Solid Lipid Nanoparticles Formulations Research Articles

Preparation and Optimization of Fexofenadine HCl Solid lipid Nanoparticles

Solid lipid nanoparticles (SLNs) are introduced as an efficient carrier method for correcting dynamic medicine and water-soluble medication. Fexofenadine HCl is a long-acting selective histamine (H1) receptor antagonist with anti-inflammatory properties of the second generation. Allergic rhinitis, angioedema, and chronic urticaria are treated with fexofenadine HCl. Solid lipid nanoparticles were prepared by hot homogenization method using a solid lipid of and different polymers. A solid lipid nanoparticle created by drug and polymer poloxamer 188 in ratio showed highest entrapment efficiency as well as drug release of the medication from the solid lipid nanoparticle formulation. The prepared nanoparticles were used to formulate the nanogel using Carbopol 934. The nano-drug delivery system developed by the hot homogenization method has demonstrated their suitability for a topical route for the treatment of skin allergy. Thus, the studies revealed that the developed system has a great appeal for the convenient treatment of dermatological allergy that may overcome in improving the limitations of the existing drug delivery system. Fexofenadine HCl is a white colored powder. It is practically insoluble in water and soluble in methanol. The melting point was found to be 194.1-195.2. The FTIR spectra of Fexofenadine HCl and the mixture of drug and excipients used in the formulation of nanoparticles reveal that there was no significant interaction between the drug and polymer and other excipients used in the formulation. The optimized batches (F2) showed highest entrapment efficiency. It was observed that as there is increase in concentration of surfactant increases the entrapment efficiency. The optimized solid lipid nanoparticle formulation showed maximum drug release within 6 hr. This showed that the increase in the concentration of surfactant there was increase in drug release from the SLN.

Design and Optimization of Solid Lipid Nanoparticles Loaded with Triamcinolone Acetonide.

Principles of quality by design and design of experiments are acquiring more importance in the discovery and application of new drug carriers, such as solid lipid nanoparticles. In this work, an optimized synthesis of solid lipid nanoparticles loaded with Triamcinolone Acetonide is presented using an approach that involves Stearic Acid as a lipid, soy PC as an ionic surfactant, and Tween 80 as a nonionic surfactant. The constructed circumscribed Central Composite Design considers the lipid and nonionic surfactant quantities and the sonication amplitude in order to optimize particle size and Zeta potential, both measured by means of Dynamic Light Scattering, while the separation of unentrapped drug from the optimized Triamcinolone Acetonide-loaded solid lipid nanoparticles formulation is performed by Size Exclusion Chromatography and, subsequently, the encapsulation efficiency is determined by HPLC-DAD. The proposed optimized formulation-with the goal of maximizing Zeta potential and minimizing particle size-has shown good accordance with predicted values of Zeta potential and dimensions, as well as a high value of encapsulated Triamcinolone Acetonide. Experimental values obtained from the optimized synthesis reports a dimension of 683 ± 5 nm, which differs by 3% from the predicted value, and a Zeta potential of -38.0 ± 7.6 mV (12% difference from the predicted value).

Formulation and evaluation of solid lipid nanoparticles loaded with papaya seed chloroform extract for long-term antifertility effects on the male rat, Bandicota bengalensis

The study is the first to formulate and investigate potential of papaya seed chloroform extract based solid lipid nanoparticles (PSCEN) as antifertility agents on male Bandicota bengalensis. The prepared nanoparticles were spherical of size 300–600 nm. The release kinetics showed a controlled release of the drug with major release over 48 h. To assess the antifertility effects of PSCEN, adult male rats were fed a diet containing two different concentrations of PSCEN (5% and 10%) for 15 days under bi-choice conditions. The mean total active ingredient ingestion of the rats in the two treated groups ranged from 2.13–3.31 and 3.92–5.87 g/100g body weight, respectively. No adverse effects of treatment on body weight were observed. Also, no mortality of rats was observed. The treatment had a significant effect on the weight of the testis and the epididymis, but not on the other organs. Sperm motility (%), sperm viability (%), sperm count (millions/ml), sperm mitochondrial activity (%), sperm nuclear chromatin de-condensation (%) and sperm hypo-osmotic swelling (%) were significantly decreased, and sperm abnormality (%) significantly increased compared to the vehicle control group. The reproductive success rates of male rats treated with 5% and 10% PSCEN and mated with untreated female rats were 20.00–66.67% and 16.67%, respectively, while in untreated female rats mated with male rats of vehicle control group, reproductive success rate was 33.33 to 80%. The study found a maximal antifertility effect of the 10% PSCEN containing bait, which was irreversible up to 105 days after stopping treatment, suggesting long-term efficacy.

Ocular Delivery of Bimatoprost-Loaded Solid Lipid Nanoparticles for Effective Management of Glaucoma.

Glaucoma is a progressive optic neuropathy characterized by a rise in the intraocular pressure (IOP) leading to optic nerve damage. Bimatoprost is a prostaglandin analogue used to reduce the elevated IOP in patients with glaucoma. The currently available dosage forms for Bimatoprost suffer from relatively low ocular bioavailability. The objective of this study was to fabricate and optimize solid lipid nanoparticles (SLNs) containing Bimatoprost for ocular administration for the management of glaucoma. Bimatoprost-loaded SLNs were fabricated by solvent evaporation/ultrasonication technique. Glyceryl Monostearate (GMS) was adopted as solid lipid and poloxamer 407 as surfactant. Optimization of SLNs was conducted by central composite design. The optimized formulation was assessed for average particle size, entrapment efficiency (%), zeta potential, surface morphology, drug release study, sterility test, isotonicity test, Hen's egg test-chorioallantoic membrane (HET-CAM) test and histopathology studies. The optimized Bimatoprost-loaded SLNs formulation had an average size of 183.3 ± 13.3 nm, zeta potential of -9.96 ± 1.2 mV, and encapsulation efficiency percentage of 71.8 ± 1.1%. Transmission electron microscopy (TEM) study revealed the nearly smooth surface of formulated particles with a nano-scale size range. In addition, SLNs significantly sustained Bimatoprost release for up to 12 h, compared to free drug (p < 005). Most importantly, HET-CAM test nullified the irritancy of the formulation was verified its tolerability upon ocular use, as manifested by a significant reduction in mean irritation score, compared to positive control (1% sodium dodecyl sulfate; p < 0.001). Histopathology study inferred the absence of any signs of cornea tissue damage upon treatment with Bimatoprost optimized formulation. Collectively, it was concluded that SLNs might represent a viable vehicle for enhancing the corneal permeation and ocular bioavailability of Bimatoprost for the management of glaucoma.

Formulation and Characterization of Solid Lipid Nanoparticles for Topical Delivery of Antibacterial Drug

Formulation and Characterization of Solid Lipid Nanoparticles for Topical Delivery of Antibacterial Drug

Enhanced Cytotoxic Activity of 6-Mercaptopurine-Loaded Solid Lipid Nanoparticles in Hepatic Cancer Treatment.

6-Mercaptopurine (6-MCP) is an antiproliferative purine analog used in acute lymphoblastic leukemia, non-Hodgkin lymphoma, and inflammatory bowel disease (Crohn's disease, ulcerative colitis). Although 6-MCP has the great therapeutic potential for cancer and immunosuppressant-related diseases, 6-MCP is not readily soluble in water, presents a high first-pass effect, short half-life (0.5-1.5 h), and implies a low bioavailability (16%). On the contrary, solid lipid nanoparticles (SLNs) are prepared from solid lipids at room temperature and body temperature. In this study, SLNs were prepared w/o/w double emulsion-solvent evaporation method using Precirol ATO5 as matrix lipid. In the emulsion stabilization, surfactant (Tween 80) and polymeric stabilizer (polyvinyl alcohol [PVA]) were used. Two group formulations using Tween 80 and PVA were compared in terms of particle size, polydispersity index, zeta potential encapsulation efficiency%, and process yield%. Differential calorimetric analysis and release properties were examined for optimum formulation, and release kinetics were calculated. According to studies, sustained release was obtained with SLNs by the Korsmayer-Peppas kinetic model. The in vitro cytotoxicity studies were performed on the hepatocarcinoma (HEP3G) cell line. According to the results, successful SLN formulations were produced, and PVA was found best stabilizer. Optimum formulation exhibited significantly higher cytotoxic effects on HEP3G than on pure 6-MCP. These results demonstrated that solid lipid nanodrug delivery systems have great potential for formulation of 6-MCP.

SLN Mediate Active Delivery of Gefitinib into A549 Cell Line: Optimization, Biosafety and Cytotoxicity Studies

Background: Conventional administration of chemotherapeutic agents associated with low drug distribution to cancer cells with multiple systemic toxicities. Thus, enhancing the active delivery of chemotherapeutic agents to cancer cells increases drug distribution and internalization to targeted cells with minimal systemic toxicities. Objective and Aim: The current study was designed to prepare and optimize solid lipid nanoparti-cles (SLN) containing stearic acid (SA) that mediate active delivery and uptake of gefitinib (GEF) to cancer cells. Methods: The stability of the prepared Plain-SLN formulations was characterized for 90 days. The most stable formulations were loaded with GEF (GEF-SLN) and subjected to pharmaceutical char-acterization. In-vitro dissolution of GEF-SLN formulations was studied using the dialysis method. Biosafety in the terms of hemocompatibility was investigated using fresh blood samples. Addition-ally, the cytotoxicity of GEF-SLN was examined against the lung cancer cell line (A549). Results: The obtained results showed that the prepared formulations fall in the nanosize range from 114 to 411 nm with a negative zeta-potential value from -17 to -27 mV. The particle size of Plain-SLN formulations was increased when the GEF is incorporated during preparation. Besides, the crystallinity of SA was disordered following the incorporation of GEF. In addition, GEF entrapment efficiency into SLN was 88% with a sustained-release profile of about 75% in 24 h. Additionally, the present results revealed that using surfactants with high drug solubility negatively impacts the stability of SLN formulation. Furthermore, hemocompatibility results revealed that all SLN formu-lations showed insignificant hemolysis (1- 4%) at all concentrations. Moreover, cytotoxicity exami-nations revealed that SLN enhanced the antiprofilated activity of GEF compared to free GEF. Conclusion: These data concluded that SLN is a hopeful approach to enhancing the selective depo-sition of GEF into cancer cells and reducing the lymphatic metastasis of lung cancer.

SOLID LIPID NANOPARTICLES OF GABAPENTIN FOR PARTIAL SEIZURES

The goal of this research was to create a stable formulation of gabapentin solid lipid nanoparticles which would allow it to pass across the blood-brain barrier more easily. They were prepared by solvent evaporation method. In the present investigation, beeswax and carnauba wax were used as solid lipids, egg lecithin was used as a surfactant and Tween 80 was used as a co-surfactant. Nine formulations were formulated using different concentrations of solid lipid and surfactant. The prepared formulations were evaluated for various tests. The results shown that F6 formulation, containing higher concentration of egg lecithin, was a better formulation as percentage drug content was 97.57±0.62%, entrapment efficiency was 95.95±0.07% and in vitro release of gabapentin was 97.18±1.02% at the end of 12 h. After in vivo testing, it was observed that animals treated with gabapentin loaded solid lipid nanoparticles had seizures that appeared later than animals treated with traditional gabapentin formulations. Hence it was concluded that solid lipid nanoparticles is a promising drug delivery system to achieve increased permeability through blood brain barrier.

A proof-of-concept study of coupled supercritical CO2-assisted processes to produce solid self-assembled drug delivery systems (S-SADDS)

The development of innovative drug delivery systems is currently under intense consideration to overcome bioavailability issues of poorly water-soluble drugs. Among the many existing delivery systems, self-assembled drug delivery systems (SADDS) are of great interest. Solid Lipid Nanoparticles (SLN), which are part of SADDS, have been widely studied in the pharmaceutical field since they are biodegradables and biocompatibles. However, stability of SLN suspension over time is limited and quick drug released were frequently observed. The development of solid SADDS (S- SADDS), to produce an on-demand delivery system, through a one-step production process has been designed to overcome these issues. The coupling of both Supercritical Carbon Dioxide (scCO2) assisted RESS and SAS processes (RESS/SAS) have been proposed as a proof-of-concept. This study was carried out in three steps: (i) the development and adjustment of operating conditions to produce SLN suspension using solvent injection process, (ii) the optimization of the formulation to produce SLN with a mean particle size diameter close to 100 nm and stable at least 24 h, (iii) the transposition of the SLN formulation composition into the RESS/SAS coupled process for the production of S-SADDS. SLN composed of stearic acid, PVP K30, phosphatidylcholine and nifedipine, with an average size under 100 nm and a zeta potential about −35 mV were obtained from the preliminary study. These results allowed the transposition of the optimal formulation into RESS/SAS crystallization process. The developed RESS/SAS scCO2-assisted processes demonstrate the simultaneous crystallization of a self-assembled formulation in a one step process. A control of operating conditions was also demonstrated through the generation of S- SADDS containing desired amount of nifedipine. The proof-of-concept process studied, seems to be very promising tool for the generation of complex solids, intermediate products or for the development of innovative drug delivery systems.

Targeted Solid Lipid Nanoparticles Formulation for Colon Cancer Treatment and Cytotoxicity Assessment Using HT29 Cell Line

Background: Several pharmacological effects have been attributed to thymol. However, limitations such as low solubility in water, low bioavailability, and high volatility have limited its use. Objectives: The present study aimed to prepare and characterize thymol-loaded solid lipid nanoparticles (SLNs) to improve the efficacy of thymol. Methods: Thymol-loaded SLNs were characterized by atomic force microscopy (AFM), differential scanning calorimetry (DSC), and Fourier transformed infrared spectroscopy (FT-IR). Cytotoxicity study and hemolysis assay were also performed. Results: The in vitro drug release showed a sustained manner. Also, SLNs loaded with thymol showed higher cytotoxicity than free thymol, and the hemolysis results indicated the blood biocompatibility of SLNs. Conclusions: As nanocarriers, SLNs can open a new avenue for improving the efficacy of thymol in cancer treatment.

Preparation of Thymol Nanoliposome and Solid Lipid Nanoparticle and Evaluation of their Inhibitory Effects on Leishmania Major Promastigotes

Introduction: Thymol has an antiprotozoal effect. Nanoparticulate systems are useful carriers for both small and large drug molecules, which can protect them from some chemical and biological damages as well as target drug delivery to specific organs or receptors. In this work, the nano-liposomal system and solid lipid nanoparticles loaded by thymol were prepared and the effectiveness of them were evaluated on Leishmania major promastigotes.&#x0D; Methods: Several formulations of nano-liposomes and solid lipid nanoparticles were prepared, and the amount of thymol loading, in-vitro release profile, particle size, and zeta potential were evaluated. Finally, the best formulations were serially diluted and incubated for 24, 48, and 72 hours on Leishmania major promastigotes, which cultured on Novy–MacNeal–Nicolle medium, and the results were analyzed.&#x0D; Results: The highest loading of thymol in nano-liposomes (92%) was seen in the formulations made with phosphatidylcholine (Called L3), and among the solid lipid nanoparticles, the formulation prepared with glycerol monostearate (S1) had the most entrapment efficiency of thymol (87%). These formulations were selected to evaluate the release rate of thymol. The results showed that S1 has a slower release rate than L3; this may be due to the presence of Glycerol monostearate in solid lipid nanoparticles structure. The best formulations, L3 and S1, were chosen for anti-Leishmaniosis assessment; which showed that all three forms of free thymol, nanoliposomes, and solid lipid nanoparticles inhibited Leishmania major. The half maximal inhibitory concentration (IC50) of free thymol, nanoliposome, and solid lipid nanoparticles for a 24-hour incubation are 7.8, 62.5, and 125, respectively, which decrease to 7.8, 7.8, and 15.6 for 48 hours and 7.8, 0.49, and 0 for 72 hours of incubation.&#x0D; Conclusion: Thymol has a significant effect on the inhibition of Leishmania major promastigotes and usage of thymol in the form of liposomes or solid lipid nanoparticles can sustain the drug release and have a lower IC50 during the longer incubation time.

Evaluation of solid-lipid nanoparticles formulation of methotrexate for anti-psoriatic activity

Background & ObjectivesMethotrexate (MTX) is commonly used to manage psoriasis. The drug has erratic absorption characteristics and shows several complications. The present study uses different experimental models to evaluate the solid-lipid nanoparticles of MTX (SLN-MTX) for the anti-psoriatic effect. MethodsA prepared SLN-MTX formulation was used and its permeability studies were conducted on Wistar rat abdominal skin. The organ-level distribution of the drug in the formulation was tested in mice and the in-vitroanti-psoriatic activity was determined in CL-177; XB-2 keratinocytes cell lines. The efficacy of SLN-MTX formulation was compared with standard MTX and marketed MTX preparations. The results are analyzed statistically using the student’s t-test. ResultsThe data suggested that MTX from the formulation was slowly released and completely (80.36%) permeated through the skin. The flux and permeation data were found to be maximum for SLN-MTX compared to marketed and standard preparations. MTX in the formulation was found to be distributed more in the liver (67.5%) and kidney (2.34%). Further, SLN-MTXformulation showed dose-dependent inhibition on the growth of keratinocytes, and the cytotoxic concentration (CTC50) was found to be the least (518 mcg/ml). Interpretation & ConclusionThe findings suggested that MTX in solid-lipid nanoparticles could be a promising formulation for the management of psoriasis since the drug was slowly released, progressively inhibited the growth of keratinocytes, and distributed mostly in organs meant for elimination. More studies in this direction might establish the precise safety and efficacy of SLN-MTX formulation in psoriasis.

Loteprednol-Loaded Nanoformulations for Corneal Delivery by Quality-by-Design Concepts: Optimization, Characterization, and Anti-inflammatory Activity.

Loteprednol etabonate (LE) is a topical corticosteroid that uses inflammatory conditions of the eye. It has a low ocular bioavailability and side effects such as corneal disorder, eye discharge, and ocular discomfort. Therefore, it was decided to select the delivery systems, which are solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE). Design of experiments (DoE) of SLN, NLC, and NE formulations were formulated by using the quality by design (QbD) approach. Precirol® ATO 5 and oleic acid were used as solid and liquid lipids, respectively, in SLN, NLC, and NE formulations. Physiochemical characterization was performed on the formulations. The optimized formulations' inflammatory effects have been appraised on human corneal epithelial cells employing the ELISA test. Physicochemical characterization studies and inflammatory effects were appraised. The sizes of optimized formulations of SLN, NLC, and NE were 86.19nm, 82.38nm, and 126.35nm, respectively, with minimum polydispersity. The release behavior of the formulations is composed of both diffusion and erosion. ELISA test results proved that the formulations significantly reduced IL-1 and IL-6 levels (p < 0.05). D-optimal mixture experimental design allowed us to develop the most precise formulations of SLN, NLC, and NE. Furthermore, the optimized formulations could be promising candidates for treating an inflammation-based corneal disease of the eye.

Fabrication of Transdermal Gel Embedded with Solid Lipid Nanoparticles of Indomethacin

Rheumatoid/osteoarthritis is one of the most common causes for lacking behind in the health sector. Medication in the form of tablets are already available in the market but has disadvantages. When these medicines are taken orally it cause heartburn and discomfort. The introduction of transdermal drug delivery is expected to solve this problem of side eff ects associated with oral delivery of drug. In the present study, indomethacin was loaded in solid lipid nanoparticles (SLN) which are then embedded in Carbopol gel for transdermal application. The solvent evaporation ultrasonication method was used for making SLNs. The formulation was evaluated for various parameters such as ; particle size and zeta potential of SLN using zetasizer as an instrument and gel formulations were evaluated for pH, spreading coeffi cient, viscosity, visual appearance and clarity. Gel-embedded SLN formulation was found to be a potential transdermal drug delivery system for NSAIDs like indomethacin to treat ailments like rheumatoid arthritis or osteoarthritis.

An In Vitro Evaluation of the Potential Neuroprotective Effects of Intranasal Lipid Nanoparticles Containing Astaxanthin Obtained from Different Sources: Comparative Studies.

The intranasal route has been suggested as a promising alternative to improve the direct transport of molecules to the brain, avoiding the need to cross the blood-brain barrier (BBB). In this area, the use of lipid nanoparticles, namely solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has been highlighted as a promising strategy to improve the treatment of neurodegenerative diseases. In this work, formulations containing SLN and NLC that were loaded with astaxanthin that was obtained from different sources (astaxanthin extract (AE) from the algae Haematococcus pluvialis and pure astaxanthin (PA) from the fungi Blakeslea trispora) were prepared for nose-to-brain administration, and comparative in vitro experiments were performed to evaluate the biocompatibility of the formulations with nasal (RPMI 2650) and neuronal (SH-SY5Y) cells. Afterwards, the antioxidant activity of the formulations was evaluated for its potential neuroprotective effects, using different chemical aggressors. Finally, the cellular uptake of the astaxanthin was evaluated for the formulations that showed the greatest neuroprotection of the neuronal cells against chemical-induced damage. On the production day, all the formulations showed a particle size, a high encapsulation efficiency (EE), the presence of nanoparticles with a typical spherical shape, and a polydispersity index (PDI) and zeta potential (ZP) that are suitable for nose-to-brain administration. After three months of storage at room temperature, no significant changes were observed in the characterization parameters, predicting a good long-term stability. Furthermore, these formulations were shown to be safe with concentrations of up to 100 µg/mL in differentiated SH-SY5Y and RPMI 2650 cells. Regarding neuroprotection studies, the PA-loaded SLN and NLC formulations showed an ability to counteract some mechanisms of neurodegeneration, including oxidative stress. Moreover, when compared with the PA-loaded SLN, the PA-loaded NLC showed greater neuroprotective effects against the cytotoxicity induced by aggressors. In contrast, the AE-loaded SLN and NLC formulations showed no significant neuroprotective effects. Although further studies are needed to confirm these neuroprotective effects, the results of this study suggest that the intranasal administration of PA-loaded NLC may be a promising alternative to improve the treatment of neurodegenerative diseases.

Solid Lipid Nanoparticles: Review of the Current Research on Encapsulation and Delivery Systems for Active and Antioxidant Compounds

Various active compounds are easily damaged, so they need protection and must be easily absorbed and targeted. This problem can be overcome by encapsulating in the form of solid lipid nanoparticles (SLNs). Initially, SLNs were widely used to encapsulate hydrophobic (non-polar) active compounds because of their matched affinity and interactions. Currently, SLNs are being widely used for the encapsulation of hydrophilic (polar) and semipolar active compounds, but there are challenges, including increasing their entrapment efficiency. This review provides information on current research on SLNs for encapsulation and delivery systems for active and antioxidant compounds, which includes various synthesis methods and applications of SLNs in various fields of utilization. SLNs can be developed starting from the selection of solid lipid matrices, emulsifiers/surfactants, types of active compounds or antioxidants, synthesis methods, and their applications or utilization. The type of lipid used determines crystal formation, control of active compound release, and encapsulation efficiency. Various methods can be used in the SLN fabrication of active compounds and hydrophilic/hydrophobic antioxidants, which have advantages and disadvantages. Fabrication design, which includes the selection of lipid matrices, surfactants, and fabrication methods, determines the characteristics of SLNs. High-shear homogenization combined with ultrasonication is the recommended method and has been widely used because of the ease of preparation and good results. Appropriate fabrication design can produce SLNs with stable active compounds and antioxidants that become suitable encapsulation systems for various applications or uses.

Fabrication of solid lipid nanoparticles-based patches of paroxetine and their ex-vivo permeation behaviour

Paroxetine is not suitable for oral administration due to its extensive first-pass metabolism, thus resulting in less bioavailability. This study aimed to prepare novel paroxetine-loaded solid lipid nanoparticles (SLNs) based sustained-release transdermal patches to overcome these problems by enhancing drug absorption and bioavailability. Nine formulations of paroxetine SLNs were prepared by the hot melt-homogenization method using different concentrations of glycerol monostearate (Kolliwax) and Tween 80. Then these prepared SLNs were incorporated in a matrix type transdermal patch having a matrix of ethyl cellulose and polyvinyl pyrrolidone in 3:2 with polyvinyl alcohol. The SLNs showed a particle size range of 113–230 nm and an entrapment efficiency of 85.14%. The SLNs showed sustained paroxetine release (77.86–95.63% release) up to 48 h. FTIR studies showed no interaction between drug and formulation components. Paroxetine is evenly distributed in an amorphous form in SLNs, as demonstrated by DSC as well as PXRD analysis. SLNs formulated patches showed higher drug permeation through the skin than drug-based transdermal patches., Draize patch test revealed no sign of erythema after applying paroxetine-loaded SLN patches (score 0) as observed with the marketed product. The developed SLNs based transdermal patches showed increased permeability and sustained release behaviour.

Brain-targeted delivery of Valsartan using solid lipid nanoparticles labeled with Rhodamine B; a promising technique for mitigating the negative effects of stroke

The brain is a vital organ that is protected from the general circulation and is distinguished by the presence of a relatively impermeable blood brain barrier (BBB). Blood brain barrier prevents the entry of foreign molecules. The current research aims to transport valsartan (Val) across BBB utilizing solid lipid nanoparticles (SLNs) approach to mitigate the adverse effects of stroke. Using a 32-factorial design, we could investigate and optimize the effect of several variables in order to improve brain permeability of valsartan in a target-specific and sustained-release manner, which led to alleviation of ischemia-induced brain damage. The impact of each of the following independent variables was investigated: lipid concentration (% w/v), surfactant concentration (% w/v), and homogenization speed (RPM) on particle size, zeta potential (ZP), entrapment efficiency (EE) %, and cumulative drug release percentage (CDR) %. TEM images revealed a spherical form of the optimized nanoparticles, with particle size (215.76 ± 7.63 nm), PDI (0.311 ± 0.02), ZP (-15.26 ± 0.58 mV), EE (59.45 ± 0.88%), and CDR (87.59 ± 1.67%) for 72 hours. SLNs formulations showed sustained drug release, which could effectively reduce the dose frequency and improve patient compliance. DSC and X-ray emphasize that Val was encapsulated in the amorphous form. The in-vivo results revealed that the optimized formula successfully delivered Val to the brain through intranasal rout as compared to a pure Val solution and evidenced by the photon imaging and florescence intensity quantification. In a conclusion, the optimized SLN formula (F9) could be a promising therapy for delivering Val to brain, alleviating the negative consequences associated with stroke.

Formulation and Evaluation of Mucoadhesive Buccal tablets using Nimodipine Solid Lipid Nanoparticles

This study aimed to create and describe mucoadhesive nimodipine solid lipid nanoparticles as buccal tablets by altering the amounts of three polymers: Carbopol 934, Hydroxypropyl methylcellulose and Hydroxyethyl cellulose. The Nimodipine-loaded solid lipid nanoparticles (SLN) were formulated by high shear homogenization and ultrasonication process using palmitic and stearic acid as the lipid matrix and Tween-80 as the surfactant. The swelling properties of all formulations were investigated, and it was discovered that all formulations have a good swelling index at 6 hours. The surface pH of each batch varied between 5.6 and 6.1. The mucoadhesive strengths (15.3-29.5 g) varied with polymer concentrations, particularly Carbopol 934. All batches had considerably different dissolution profiles, ranging from a maximum release of 89.08% (at 8h in batch NT3) to a minimum release of 80.32% (at 8h in batch NT2). SLN formulations had the best results in both Entrapment efficiency and In-vitro drug release, showing that SLN may be a promising delivery strategy for improving Nimodipine release.

Preparation and characterization of the myricetin-loaded solid lipid nanoparticles decorated with folic acid-bound chitosan and evaluation of its antitumor and anti-angiogenic activities in vitro and in vivo in mice bearing tumor models

Myricetin is a flavonoid with anticancer properties. This study aimed to formulate myricetin in the form of solid lipid nanoparticles (SLN), decorated with chitosan (CS) and active-targeted with folic acid (FA). After characterization, the in vitro release, cytotoxicity, antioxidant, and ability of the formulation to induce apoptosis using flow cytometry, fluorescent microscopy, and real-time qPCR were examined. Then in vivo anti-angiogenesis on chick chorioallantoic membrane (CAM) and antitumor activities on mice bearing tumor models were investigated. The present study showed that the size of 310 nm and zeta potential of + 30 mV were acceptable for oral administration. The Michaelis–Menten model fitted the drug release pattern with lag during 144 h of the study. The cytotoxicity assay showed that myricetin-SLN-CS-FA significantly killed cancer cells at the concentrations of 6.25, 12.5, 25, 50 and 100 µg/mL (*p < 0.05, **p < 0.01, and ***p < 0.001). The highest level of apoptosis was shown at the concentration of 45 µg/ml in flow cytometry, and fluorescent studies. These results showed the anticancer properties of myricetin-SLN-CS-FA in a dose-dependent manner. The real-time results also indicated that the formulation exerted its cytotoxic effect by activating apoptosis genes. The DPPH, ABTS, and FRAP studies also demonstrated the significant antioxidant properties of the myricetin-SLN-CS-FA (*p < 0.05, **p < 0.01, and ***p < 0.001). The anti-angiogenic activities of the formulations depicted in the CAM assay significantly decrease the number and length of the vessels (*p < 0.05, **p < 0.01, and ***p < 0.001), and also affect VEGF and VEGFR, genes involved in angiogenesis (**p < 0.01, and ***p < 0.001). The antitumor studies indicated the statistically significant effects of myricetin-SLN-CS-FA on reducing tumor volume (*p < 0.05 and ***p < 0.001). The H&E staining of the liver and monitoring of the animal weights also indicated the safety of the formulation. The analysis of mRNA expression in liver and tumor demonstrated that myricetin-SLN-CS-FA exerts its antitumor activities by modulating the inflammatory and oxidative responses in the tissues.