TL;DR
The nasal GLDL spray is anticipated to be a promising and effective treatment option for BC by developing a nasal spray containing GCN-loaded liposomes (GLDL), and exhibited antiproliferative properties, as demonstrated by histopathological analysis of the formulation.
One of the most deadly and malignant cancers is pancreatic cancer, and there is a very limited available therapy, and the patients die from the cancer. For treating pancreatic cancer, one of the most extensively used chemotherapeutic agents is gemcitabine, and its clinical efficiency is hindered by its rapid metabolism, minimal tumor accumulation, and systemic toxicity. The aim of this study is to construct a dual-responsive nanoparticle system for targeting and controlled release of gemcitabine in the pancreatic tumor microenvironment for enhanced therapeutic outcome of the drug. These prepared nanoparticles were sensitive to pH as well as temperature and consequently showed tumor-specific release of gemcitabine with reduced off-target side effects. In vitro and in vivo studies with pancreatic cancer models were performed to assess the therapeutic activity of the formulation. The cellular uptake experiments showed efficient uptake of the nanoparticles by PANC-1 pancreatic cancer cells, leading to improved drug delivery into cells. Evaluation of the cytotoxicity showed that the anticancer activity of the therapy using the nanoparticles was significantly better with an IC50 value of 4.8µM versus 12.5µM for free gemcitabine. In a murine pancreatic tumor xenograft, gemcitabine-loaded nanoparticles were able to inhibit tumor growth by 45%, while free gemcitabine was able to inhibit tumor growth by 20%. Moreover, the dual-responsive system showed controlled and sustained drug release in tumor-relevant conditions, which improved the therapeutic targeting. The plasma exposure of the drug in the nanoparticle formulation was enhanced by about 4-fold (AUC0-24h 86.4 vs. 21.7 µg·h/mL) and the tumor accumulation of the drug was enhanced by about 5-fold (8.4 vs. 1.6 %ID/g) compared to free gemcitabine, and the plasma level of hepatic enzymes was within normal range in the nanoparticle animals, while plasma exposure of free gemcitabine showed significant elevation in levels of ALT (p = 0.01), directly supporting the reduced systemic toxicity of the formulation. The results show that delivery of gemcitabine using nanoparticles with dual responsiveness can significantly improve the antitumor activity and drug bioavailability and decrease systemic toxicity based on preclinical pharmacokinetic and biochemical evidence in a single xenograft model. The proposed strategy is a promising proof-of-concept strategy for the enhancement of pancreatic cancer treatment and an example of stimulus-responsive nanomedicine platforms in precision oncology. Additional preclinical studies are needed to prove long-term safety and to translate it into clinical use.
Despite improvements in screening and treatment, breast cancer is still one of the most common cancers diagnosed in women globally and a major cause of cancer-related death. Although 5-fluorouracil (5-FU), a pyrimidine derivative, has long been used in systemic treatments for breast cancer, its low oral bioavailability, dose-limiting toxicities, and acquired resistance restrict its clinical efficacy. By enhancing drug stability, permitting controlled and stimuli-responsive release, and facilitating both passive and active tumor targeting, nanocarrier-based delivery platforms such as lipid-based systems, polymeric nanoparticles, dendrimers, nanogels, inorganic nanostructures, and hybrid nanoplatforms offer promising ways to get around these restrictions. This review synthesizes recent high-impact literature on nanocarrier-mediated delivery of 5-FU for breast cancer, covering pharmacological considerations, nanocarrier classes, targeted and co-delivery approaches, stimuli-responsive designs, challenges to clinical translation, and emerging trends such as personalized nanomedicine and AI-guided carrier optimization.
Histopathological and toxicity studies confirm the antiproliferative effects and safety of the transdermal LLT formulation and support the potential of transdermal LLT formulation to be an effective and safe treatment for BC.
