Nucleic acid–based therapeutics are a rapidly expanding class of precision medicines capable of directly modulating gene expression. However, their clinical application is limited by challenges in cellular delivery, including large molecular size, hydrophilicity, and susceptibility to enzymatic degradation. To address these barriers, advanced delivery platforms such as cell-penetrating peptides and lipid nanoparticles (LNPs) have been developed. This study evaluates two delivery systems: the cell-penetrating peptide PepFect-14 (PF14) and LNP formulations, for enhancing nucleic acid delivery and cellular uptake. PF14 facilitates intracellular transport through peptide–nucleic acid complex formation, while LNPs protect cargo from degradation and can promote endosomal escape. Their performance was assessed under different conditions using luciferase-based reporter systems in HeLa cells. PF14-mediated delivery of the splice-switching oligonucleotide ON-705 in HeLa 705 cells showed efficient splice correction, with activity increasing in a dose- and molar ratio- dependent manner, reaching a plateau at a 1:10 ratio. Delivery efficiency was significantly influenced by formulation conditions, with Opti-MEM outperforming standard media and sugar-based buffers. Polymer excipients also affected activity as PVA18, PVA40, and PVP40 enhanced performance, while low molecular weight PVP reduced efficacy. In parallel, LNP-mediated delivery of luciferase mRNA in wild-type HeLa cells demonstrated robust, dose-dependent protein expression. Both systems maintained high cell viability (80–100%). Overall, these findings highlight the importance of formulation optimization in improving nucleic acid delivery and provide practical insights for enhancing peptide- and lipid-based therapeutic platforms.
D. Daniele, Z. Hein, O. Saher et al.· International Journal of Pha...· 0 citations
The kidney plays a critical role in metabolite excretion, fluid regulation, and homeostasis, yet remains highly vulnerable to structural and functional disorders. Kidney diseases represent a major global health burden, often progressing to chronic complications due to the limited efficacy and poor selectivity of conventional therapies, which are frequently associated with systemic toxicity. Accordingly, the development of targeted drug delivery systems is essential to improve therapeutic outcomes. In this study, advanced quatsomes were developed as a kidney-targeted nanosystem to enhance the delivery of curcumin, a natural polyphenolic compound with potent antioxidant and nephroprotective properties. The system was composed of di-dodecyl-dimethyl-ammonium bromide (DDAB), cholesterol, limonene, hyaluronic acid (HA) and surfactants, and was fabricated using the ethanol injection method. A 23 factorial design was employed to optimize formulation variables, including DDAB:cholesterol ratio, limonene:drug ratio, and surfactant concentration. The optimized formulation (desirability = 0.950) exhibited high entrapment efficiency (87.80%), nanosized vesicles (120.55 nm), and a positive surface charge (+38.30 mV). Transmission electron microscopy confirmed spherical morphology, while in-vitro release studies demonstrated a biphasic profile. The formulation also showed good physicochemical stability and enhanced antioxidant activity. Mechanistically, passive targeting via nanoscale size and cationic charge facilitated interaction with the glomerular filtration barrier and mesangial uptake, while limonene improved vesicle deformability. HA functionalization further enabled CD44-mediated active targeting. In vivo, the optimized system significantly reduced serum creatinine and blood urea nitrogen levels in a cisplatin-induced nephrotoxicity model, with histological evidence of renal protection. Overall, the developed quatsomes demonstrate promising potential as an efficient renal-targeted nanocarrier.
Sadek Ahmed, Rana M. ElBishbishy, Mohamed A. Sadek et al.· Journal of Pharmacy & Pharma...· 1 citation
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
