and siRNA. We successfully developed SLN loaded with TGF-ß1 siRNA and CUR (siRNA/CUR@SLN) that adhere to the requirements of drug delivery system by transnasal brain targeting. Through the characterization of nanoparticle properties, cytotoxicity assessment, in vitro pharmacological evaluation, and brain-targeting evaluation after nasal administration, siRNA/CUR@SLN exhibited a nearly spherical structure with a particle size of 125.0±1.93 nm, low cytotoxicity, high drug loading capacity, good sustained release function and good stability. In vitro anti-inflammatory results showcasing its remarkable anti-inflammatory activity. Moreover, in vivo pharmacological studies revealed that siRNA/CUR@SLN can be successfully delivered to brain tissue. Furthermore, it also elicited an effective anti-inflammatory response, alleviating brain inflammation. These results indicated that favorable brain-targeting ability and anti-inflammatory effects of siRNA/CUR@SLN in ICH model mice. In conclusion, our designed siRNA/CUR@SLN showed good brain targeting and anti-inflammatory effect ability after nasal administration, which lays the foundation for the treatment of inflammation caused by ICH and offers a novel approach for brain-targeted drug delivery and brings new hope.

Anticancer and Chemosensitizing Effects of Menadione-Containing Peptide-Targeted Solid Lipid Nanoparticles.

Vitamin K derivatives such as menadione (MD) have been recognized as promising redox-modulating and chemosensitizing agents for anticancer therapy, however, their cellular activities in peptide-targeted nanocarriers have not been elucidated to date. This study provides the guidelines for developing MD-loaded solid lipid nanoparticles (SLN) modified with extracellular matrix (ECM)-derived peptides. Relationships between RGD peptide concentration and changes in DLS characteristics as well as accumulation of SLN in cancer cells were revealed to adjust the peptide-lipid ratio. SLN system maintained adequate nanoparticle concentration and low dispersity after introduction of MD and MD/RGD, whereas formulated MD was protected from immediate conjugation with reduced glutathione (GSH). RGD-modified MD-containing SLN showed enhanced prooxidant, GSH-depleting and cytotoxic activities toward PC-3 prostate cancer cells attributed to improved cellular pharmacokinetics of the targeted formulation. Furthermore, this formulation effectively sensitized PC-3 cells and OVCAR-4 ovarian cancer cells to free doxorubicin and cisplatin so that cell growth was inhibited by MD-drug composition at nontoxic concentrations of the ingredients. These results provide an important background for further improving chemotherapeutic methods based on combination of conventional cytostatics with peptide-targeted SLN formulations of MD.

Solid lipid nanoparticles and their application in the treatment of bacterial infectious diseases.

Nano pharmacology is considered an effective, safe, and applicable approach for drug delivery applications. Solid lipid nanoparticle (SLNs) colloids contain biocompatible lipids which are capable of encapsulating and maintaining hydrophilic or hydrophobic drugs in the solid matrix followed by releasing the drug in a sustained manner in the target site. SLNs have more promising potential than other drug delivery systems for various purposes. Nowadays, the SLNs are used as a carrier for antibiotics, chemotherapeutic drugs, nucleic acids, herbal compounds, etc. The SLNs have been widely applied in biomedicine because of their non-toxicity, biocompatibility, and simple production procedures. In this review, the complications related to the optimization, preparation process, routes of transplantation, uptake and delivery system, and release of the loaded drug along with the advantages of SLNs as therapeutic agents were discussed.

Monitoring the Interaction Between Solid Lipid Nanoparticles and Alveolar Macrophages Via the Label-Free Technique.

Macrophages are employed as targets for delivering genes, drugs, or lipid nanoparticles into tumors or other specific sites. Studying the interaction between solid lipid nanoparticles (SLNs) and macrophages is essential for assessing nanotoxicity and advancing the development of nanomedicines. However, limited data are currently available on the membrane microstructure and biochemical changes that occur when macrophages interact with SLNs. We conducted a label-free morphological and biochemical investigation of NR8383 macrophages using optical diffraction tomography (ODT), which validated the efficiency of the SLNs as a drug delivery system. ODT provided intracellular holotomography to characterize the macrophages and fluorescence imaging to analyze delivery efficiency. ODT analysis revealed the responses of phagocytic macrophages. Additionally, a quantitative analysis of lipid droplets using refractive indices revealed that, compared with incubation with normal cells, incubation with SLNs significantly increased the lipid droplet volume and surface area. The uptake of SLNs into macrophages resulted in increased cell volume, surface area, and concentration, which indicated greater morphological and biochemical variability in the treated cells than in the control cells. The results suggest that ODT imaging is promising for understanding the intracellular distribution of SLNs and useful for validating the efficacy of delivery of SLNs to macrophages.

A Design-Conversed Strategy Establishes the Performance Safe Space for Doxorubicin Nanosimilars.

Nanomedicines exhibit multifaceted performances, yet their biopharmaceutics remain poorly understood and present several challenges in the translation from preclinical to clinical research. To address this issue and promote the production of high-quality nanomedicines, a systematic screening of the design space and in vivo performance is necessary. Establishing formulation performance specifications early on enables an informed selection of candidates and promotes the development of nanosimilars. The deconvolution of the pharmacokinetics enables the identification of key characteristics that influence their performances and disposition. Using an in vitro-in vivo rank-order relationship for doxorubicin nanoformulations, we defined in vitro release specifications for Doxil/Caelyx-like follow-on products. Additionally, our model predictions were used to establish the bioequivalence of Lipodox, a nanosimilar of Doxil/Caelyx. Furthermore, a virtual safe space was established, providing crucial insights into expected disposition kinetics and informing formulation development. By addressing bottlenecks in biopharmaceutics and formulation screening, our research advances the translation of nanomedicine from bench to bedside.

Solid Lipid Nanoparticles as an Innovative Lipidic Drug Delivery System.

In order to overcome some of the drawbacks of traditional formulations, increasing emphasis has recently been paid to lipid-based drug delivery systems. Solid lipid nanoparticles (SLNs) are among these delivery methods, and they hold promise because of their simplicity in production, capacity to scale up, biocompatibility, and biodegradability of formulation components. Other benefits could be connected to a particular route of administration or the makeup of the ingredients being placed into these delivery systems. This article aims to review the significance of solid lipid nanocarriers, their benefits and drawbacks, as well as their types, compositions, methods of preparation, mechanisms of drug release, characterization, routes of administration, and applications in a variety of delivery systems with a focus on their efficacy.

Development and optimization of vildagliptin solid lipid nanoparticles loaded ocuserts for controlled ocular delivery: A promising approach towards treating diabetic retinopathy.

Diabetes mellitus (DM) is the most prevalent cause of diabetic retinopathy (DRP). DRP has been recognized for a long time as a microvascular disease. Many drugs were used to treat DRP, including vildagliptin (VLD). In addition to its hypoglycemic effect, VLD minimizes ocular inflammation and improves retinal blood flow for individuals with type 2 diabetes mellitus. Nevertheless, VLD can cause upper respiratory tract infections, diarrhea, nausea, hypoglycemia, and poor tolerability when taken orally regularly due to its high water solubility and permeability. Effective ocular administration of VLD is achieved using solid lipid nanoparticles (SLNPs), which improve corneal absorption, prolonged retention, and extended drug release. Ocuserts (OCUs) are sterile, long-acting ocular dosage forms that diminish the need for frequent dosing while improving residence time and stability. Therefore, this study intends to develop VLD solid lipid nanoparticle OCUs (VLD-SLNPs-OCUs) to circumvent the issues commonly associated with VLD. SLNPs were prepared using the double-emulsion/melt dispersion technique. The optimal formula has been implemented in OCUs. Optimization and development of VLD-SLNPs-OCUs were performed using a Box-Behnken Design (BBD). VLD-SLNPs-OCUs loading efficiency was 95.28 ± 2.87%, and differential scanning calorimetry data (DSC) showed the full transformation of VLD to an amorphous state and the excellent distribution in the prepared OCUs matrices. The in vivo release of VLD from the optimized OCUs after 24 h was 35.12 ± 2.47%, consistent with in vitro drug release data of 36.89 ± 3.11. The optimized OCUs are safe to use in the eye, as shown by the ocular irritation test. VLD-SLNPs-OCUs provide extended VLD release, an advantageous alternative to conventional oral dose forms, resulting in fewer systemic adverse effects and less variation in plasma drug levels. VLD-SLNPs-OCUs might benefit retinal microvascular blood flow beyond blood glucose control and may be considered a promising approach to treating diabetic retinopathy.

Artesunate-loaded solid lipid nanoparticles resist esophageal squamous cell carcinoma by inducing Ferroptosis through inhibiting the AKT/mTOR signaling.

Esophageal squamous cell carcinoma (ESCC) is a severe malignancy with high incidence and mortality rate in China, while the application of standard chemotherapeutic drugs for ESCC meets the barriers of high toxicity and multiple drug resistance (MDR). In recent years, the anticancer effects of artesunate (ART), a Chinese medicine monomer have gained extensive attentions due to its characteristics of low toxicity, high potency, and reversal of MDR. In this study, we develop the artesunate-loaded solid lipid nanoparticles (SLNART) to overcome the poor water solubility and bioavailability of ART, further improving the efficiency of ART on ESCC treatment. Especially mentioned, SLNART is shown to present marked inhibitory effects on ESCC development based on the induction of ferroptosis by two pathways included upregulating TFR to increase Fe2+ ions and inhibiting the AKT/mTOR signaling to downregulate GPX4. Collectively, this study is the first to pave a promising approach for ESCC therapy based on a strategy of developing SLNART to induce ferroptosis by mediating Fe2+ ions and AKT/mTOR signaling.

Development of cationic solid lipid nanoparticles incorporating cholesteryl-9-carboxynonanoate (9CCN) for delivery of antagomiRs to macrophages.

Lipid-based nanoparticles are a useful tool for nucleic acids delivery and have been regarded as a promising approach for diverse diseases. However, off-targets effects are a matter of concern and some strategies to improve selectivity of solid lipid nanoparticles (SLNs) were reported. The goal of this study was to test formulations of SLNs incorporating lipid cholesteryl-9-carboxynonanoate (9CCN) as "eat-me" signal to target antagomiR oligonucleotides to macrophages. We formulate four SLNs, and those with a mean diameter of 200 nm and a Z-potential values between 25 and 40 mV, which allowed the antagomiR binding, were selected for in vitro studies. Cell viability, transfection efficiency and cellular uptake assays were performed within in vitro macrophages using flow cytometry and confocal imaging and the SLNs incorporating 25 mg of 9CCN proved to be the best formulation. Subsequently, we used a labeled antagomiR to study tissue distribution in in-vivo ApoE-/- model of atherosclerosis. Using the ApoE-/- model we demonstrated that SLNs with phagocytic signal 9-CCN target macrophages and release the antagomiR cargo in a selective way.

Evaluation of Drug-Loaded and Surface-Adsorbed DNase/Tween-80 Solid Lipid Nanoparticles against Staphylococcus aureus Biofilms.

The aim of this study was to explore the suitability of Tween-80 or DNase I adsorbed onto the surface of gentamicin-loaded solid lipid nanoparticles (SLNs) to disrupt Staphylococcus aureus biofilms in vitro. We hypothesized that surface-adsorbed DNase I or Tween-80 of SLNs will degrade the biofilm component, extracellular DNA (e-DNA), and extracellular matrix (ECM) of S. aureus biofilms. The SLNs loaded with drug (core) and surface-adsorbed disruptors (Tween-80 or DNase I) to deliver biofilm disruptors first at the site of action, which will help to break down the biofilm, and further drug release from the core will easily penetrate the biofilm and facilitate the killing of bacteria residing in S. aureus biofilms. The SLNs were synthesized by the double emulsion method; the size was 287.3 ± 7.4 nm for blank SLNs and 292.4 ± 2.36 nm for drug-loaded SLNs. The ζ-potential of blank SLNs was -25.6 ± 0.26 mV and that of drug-loaded SLNs was -13.16 ± 0.51 mV, respectively. The successful adsorption of DNase I or Tween-80 was confirmed by the activity of DNase I in blank surface-adsorbed SLNs and the change in the ζ-potential of SLNs after adsorbing DNase I or Tween-80. The surface morphology and size of the SLNs were further characterized using scanning electron microscopy. The encapsulation efficiency of the drug was 16.85 ± 0.84%. The compatibility of the drug with the excipient was confirmed by Fourier transform infrared spectroscopy and the degree of crystallinity was confirmed by X-ray diffraction (XRD) analysis. SLNs showed a sustained release of the drug up to 360 h. SLNs were easily taken up by A549 cells with minimal or no toxicity. The present study showed that Tween-80- or DNase I-adsorbed SLNs efficiently disrupt S. aureus biofilms and possess no or minimal toxicity against cells and red blood cells (RBCs).

Dopamine-loaded chitosan-coated solid lipid nanoparticles as a promise nanocarriers to the CNS.

Dopamine is unable to access the central nervous system through the bloodstream. Only its precursor can do so, and with an effectiveness below 100% of the dose administered, as it is metabolized before crossing the blood-brain barrier. In this study, we describe a new solid lipid nanocarrier system designed and developed for dopamine. The nanoparticles were prepared by the melt-emulsification method and then coated with chitosan. The nanocarriers developed had a droplet size of about 250 nm, a polydispersity index of 0.2, a positive surface charge (+30 mV), and a percentage encapsulation efficiency of 36.3 ± 5.4. Transmission and scanning electron microscopy verified uniformity of particle size with spherical morphology. Various types of tests were performed to confirm that the nanoparticles designed are suitable for carrying dopamine through the blood-brain barrier. In vitro tests demonstrated the ability of these nanocarriers to pass through endothelial cell monolayers without affecting their integrity. This study shows that the formulation of dopamine in chitosan-coated solid lipid nanoparticles is a potentially viable formulation strategy to achieve the bioavailability of the drug for the treatment of Parkinson's disease in the central nervous system.

Fexofenadine-loaded chitosan coated solid lipid nanoparticles (SLNs): A potential oral therapy for ulcerative colitis.

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.08 nm nanometric size, 36.3 ± 3.18 mV zeta potential, 64.9 % EE, and a controlled release profile. FTIR, DSC, and TEM confirmed good drug entrapment and spherical particles. Mucoadhesive properties of FEX-CS-SLNs were investigated through mucin incubation and exhibited considerable mucoadhesion. The protective effect of FEX-pure, FEX-market, and FEX-CS-SLNs against acetic acid-induced ulcerative colitis in rats was examined. Oral administration of FEX-CS-SLNs for 14 days before ulcerative colitis induction reversed UC symptoms and almost restored the intestinal mucosa to normal integrity and inhibited Phosphatidylinositol-3 kinase (73.6 %), protein kinase B (73.28 %), and elevated nuclear factor erythroid 2-related factor 2 (185.9 %) in colonic tissue. Additionally, FEX-CS-SLNs inhibited tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) to (70.79 % & 72.99 %) in colonic tissue. The ameliorative potential of FEX-CS-SLNs outperformed that of FEX-pure and FEX-market. The exceptional protective effect of FEX-CS-SLNs makes it a potentially effective oral system for managing ulcerative colitis.