This study aimed to develop a chemically stable niosomal eye drop containing fosinopril (FOS) for lowering intraocular pressure. The effects of cyclodextrin (CD), surfactant types and membrane stabilizer/charged inducers on physiochemical and chemical properties of niosome were evaluated. The pH value, average particle size, size distribution and zeta potentials were within the acceptable range. All niosomal formulations were shown to be slightly hypertonic with low viscosity. Span^® 60/dicetyl phosphate niosomes in the presence and absence of γCD were selected as the optimum formulations according to their high %entrapment efficiency and negative zeta potential values as well as controlled release profile. According to ex vivo permeation study, the obtained lowest flux and apparent permeability coefficient values confirmed that FOS/γCD complex was encapsulated within the inner aqueous core of niosome and could be able to protect FOS from its hydrolytic degradation. The in vitro cytotoxicity revealed that niosome entrapped FOS or FOS/γCD formulations were moderate irritation to the eyes. Furthermore, FOS-loaded niosomal preparations exhibited good physical and chemical stabilities especially of those in the presence of γCD, for at least three months under the storage condition of 2–8 °C.

Celecoxib (CCB), a cyclooxygenase-2 inhibitor, is capable of reducing oxidative stress and vascular endothelial growth factor (VEGF) expression in retinal cells and has been shown to be effective in the treatment of diabetic retinopathy and age-related macular degeneration. However, the ocular bioavailability of CCB is hampered due to its very low aqueous solubility. In a previous study, we developed 0.5% (w/v) aqueous CCB eye drop microsuspensions (MS) containing randomly methylated β-cyclodextrin (RMβCD) or γ-cyclodextrin (γCD) and hyaluronic acid (HA) as ternary CCB/CD/HA nanoaggregates. Both formulations exhibited good physicochemical properties. Therefore, we further investigated their cytotoxicity and efficacy in a human retina cell line in this study. At a CCB concentration of 1000 μg/mL, both CCB/RMβCD and CCB/γCD eye drop MS showed low hemolysis activity (11.1 ± 0.3% or 4.9 ± 0.2%, respectively). They revealed no signs of causing irritation and were nontoxic to retinal pigment epithelial cells. Moreover, the CCB eye drop MS exhibited significant anti-VEGF activity by reducing VEGF mRNA and protein levels compared to CCB suspended in phosphate buffer saline. The ex vivo transscleral diffusion demonstrated that a high quantity of CCB (112.47 ± 37.27 μg/mL) from CCB/γCD eye drop MS was deposited in the porcine sclera. Our new findings suggest that CCB/CD eye drop MS could be safely delivered to the ocular tissues and demonstrate promising eye drop formulations for retinal disease treatment.

Pediatric drug development faces significant challenges due to age-specific physiological differences, with limited approved formulations often resulting in off-label or extemporaneous uses. Oral administration remains the most common route in children, with ideal formulations requiring dosing flexibility and palatability. Cyclodextrins (CDs) have emerged as effective excipients for pediatric applications due to their ability to enhance aqueous solubility, improve chemical stability, and mask unpleasant tastes. Despite their extensive use in adult formulations, their application in pediatric formulations remains limited. Pharmacokinetic studies in juvenile animals reveal age-dependent renal clearance of CDs, with neonates demonstrating delayed elimination. Clinical findings indicate that hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin are generally well tolerated in pediatric populations; however, neonatal use requires caution due to potential accumulation related to immature renal function. Despite limited regulatory approval, CD-based systems have effectively improved pediatric formulations. Advances in pediatric-friendly dosage forms, such as orodisperable tablets, mucoadhesive films, and 3D-printed mini-tablets, have further highlighted the versatility of CDs. Nonetheless, comprehensive safety data and defined regulatory guidelines are essential for broader clinical application. This review outlines the role of CD complexation in pediatric drug delivery, summarizes the relevant pharmacokinetic and toxicity findings in children, and presents examples of CD-based pediatric formulations.