Pharmaceutical Nanotechnology - Online First

The study employed Response Surface Methodology (RSM) with a Central Composite Rotatable Design (CCRD) model to optimise the formulations of Levomilnacipran nanostructured lipid carriers (LEV-NLC).

This study utilised a CCRD (Central Composite Rotatable Design) with a three-factor factorial design and three levels. It examined the particle size, zeta potential, and entrapment efficiency of LEV-NLC in relation to three independent variables: the ratio of aqueous to organic phase (X1), the ratio of drug to lipid (X2), and the concentration of surfactant (X3).

The results demonstrated that the most favourable composition could be achieved using Response Surface Methodology (RSM). The most effective composition for LEV-NLC consisted of a 1:1 ratio of aqueous to organic phase (X1), a 1:7 ratio of drug to lipid (X2), and a surfactant concentration (X3) of 0.5%. Under the optimised conditions, the LEV-NLC formulation resulted in a particle size of 148 nm, a zeta potential of 36 mV, and an entrapment efficiency of 88%. The optimised LEV-NLC was examined using Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM), which revealed the presence of spherical particles. The total percentage of Levomilnacipran released from the NLC was 77% at pH 7.4 and 76% at pH 6.0 over 24 hours, exhibiting a sustained release profile that could enhance the therapeutic benefits of the drug.

This study demonstrated the effective application of RSM-CCRD for modelling LEV-NLC.

This study aimed to develop and optimize a cilostazol-loaded nanomicelle transdermal patch to enhance solubility, stability, and controlled drug release.

To improve cilostazol bioavailability by formulating a stable, nanomicelle-loaded transdermal patch.

Nanomicelles were prepared using the thin-film hydration method with Soluplus and Poloxamer 188 as the polymer and surfactant. The transdermal patch was fabricated using the solvent casting method and evaluated for tensile strength, folding endurance, and in vitro drug diffusion.

The optimized formulation showed 97.71% entrapment efficiency, 48.86% drug loading, a particle size of 129.07 nm, and a zeta potential of −21.5 mV. The patch exhibited a tensile strength of 141.83 MPa, folding endurance of over 300 folds, and sustained in vitro drug diffusion.

The developed transdermal patch offers a promising strategy to enhance cilostazol bioavailability by bypassing first-pass metabolism, promoting better penetration, and ensuring improved patient compliance.

Intracellular calcium in pancreatic beta cells plays a crucial role in insulin synthesis and secretion. Diabetes impairs this calcium-mediated action, necessitating an effective delivery system such as liposomes to facilitate calcium uptake.

Calcium lactate nanoliposomes (6.25 mg/mL) were prepared via the thin-film hydration method using lecithin and cholesterol as bilayer lipids. Their glucose-lowering efficacy was tested in hyperglycemic mice induced by oral glucose (1 g/kg) and intraperitoneal streptozotocin (45 mg/kg). Pancreatic calcium levels were measured using X-ray fluorescence to verify calcium delivery to beta cells.

The nanoliposomes exhibited a diameter of 172.1 nm, zeta potential of -53.45 mV, polydispersity index of 0.203, and pH 7.2. Entrapment efficiency was 93.42%, with stable pH and particle size over six cycles. Treatment with calcium nanoliposomes significantly reduced blood glucose levels in both diabetic and glucose-loaded mice. Pancreatic calcium concentrations were higher in animals receiving calcium nanoliposomes compared to controls.

Calcium nanoliposomes induced a significant glucose reduction relative to controls (empty liposomes, distilled water, and calcium in distilled water). Encapsulation within liposomal vesicles enhanced calcium delivery to pancreatic beta cells, increasing intracellular calcium and stimulating insulin production and release. This was corroborated by elevated pancreatic calcium levels observed via X-ray fluorescence in treated animals.

Calcium nanoliposomes effectively improve glycemic control in diabetic and glucose-challenged animal models by enhancing calcium delivery to pancreatic beta cells.

To develop medicinal plant nanoparticles as colitis alternative/supplementary therapy.

Limited reports about the effectiveness of medicinal plant nanocrystals in treating or preventing colitis.

We investigated the effect of nanonizing Apium graveolens (AG) on improving dextran sodium sulfate (DSS)- induced colitis.

Nanonization was performed via the bead milling process. The nanocrystal product was characterized (i.e., particle size, zeta potential (ZP), polydispersity index (PDI) values) and freeze-dried. Total flavonoids and phenolic compounds in nanocrystal products were compared with ethanolic extract of AG (AGEE). Anti-colitis activity of AG-nanocrystal water suspensions (AGNS) was compared to AG bulk powder suspensions (AGBS). Colitis severity was determined via physiological, macroscopic, and microscopic colon assessment. In addition, the fecal Enterobacteriaceae population and urine glucose levels were determined.

The AG nanoparticle products are 200-400 nm, with PDI values 0.5-0.6, and ZP values -12 to -20 mV. The total flavonoid and phenolic compounds of AGNS were 115.12±4.32 ppm and 37.11±0.34 ppm, respectively. This value is higher compared to the content in AGEE. AGNS (350 mg/kg) improves physiological (i.e., fecal blood), macroscopic (i.e., length, diameter), and microscopic (i.e., structure and immune cell infiltration) colon conditions in a comparable level to the positive control of 5-aminosalicylic acid (100 mg/kg). AGNS have a compelling ability to restore colon microscopic and Enterobacteriaceae population compared to AGBS (700 mg/kg). AGNS (350 mg/kg) also recovered colon permeability as marked by the lower urine glucose concentration (9.90±0.15 mg/dL) compared to colitis mice (12.43±0.09 mg/dL).

The nanonization of AG contributes to improved anti-colitis activities compared to AGBS. Nanonization of medicinal plants will reduce organic solvent extraction, which supports the sustainable development goals.

Different variables have been used for the preparation of elastic nanovesicles. In this work, the ethanol injection method has been used to prepare flunarizine spanlastic nanovesicles and study the potential of these variables on vesicle size, encapsulation efficiency, and vesicle elasticity.

The objective of this study was to encapsulate flunarizine dihydrochloride (FHC), a medication with low solubility in water, within nano-elastic vesicles made from Span 60. These vesicles, known as nano-spanlastics, were developed to provide non-invasive trans-nasal delivery and offer a potential therapeutic option for migraines. The ideal formula for flunarizine spanlastic nanovesicles should have the lowest possible particle size and PdI, highest possible zeta potential, vesicle elasticity, drug entrapment, and dissolving efficiency.

An experimental design was followed during the preparation of flunarizine-loaded nanospanlastics utilizing the ethanol injection method and a number of edge activators (EAs). To investigate how the independent parameters affected the features of elastic vesicles and choose the best formula, Design-Expert^®, software was used. The screening of 18 formulation and process aspects affecting vesicle size, polydispersity index, deformability index, zeta potential, drug entrapment, and in-vitro release was made easier by the experimental design.

The selected Flunarizine spanlastic nanovesicles exhibited a vesicle size of 135 ± 2.81 nm, PdI 0.2462 ± 0.01, ZP -28 ± 0.92 mV, relative deformability of 13.96 ± 0.76 g, EE% of 78.37 ± 1.42, and dissolution efficiency of about 90%.

The successful preparation of Flunarizine-loaded spanlastic nanovesicles using ethanol injection method significantly improved the drug's solubility. Flunarizine spanlastic formulations made up of Span 60 and EAs (Tween 40 and SDC) were prepared using various weight ratios of Span 60: EA. The study presented a viable and successful method for nasal delivery of the medication for migraine treatment.