Pharmacological treatment of central nervous system (CNS) disorders is difficult, because the blood–brain barrier (BBB) restricts the penetration of many drugs into the brain. To solve this unmet therapeutic need, nanosized drug carriers are the focus of research efforts to develop drug delivery systems for the CNS. For the successful delivery of nanoparticles (NPs) to the brain, targeting ligands on their surface is necessary. Our research aim was to design a nanoscale drug delivery system for a more efficient transfer of donepezil, an anticholinergic drug in the therapy of Alzheimer’s disease across the BBB. Rhodamine B-labeled solid lipid nanoparticles with donepezil cargo were prepared and targeted with apolipoprotein E (ApoE), a ligand of BBB receptors. Nanoparticles were characterized by measurement of size, polydispersity index, zeta potential, thermal analysis, Fourier-transform infrared spectroscopy, in vitro release, and stability. Cytotoxicity of nanoparticles were investigated by metabolic assay and impedance-based cell analysis. ApoE-targeting increased the uptake of lipid nanoparticles in cultured brain endothelial cells and neurons. Furthermore, the permeability of ApoE-targeted nanoparticles across a co-culture model of the BBB was also elevated. Our data indicate that ApoE, which binds BBB receptors, can potentially be exploited for successful CNS targeting of solid lipid nanoparticles.

In this study, ciprofloxacin hydrochloride (CIP)-loaded poly-ε-caprolactone (PCL) nanoparticles were prepared for pulmonary administration. CIP-loaded PCL nanoparticles were prepared using solid-in-oil-in-water (s/o/w) emulsion solvent evaporation method, and the effects of various formulation parameters on the physicochemical properties of the nanoparticles were investigated. PCL nanoparticles showed spherical shapes with particle sizes around 143–489 nm. Encapsulation efficiency was found to be very low because of water-solubility properties of CIP. However, the surface modification of nanoparticles with chitosan caused an increase in the encapsulation efficiency of nanoparticles. At drug release study, CIP-loaded PCL nanoparticles showed initial burst effect for 4 h and then continuously released for 72 h. Nanocomposite microparticles containing CIP-loaded PCL nanoparticles were prepared freeze-drying method and mannitol was used as carrier material. Tapped density and MMADt results show that nanocomposite microparticles have suitable aerodynamic properties for pulmonary administration. Antimicrobial efficacy investigations showed that CIP-encapsulated PCL nanoparticles and nanocomposite microparticles inhibited the growth of bacteria. Also, when the antimicrobial activity of the nanoparticles at the beginning and at the sixth month was examined, it was found that the structure of the particulate system was still preserved. These results indicated that nanocomposite microparticles containing CIP-loaded PCL nanoparticles can be used for pulmonary delivery.

Donepezil-HCl is a member of the acetylcholinesterase inhibitors that is indicated for the symptomatic treatment of Alzheimer’s disease (AD) and has many side effects. In this study, to reduce the side effects of Donepezil-HCl and increase the penetration of the drug through the blood-brain barrier, we aimed to design a solid lipid nanoparticle (SLN) formulation. The effects of the different formulation parameters, such as homogenization speed, sonication time, lipid and drug concentration, surfactant type and concentration, and volume of the aqueous phase, were assessed for optimization. The particle size and PDI increased with increasing lipid concentration but decreased with increasing amounts of surfactant (Tween 80) and co-surfactant (lecithin). When the homogenization rate and sonication time increased, the particle size decreased and the encapsulation efficiency increased. The optimized formulation exhibited particle size, PDI, encapsulation efficiency, and zeta potential of 87.2±0.11 nm; 0.22±0.02; 93.84±0.01 %; -17.0±0.12 mV respectively. The in vitro release investigation revealed that approximately 70% of Donepezil-HCl was cumulatively released after 24 hours. TEM analysis proved that spherical and smooth particles were obtained and formulations had no toxic effect on cells. The final optimized formulation could be a candidate for Donepezil-HCl application in Alzheimer’s treatment with reduced side effects and doses for patients.

Inflammation is a natural response of the organism, involving events responsible for releasing chemical mediators and requiring treatments of symptoms such as pain, redness, heat, swelling, and loss of tissue function. Piroxicam (PRX) is a non-steroidal anti-inflammatory drug with the effect of nonselective COX inhibitor activity; however, it shows poor bioavailability caused by the poor and slow water solubility. In this study, we developed PRX nanosuspensions with 200-500 nm in diameter to increase the bioavailability of PRX by improving its solubility. PRX nanosuspensions were fabricated by High pressure homogenization method with PVA, SDS and Tween 80. The nanosuspensions were characterized by XRD, FTIR, DSC, and in vitro release. In vivo pharmacokinetic properties and anti-inflammatory effects were also investigated in rabbits. PRX nanosuspensions significantly increased the solubility (14.89 ± 0.03 mg/L for pure PRX and 16.75 ± 0.05 mg/L for PRX nanosuspensions) and dissolution rate as compared to the pure PRX (p < 0.05). Orally administered PRX nanosuspension (AUC 0-t is 49.26 ± 4.29 μg/mL × h) significantly improved the bioavailability of PRX (AUC 0-t is 28.40 ± 12.11 μg/mL × h). The anti-inflammatory effect of PRX nanosuspension was also investigated in rabbits and it was observed that PRX nanosuspension treatment significantly improved the inhibition of COX-2 and NFκB expression as compared to the PRX treatment (p < 0.05). The results in this study indicate that PRX nanosuspension is a promising nanomedicine for enhancing the anti-inflammatory activity of PRX and has a high potential for the treatment of inflammation.

Breast cancer remains the most frequently diagnosed cancer worldwide and the second leading cause of cancer-related mortality among women. Drug resistance and significant adverse effects limit anticancer drugs efficacy despite their availability. Oxaliplatin (OXA), a platinum-based chemotherapeutic agent, has shown potential in metastatic breast cancer, however its toxicity limit its use. Melatonin (MEL) demonstrates anticancer activity and improves chemotherapy efficacy, but its therapeutic use is limited by poor stability and short half-life. Nanocarriers, particularly lipid-polymer-hybrid nanoparticles (LPNs), offer an innovative approach to improve drug delivery, enhance bioavailability, and limited systemic toxicity. OXA and MEL co-encapsulated LPNs were prepared. Design of Experiments (DoE)-based optimization was employed using the Box-Behnken design (BBD) to systematically evaluate critical formulation parameters. Particle size, polydispersity index, zeta potential, encapsulation efficiency, release, FTIR, DSC and stability studies were carried out. The effects of OXA-MEL-loaded-LPNs were assessed on human breast cancer cell line (MCF-7). Optimized LPNs exhibited a particle size of ∼240 nm, PDI of 0.17, zeta potential of -30 mV, and encapsulation efficiencies of 99.1% for MEL and 96.1% for OXA. In vitro release studies showed sustained release, with ∼26% OXA and ∼18% MEL released over 8hours. FTIR and DSC analysis showed all substances were loaded into particles. Stability data indicate that particle size remains within the acceptable range for up to one week. Lyophilization resulted in a slight increase in particle size and PDI. Co-loaded LPNs exhibited significant cellular cytotoxicity. The findings suggest that LPNs offer a promising platform for combination therapy, potentially improving treatment outcomes in breast cancer.

Objectives: Limited intracellular exposure can reduce the in vitro activity of pazopanib (PAZ) and enzalutamide (ENZ). This study developed bovine serum albumin (BSA) particles co-encapsulating PAZ and ENZ (PE-BSA) and evaluated physicochemical properties, release kinetics, 4T1 cellular uptake, and in vitro cytotoxicity versus free drugs and single-drug particles. Methods: Drug-loaded BSA particles were prepared using a crosslinking-based method. Particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) were determined. In vitro release was assessed over 48 h and fitted to kinetic models. 4T1 uptake was quantified after 2 and 4 h by intracellular drug levels. Cytotoxicity was measured by MTT at 24 and 72 h (1–100 µg/mL). Moreover, cell death analyses were conducted. Stability studies at +4 °C and serum were also carried out. Results: PE-BSA was nanoscale and monodisperse (PS 128.7 ± 2.6 nm; PDI 0.026 ± 0.01) with ZP −31.65 ± 1.13 mV and high EE (PAZ 98.59 ± 1.78%; ENZ 69.79 ± 0.02%). At 24/48 h, cumulative release from PE-BSA was 11.96/12.31% for PAZ and 52.26/85.95% for ENZ. The release kinetics were best described by the Korsmeyer–Peppas model for PAZ (r² = 0.9578) and the Higuchi model for ENZ (r² = 0.9605), indicating diffusion-controlled release. PE-BSA increased 4T1 uptake versus free drugs (2 h: 10.02% PAZ and 21.9% ENZ; 1.77-fold and 4.15-fold), with sustained enhancement at 4 h (2.2- and 4.69-fold, respectively). After 24 h, PE-BSA induced a markedly higher apoptotic response in 4T1 cells (32.5% early apoptosis and 0.8% late apoptosis/early necrosis) compared with free-PAZ (6.6% early apoptosis) and P-BSA (7.3% early apoptosis). Particles were stable. Conclusions: PE-BSA produced BSA particles with diffusion-governed release and enhanced 4T1 internalization, supporting albumin particles as a delivery platform to increase intracellular exposure of PAZ/ENZ in vitro.