Self-assembled Gallic acid loaded lecithin-chitosan hybrid nanostructured gel as a potential tool against imiquimod-induced psoriasis.

Increased thickness of the skin and hyperproliferation of keratinocyte cell is the main obstacle in the treatment of psoriasis. Gallic Acid (GA) has shown efficacious results against the hyperproliferation of keratinocytes while lipid-polymer loaded hybrid nanoparticles (LPHNs) have an edge over lipidic and polymeric nanoparticles considering drug loading, controlled release, stability, and retention. The LPHNs were optimized using Box-Behnken method and was further characterized by FTIR, DSC and Zetasizer. The optimized preparation demonstrated a size of 170.5 ± 0.087 nm and a PDI of 0.19 ± 0.0015, respectively. The confocal study has suggested that the hybrid nanosystem enhanced the drug penetration into the deeper layer with a higher drug release of 79 ± 0.001% as compared to the gallic acid-loaded gel. In addition, the formulation significantly reduced PASI score and splenomegaly without causing any serious irritation. The morphological study of the spleen suggested that the prepared formulation has well controlled the disease compared to the marketed formulation while maintaining a normal level of immune cells after treatment. Hence GALPHN could be accepted as one of the excellent vehicles for the topical conveyance of GA (gallic acid) due to enhanced penetration, and good retention, along with fewer side effects and higher efficacy of the GALPHN gel against imiquimod (IMQ) induced psoriasis.

In vitro evaluation of nebulized eucalyptol nano-emulsion formulation as a potential COVID-19 treatment.

Coronavirus is a type of acute atypical respiratory disease representing the leading cause of death worldwide. Eucalyptol (EUC) known also as 1,8-cineole is a potential inhibitor candidate for COVID-19 (main protease-Mpro) with effective antiviral properties but undergoes physico-chemical instability and poor water solubility. Nano-emulsion (NE) is a promising drug delivery system to improve the stability and efficacy of drugs. This work focuses on studying the anti- COVID-19 activity of EUC by developing nebulized eucalyptol nano-emulsion (EUC-NE) as a potentially effective treatment for COVID-19. The EUC -NE formulation was prepared using Tween 80 as a surfactant. In vitro evaluation of the EUC-NE formulation displayed an entrapment efficiency of 77.49 %, a droplet size of 122.37 nm, and an EUC % release of 84.7 %. The aerodynamic characterization and cytotoxicity of EUC-NE formulation were assessed, and results showed high lung deposition and low inhibitory concentration. The antiviral mechanism of the EUC-NE formulation was performed, and it was found that it exerts its action by virucidal, viral replication, and viral adsorption. Our results confirmed the antiviral activity of the EUC-NE formulation against COVID-19 and the efficacy of nano-emulsion as a delivery system, which can improve the cytotoxicity and inhibitory activity of EUC.

Assessment and characteristics of Erenumab therapy on migraine management.

Background: Migraine is one of the neurological diseases that have a negative impact on subjects' productivity and daily activity of patients. Introducing monoclonal antibodies as a valuable option for resolving the persistent problem of migraine is still under investigation. The current study aimed to evaluate the efficacy and safety profile related to Erenumab. Methods: A prospective study for clinical data collection and analysis from recruited therapy-refractory migraine subjects were carried through 6 months for each subject. All subjects received Erenumab 70 mg monthly. Each patient provided the clinical data monthly starting from 0 months and for the next 6 months. Migraine disability assessment (MIDAS) questionnaire was used for evaluation of the Erenumab efficacy every 3 months. In addition, data regarding adverse effects, migraine triggers, and the impact of previous COVID-19 on migraine severity were collected and analyzed. Results: Ninety subjects were recruited in the study. Erenumab injections resulted in a significant (p < 0.001) reduction in MIDAS score in the 3rd month compared with baseline, also this significance was continuous in the 6th month. In contrast, there was no significant difference in the 6th month compared with the 3rd. Previously infected COVID-19 subjects showed a higher severity of migraine attacks compared with non-infected subjects. Skin redness and local pain were the most common adverse effects 63.3%, 47.77% respectively associated with Erenumab. Conclusion: Using Erenumab therapy showed a great beneficial impact regarding the reduction of migraine-related disabilities. COVID-19 was related to the increased severity of migraine attacks.

Design and Characterization of Atorvastatin Dry Powder Formulation as a potential Lung Cancer Treatment.

Lung cancer is the leading cause of cancer death. Many studies have shown the beneficial effects of Atorvastatin in decreasing the mortality risk and improving survival among patients with lung cancer. This research paper focuses on improving AVT cytotoxic activity and cellular uptake by developing mannitol microcarriers as a promising drug delivery system for lung cancer treatment and, studying the impact of improving inhalation deposition on the delivery and Dry Powder formulations efficiency. The AVT loaded mannitol (AM) microparticles (AVT-AM) formulation was prepared by spray drying and characterized for its physicochemical properties and aerodynamic deposition. The results revealed that the AVT-AM formulation has good flow properties and aerosol deposition with a particle size of 3418 nm ± 26.86. The formulation was also assessed in vitro for cytotoxicity effects (proliferation, apoptosis, and cell cycle progression) on A549 human lung adenocarcinoma. Compared with free AVT, the AVT-AM formulation has significantly higher cellular uptake and anti-cancer properties by disrupting cell cycle progression via either apoptosis or cell cycle arrest in the G2/M phase. This study shows that AVT loaded mannitol microcarriers may provide a potentially effective and sustained pulmonary drug delivery for lung cancer treatment.

The potential of Atorvastatin for chronic lung diseases therapy.

Atorvastatin (ATO) is of the statin class and is used as an orally administered lipid-lowering drug. ATO is a reversible synthetic competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase thus leading to a reduction in cholesterol synthesis. It has recently been demonstrated that ATO has different pharmacological actions, which are unrelated to its lipid-lowering effects and has the ability to treat chronic airway diseases. This paper reviews the potential of ATO as an anti-inflammatory, antioxidant, and anti-proliferative agent after oral or inhaled administration. This paper discusses the advantages and disadvantages of using ATO under conditions associated with those found in the airways. This treatment could potentially be used to support the formulating of ATO as an inhaler for the treatment of chronic respiratory diseases.

Biological Effects of Simvastatin Formulated as pMDI on Pulmonary Epithelial Cells.

PURPOSE: The aim of this study is to evaluate the biological effects of Calu-3 epithelial cells in response to the delivery of simvastatin (SV) via solution pressurized metered dose inhaler (pMDI). METHODS: SV pMDI was aerosolised onto Calu-3 air-interface epithelial cells using a modified glass twin stage impinger. The transport of SV across Calu-3 cells, mucus production, inflammatory cytokines production i.e., interleukin (IL) 6, 8 and tumour necrosis factor alpha (TNF- α) and oxidative stress from Calu-3 cells following treatment with SV pMDI was investigated and compared to untreated cells. RESULTS: It was found that SV had the ability to penetrate into the respiratory epithelium and convert into its active SV hydroxy acid (SVA) metabolite. Furthermore, the amount of mucus produced was significantly reduced when SV was deposited on Calu-3 compared to untreated cells. Additionally, SV delivered by pMDI reduces production of IL-6, 8 and TNF-α from Calu-3 following stimulation with lipopolysaccharide (LPS). SV also showed equivalent antioxidant property to vitamin E. CONCLUSIONS: Treatment with SV solution pMDI formulation on Calu-3 cells reduces mucus production, inflammatory cytokines and oxidative stress. This formulation could potentially be used clinically as muco-inhibitory and anti-inflammatory therapy for treatment of chronic lung diseases.

Novel simvastatin inhalation formulation and characterisation.

Simvastatin (SV), a drug of the statin class currently used orally as an anti-cholesterolemic via the inhibition of the 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMG-CoA) reductase, has been found not only to reduce cholesterol but also to have several other pharmacological actions that might be beneficial in airway inflammatory diseases. Currently, there is no inhalable formulation that could deliver SV to the lungs. In this study, a pressurised metered-dose inhaler (pMDI) solution formulation of SV was manufactured, with ethanol as a co-solvent, and its aerosol performance and physico-chemical properties investigated. A pMDI solution formulation containing SV and 6% w/w ethanol was prepared. This formulation was assessed visually and quantitatively for SV solubility. Furthermore, the aerosol performance (using Andersen Cascade impactor at 28.3 L/min) and active ingredient chemical stability up to 6 months at different storage temperatures, 4 and 25°C, were also evaluated. The physico-chemical properties of the SV solution pMDI were also characterised by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and laser diffraction. The aerosol particles, determined using scanning electron microscopy (SEM), presented a smooth surface morphology and were spherical in shape. The aerosol produced had a fine particle fraction of 30.77 ± 2.44% and a particle size distribution suitable for inhalation drug delivery. Furthermore, the short-term chemical stability showed the formulation to be stable at 4°C for up to 6 months, whilst at 25°C, the formulation was stable up to 3 months. In this study, a respirable and stable SV solution pMDI formulation for inhalation has been presented that could potentially be used clinically as an anti-inflammatory therapy for the treatment of several lung diseases.

Evaluation of the effects of a dasatinib-containing, self-emulsifying, drug delivery system on HT29 and SW420 human colorectal carcinoma cells, and MCF7 human breast adenocarcinoma cells.

Background/Aim: Dasatinib (DS), a second-generation tyrosine kinase inhibitor, functions as a multi-target small-molecule drug via targeting various tyrosine kinases involved in neoplastic cell growth. DS inhibits cancer cell replication and migration, and induces tumor cell apoptosis in a variety of solid tumors. However, it is poorly soluble in water under some pH values. Therefore, the development of a DS-containing, self-emulsifying, drug delivery system (SeDDs) could help overcome these problems in treating cancer cells. Methods: Various SeDD formulations loaded with DS were developed with isopropyl myristate (oil phase), Labrafil (surfactant), and polyethylene glycol (co-surfactant). The physicochemical properties of the formulations were assessed according to droplet size, encapsulation efficiency, and in vitro drug release. The cytotoxicity of the formulations on the cancer cell lines HT29 and SW420 (human colorectal carcinoma), and MCF7 (human breast adenocarcinoma), in addition to MRC5 normal human fetal lung fibroblasts, was evaluated to assess selectivity. Results: The DS-SeDD formulation showed favorable particle size, encapsulation efficiency, and in vitro drug release. The anti-cancer potency of DS-SeDDs had greater cytotoxicity effects than pure DA on the three cancer cell lines, MCF7, HT29, and SW420l. Conclusion: The developed DS-SeDD formulations may potentially be an effective sustained drug delivery method for cancer therapy.

Evaluating dasatinib nanocarrier: Physicochemical properties and cytotoxicity activity on cancer cells.

Objective: Dasatinib-(DAS) is a tyrosine kinase inhibitor usually used to treat leukemia. However, DAS is a poorly water-soluble drug. Therefore, oil-in-water emulsions were used for DAS to enhance its solubility and cancer treatment efficacy. This study aims to develop an appropriate DAS nanoemulsion (NE) that can overcome the issue of DAS solubility and provide an effective anticancer effect. Methods: Spherical particles dispersed in an aqueous media approach within an oily phase (oleic acid, Kolliphor RH40, and dipropylene glycol) were used to formulate DAS-NE using high-energy methods. Different formulas were developed and an appropriate formula was analyzed to identify its physicochemical properties. Raw DAS and nonformula cytotoxicity were evaluated through MTT assay against three cancer cell lines, MCF7 (human breast adenocarcinoma), HT29, and SW480 (human colorectal carcinomas), in addition to MRC5 (Normal human fetal lung fibroblast). Results: Different DAS-NEs (1-7) have been developed successfully. Formulas had a droplet size of a diameter ranging from 84.167 ± 10.178 nm to 273.433 ± 45.267 nm. The drug content of the appropriate formula (DAS-NE3) was found to be 83.2%. The drug release result of DAS-NE3 when compared to raw DAS was about 58%, falling to 13% after 24 h. The DAS-NE3 showed cytotoxicity against the three cancer cells below 26.11 µM but showed 30-fold significantly increased selectivity against MRC5 normal cells compared to that of raw DAS. Conclusion: This study shows that the DAS-NE3 formula may provide a potentially effective and sustained drug delivery for cancer treatment. This provides valuable information to the scientific community and the pharmaceutical industry.

Brain Targeting of Venlafaxine via Intranasal Transbilosomes Thermogel for Improved Management of Depressive Disorder.

The current research aimed to design and optimize hyaluronic acid-coated transbilosomes containing venlafaxine (VLF-HA-TBLs) for nose-to-brain delivery for improved management of depressive disorder. Venlafaxine-loaded transbilosomes (VLF-TBLs) were developed according to the film hydration procedure, optimized for maximum efficiency using the quality by design-based Box-Behnken design (BBD), and then coated with hyaluronic acid (HA). The optimized VLF-HA-TBLs were subjected to in vitro characterization, integrated into a thermolabile gel, and then exposed to in vivo evaluation studies. The results revealed that the VLF-HA-TBLs formulation exhibited acceptable size (185.6 ± 4.9 nm), surface charge (-39.8 ± 1.7 mV), and entrapment efficiency (69.6 ± 2.6 %). The morphological study revealed that nanovesicles were spherical and displayed a consistent size distribution without particle aggregation. It also showed improved ex vivo nasal diffusion and a prolonged release profile. In addition, the formulated VLF-HA-TBLs were stable under the studied conditions and tolerable when applied intranasally. Compared to the intranasal administration of VLF solution (VLF-SOL), the biodistribution analysis showed that VLF-HA-TBLs delivered intranasally had a relative bioavailability of 441 % in the brain and 288 % in plasma. Moreover, the intranasal delivery of VLF-HA-TBLs demonstrated much higher bioavailability (512 %) in the brain compared to VLF-SOL administered intravenously. Collectively, it could be possible to infer that HA-TBLs might be an effective nanocarrier to administer VLF to the brain via the nasal route.

Functional candesartan loaded lipid nanoparticles for the control of diabetes-associated stroke: In vitro and in vivo studies.

Diabetes mellitus is a metabolic disease that raises the odds of developing stroke. Candesartan has been used to prevent stroke due to its inhibitory effects on blood pressure, angiogenesis, oxidative damage, and apoptosis. However, oral candesartan has very limited bioavailability and efficacy due to its weak solubility and slow release. The study aimed to develop a nasal formulation of candesartan-loaded liposomes containing ethanol and propylene glycol (CLEP) to improve candesartan's delivery, release, permeation, and efficacy as a potential diabetes-associated stroke treatment. Using design expert software, different CLEP formulations were prepared and evaluated in vitro to identify the optimum formulation, which. The selected optimum formulation composed of 3.3% phospholipid, 10% ethanol, and 15% propylene glycol significantly increased the release and permeation of candesartan relative to free candesartan by a factor of 1.52 and 1.47, respectively. The optimum formulation significantly reduced the infarction after stroke in rats; decreased flexion, spontaneous motor activity, and time spent in the target quadrant by 70%, 64.71%, and 92.31%, respectively, and enhanced grip strength by a ratio of 2.3. Therefore, nasal administration of the CLEP formulation could be a potential diabetes-associated stroke treatment.

In vitro bio-characterization of solid lipid nanoparticles of favipiravir in A549 human lung epithelial cancer cells.

Objectives: Lung cancer is a leading cause of mortality worldwide. In lung cancer treatment, nebulized solid lipid nanoparticles may be a viable drug delivery method, helping the drug reach sites of action, and improving its inhalation efficiency and pulmonary deposition. This research focused on evaluating the effectiveness of solid lipid nanoparticles of favipiravir (Fav-SLNps) in facilitating drug delivery to sites of action in lung cancer treatment. Methods: The hot-evaporation method was used to formulate Fav-SLNps. The in vitro cell viability, anti-cancer effects, and cellular uptake activity were evaluated in A549 human lung adenocarcinoma cells treated with the Fav-SLNp formulation. Results: The Fav-SLNps were formulated successfully. Importantly, Fav-SLNps at a concentration of 322.6 µg/ml were found to be safe and non-toxic toward A549 cells in vitro. The formulation had potential anti-proliferative properties via increasing the proportions of cells in G2/M and G0/G1 phases to 1.20 and 1.13 times those in untreated cells. Additionally, Fav-SLNp treatment significantly induced necrosis in A549 cells. Furthermore, the use of SLNps in the Fav formulation resulted in a macrophage drug uptake 1.23 times that of the free drug. Conclusion: Our results confirmed the internalization and anti-cancer activity of the Fav-SLNp formulation in the A549 lung cancer cell line. Our findings suggest that Fav-SLNps could potentially be used as lung cancer treatment to facilitate drug delivery to sites of action in the lungs.

Quetiapine Albumin Nanoparticles as an Efficacious Platform for Brain Deposition and Potentially Improved Antipsychotic Activity.

Quetiapine (QP) is a second-generation short-acting antipsychotic drug extensively metabolized in the liver, producing pharmacologically inactive metabolites and leading to diminished bioavailability. Therefore, this study aimed to develop an intravenous QP albumin nanoparticles (NPs) system for improving QP antipsychotic activity and brain targeting. QP-loaded albumin NPs were prepared by the desolvation method. The fabricated NPs were characterized in terms of particle size, zeta potential, entrapment efficiency (EE%), and in vitro drug release. In vivo pharmacokinetics and biodistribution in rats were studied. In addition, the antipsychotic activity of the optimized platform was also investigated. Human serum albumin (HSA) concentration, pH, and stirring time were modulated to optimize QP albumin NPs with a particle size of 103.54 ± 2.36 nm and a QP EE% of 96.32 ± 3.98%. In addition, the intravenous administration of QP albumin NPs facilitated QP brain targeting with a 4.9-fold increase in targeting efficiency compared to the oral QP solution. The QP albumin NPs improved the QP antipsychotic activity, indicated by suppressing rats' hypermobility and reducing the QP's extrapyramidal side effects. The obtained results proposed that intravenous QP- NPs could improve QP brain targeting and its antipsychotic efficiency.

Evaluation of Brain Targeting and Antipsychotic Activity of Nasally Administrated Ziprasidone Lipid-Polymer Hybrid Nanocarriers.

The feasibility of using lipid-polymer hybrid (LPH) nanocarriers as a potential platform for the intranasal delivery of ziprasidone (ZP), a second-generation antipsychotic, was explored. Different ZP-loaded LPH composed of a PLGA core and cholesterol-lecithin lipid coat were prepared using a single step nano-precipitation self-assembly technique. Modulation of polymer, lipid and drug amounts, as well as stirring-speed-optimized LPH with a particle size of 97.56 ± 4.55 nm and a ZP entrapment efficiency (EE%) of 97.98 ± 1.22%. The brain deposition and pharmacokinetics studies proved the efficiency of LPH to traverse the blood-brain barrier (BBB) following intranasal delivery with a 3.9-fold increase in targeting efficiency compared to the intravenous (IV) ZP solution with a direct nose-to-brain transport percentage (DTP) of 74.68%. The ZP-LPH showed enhanced antipsychotic activity in terms of animals' hypermobility over an IV drug solution in schizophrenic rats. The obtained results showed that the fabricated LPH was able to improve ZP brain uptake and proved its antipsychotic efficiency.

Novel nasal niosomes loaded with lacosamide and coated with chitosan: A possible pathway to target the brain to control partial-onset seizures.

This work aimed to develop and produce lacosamide-loaded niosomes coated with chitosan (LCA-CTS-NSM) using a thin-film hydration method and the Box-Behnken design. The effect of three independent factors (Span 60 amount, chitosan concentration, and cholesterol amount) on vesicle size, entrapment efficiency, zeta potential, and cumulative release (8 h) was studied. The optimal formulation of LCA-CTS-NSM was chosen from the design space and assessed for morphology, in vitro release, nasal diffusion, stability, tolerability, and in vivo biodistribution for brain targeting after intranasal delivery. The vesicle size, entrapment, surface charge, and in vitro release of the optimal formula were found to be 194.3 nm, 58.3%, +35.6 mV, and 81.3%, respectively. Besides, it exhibits sustained release behavior, enhanced nasal diffusion, and improved physical stability. Histopathological testing revealed no evidence of toxicity or structural damage to the nasal mucosa. It demonstrated significantly more brain distribution than the drug solution. Overall, the data is encouraging since it points to the potential for non-invasive intranasal administration of LCA as an alternative to oral or parenteral routes.

Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke.

Ischemic stroke is the second-leading cause of death. Hyperglycemia, which is characteristic of diabetes mellitus, contributes to the development of endothelial dysfunction and increases the risk of stroke. Isoxsuprine is an efficient beta-adrenergic agonist that improves blood flow to the ischemic aria and stops the infarct core from growing. However, low bioavailability, a short biological half-life, and first-pass hepatic metabolism reduce the therapeutic efficacy of oral isoxsuprine. Therefore, the authors focused on developing isoxsuprine-loaded liposomes containing ethanol and propylene glycol (ILEP) formulation as nasal drops for the treatment of ischemic stroke in diabetic patients. Different ILEP formulations were optimized using Design Expert software, and the selected formulation was examined in vivo for its anti-stroke effect using a rat model of diabetes and stroke. The optimized ILEP, composed of 15% propylene glycol, 0.16% cholesterol, 10% ethanol, and 3.29% phospholipid, improved the sustainability, permeation, and targeting of isoxsuprine. Furthermore, the in vivo studies verified the improved neurological behavior and decreased dead shrunken neurons and vascular congestion of the rats treated with the optimized ILEP formulation, demonstrating its anti-stroke activity. In conclusion, our study found that treatment with an optimized ILEP formulation prevented the initiation and severity of stroke, especially in diabetic patients.

Inhaled Atorvastatin Nanoparticles for Lung Cancer.

OBJECTIVE: Lung cancer is one of the main causes of mortality globally. This research paper aims a the development of inhaled nanotechnology for lung cancer to deliver an atorvastatin calcium compound, for lung cancer, capable of reaching the tumor site directly via inhalation. METHODS: Atorvastatin calcium micellar nanoparticles (ATO-NPs) encapsulated with Pluronic F-127 and polyvinyl alcohol (PVA) were manufactured utilizing the solvent and anti-solvent precipitation technique. The physicochemical features of the formulation were evaluated in terms of their physicochemical characteristics using Fourier transform infrared spectroscopy, differential scanning calorimetry, and dynamic light scattering. Additionally, the Andersen Cascade impactor was used at 15 L/minutes to assist in the aerosols performances of the formulation. The ATO-NPs formula's cell viability was tested in vitro using the A549 non-small cell lung cancer cell type. RESULTS: Transmission electron microscopy was utilized to determine the ATO-NPs particle morphology, demonstrating a spherical shape with a smooth surface. The fine particle fraction of the aerosol produced was 62.70 ± 1.18%. This finding suggests that atorvastatin micellar nanoparticles are suitable for medication administration by inhalation with a wide particle size dispersion. Moreover, it was found in vitro that concentrations of up to 21 µg/mL of the atorvastatin nanoparticles were safe and non-toxic in the cell model. CONCLUSION: This study found that atorvastatin micellar nanoparticles for inhalation could potentially be used for lung cancer treatment.

Enhancing the Bioavailability and Efficacy of Vismodegib for the Control of Skin Cancer: In Vitro and In Vivo Studies.

Skin cancer is the most frequent cancer throughout the world. Vismodegib (VSD) is a hedgehog blocker approved for the prevention and treatment of skin cancer. VSD, however, is poorly bioavailable and has been linked to side effects. This work focused on designing a nano-invasome gel as a vehicle for enhancing the permeation, bioavailability, and efficacy of VSD. Additionally, the combined effect of terpenes and ethanol was studied on the permeation of VSD compared with liposomes. The prepared VSD-loaded invasomes (VLI) formulation included cineole (1%v/v), cholesterol (0.15%w/w), phospholipid (2%w/w), and ethanol (3%v/v) and displayed an entrapment efficiency of 87.73 ± 3.82%, a vesicle size of 188.27 ± 3.25 nm, and a steady-state flux of 9.83 ± 0.11 µg/cm2/h. The VLI formulation was vigorously stirred into a carbopol base before being characterized in vivo to investigate the permeation, bioavailability, and efficacy of VSD. The VLI gel enhanced the dermal permeation of VSD and, as a result, had 3.59 times higher bioavailability with excellent antitumor action as compared to oral VSD. In summary, as an alternative to oral administration for skin cancer treatment, invasomes are efficient carriers for delivering VSD and enhancing its transdermal flux into deep skin layers.

In Vitro and In Vivo Evaluation of the Effectiveness and Safety of Amygdalin as a Cancer Therapy.

Cancer is one of the most important causes of death worldwide. Several studies have shown the efficacy of apricot kernel seed as a cancer therapy due to the presence of amygdalin. These studies have demonstrated amygdalin's cytotoxicity, antioxidant activity, and apoptosis in vitro using human cancer cell lines. However, no studies have demonstrated their cancer activity in vivo. The aim of this study is to develop an amygdalin-loaded niosomes (ALN) gel formulation as a drug delivery system in order to investigate the selectivity, efficacy, and toxicity of amygdalin as a cancer therapy in vivo using the 7,12-dimethylbenz (a) anthracene (DMBA) carcinoma rat model. Based on pre-formulation studies, the ALN formulation composed of Tween 60: cholesterol: dihexadecyl phosphate in a molar ratio of 1:2:0.1 was chosen as an optimum formulation because it has a percent of EE of 66.52% with a particle size of 269.3 nm and a reflux of 3.54 µg.cm-2.h-1. The ALN gel formulation was integrated into carbopol gel to be evaluated in vivo. Compared to DMBA control, treatment with ALN gel showed a reduction in the carcinoma volume and in the hyperplasia of the epidermis with no signs of edema. In conclusion, the ALN gel formulation could be an efficient cancer therapy.

Physicochemical Characteristics and In Vitro Toxicity/Anti-SARS-CoV-2 Activity of Favipiravir Solid Lipid Nanoparticles (SLNs).

The rise of coronavirus (COVID-19) cases worldwide has driven the need to discover and develop novel therapeutics with superior efficacy to treat this disease. This study aims to develop an innovative aerosolized nano-formulation of favipiravir (FPV) as an anti-viral agent against coronavirus infection. The local delivery of FPV nanoparticles (NPs) via nebulization ensures that the drug can reach the site of infection, the lungs. Solid lipid NPs of favipiravir (FPV-SLNs) were formulated utilizing the hot-evaporation method. The physicochemical formulation properties were evaluated using dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The aerosol formulation performance was evaluated using an Andersen Cascade Impactor (ACI) at a flow rate of 15 L/min. The FPV-SLN formulation's in vitro anti-viral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was also evaluated using the SARS-CoV-2 pathogen (hCoV-19/Egypt/NRC-3/2020 isolate). The FPV-SLNs' morphology was defined utilizing transmission electron microscopy, showing an irregular shape. By means of FPV-SLNs' nebulization, a fine particle fraction of 60.2 ± 1.7% was produced with 60.2 ± 1.7%, and this finding suggests that FPV-SLNs were appropriate for inhalation drug delivery with a particle size of 537.6 ± 55.72 nm. Importantly, the FPV-SLNs showed anti-viral activity against SARS-CoV-2 with CC50 and IC50 values of 449.6 and 29.9 µg/mL, respectively. This study suggests that inhaled solid lipid NPs of favipiravir could potentially be used against coronavirus.